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Minneapolis, MN, United States

The University of Minnesota, Twin Cities is a public research university located in Minneapolis and St. Paul, Minnesota, United States. The Minneapolis and St. Paul campuses are approximately 5 miles apart, and the Saint Paul campus is actually in neighboring Falcon Heights. It is the oldest and largest campus within the University of Minnesota system and has the sixth-largest main campus student body in the United States, with 51,853 students in 2012–2013. The university is organized into 19 colleges and schools, and it has sister campuses in Crookston, Duluth, Morris, and Rochester.Minnesota's athletic teams are known collectively as the Minnesota Golden Gophers and compete in the NCAA's Division I as members of the Big Ten Conference. Wikipedia.


Molina J.E.,University of Minnesota
Annals of Thoracic Surgery | Year: 2011

Background: A series of 15 patients previously treated for Paget-Schroetter syndrome with a transaxillary first rib resection (TARR) were seen with recurrent thrombosis. Methods: Ten were reoperated using an anterior subclavicular approach. The time of reoperation ranged from 5 months to 7 years (mean, 23.4 months). All patients had been subjected to multiple balloon plasties and 4 of them in addition had up to 3 stents implanted, which also failed. Reevaluation was done with venography. Ten patients were considered to be still salvageable and were reoperated, but 5 were inoperable due to progressive obliteration of the venous channel as early as 2 weeks after TARR. Results: All 10 patients had successful reestablishment of the subclavian vein patency and caliber and have remained patent without anticoagulants. Conclusions: The patients who re-thrombose or remain obstructed after TARR should be reoperated instead of resourcing to implanting stents or multiple balloon plasties that invariably fail, and patients should not be kept on anticoagulation indefinitely hoping to maintain the vein open. © 2011 The Society of Thoracic Surgeons.


Allen J.I.,University of Minnesota
Current Opinion in Gastroenterology | Year: 2012

PURPOSE OF REVIEW: This review concerns quality assurance for gastrointestinal endoscopic procedures, especially colonoscopy and will emphasize research and guidelines published since January 2011. Important articles from previous years have been included for background. RECENT FINDINGS: Critical lapses in endoscope processing and administration of intravenous sedation alerted us to the infection risk of endoscopy. Increases in cost of colonoscopy, evidence for overuse and studies demonstrating missed cancers have led some to question the value of endoscopy. Despite these setbacks, the National Polyp Study (NPS) consortium published their long-term follow-up of the original NPS patients and confirmed that colonoscopy with polyp removal can reduce the risk of colorectal cancer for an extended period. In this article, we will focus on ways to improve the value of outpatient colonoscopy. SUMMARY: The United States national quality improvement agenda recently became organized into a more coordinated effort spearheaded by several public and private entities. They comprise the infrastructure by which performance measures are developed and implemented as accountability standards. Understanding wherein a gastroenterology (GI) practice fits into this infrastructure and learning ways we can improve our endoscopic practice is important for physicians who provide this vital service to patients. This article will provide a roadmap for developing a quality assurance program for endoscopic practice. Copyright © Lippincott Williams & Wilkins.


Jacobs Jr. D.R.,University of Minnesota | Orlich M.J.,Loma Linda University
American Journal of Clinical Nutrition | Year: 2014

Nutritionism reduces dietary advice to statements about a few nutrients, with sometimes unintended implications for science, industry, and the public. Although reductionist questions about nutrition are legitimate scientifically, a nutrient focus in the public arena forces the food industry to compete with the use of nutrient statements. Consumers must interpret information that may not be correct or relevant. The theory of food synergy, which postulates that the many constituents of individual foods and dietary patterns act together on health, leads to the idea that dietary policy would be clearer if it focused on foods. To illustrate this method, the food-based A Priori Diet Quality Score was described in the IowaWomen's Health Study; a substantial total mortality reduction for increasing quartiles of the score was found. The simple food-based rules implied in this a priori score support minimizing meat, salt, added sugar, and heavily processed foods while emphasizing phytochemical-rich foods. These principles could help improve nutrition policy, help industry to supply better food, and help to focus future scientific research. Although an understanding of what foods are best for health is a step forward in nutrition, other major challenges remain, including getting high-quality food to the masses and food sustainability. © 2014 American Society for Nutrition.


Little J.W.,University of Minnesota
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology | Year: 2012

Vitamin K antagonists, such as warfarin, are considered to be the treatment of choice to prevent thromboembolic events, but problems, such as the need for frequent dose adjustment and monitoring of coagulation status, as well as multiple drug and food interactions, make their use difficult for both physician and patient. Two new anticoagulants are now being considered as possible replacements of vitamin K antagonists. Dabigatran, an oral direct thrombin inhibitor has already been approved in the USA for prevention of stroke in patients with atrial fibrillation. Rivaroxaban, a factor Xa inhibitor, and dabigatran are licensed in Europe and Canada for short-term thromboprophylaxis after elective hip or knee replacement surgery. The advantages of these drugs are that they are safe and effective, require no monitoring, have a direct mode of action against only one clotting factor (thrombin or factor Xa), have limited drug interactions, and have rapid peak blood levels. Based on the fact that dabigatran has already been approved for use in the USA, it would appear that it has an advantage over rivaroxaban in becoming the replacement drug for vitamin K antagonists. © 2012 Elsevier Inc. All rights reserved.


Concern about the role of beverages, especially those containing sugar, in the obesity epidemic continues to escalate. Bans on sugar-sweetened beverages and chocolate milk have expanded from the school cafeteria to the ballpark and convenience store. This review describes the experience of the 2010 Dietary Guidelines Advisory Committee (DGAC) in conducting an evidence-based review of dietary exposure and health outcomes. The following four topics relevant to fluids and body weight were reviewed: added sugar, noncaloric sweeteners, food form and body weight, and macronutrients and satiety. There were limited and conflicting data on how liquids and solids affect energy intake and body weight. Fluid intake is typically not tracked in prospective, cohort longitudinal studies; thus, data are not available on fluid intake and health status from studies using the strongest epidemiologic designs. Despite public perception that beverages are linked to increased body weight compared with whole foods, evidence-based reviews of this topic do not support that liquid calories are processed differently in the body. The practical recommendation to replace caloric beverages with water as an aid to control weight is based on calorie reduction, rather than a link between added-sugar intake and obesity. © 2012 International Life Sciences Institute.


Haus E.L.,University of Minnesota | Smolensky M.H.,University of Texas at Austin
Sleep Medicine Reviews | Year: 2013

Shift work that includes a nighttime rotation has become an unavoidable attribute of today's 24-h society. The related disruption of the human circadian time organization leads in the short-term to an array of jet-lag-like symptoms, and in the long-run it may contribute to weight gain/obesity, metabolic syndrome/type II diabetes, and cardiovascular disease. Epidemiologic studies also suggest increased cancer risk, especially for breast cancer, in night and rotating female shift workers. If confirmed in more controlled and detailed studies, the carcinogenic effect of night and shift work will constitute additional serious medical, economic, and social problems for a substantial proportion of the working population. Here, we examine the possible multiple and interconnected cancer-promoting mechanisms as a consequence of shift work, i.e., repeated disruption of the circadian system, pineal hormone melatonin suppression by exposure to light at night, sleep-deprivation-caused impairment of the immune system, plus metabolic changes favoring obesity and generation of proinflammatory reactive oxygen species. © 2012 Elsevier Ltd.


Anderson T.M.,University of Minnesota
Journal of neurophysiology | Year: 2012

In this study, we examined the contribution of a low-threshold calcium current [I(Ca(T))] to locomotor-related activity in the neonatal mouse. Specifically, the role of I(Ca(T)) was studied during chemically induced, locomotor-like activity in the isolated whole cord and in a genetically distinct population of ventromedial spinal interneurons marked by the homeobox gene Hb9. In isolated whole spinal cords, cycle frequency was decreased in the presence of low-threshold calcium channel blockers, which suggests a role for I(Ca(T)) in the network that produces rhythmic, locomotor-like activity. Additionally, we used Hb9 interneurons as a model to study the cellular responses to application of low-threshold calcium channel blockers. In transverse slice preparations from transgenic Hb9::enhanced green fluorescent protein neonatal mice, N-methyl-d-aspartate-induced membrane potential oscillations in identified Hb9 interneurons also slowed in frequency with application of nickel when fast, spike-mediated, synaptic transmission was blocked with TTX. Voltage-clamp and immunolabeling experiments confirmed expression of I(Ca(T)) and channels, respectively, in Hb9 interneurons located in the ventromedial spinal cord. Taken together, these results provide support that T-type calcium currents play an important role in network-wide rhythm generation during chemically evoked, fictive locomotor activity.


DeYoung C.G.,University of Minnesota
Frontiers in Human Neuroscience | Year: 2013

The neuromodulator dopamine is centrally involved in reward, approach behavior, exploration, and various aspects of cognition. Variations in dopaminergic function appear to be associated with variations in personality, but exactly which traits are influenced by dopamine remains an open question. This paper proposes a theory of the role of dopamine in personality that organizes and explains the diversity of findings, utilizing the division of the dopaminergic system into value coding and salience coding neurons (Bromberg-Martin et al., 2010). The value coding system is proposed to be related primarily to Extraversion and the salience coding system to Openness/Intellect. Global levels of dopamine influence the higher order personality factor, Plasticity, which comprises the shared variance of Extraversion and Openness/Intellect. All other traits related to dopamine are linked to Plasticity or its subtraits. The general function of dopamine is to promote exploration, by facilitating engagement with cues of specific reward (value) and cues of the reward value of information (salience). This theory constitutes an extension of the entropy model of uncertainty (EMU; Hirsh et al., 2012), enabling EMU to account for the fact that uncertainty is an innate incentive reward as well as an innate threat. The theory accounts for the association of dopamine with traits ranging from sensation and novelty seeking, to impulsivity and aggression, to achievement striving, creativity, and cognitive abilities, to the overinclusive thinking characteristic of schizotypy. © 2013 DeYoung.


Arendt E.A.,University of Minnesota | Dejour D.,Lyon Ortho Clinic
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2013

The diagnosis of and treatment for musculoskeletal disease and injuries have seen an explosion of new knowledge. More precise imaging, correlative injury anatomy, more focused physical examination features, among others, have led this upsurge of current insight. Crucial to this knowledge revolution is the expansion of international knowledge, which is aided by an adoption of a universal scientific language, electronic transfer of information, and personal communication of surgeons and scientists across national boundaries. One area where this is particularly evident is in our knowledge and treatment for patellofemoral disorders. This article will review the developments in the management of patellar dislocations by tracing their historical roots. This is not meant to be a comprehensive review, but rather to give current readers a "historical memory" upon which to judge and interpret our present-day bridge of knowledge. Level of evidence V. © 2012 Springer-Verlag Berlin Heidelberg.


Phillips R.L.,University of Minnesota
Crop Science | Year: 2010

Yield barriers must be broken. The diminished stock of staple foods, higher grain prices, and increases in production failing to keep up with demand, coupled with 80 million people being added to the world population every year, suggests that we are on a collision course with famine unless greater investments are made in research and development, as well as education. Genetic improvement of staples has accounted for more than half of the past increases in yields. Fortunately, a revolution in genetic knowledge is co-evolving with the increased demand for food, feed, fiber, and fuel. Utilizing genetic diversity has been a mainstay of past production improvements High throughput DNA sequencing, the related bioinformatics, and a cascade of genetic technologies can now be employed to detect previously hidden genetic variability, to understand gene functions, to make greater use of accessions in germplasm banks, and to make breeding schemes more efficacious. The involvement of outstanding scientists who can bring interdisciplinary ideas to the question of how to break yield barriers must be part of the strategy. Educational programs at all levels, even high school, should emphasize the opportunities in international agriculture to build a cadre of dedicated scientists for the future. © Crop Science Society of America.


To detect genetic association with common and complex diseases, two powerful yet quite different multimarker association tests have been proposed, genomic distance-based regression (GDBR) (Wessel and Schork [2006] Am J Hum Genet 79:821-833) and kernel machine regression (KMR) (Kwee et al. [2008] Am J Hum Genet 82:386-397; Wu et al. [2010] Am J Hum Genet 86:929-942). GDBR is based on relating a multimarker similarity metric for a group of subjects to variation in their trait values, while KMR is based on nonparametric estimates of the effects of the multiple markers on the trait through a kernel function or kernel matrix. Since the two approaches are both powerful and general, but appear quite different, it is important to know their specific relationships. In this report, we show that, under the condition that there is no other covariate, there is a striking correspondence between the two approaches for a quantitative or a binary trait: if the same positive semi-definite matrix is used as the centered similarity matrix in GDBR and as the kernel matrix in KMR, the F-test statistic in GDBR and the score test statistic in KMR are equal (up to some ignorable constants). The result is based on the connections of both methods to linear or logistic (random-effects) regression models. © 2011 Wiley-Liss, Inc.


Voytas D.F.,University of Minnesota | Gao C.,CAS Institute of Genetics and Developmental Biology
PLoS Biology | Year: 2014

Plant agriculture is poised at a technological inflection point. Recent advances in genome engineering make it possible to precisely alter DNA sequences in living cells, providing unprecedented control over a plant's genetic material. Potential future crops derived through genome engineering include those that better withstand pests, that have enhanced nutritional value, and that are able to grow on marginal lands. In many instances, crops with such traits will be created by altering only a few nucleotides among the billions that comprise plant genomes. As such, and with the appropriate regulatory structures in place, crops created through genome engineering might prove to be more acceptable to the public than plants that carry foreign DNA in their genomes. Public perception and the performance of the engineered crop varieties will determine the extent to which this powerful technology contributes towards securing the world's food supply. © 2014 Voytas, Gao.


Koenig M.A.,University of Minnesota
Child Development | Year: 2012

Children's sensitivity to the quality of epistemic reasons and their selective trust in the more reasonable of 2 informants was investigated in 2 experiments. Three-, 4-, and 5-year-old children (N = 90) were presented with speakers who stated different kinds of evidence for what they believed. Experiment 1 showed that children of all age groups appropriately judged looking, reliable testimony, and inference as better reasons for belief than pretense, guessing, and desiring. Experiment 2 showed that 3- and 4-year-old children preferred to seek and accept new information from a speaker who was previously judged to use the "best" way of thinking. The findings demonstrate that children distinguish certain good from bad reasons and prefer to learn from those who showcased good reasoning in the past. © 2012 The Author. Child Development © 2012 Society for Research in Child Development, Inc.


Masgrau L.,Autonomous University of Barcelona | Truhlar D.G.,University of Minnesota
Accounts of Chemical Research | Year: 2015

ConspectusThe active site of an enzyme is surrounded by a fluctuating environment of protein and solvent conformational states, and a realistic calculation of chemical reaction rates and kinetic isotope effects of enzyme-catalyzed reactions must take account of this environmental diversity. Ensemble-averaged variational transition state theory with multidimensional tunneling (EA-VTST/MT) was developed as a way to carry out such calculations. This theory incorporates ensemble averaging, quantized vibrational energies, energy, tunneling, and recrossing of transition state dividing surfaces in a systematic way. It has been applied successfully to a number of hydrogen-, proton-, and hydride-transfer reactions. The theory also exposes the set of effects that should be considered in reliable rate constants calculations.We first review the basic theory and the steps in the calculation. A key role is played by the generalized free energy of activation profile, which is obtained by quantizing the classical potential of mean force as a function of a reaction coordinate because the one-way flux through the transition state dividing surface can be written in terms of the generalized free energy of activation. A recrossing transmission coefficient accounts for the difference between the one-way flux through the chosen transition state dividing surface and the net flux, and a tunneling transmission coefficient converts classical motion along the reaction coordinate to quantum mechanical motion. The tunneling calculation is multidimensional, accounting for the change in vibrational frequencies along the tunneling path and shortening of the tunneling path with respect to the minimum energy path (MEP), as promoted by reaction-path curvature. The generalized free energy of activation and the transmission coefficients both involve averaging over an ensemble of reaction paths and conformations, and this includes the coupling of protein motions to the rearrangement of chemical bonds in a statistical mechanically correct way. The standard deviations of the transmissions coefficients provide information on the diversity of the distribution of reaction paths, barriers, and protein conformations along the members of an ensemble of reaction paths passing through the transition state.We first illustrate the theory by discussing the application to both wild-type and mutant Escherichia coli dihydrofolate reductase and hyperthermophilic Thermotoga maritima dihydrofolate reductase (DHFR); DHFR is of special interest because the protein conformational changes have been widely studied. Then we present shorter discussions of several other applications of EA-VTST/MT to transfer of protons, hydrogen atoms, and hydride ions and their deuterated analogs. Systems discussed include hydride transfer in alcohol dehydrogenase, xylose isomerase, and thymidylate synthase, proton transfer in methylamine dehydrogenase, hydrogen atom transfer in methylmalonyl-CoA mutase, and nucleophilic substitution in haloalkane dehalogenase and two-dimensional potentials of mean force for potentially coupled proton and hydride transfer in the β-oxidation of butyryl-coenzyme A catalyzed by short-chain acyl-CoA dehydrogenase and in the pyruvate to lactate transformation catalyzed by lactate dehydrogenase. © 2014 American Chemical Society.


Kozak K.H.,University of Minnesota | Wiens J.J.,State University of New York at Stony Brook
Ecology Letters | Year: 2010

A major goal of ecology is to explain differences in species richness between regions and among clades. The diversification rate of clades is a key parameter for understanding both patterns. Here, we combine phylogenetic and climatic data for 250 species of plethodontid salamanders and show for the first time that rapid species diversification is associated with accelerated climatic-niche evolution among species. Both rates are particularly rapid in tropical regions, and where few clades geographically overlap. These results offer a surprising ecological explanation for why diversification rates are often higher in the tropics: rapid shifts between climatic regimes, rather than specific environmental conditions (e.g. high productivity, energy) drive higher diversity. They also suggest that climatic-niche evolution may be particularly rapid in regions where climate is particularly stable. Finally, these results indicate that evolutionary conservatism in climatic niches may be influenced by interactions between species and clades, rather than physiological tolerances alone. © 2010 Blackwell Publishing Ltd/CNRS.


Verneris M.R.,University of Minnesota
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

Two of the major complications that limit the efficacy of allogeneic hematopoietic cell transplantation (allo-HCT) are disease relapse and GVHD. Due to their rapid recovery early after allo-HCT and their ability to kill malignant targets without prior exposure, natural killer (NK) cells have been considered one of the main effector cells that mediate early GVL reactions. Conversely, regulatory T ells (Tregs) have proven to be critical in facilitating self-tolerance. Both murine and human studies have demonstrated a significant role for Tregs in the modulation of GVHD after allo-HCT. This article reviews the mechanisms of how these 2 cell types carry out these functions, focusing on the post-allo-HCT period. Surprisingly, relatively few studies have addressed how Tregs and NK cells interact with one another and whether these interactions are antagonistic. Although preclinical studies suggest active cross-talk between NK cells and Tregs, early clinical studies have not shown a detrimental impact of Treg therapy on relapse. Despite this, interruption of tolerogenic signals may enhance the efficacy of NK effector functions. Methods to transiently impair Treg functions and augment NK cell alloreactivity will be discussed.


Hordinsky M.K.,University of Minnesota
The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research | Year: 2013

Alopecia areata is a complex genetic, immune-mediated disease that targets anagen hair follicles. The disease affects children and adults and is characterized by round or oval patches of hair loss, loss of all scalp hair (alopecia totalis), body hair (alopecia universalis), or ophiasis pattern hair loss. Patients may also present with patchy loss in multiple hair-bearing areas. Commonly associated diseases include asthma, allergic rhinitis, atopic dermatitis, thyroid disease, and automimmune diseases, such as thyroiditis and vitiligo. Nail abnormalities may precede, follow, or occur concurrently with hair loss activity. Alopecia areata has no known age, race, or ethnic preponderance and in contrast to other autoimmune diseases such as thyroiditis or lupus, the hair follicle does not usually sustain permanent injury and maintains its potential to regrow hair. It is estimated that alopecia areata affects between six and seven million individuals in the United States. Genes, the immune and nervous systems have all been implicated in the pathogenesis of alopecia areata. Although many treatments are available, there is still no cure. Bolstered by new scientific and translational opportunities from recently published genome-wide association studies, an ambitious treatment development program has recently been initiated by the National Alopecia Areata Foundation.


Zink R.M.,University of Minnesota
Journal of Avian Biology | Year: 2010

Microsatellites are commonly used molecular markers in phylogeography, and many view them as superior to mitochondrial DNA (mtDNA) gene trees. Being based on frequencies of alleles, and not gene trees, microsatellites exhibit the same analytical drawbacks that resulted in the abandonment of allozymes in genetic studies of population history. I illustrate some these familiar drawbacks by reanalyzing microsatellite data on the song sparrow. Subspecies were previously evaluated with hierarchical analyses of molecular variance, suggesting that subspecies explain 8% of the total variance in microsatellite frequencies. However, this useful heuristic technique only evaluates a priori groupings, and the objective of the study ought to be to discover such groupings, not assume them. In fact, other arbitrary groupings of samples explained the same or greater amounts of variance, and I suggest that for testing subspecies limits, a gene tree is preferable. Grouping population samples by subspecies in the San Francisco Bay area accounts for 1.2% of the microsatellite variation, and despite claims that this informs conservation planning, the data do not support any particular population or subspecies as being genetically or evolutionarily significant. A distance phenogram was used to infer a sequential colonization of the Aleutian Islands, but because individuals were pooled into a priori groups and the phenogram was arbitrarily rooted, this conclusion is tenuous. A plot of heterozygosity vs number of alleles per sample showed that an equally parsimonious interpretation is that current genetic diversity tracks effective population size. Microsatellites should be replaced in nuclear-gene phylogeography by analyses of sequences, which will benefit the study of phylogeography, comparison of nuclear and mtDNA results, and aid in interpreting the results in a conservation context. © 2010 The Authors. Journal compilation © 2010 Journal of Avian Biology.


Georgieff M.K.,University of Minnesota
Nutrition Reviews | Year: 2011

Early iron deficiency not only affects brain and behavioral function during the period of iron deficiency, it persists long after treatment. The mechanisms include long-term alterations in dopamine metabolism, myelination, and hippocampal structure and function. Recent studies have demonstrated long-term genomic changes, which suggests the regulation of brain function is fundamentally altered. © 2011 International Life Sciences Institute.


DeLong R.,University of Minnesota
Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2012

The study objective was to correlate wear between an in vitro method for simulating wear and in vivo wear of a posterior dental composite. Ten subjects (12 restorations) were selected from a five-year clinical study (University of North Carolina, School of Dentistry) that assessed wear of SureFil composite (Caulk, Dentsply). Subject casts were digitized and changes in volume and mean depth with time were calculated from the 3D digital models for contact and contact-free wear. SureFil composite disks were mounted in the University of Minnesota's Artificial Oral Environment, opposed by natural enamel, subjected to mandibular-like movements for 150 K, 300 K, 600 K, 1.2 M, and 1.5 M cycles, and loaded with peak forces of 13 N (n = 7) or 30 N (n = 3). Wear rates were calculated as the slope of the linear regressions fitting the wear data. Data were analyzed using one-way ANOVAs and post hoc t-tests where appropriate (p = 0.05). Clinical restorations included contact wear on seven restorations and contact-free wear on all restorations. Contact-free wear was less than contact wear (p < 0.01). SureFil clinical wear rates were 0.012 mm/year (mean depth) and 0.023 mm(3)/year (volume). Clinical restorations expanded slightly during the first year. Using a conversion rate of one year equals 3 × 10(5) cycles, there were no significant differences between the clinical and simulated data except depths at Year 5 and 13 N volume at Year 4. The 30 N simulation reproduced the clinical data if contact-free wear was taken into account. Good agreement between simulated and clinical wear implies that in vitro simulation can screen new composite formulations. Copyright © 2012 Wiley Periodicals, Inc.


Trikudanathan G.,University of Minnesota
Nature Reviews Gastroenterology and Hepatology | Year: 2014

Extraction of common bile duct stones by endoscopic retrograde cholangiopancreatography generally involves biliary sphincterotomy, endoscopic papillary balloon dilation or a combination of both. Endoscopic papillary large-balloon dilation after sphincterotomy has increased the safety of large stone extraction. Cholangioscopically directed electrohydraulic and laser lithotripsy using single-operator mother-daughter systems or direct peroral cholangioscopy using ultraslim endoscopes are increasingly utilized for the management of refractory stones. In this Review, we focus on advances in endoscopic approaches and techniques, with a special emphasis on management strategies for 'difficult' common bile duct stones.


Kapusta J.I.,University of Minnesota
Physical Review C - Nuclear Physics | Year: 2010

The thermodynamics and critical exponents and amplitudes of high temperature and dense matter near the chiral critical point are studied. The parameterized equation of state matches that calculated with lattice QCD at zero chemical potential and to the known properties of nuclear matter at zero temperature. The extent to which finite size effects wash out the phase separation near the critical point is determined. © 2010 The American Physical Society.


Gangardt D.M.,University of Birmingham | Kamenev A.,University of Minnesota
Physical Review Letters | Year: 2010

Unless protected by the exact integrability, solitons are subject to dissipative forces, originating from a thermally fluctuating background. At low enough temperatures T background fluctuations should be considered as being quantized which enables us to calculate finite lifetime of the solitons τ∼T-4. We also find that the coherent nature of the quantum fluctuations leads to long-range interactions between the solitons mediated by the superradiation. Our results are of relevance to current experiments with ultracold atoms, while the approach may be extended to solitons in other media. © 2010 The American Physical Society.


Tseng W.-L.,University of Minnesota | Gau S.S.-F.,National Taiwan University Hospital
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2013

Background Cognitive processes and mechanisms underlying the strong link between attention-deficit/hyperactivity disorder (ADHD) and social problems remain unclear. Limited knowledge also exists regarding a subgroup of youth with ADHD who do not have social problems. This study investigated the extent to which executive function (EF) mediated the association between ADHD and social problems and compared ADHD symptoms, comorbidities, and EF among ADHD youth with and without social problems and controls. Methods The sample consisted of 279 youth with ADHD and 173 controls without ADHD (11-17 years of age) in Taiwan. Among youth with ADHD, two subgroups were further identified: 70 ADHD youth with social problems and 31 ADHD youth without social problems. EF was assessed with four subtests from the Cambridge Neuropsychological Test Automated Battery (Spatial span, Spatial working memory, Intra-dimensional/extra-dimensional shifts, Stockings of Cambridge). Social problems were assessed by mother and child reports. Results Executive function measures in working memory and planning mediated the effect of ADHD on social problems, independent of age, gender, and IQ. The two ADHD groups with and without social problems did not differ in ADHD severity or comorbidities; however, ADHD youth without social problems performed better on certain measures of EF such as working memory, planning, and response inhibition. Conclusions These findings suggest that deficits in some aspects of EF may account for social problems often experienced by youth with ADHD. © 2013 The Authors Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.


Pereira M.A.,University of Minnesota
Nutrition Reviews | Year: 2013

"Diet beverage" is a common term used to describe beverages that are sweetened with non-nutritive or artificial sweeteners (ASBs). Marketing strategies often imply that consuming these beverages holds promise for weight control or weight loss. The objective of the present review is to provide a synthesis of the literature on the effects of ASBs on body weight, cardiovascular disease, and type 2 diabetes. Consumption of diet beverages is much lower than that of sugar-sweetened beverages (SSBs), and people trying to lose weight report the highest levels of ASB consumption. To date, prospective observational studies have revealed mixed results, and it appears that reverse causality is a particular problem, since individuals who are at higher risk for weight gain may choose to consume ASBs in an attempt to control their weight or reduce disease risk. As for experimental studies, the evidence currently suggests that obesity risk may be lower when ASBs replace SSBs in the diet. Still, additional evidence from experimental studies is needed to more definitively determine the benefits and risks of frequent ASB consumption. © 2013 International Life Sciences Institute.


Purpose of Review: Adolescence is a developmental period characterized by relatively high rates of substance use and substance use disorders. Precise assessment and classification of adolescent drug use behaviors are essential in gaining an accurate understanding of the nature and extent of adolescent drug use, and possible intervention or treatment needs. There has been a select group of recently published research reports and manuscripts that address critical and emerging issues pertaining to the classification and assessment of alcohol and other drug use behaviors among adolescents. An overview of these publications is provided and their clinical relevance is discussed. Recent Findings: The paper will focus on recent research, most from the United States, that addresses four main issues. One is the application of the new DSM-5 criteria to adolescents, including the advantages and disadvantages of the new criteria for substance use disorders. The second issue pertains to advances in instrumentation that provide new tools for researchers and clinicians in assessing substance use in adolescents. A significant public health issue is addressed as the third theme in the paper-screening for alcohol abuse in college settings. Finally, the paper reviews how the emerging science of brain development can inform the assessment process. Summary: Recent advances in the adolescent drug abuse assessment field continue to inform clinical service and research. As a whole, these advances have strengthened the field, but continued research is needed to further refine assessment practices and standards and to better understand how to define a substance use disorder in youth. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Turner L.,University of Minnesota
Globalization and Health | Year: 2012

Background: Despite having access to medically necessary care available through publicly funded provincial health care systems, some Canadians travel for treatment provided at international medical facilities as well as for-profit clinics found in several Canadian provinces. Canadians travel abroad for orthopaedic surgery, bariatric surgery, ophthalmologic surgery, stem cell injections, " Liberation therapy" for multiple sclerosis, and additional interventions. Both responding to public interest in medical travel and playing an important part in promoting the notion of a global marketplace for health services, many Canadian companies market medical travel.Methods: Research began with the goal of locating all medical tourism companies based in Canada. Various strategies were used to find such businesses. During the search process it became apparent that many Canadian business promoting medical travel are not medical tourism companies. To the contrary, numerous types of businesses promote medical travel. Once businesses promoting medical travel were identified, content analysis was used to extract information from company websites. Company websites were analyzed to establish: 1) where in Canada these businesses are located; 2) the destination countries and health care facilities that they market; 3) the medical procedures they promote; 4) core marketing messages; and 5) whether businesses market air travel, hotel accommodations, and holiday tours in addition to medical procedures.Results: Searches conducted from 2006 to 2011 resulted in identification of thirty-five Canadian businesses currently marketing various kinds of medical travel. The research project began with what seemed to be the straightforward goal of establishing how many medical tourism companies are based in Canada. Refinement of categories resulted in the identification of eighteen businesses fitting the category of what most researchers would identify as medical tourism companies. Seven other businesses market regional, cross-border health services available in the United States and intranational travel to clinics in Canada. In contrast to medical tourism companies, they do not market holiday tours in addition to medical care. Two companies occupy a narrow market niche and promote testing for CCSVI and " Liberation therapy" for multiple sclerosis. Three additional companies offer bariatric surgery and cosmetic surgery at facilities in Mexico. Four businesses offer health insurance products intended to cover the cost of obtaining privately financed health care in the U.S. These businesses also help their clients arrange treatment beyond Canada's borders. Finally, one medical travel company based in Canada markets health services primarily to U.S. citizens.Conclusions: This article uses content analysis of websites of Canadian companies marketing medical travel to provide insight into Canada's medical travel industry. The article reveals a complex marketplace with different types of companies taking distinct approaches to marketing medical travel. © 2012 Turner; licensee BioMed Central Ltd.


Schleiss M.R.,University of Minnesota
Infectious Disorders - Drug Targets | Year: 2011

Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection. © 2011 Bentham Science Publishers.


Spokas K.A.,University of Minnesota
GCB Bioenergy | Year: 2013

Recent observations of decreased greenhouse gas (GHG) production from biochar amended soils have been used to further substantiate the environmental benefit of biochar production and soil incorporation strategies. However, the mechanisms behind this biochar-mediated response have not been fully elucidated. In addition, the duration of these GHG reductions is not known and is of pivotal importance for the inclusion of biochar into future bioenergy production and climate abatement strategies. In this study, the impacts of biochar field aging on the observed GHG production/consumption were evaluated. Two different wood-derived biochars and a macadamia nut shell biochar were weathered in an agricultural field in Rosemount, MN (2008-2011) and the impacts on net soil GHG production/consumption were assessed through laboratory incubations. For the three biochars evaluated here, weathering negated the suppression of N2O production that was originally observed from the fresh biochar in laboratory incubations. On the other hand, all three weathered biochars enhanced CO2 production (three- to tenfold compared with the fresh biochar amendments) in laboratory soil incubations, suggesting an enhanced microbial mineralization rate of the weathered biochar. This enhanced mineralization could be aided by the chemical oxidation of the biochar surfaces during weathering. Fresh biochar reduced observed soil methane oxidation rates, whereas the weathered biochars had no significant impacts on the observed soil methanotrophic activity. This study demonstrates that for these three biochars, weathering greatly alters the GHG response of the soil systems to biochar amendments. © 2013 Blackwell Published 2012. This article is a U.S. Government work and is in the public domain in the USA.


Masten A.S.,University of Minnesota
Clinical Child and Family Psychology Review | Year: 2013

This commentary highlights conceptual themes in the opening section of this special issue on military families in relation to a new synthesis of developmental systems theory that emerged from developmental, ecological, and family systems theory, as well as developmental psychopathology and risk/resilience frameworks. Articles in this special issue draw on these concepts to characterize and guide the burgeoning research on military families. This perspective emphasizes that multiple dynamic systems interact across levels to shape individual development, as well as the function of families and military units. Developmental timing is important for understanding how challenges of military life may impact individuals and families. Cascade effects are noted, where stress experienced by one family or service member can influence the function of other individuals or larger systems. Capacity for resilience is distributed across systems, including families and cultures, as well as resources or supports provided by military organizations to foster adaptive responses or recovery. These systems include schools and educational programs that play key roles in fostering and supporting resilience for children. Overall, developmental system concepts have considerable utility for guiding research with military families, particularly in regard to promoting resilience. Moreover, lessons learned from military families and programs may have much broader implications for many other nonmilitary children, families, and organizations that share similar goals and challenges. © 2013 Springer Science+Business Media New York.


Tess P.A.,University of Minnesota
Computers in Human Behavior | Year: 2013

The ubiquity of social media (e.g., Facebook, Twitter) is no more apparent than at the university. Social media are increasingly visible in higher education settings as instructors look to technology to mediate and enhance their instruction as well as promote active learning for students. Many scholars argue for the purposeful integration of social media as an educational tool. Empirical evidence, however, has lagged in supporting the claim. Most of the existing research on the utility and effectiveness of social media in the higher education class is limited to self-reported data (e.g., surveys, questionnaires) and content analyses. This paper summarizes the scholarly writings as well as reviews the findings of empirical investigations. Some limitations are discussed, and future areas of research are proposed. © 2013 Elsevier Ltd. All rights reserved.


Skubitz K.M.,University of Minnesota
Current Treatment Options in Oncology | Year: 2014

Opinion statement Giant cell tumor of bone (GCTB) comprises up to 20 % of benign bone tumors in the US. GCTB are typically locally aggressive, but metastasize to the lung in ~5 % of cases. Malignant transformation occurs in a small percentage of cases, usually following radiation therapy. Historically, GCTB have been treated primarily with surgery. When the morbidity of surgery would be excessive, radiation therapy may achieve local control. In most cases the primary driver of the malignant cell appears to be a mutation in H3F3A leading to a substitution of Gly34 to either Trp or Leu in Histone H3.3. This change presumably alters the methylation of the protein, and thus, its effect on gene expression. The malignant stromal cells of GCTB secrete RANKL, which recruits osteoclast precursors to the tumor and stimulates their differentiation to osteoclasts. The elucidation of the biology of GCTB led to trials of the anti-RANKL monoclonal antibody denosumab in this disease, with a clear demonstration of beneficial clinical effect. Surgery remains the primary treatment of localized GCTB. When surgery is not possible or would be associated with excessive morbidity, denosumab is a good treatment option. The optimal length of treatment and schedule of denosumab is unknown, but recurrences after apparent complete responses have been observed after stopping denosumab, and long-term follow-up of denosumab treatment may reveal unrecognized effects. The role of denosumab in the preoperative or adjuvant setting will require clinical trials. In some cases local radiation therapy may be useful, although long term effects should be considered. © 2014 Springer Science+Business Media New York.


Miller J.S.,University of Minnesota
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

Natural killer (NK) cells recognize targets stressed by malignant transformation or infection (particularly CMV). We now know that NK cells can be long-lived and remember past exposures. They become educated by interaction with MHC class I molecules to gain potent function to kill targets and produce cytokines. In the clinical setting, haploidentical NK cells can be transferred adoptively to treat cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting chemotherapy to make space for the release of endogenous IL-15. In vivo expansion is also enhanced by cytokine administration. IL-2 has been used at low doses to stimulate NK cells in vivo, but has the down side of stimulating CD25hi regulatory T cells. IL-15 is now being tested and has the advantage of avoiding inhibitory regulatory T cell stimulation. In refractory acute myeloid leukemia, leukemia clearance is correlated with the persistence and in vivo expansion of NK cells after adoptive transfer. Limitations to NK cell therapy include poor in vivo survival and lack of specificity. Monoclonal antibodies and bispecific or trispecific killer engagers to target CD16 on NK cells to enhance recognition of various tumor antigens and ADAM17 inhibition to prevent CD16 shedding after NK cell activation should promote enhanced killing of cancer with specificity. Future strategies to exploit favorable donor immunogenetics or to expand NK cells ex vivo from blood, progenitors, or pluripotent progenitors may overcome immune barriers of adoptive transfer and comparative clinical trials will be needed to test these approaches.


Luepker R.V.,University of Minnesota
Annual Review of Public Health | Year: 2011

Cardiovascular disease (CVD) became the leading cause of chronic disease morbidity and mortality in industrialized countries in the twentieth century. In many nations, it peaked and began to decline, while in developing countries it is rising. The contributions of risk factors, sociocultural changes, and medical care are debated, but all play a role in understanding these disease patterns. Public health approaches such as dietary change along with widespread use of medications such as aspirin, statins, diuretics, and beta-blockers may impact future trends in this chronic disease epidemic. © 2011 by Annual Reviews. rights reserved.


Masten A.S.,University of Minnesota
Development and Psychopathology | Year: 2011

This article delineates parallel frameworks that grew out of the research on risk and resilience over the past four decades, a framework for research and a framework for practice, and then discusses the promise of an emerging synthesis. The research framework defined the meaning, models, and methods that successfully guided four waves of research to date on the nature and processes involved in human resilience. The applied framework emerged in response to urgent needs of children and families faced by adversity and those charged with helping them, resulting in guidelines for translating the unfolding but incomplete research evidence into action. The application of a resilience approach transformed practice in many fields concerned with promoting resilience in people at risk for problems, revolutionizing the mission, models, measures, and methods of practice to align with the emphasis on positive adaptation and strengths defining a resilience-based approach. Yet these interventions rarely translated back to inform and refine resilience theory in ways that would accelerate progress to promote resilience more effectively. The concluding section on translational synergy discusses the potential for a synthesis of basic and applied resilience frameworks as the next steps toward realizing the original objective and promise of resilience science. © 2011 Cambridge University Press.


Wang C.,University of Minnesota
Psychometrika | Year: 2015

Making inferences from IRT-based test scores requires accurate and reliable methods of person parameter estimation. Given an already calibrated set of item parameters, the latent trait could be estimated either via maximum likelihood estimation (MLE) or using Bayesian methods such as maximum a posteriori (MAP) estimation or expected a posteriori (EAP) estimation. In addition, Warm’s (Psychometrika 54:427–450, 1989) weighted likelihood estimation method was proposed to reduce the bias of the latent trait estimate in unidimensional models. In this paper, we extend the weighted MLE method to multidimensional models. This new method, denoted as multivariate weighted MLE (MWLE), is proposed to reduce the bias of the MLE even for short tests. MWLE is compared to alternative estimators (i.e., MLE, MAP and EAP) and shown, both analytically and through simulations studies, to be more accurate in terms of bias than MLE while maintaining a similar variance. In contrast, Bayesian estimators (i.e., MAP and EAP) result in biased estimates with smaller variability. © 2014, The Psychometric Society.


Kelly A.,Childrens Hospital of Philadelphia | Moran A.,University of Minnesota
Journal of Cystic Fibrosis | Year: 2013

Diabetes mellitus has emerged as a common comorbidity in cystic fibrosis and is considered a clinical entity (cystic fibrosis-related diabetes, CFRD) distinct from that of type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The relevance of this diagnosis extends not only from its imposition of additional medical burden but its association with worse health outcomes in individuals with CF. This paper will review the 2010 U.S. and other international guidelines for screening and treating CFRD. It will highlight newer data regarding early glucose and insulin secretion defects, mechanisms linking CFRD to worse outcomes, and recent advances in T2DM that may provide insights for CFRD; insulin secretion will be reviewed as background for these recent developments. © 2013 European Cystic Fibrosis Society.


Craft M.E.,University of Minnesota
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2015

The use of social and contact networks to answer basic and applied questions about infectious disease transmission in wildlife and livestock is receiving increased attention. Through social network analysis, we understand that wild animal and livestock populations, including farmed fish and poultry, often have a heterogeneous contact structure owing to social structure or trade networks. Network modelling is a flexible tool used to capture the heterogeneous contacts of a population in order to test hypotheses about the mechanisms of disease transmission, simulate and predict disease spread, and test disease control strategies. This review highlights how to use animal contact data, including social networks, for network modelling, and emphasizes that researchers should have a pathogen of interest in mind before collecting or using contact data. This paper describes the rising popularity of network approaches for understanding transmission dynamics in wild animal and livestock populations; discusses the common mismatch between contact networks as measured in animal behaviour and relevant parasites to match those networks; and highlights knowledge gaps in how to collect and analyse contact data. Opportunities for the future include increased attention to experiments, pathogen genetic markers and novel computational tools. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Orr H.T.,University of Minnesota
Cold Spring Harbor perspectives in biology | Year: 2010

Historically basic neuroscience research has made several important contributions to the cell biology of the nucleus, in particular the elucidation of nuclear structures and compartments. As research progressed towards elucidating the mechanism of neurological disease at the cellular and molecular levels, it is now providing insight into the importance and basis of coordination of nuclear pathways within the nucleus and with other cellular compartments. Ataxias, lethal neurodegenerative diseases that are distinguished by a progressive loss of motor coordination, stem from disruption of nuclear function.


Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.


Refsland E.W.,University of Minnesota
Current topics in microbiology and immunology | Year: 2013

The ability to regulate and even target mutagenesis is an extremely valuable cellular asset. Enzyme-catalyzed DNA cytosine deamination is a molecular strategy employed by vertebrates to promote antibody diversity and defend against foreign nucleic acids. Ten years ago, a family of cellular enzymes was first described with several proving capable of deaminating DNA and inhibiting HIV-1 replication. Ensuing studies on the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) restriction factors have uncovered a broad-spectrum innate defense network that suppresses the replication of numerous endogenous and exogenous DNA-based parasites. Although many viruses possess equally elaborate counter-defense mechanisms, the APOBEC3 enzymes offer a tantalizing possibility of leveraging innate immunity to fend off viral infection. Here, we focus on mechanisms of retroelement restriction by the APOBEC3 family of restriction enzymes, and we consider the therapeutic benefits, as well as the possible pathological consequences, of arming cells with active DNA deaminases.


Jeffery R.W.,University of Minnesota
Preventive Medicine | Year: 2012

This paper reviews research studies evaluating the use of financial incentives to promote weight control conducted between 1972 and 2010. It provides an overview of behavioral theories pertaining to incentives and describes empirical studies evaluating specific aspects of incentives. Research on financial incentives and weight control has a history spanning more than 30. years. Early studies were guided by operant learning concepts from Psychology, while more recent studies have relied on economic theory. Both theoretical orientations argue that providing financial rewards for losing weight should motivate people to engage in behaviors that produce weight loss. Empirical research has strongly supported this idea. However, results vary widely due to differences in incentive size and schedule, as well as contextual factors. Thus, many important questions about the use of incentives have not yet been clearly answered. Weight-maintenance studies using financial incentives are particularly sparse, so that their long-term efficacy and thus, value in addressing the public health problem of obesity is unclear. Major obstacles to sustained applications of incentive in weight control are funding sources and acceptance by those who might benefit. © 2011 Elsevier Inc.


Aggarwal C.,IBM | Subbian K.,University of Minnesota
ACM Computing Surveys | Year: 2014

Evolutionary network analysis has found an increasing interest in the literature because of the importance of different kinds of dynamic social networks, email networks, biological networks, and social streams. When a network evolves, the results of data mining algorithms such as community detection need to be correspondingly updated. Furthermore, the specific kinds of changes to the structure of the network, such as the impact on community structure or the impact on network structural parameters, such as node degrees, also needs to be analyzed. Some dynamic networks have a much faster rate of edge arrival and are referred to as network streams or graph streams. The analysis of such networks is especially challenging, because it needs to be performed with an online approach, under the one-pass constraint of data streams. The incorporation of content can add further complexity to the evolution analysis process. This survey provides an overview of the vast literature on graph evolution analysis and the numerous applications that arise in different contexts. © 2014 ACM.


St. Hill C.A.,University of Minnesota
Frontiers in Bioscience | Year: 2011

The selectins: E-selectin, P-selectin, and L-selectin are adhesion molecules that are crucial for binding of circulating leukocytes to vascular endothelium during the inflammatory response to injury or infection. Accumulated evidence indicates that selectins regulate adhesion of circulating cancer cells to the walls of blood vessels. Selectin ligands are transmembrane glycoproteins expressed on leukocytes and cancer cells that promote bond formations with selectins to mediate inflammatory processes. Selectins and selectin ligands also participate in signal transduction to regulate diverse cellular functions. Sialyl Lewis X (sLex) and sialyl Lewis A (sLea) tetrasaccharides are carbohydrate motifs displayed on protein or lipid scaffolds that are critical components of functional selectin ligands. Selectin binding to sLex and sLea present on colon, gastric, bladder, pancreatic, breast, and prostate carcinomas enhances distant organ metastasis. High expression of sialyl Lewis ligands on these cancers is significantly correlated with a poor post-operative prognosis. This review will focus on the roles of E-selectin and P-selectin in cancer progression. Understanding the role of selectins in cancer supports the development of novel selectin-based therapies to control metastasis.


Gomez T.M.,University of Wisconsin - Madison | Letourneau P.C.,University of Minnesota
Journal of Neurochemistry | Year: 2014

Motile growth cones lead growing axons through developing tissues to synaptic targets. These behaviors depend on the organization and dynamics of actin filaments that fill the growth cone leading margin [peripheral (P-) domain]. Actin filament organization in growth cones is regulated by actin-binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments and cytoplasmic components, and participation in producing mechanical forces. Actin filament polymerization drives protrusion of sensory filopodia and lamellipodia, and actin filament connections to the plasma membrane link the filament network to adhesive contacts of filopodia and lamellipodia with other surfaces. These contacts stabilize protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path toward its target. Adhesive ligands and extrinsic guidance cues bind growth cone receptors and trigger signaling activities involving Rho GTPases, kinases, phosphatases, cyclic nucleotides, and [Ca++] fluxes. These signals regulate actin-binding proteins to locally modulate actin polymerization, interactions, and force transduction to steer the growth cone leading margin toward the sources of attractive cues and away from repellent guidance cues. © 2013 International Society for Neurochemistry.


Denison R.F.,University of Minnesota
Evolutionary Applications | Year: 2011

The repeated evolution of complex adaptations - crop mimicry by weeds, for example, or CO2-concentrating C4 photosynthesis - shows the power of natural selection to solve difficult problems that limited fitness in past environments. The sophistication of natural selection's innovations contrasts with the relatively simple changes (e.g., increasing the expression of existing genes) readily achievable by today's biotechnology. Mutants with greater expression of these genes arose repeatedly over the course of evolution, so their present rarity indicates rejection by natural selection. Similarly, medical interventions that simply up- or down-regulate existing physiological mechanisms presumably recreate phenotypes also rejected by past natural selection. Some tradeoffs that constrained past natural selection still apply, such as those resulting from conservation of matter. But tradeoffs between present human goals and individual fitness in past environments may represent fairly easy opportunities to achieve our goals by reversing some effects of past selection. This point is illustrated with three examples, based on tradeoffs between (i) individual-plant fitness versus whole-crop performance, (ii) the fitness of symbionts (rhizobia) versus that of their legume hosts, and (iii) human fertility versus longevity in the context of environmental cues, such as consumption of 'famine foods', that predict trends in population size. © 2010 Blackwell Publishing Ltd.


Rep M.,University of Amsterdam | Kistler H.C.,University of Minnesota
Current Opinion in Plant Biology | Year: 2010

Comparative genomics is a powerful tool to infer the molecular basis of fungal pathogenicity and its evolution by identifying differences in gene content and genomic organization between fungi with different hosts or modes of infection. Through comparative analysis, pathogenicity-related chromosomes have been identified in Fusarium oxysporum and Fusarium solani that contain genes for host-specific virulence. Lateral transfer of pathogenicity chromosomes, inferred from genomic data, now has been experimentally confirmed. Likewise, comparative genomics reveals the evolutionary relationships among toxin gene clusters whereby the loss and gain of genes from the cluster may be understood in an evolutionary context of toxin diversification. The genomic milieu of effector genes, encoding small secreted proteins, also suggests mechanisms that promote genetic diversification for the benefit of the pathogen. © 2010.


Hirschmann M.M.,University of Minnesota
Physics of the Earth and Planetary Interiors | Year: 2010

Parameterizations of experimental data constraining the influence of CO2 and H2O on silicate melting, combined with experimental data on the stability of carbonatite in the upper mantle, allow calculation of the stability of partial melts in the seismic low velocity zone (LVZ) beneath oceanic lithosphere. For mantle with volatile contents similar to the sources of mid-ocean ridge basalt (100 ppm H2O, 60 ppm CO2), small amounts of melt are thermodynamically stable throughout the LVZ. On a weight basis, CO2 has less influence than H2O in stabilizing near-solidus partial melts of peridotite, but stability of volatile-rich near-solidus melts is dominated by CO2 rather than H2O because CO2 is less compatible than H2O in peridotite. For mantle potential temperatures (MPT) ranging from 1300 to 1400 °C, CO2-rich silicate melts are stable to depths of 130-180 km and carbonatite stable at greater depths and also in the shallow regions (70-100 km) beneath older lithosphere. Calculated melt fractions of carbonatite do not exceed 0.024% and silicate melt fractions are <0.1% beneath older (>40 Ma) lithosphere, except for a thin region at ∼120 km when the MPT approaches 1400 °C. These melt fractions are maxima if compaction is effective over the ∼100 Ma life of oceanic lithosphere. The regions of high melt fraction correspond broadly with the locus of low shear wave velocity imaged tomographically, though the melt fractions present may be too small to account for the seismic characteristics of the LVZ. Carbonatite cannot be present in large regions of the LVZ, particularly at intermediate depths (60-145 km) beneath young lithosphere (<40 Ma), and therefore cannot be responsible for the high electrical conductivity of this part of the LVZ, as has recently been proposed (Gaillard et al., 2008). Horizontal lenses of melt beneath the lithosphere/asthenosphere boundary may be responsible for the sharp seismic G discontinuity that marks the lithosphere/asthenosphere boundary in oceanic domains, but if so they must consist of melt collected at that horizon by percolation of deeper magmas or melt concentrated in high aspect ratio enriched heterogeneities. © 2009 Elsevier B.V. All rights reserved.


Jerolmack D.J.,University of Pennsylvania | Paola C.,University of Minnesota
Geophysical Research Letters | Year: 2010

Landscapes respond to climate, tectonic motions and sea level, but this response is mediated by sediment transport. Understanding transmission of environmental signals is crucial for predicting landscape response to climate change, and interpreting paleo-climate and tectonics from stratigraphy. Here we propose that sediment transport can act as a nonlinear filter that completely destroys ("shreds") environmental signals. This results from ubiquitous thresholds in sediment transport systems; e.g., landsliding, bed load transport, and river avulsion. This "morphodynamic turbulence" is analogous to turbulence in fluid flows, where energy injected at one frequency is smeared across a range of scales. We show with a numerical model that external signals are shredded when their time and amplitude scales fall within the ranges of morphodynamic turbulence. As signal frequency increases, signal preservation becomes the exception rather than the rule, suggesting a critical re-examination of purported sedimentary signals of external forcing. © 2010 by the American Geophysical Union.


Gupta V.,University of Toronto | Tallman M.S.,Sloan Kettering Cancer Center | Weisdorf D.J.,University of Minnesota
Blood | Year: 2011

Progress in the last decade has improved the understanding of leukemia biology. Molecular markers in combinations with cytogenetics have improved the risk stratification of acute myeloid leukemia (AML) and informed decision-making. In parallel, several important advances in the transplant field, such as better supportive care, improved transplant technology, increased availability of alternative donors, and reduced-intensity conditioning have improved the safety as well as access of allogeneic hematopoietic cell transplantation (HCT) for a larger number of patients. In this review, the positioning of HCT in the management of patients with AML is evaluated in view of changing risk/benefit ratios associated with both conventional treatments and transplantation, and some of the controversies are addressed in light of emerging data. Increasing data demonstrate outcomes of alternative donor transplantation approaching HLA-identical sibling donors in high-risk AML supporting the inclusion of alternative donors in trials of prospective studies evaluating post remission strategies for high-risk AML. The use of reduced-intensity conditioning has expanded the eligibility of HCT to older patients with AML, and outcome data are encouraging. Continued study of HCT versus alternative therapies is required to optimize patients' outcomes in AML. © 2011 by The American Society of Hematology.


Van Den Broek P.,Leiden University | Van Den Broek P.,University of Minnesota
Science | Year: 2010

Texts form a powerful tool in teaching concepts and principles in science. How do readers extract information from a text, and what are the limitations in this process? Central to comprehension of and learning from a text is the construction of a coherent mental representation that integrates the textual information and relevant background knowledge. This representation engenders learning if it expands the reader's existing knowledge base or if it corrects misconceptions in this knowledge base. The Landscape Model captures the reading process and the influences of reader characteristics (such as working-memory capacity, reading goal, prior knowledge, and inferential skills) and text characteristics (such as content/structure of presented information, processing demands, and textual cues). The model suggests factors that can optimize-or jeopardize-learning science from text.


Vohs K.D.,University of Minnesota
Journal of Experimental Psychology: General | Year: 2015

Caruso, Vohs, Baxter, and Waytz (2013) posited that because money is used in free market exchanges, cues of money would lead people to justify and support the systems that allow those exchanges to take place. Hence, the authors predicted that money primes would boost system justification, social dominance, belief in a just world, and free market ideology, and found supportive evidence. Rohrer, Pashler, and Harris (2015) failed to replicate those effects. This article discusses the factors that predict priming effects, and particularly those pertinent to differences between Caruso et al. and Rohrer et al. Variations in a prime's meaning, the ease with which primed content comes to mind, the prime's motivational importance, and the ambiguity of the outcome situation influence the impact of the prime. Money priming experiments (totaling 165 to date, from 18 countries) point to at least 2 major effects. First, compared to neutral primes, people reminded of money are less interpersonally attuned. They are not prosocial, caring, or warm. They eschew interdependence. Second, people reminded of money shift into professional, business, and work mentality. They exert effort on challenging tasks, demonstrate good performance, and feel efficacious. Money priming is not the same as priming another popular means of exchange, credit cards, and can have bigger effects when there is an implied connection between the self and having money. The practical benefits of money have been studied by other disciplines for decades, and the time is now for psychologists to study the effects of merely being reminded of money. © 2015 American Psychological Association.


Cohn C.S.,University of Minnesota
Cancer Control | Year: 2015

Background: Patients receiving hematopoietic stem cell transplantation require extensive transfusion support until red blood cell and platelet engraftment occurs. Rare but predictable complications may arise when the transplanted stem cells are incompatible with the native ABO type of the patient. Immediate and delayed hemolysis is often seen.Methods: A literature review was performed and the results from peer-reviewed papers that contained reproducible findings were integrated.Results: A strong body of clinical evidence has developed around the common complications experienced with ABO-incompatible hematopoietic stem cell transplantation. These complications are discussed and the underlying pathophysiology is explained. General treatment options and guidelines are enumerated.Conclusions: ABO-incompatible hematopoietic stem cell transplantations are frequently performed. Immune-related hemolysis is a commonly encountered complication; therefore, health care professionals must recognize the signs of immune-mediated hemolysis and understand the various etiologies that may drive the process. © 2015, H. Lee Moffitt Cancer Center and Research Institute. All rights reserved.


Hong H.,University of Minnesota
Medical Decision Making | Year: 2013

Objectives. Bayesian statistical methods are increasingly popular as a tool for meta-analysis of clinical trial data involving both direct and indirect treatment comparisons. However, appropriate selection of prior distributions for unknown model parameters and checking of consistency assumptions required for modeling remain particularly challenging. We compared Bayesian and traditional frequentist statistical methods for mixed treatment comparisons with multiple binary outcomes. Data. We searched major electronic bibliographic databases, Food and Drug Administration reviews, trial registries, and research grant databases up to December 2011 to find randomized studies published in English that examined drugs for female urgency urinary incontinence (UI) on continence, improvement in UI, and treatment discontinuation due to harm. Methods. We describe and fit fixed and random effects models in both Bayesian and frequentist statistical frameworks. In a hierarchical model of 8 treatments, we separately analyze 1 safety and 2 efficacy outcomes. We produce Bayesian and frequentist treatment ranks and odds ratios across all drug v placebo comparisons, as well as Bayesian probabilities that each drug is best overall through a weighted scoring rule that trades off efficacy and safety. Results. In our study, Bayesian and frequentist random effects models generally suggest the same drugs as most attractive, although neither suggests any significant differences between drugs. However, the Bayesian methods more consistently identify one drug (propiverine) as best overall, produce interval estimates that are generally better at capturing all sources of uncertainty in the data, and also permit attractive "rankograms" that visually capture the probability that each drug assumes each possible rank. Conclusions. Bayesian methods are more flexible and their results more clinically interpretable, but they require more careful development and specialized software.


Davies P.R.,University of Minnesota
Foodborne Pathogens and Disease | Year: 2011

Major structural changes in livestock production in developed countries, particularly intensive confinement production and increases in herd and flock sizes, have raised several societal concerns about the future directions and implications of livestock food production, including the safety of meat products. This review of the major parasitic and bacterial foodborne pathogens associated with pork production indicates that pork safety in the United States has improved demonstrably over recent decades. Most notably, changes in swine production methods have been associated with virtual elimination of risk of the foodborne parasites Taenia solium, Trichinella spiralis, and Toxoplasma gondii from pigs reared on modern intensive farms. This represents a substantial public health achievement that has gone largely unheralded. Regulatory changes have led to demonstrably lower prevalence of Salmonella on pork carcasses, but control of bacterial foodborne pathogens on farms remains a significant challenge. Available evidence does not support the hypothesis that intensive pork production has increased risk for the major bacterial foodborne pathogens that are common commensals of the pig (Salmonella, Campylobacter, Listeria, and Yersinia enterocolitica), or that pigs produced in alternative systems are at reduced risk of colonization with these organisms. However, pigs raised in outdoor systems inherently confront higher risks of exposure to foodborne parasites, particularly T. gondii. © Copyright 2011, Mary Ann Liebert, Inc. 2011.


Young N.D.,University of Minnesota | Bharti A.K.,National Center for Genome Resources
Annual Review of Plant Biology | Year: 2012

Legumes are the third-largest family of angiosperms, the second-most-important crop family, and a key source of biological nitrogen in agriculture. Recently, the genome sequences of Glycine max (soybean), Medicago truncatula, and Lotus japonicus were substantially completed. Comparisons among legume genomes reveal a key role for duplication, especially a whole-genome duplication event approximately 58 Mya that is shared by most agriculturally important legumes. A second and more recent genome duplication occurred only in the lineage leading to soybean. Outcomes of genome duplication, including gene fractionation and sub-and neofunctionalization, have played key roles in shaping legume genomes and in the evolution of legume-specific traits. Analysis of legume genome sequences also enables the discovery of legume-specific gene families and provides a framework for genome-wide association mapping that will target phenotypes of special importance in legumes. Translating genomic resources from sequenced species to less studied but still important orphan legumes will enhance prospects for world food production. © 2012 by Annual Reviews. All rights reserved.


Zelazo P.D.,University of Minnesota
Developmental Review | Year: 2015

Key executive function (EF) skills (cognitive flexibility, working memory, inhibitory control) are essential for goal-directed problem solving and reflective learning. This article describes executive function (EF) and its development from the perspective of the Iterative Reprocessing (IR) model. According to this model, reflection, or the reflective reprocessing of information prior to responding, provides a foundation for the control of attention - flexibly, over time, and selectively (i.e., cognitive flexibility, working memory, and inhibitory control). This goal-directed modulation of attention is typically verbally mediated and involves the formulation and maintenance in working memory of explicit action-oriented rules. The development of EF is made possible, in part, by increases in the efficiency of reflective reprocessing which allow for increases in the hierarchical complexity of the rules that can be used to characterize problems and select context-appropriate rules for responding. Research designed to test the model indicates that a brief intervention targeting reflection and rule use leads to improved EF and theory of mind, and produces corresponding changes in neural function. © 2015 Published by Elsevier Inc.


Attanasio L.,University of Minnesota
Medical Care | Year: 2015

BACKGROUND:: High-quality communication and a positive patient-provider relationship are aspects of patient-centered care, a crucial component of quality. We assessed racial/ethnic disparities in patient-reported communication problems and perceived discrimination in maternity care among women nationally and measured racial/ethnic variation in the correlates of these outcomes. METHODS:: Data for this analysis came from the Listening to Mothers III survey, a national sample of women who gave birth to a singleton baby in a US hospital in 2011–2012. Outcomes were reluctance to ask questions and barriers to open discussion in prenatal care, and perceived discrimination during the birth hospitalization, assessed using multinomial and logistic regression. We also estimated models stratified by race/ethnicity. RESULTS:: Over 40% of women reported communication problems in prenatal care, and 24% perceived discrimination during their hospitalization for birth. Having hypertension or diabetes was associated with higher levels of reluctance to ask questions and higher odds of reporting each type of perceived discrimination. Black and Hispanic (vs. white) women had higher odds of perceived discrimination due to race/ethnicity. Higher education was associated with more reported communication problems among black women only. Although having diabetes was associated with perceptions of discrimination among all women, associations were stronger for black women. CONCLUSIONS:: Race/ethnicity was associated with perceived racial discrimination, but diabetes and hypertension were consistent predictors of communication problems and perceptions of discrimination. Efforts to improve communication and reduce perceived discrimination are an important area of focus for improving patient-centered care in maternity services. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Marini J.J.,University of Minnesota
Current Opinion in Critical Care | Year: 2011

Purpose of Review: To present an updated discussion of those aspects of controlled positive pressure breathing and retained spontaneous regulation of breathing that impact the management of patients whose tissue oxygenation is compromised by acute lung injury. Recent Findings: The recent introduction of ventilation techniques geared toward integrating natural breathing rhythms into even the earliest phase of acute respiratory distress syndrome support (e.g., airway pressure release, proportional assist ventilation, and neurally adjusted ventilatory assist), has stimulated a burst of new investigations. Summary: Optimizing gas exchange, avoiding lung injury, and preserving respiratory muscle strength and endurance are vital therapeutic objectives for managing acute lung injury. Accordingly, comparing the physiology and consequences of breathing patterns that preserve and eliminate breathing effort has been a theme of persisting investigative interest throughout the several decades over which it has been possible to sustain cardiopulmonary life support outside the operating theater. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Keith Barker F.,University of Minnesota
Molecular Phylogenetics and Evolution | Year: 2014

Passerine birds compose over half of avian species diversity and exhibit an impressive array of phenotypic variation of interest to evolutionary biologists. Although this group has long been the focus of comparative study, many phylogenetic relationships within the group remain unresolved, despite an impressive number of molecular phylogenetic studies. Much of this uncertainty involves "transitional" groups potentially related to the ancestrally Australasian "core Corvoidea" and the primarily extra-Australasian Passerida, as well as basal relationships among Passerida. In this study data from mitochondrial genome sequences (mitogenomes) are brought to bear on higher-level passerine relationships. This paper reports analyses of new mitogenomes from 15 taxa carefully selected to address basal passeridan relationships, along with 110 previously-published passerine mitogenomes (most deriving from two intra-familial studies). These data corroborate many relationships previously established by multilocus nuclear data, as well as resolving several novel clades, including basal relationships of Passerida and relationships of that clade to several "transitional" forms. Although passerine mitogenomes pose significant analytical challenges (most notably substitutional saturation and base compositional heterogeneity), they appear to retain important information that should contribute to current and future understanding of passerine phylogeny. © 2014 Elsevier Inc.


Li Z.H.,Fudan University | Truhlar D.G.,University of Minnesota
Chemical Science | Year: 2014

Metal nanoparticles have been widely used as functional materials in physics, chemistry, and biology. Understanding their unique thermodynamic properties is essential both for practical applications and from a fundamental point of view. This perspective article is an overview of recent progresses on the nanothermodynamics of metal nanoparticles and it especially highlights as examples our own studies on the structural stability, phases, phase changes, and thermodynamic functions of aluminum nanoparticles. We discuss using statistical sampling by Monte Carlo and molecular dynamics algorithms to calculate nanoparticle properties, nanophase properties, free energies, and nucleation rates, and we tried to understand the results in terms of energy landscapes by using exhaustive enumeration of the multiple structures of Al nanoparticles from all sizes up to N = 65 plus selected larger calculations. © 2014 the Partner Organisations.


Rheault M.N.,University of Minnesota
Pediatric Nephrology | Year: 2012

X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous "carrier" females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural history of heterozygous XLAS females, the determinants of disease severity, and the utility of using XLAS females as kidney donors. © 2011 IPNA.


Kushner M.G.,University of Minnesota
Journal of studies on alcohol and drugs. Supplement | Year: 2014

As part of the 75th anniversary edition of the Journal of Studies on Alcohol and Drugs, this article reviews research on the relationship between mental disorders and substance use disorders ("comorbidity") from 1940--the journal's inception--to the present. First, a survey of the titles and abstracts of all articles published in the journal was used to identify those articles pertaining to comorbidity. Seminal and representative works from this set of articles and a limited selection of articles from other journals were included in the review. The early psychosocial research emphasized psychoanalytic formulations of alcohol use as a defensive symptom, which informed the early experimental research on the tension-reducing properties of alcohol. The "cognitive revolution," occurring in the 1970s, enabled an expansion of the tension-reduction theory to include a central role for mental processes (e.g., alcohol expectancies) in promoting drinking to cope with negative affectivity. The early clinical research characterized mental conditions commonly co-occurring with alcohol disorders and considered their etiological relationship to alcohol disorders. The "neo-Kraepelinian revolution" in psychiatry, which also occurred in the 1970s, infused the clinical comorbidity research with a more rigorous diagnostic technology and a range of biomedical research methodologies to study the mechanistic linkages of co-occurring disorders. Although a substantial quantity of scientific information on comorbidity has accumulated over the past 75 years, a standard model(s) of comorbidity has yet to congeal. Barriers and opportunities related to achieving this important goal are discussed.


Gamble T.,University of Minnesota
Sexual Development | Year: 2010

Geckos are a species-rich clade of reptiles possessing diverse sex determining mechanisms. Some species possess genetic sex determination, with both male and female heterogamety, while other species have temperature- dependent sex determination. I compiled information from the literature on the taxonomic distribution of these sex determining mechanisms in geckos. Using phylogenetic data from the literature, I reconstructed the minimum number of transitions among these sex determining mechanisms with parsimony-based ancestral state reconstruction. While only a small number of gecko species have been characterized, numerous changes among sex determining mechanisms were inferred. This diversity, coupled with the high frequency of transitions, makes geckos excellent candidates as a model clade for the study of vertebrate sex determination and evolution. Copyright © 2010 S. Karger AG, Basel.


Zhao Y.,Hewlett - Packard | Truhlar D.G.,University of Minnesota
Journal of Chemical Theory and Computation | Year: 2011

The present study compares the accuracy of 30 density functionals for four databases of reaction energies studied recently by Grimme and co-workers. For 20 of the density functionals, the calculations are new, and the calculations are compared to previous work for the other 10. We present the results in detail for 11 of the functionals and as mean unsigned errors for the others. The results presented in detail are for the seven most recent Minnesota functionals (M05-2X, M06-L, M06-HF, M06, M06-2X, M08-HX, and M08-SO), three range-separated functionals (HSE, LC-ωPBE, and ωB97X-D), and one dispersion-corrected global hybrid generalized gradient approximation (B97-D); the other functionals include five dispersion-corrected functionals and their uncorrected analogs, eight high-performing functionals on a recent catalytic-energies test, and the TPSSh functional because it is of special interest to compare its performance to that of M08-SO. Three of the four databases contain a total of 21 rearrangement reaction energies and 13 diverse dissociation or association energies, and the fourth contains three dissociation reaction energies of alkali metal clusters and three dissociation reaction energies of alkali-metal-cation-benzene complexes. The results are especially promising for the Minnesota hybrid meta-GGA functionals and the ωB97X-D, B2PLYP-D, and HSE functionals. © 2011 American Chemical Society.


Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector-switching" network, which effectively balances two apparently conflicting demands, robustness against pathogenic perturbations and moderation of negative impacts of immune responses on plant fitness.


Neufeld T.P.,University of Minnesota
Journal of Cell Science | Year: 2012

As a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and autophagy, and results of recent functional screens on a genomic scale support the idea that these processes might represent mutually exclusive cell fates. Understanding the ways in which autophagy and cell growth relate to one another is becoming increasingly important, as new roles for autophagy in tumorigenesis and other growth-related phenomena are uncovered. This Commentary highlights recent findings that link autophagy and cell growth, and explores the mechanisms underlying these connections and their implications for cell physiology and survival. Autophagy and cell growth can inhibit one another through a variety of direct and indirect mechanisms, and can be independently regulated by common signaling pathways. The central role of the mammalian target of rapamycin (mTOR) pathway in regulating both autophagy and cell growth exemplifies one such mechanism. In addition, mTOR-independent signaling and other more direct connections between autophagy and cell growth will also be discussed. © 2012. Published by The Company of Biologists Ltd.


Ferrieri P.,University of Minnesota
Emerging infectious diseases | Year: 2013

Group B Streptococcus (GBS) is a major cause of invasive disease in neonates in the United States. Surveillance of invasive GBS disease in Minnesota, USA, during 2000-2010 yielded 449 isolates from 449 infants; 257 had early-onset (EO) disease (by age 6 days) and 192 late-onset (LO) disease (180 at age 7-89 days, 12 at age 90-180 days). Isolates were characterized by capsular polysaccharide serotype and surface-protein profile; types III and Ia predominated. However, because previously uncommon serotype IV constitutes 5/31 EO isolates in 2010, twelve type IV isolates collected during 2000-2010 were studied further. By pulsed-field gel electrophoresis, they were classified into 3 profiles; by multilocus sequence typing, representative isolates included new sequence type 468. Resistance to clindamycin or erythromycin was detected in 4/5 serotype IV isolates. Emergence of serotype IV GBS in Minnesota highlights the need for serotype prevalence monitoring to detect trends that could affect prevention strategies.


Antigenic variation of major surface proteins is considered an immune-evasive maneuver used by pathogens as divergent as bacteria and protozoa. Likewise, major surface protein 2 (Msp2) of the tick-borne pathogen, Anaplasma marginale, is thought to be involved in antigenic variation to evade the mammalian host immune response. However, this dynamic process also works in the tick vector in the absence of immune selection pressure. We examined Msp2 variants expressed during infection of four tick and two mammalian cell-lines to determine if the presence of certain variants correlated with specific host cell types. Anaplasma marginale colonies differed in their development and appearance in each of the cell lines (P<0.001). Using Western blots probed with two Msp2-monospecific and one Msp2-monoclonal antibodies, we detected expression of variants with differences in molecular weight. Immunofluorescence-assay revealed that specific antibodies bound from 25 to 60% of colonies, depending on the host cell-line (P<0.001). Molecular analysis of cloned variant-encoding genes demonstrated expression of different predominant variants in tick (V1) and mammalian (V2) cell-lines. Analysis of the putative secondary structure of the variants revealed a change in structure when A. marginale was transferred from one cell-type to another, suggesting that the expression of particular Msp2 variants depended on the cell-type (tick or mammalian) in which A. marginale developed. Similarly, analysis of the putative secondary structure of over 200 Msp2 variants from ticks, blood samples, and other mammalian cells available in GenBank showed the predominance of a specific structure during infection of a host type (tick versus blood sample), demonstrating that selection of a possible structure also occurred in vivo. The selection of a specific structure in surface proteins may indicate that Msp2 fulfils an important role in infection and adaptation to diverse host systems. Supplemental Abstract in Spanish (File S1) is provided.


Voloshin M.B.,University of Minnesota | Voloshin M.B.,Institute of Theoretical and Experimental Physics
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

The heavy quark spin symmetry implies that in addition to the recently observed Z(10610) and Z(10650) molecular resonances with IG=1+, there should exist two or four molecular bottomonium-like states with IG=1 -. Properties of these G-odd states are considered, including their production in the radiative transitions from Υ(5S), by applying the same symmetry to the Υ(5S) resonance and the transition amplitudes. The considered radiative processes can provide a realistic option for observing the yet hypothetical states. © 2011 American Physical Society.


Background: In 2005, of the approximately 4 million births in the United States, 30% were by cesarean section (C-section) delivery, which translates to roughly over 1 million C-sections in 2005 alone. C-section is associated with higher morbidity than vaginal delivery. Women who undergo C-section are 5 times more likely to develop a postpartum infection after delivery than women who undergo vaginal delivery. Objective: Estimates of surgical site infection (SSI) after C-section range from 1.50 to 2.64. A quality improvement initiative was implemented at the University of Minnesota Medical School to reduce rates of SSI using changes based on recommended care initiatives. Methods: The multidisciplinary team developed a comprehensive staff education and training program, added a preoperative skin preparation protocol using chlorhexidine gluconate (CHG) no-rinse cloths, added CHG with alcohol for interoperative skin preparation, and modified instrument sterilization techniques. Results: Data analysis revealed a statistically significant reduction in the overall SSI rate from 7.5% (33/441) in January-July 2006 to 1.2% (5/436) in January-July 2007 (χ2 test statistic, 21.2; P < .001; relative reduction of 84%). Conclusion: Interventions, including staff education, use of CHG no-rinse cloths for preoperative skin prep, CHG with alcohol for intraoperative skin prep, and appropriate instrument sterilization management led to reductions in SSI rates in patients undergoing C-section at our institution. Rates of endometritis were also noted to be lower after implementation of the interventions. © 2010.


Bee M.A.,University of Minnesota
International Journal of Psychophysiology | Year: 2015

The perceptual analysis of acoustic scenes involves binding together sounds from the same source and separating them from other sounds in the environment. In large social groups, listeners experience increased difficulty performing these tasks due to high noise levels and interference from the concurrent signals of multiple individuals. While a substantial body of literature on these issues pertains to human hearing and speech communication, few studies have investigated how nonhuman animals may be evolutionarily adapted to solve biologically analogous communication problems. Here, I review recent and ongoing work aimed at testing hypotheses about perceptual mechanisms that enable treefrogs in the genus Hyla to communicate vocally in noisy, multi-source social environments. After briefly introducing the genus and the methods used to study hearing in frogs, I outline several functional constraints on communication posed by the acoustic environment of breeding "choruses". Then, I review studies of sound source perception aimed at uncovering how treefrog listeners may be adapted to cope with these constraints. Specifically, this review covers research on the acoustic cues used in sequential and simultaneous auditory grouping, spatial release from masking, and dip listening. Throughout the paper, I attempt to illustrate how broad-scale, comparative studies of carefully considered animal models may ultimately reveal an evolutionary diversity of underlying mechanisms for solving cocktail-party-like problems in communication. © 2014 Elsevier B.V.


Sterner R.W.,University of Minnesota
Journal of Great Lakes Research | Year: 2010

Water column primary production is a major term in the organic carbon cycle, particularly in large lakes with relatively reduced shoreline and near-shore influence. Presently, there is a large imbalance in the known inputs vs. outputs of organic carbon in Lake Superior. This study examined primary production in offshore Lake Superior using in situ incubations over a range of conditions representing an annual cycle. Primary producers were dominated by small (< 20 μm) cells and included a relatively large abundance of small, spherical flagellates. During conditions with a warm surface layer, chlorophyll concentrations were two- to three-fold higher within the deep chlorophyll maximum (DCM) than at the surface. Volumetric production (mass L- 1 d- 1) was maximal at 2-10 m depth, well above the typical DCM depth. On average, 22% of 14C label appeared in the dissolved pool at the end of the incubation period with the rest appearing in GF/F-strained particles. A statistical model for volumetric production explained 93% of the variance in individual measurements for depths > 2 m, using temperature and light as predictors. This model was applied to annual fields of temperature and light, and a new estimate for whole-lake annual primary production, 9.73 Tg y- 1, was derived. This combination of new measurements and modeling results brings the organic carbon cycle of Lake Superior closer to being balanced. © 2010 Elsevier B.V. All rights reserved.


Zhu Z.,University of Minnesota
Molecular Pharmaceutics | Year: 2014

Flash nanoprecipitation (FNP) can generate hydrophobic drug nanoparticles in ∼100 nm with a much higher drug loading (e.g., > 40 wt %) than traditional nanocarriers (e.g., < 20 wt %). This paper studies the effects of drug molecules on nanoparticle stability made via FNP and demonstrates that chemically bonding a drug compound (e.g., paclitaxel) with a cleavable hydrophobic moiety of organosilicate (e.g., triethoxysilicate) is able to enhance the particle size stability. A nonionic amphiphilic diblock copolymer, poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG), is used as a model surfactant to provide steric stabilization. The experiments here show that the lower the drug solubility in the aqueous medium, the more stable the particles in terms of Ostwald ripening, which are consistent with the prediction by the LSW theory. The initial particle size distribution is sufficiently narrow and of insignificance to Ostwald ripening. To correlate the particle stability with hydrophobicity, this study introduces the n-octanol/water partition coefficient (LogP), a hydrophobicity indication, into the FNP technique. A comparison of various drugs and their analogues shows that LogP of a drug is a better hydrophobicity indication than the solubility parameter (δ) and correlates well with the particle stability. Empirically, with ACDLogP > ∼12, nanoparticles have good stability; with ∼2 < ACDLogP < ∼9, nanoparticles show fast Ostwald ripening and interparticle recrystallization; with ACDLogP < ∼2, the drug is very likely difficult to form nanoparticles. This rule creates a quick way to predict particle stability for a randomly selected drug structure and helps to enable a fast preclinical drug screen. © 2014 American Chemical Society.


Hegeman A.D.,University of Minnesota
Briefings in Functional Genomics and Proteomics | Year: 2010

Plant metabolomics has benefited from a rich array of pre-existing methodological approaches and bioanalytical knowledge for the characterization of the many chemically diverse classes of metabolites. While the field has pushed the implementation of unbiased and generally applicable strategies for metabolite extraction, fractionation and detection, significant challenges in fundamental activities such as compound identification and quantification still exist. This review provides an introduction to metabolomics terminology, methods and resources and discusses analytical limitations. Progress in the application of stable isotope dilution and stable isotopic metabolic labeling to metabolite identification and quantification are discussed. New strategies to address spatial distribution of metabolites via mass spectrometry-based imaging are also reviewed. © The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.


Slavin J.,University of Minnesota
Nutrients | Year: 2013

The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Insulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known "prebiotics", "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health." To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora. Studies have provided evidence that insulin and oligofructose (OF), lactulose, and resistant starch (RS) meet all aspects of the definition, including the stimulation of Bifidobacterium, a beneficial bacterial genus. Other isolated carbohydrates and carbohydrate-containing foods, including galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), polydextrose, wheat dextrin, acacia gum, psyllium, banana, whole grain wheat, and whole grain corn also have prebiotic effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Legge G.E.,University of Minnesota
Journal of vision | Year: 2011

The size and shape of printed symbols determine the legibility of text. In this paper, we focus on print size because of its crucial role in understanding reading performance and its significance in the history and contemporary practice of typography. We present evidence supporting the hypothesis that the distribution of print sizes in historical and contemporary publications falls within the psychophysically defined range of fluent print size--the range over which text can be read at maximum speed. The fluent range extends over a factor of 10 in angular print size (x-height) from approximately 0.2° to 2°. Assuming a standard reading distance of 40 cm (16 inches), the corresponding physical x-heights are 1.4 mm (4 points) and 14 mm (40 points). We provide new data on the distributions of print sizes in published books and newspapers and in typefounders' specimens, and consider factors influencing these distributions. We discuss theoretical concepts from vision science concerning visual size coding that help inform our understanding of historical and modern typographical practices. While economic, social, technological, and artistic factors influence type design and selection, we conclude that properties of human visual processing play a dominant role in constraining the distribution of print sizes in common use.


Voloshin M.B.,University of Minnesota | Voloshin M.B.,Institute of Theoretical and Experimental Physics
Physical Review Letters | Year: 2010

The scattering of a neutrino on atomic electrons is considered in the situation where the energy transferred to the electrons is comparable to the characteristic atomic energies, as relevant to the current experimental search for the neutrino magnetic moment. The process is induced by the standard electroweak interaction as well as by the possible neutrino magnetic moment. Quantum-mechanical sum rules are derived for the inclusive cross section at a fixed energy deposited in the atomic system, and it is shown that the differential over the energy transfer cross section is given, modulo very small corrections, by the same expression as for free electrons, once all possible final states of the electronic system are taken into account. Thus, the atomic effects effectively cancel in the inclusive process. © 2010 The American Physical Society.


Jacobs D.R.,University of Minnesota | Tapsell L.C.,University of Wollongong
Proceedings of the Nutrition Society | Year: 2013

Food synergy is the concept that the non-random mixture of food constituents operates in concert for the life of the organism eaten and presumably for the life of the eater. Isolated nutrients have been extensively studied in well-designed, long-term, large randomised clinical trials, typically with null and sometimes with harmful effects. Therefore, although nutrient deficiency is a known phenomenon, serious for the sufferer, and curable by taking the isolated nutrient, the effect of isolated nutrients or other chemicals derived from food on chronic disease, when that chemical is not deficient, may not have the same beneficial effect. It appears that the focus on nutrients rather than foods is in many ways counterproductive. This observation is the basis for the argument that nutrition research should focus more strongly on foods and on dietary patterns. Unlike many dietary phenomena in nutritional epidemiology, diet pattern appears to be highly correlated over time within person. A consistent and robust conclusion is that certain types of beneficial diet patterns, notably described with words such as 'Mediterranean' and 'prudent', or adverse patterns, often described by the word 'Western', predict chronic disease. Food is much more complex than drugs, but essentially uninvestigated as food or pattern. The concept of food synergy leads to new thinking in nutrition science and can help to forge rational nutrition policy-making and to determine future nutrition research strategies. Copyright © The Authors 2013.


McCullough J.,University of Minnesota
Seminars in Hematology | Year: 2010

Most platelet transfusions are given to prevent bleeding in thrombocytopenic patients undergoing chemotherapy for malignancy or hematopoietic stem cell transplant. In stable, uncomplicated patients the risk of bleeding is similar until the platelet count falls to <5,000/μL. However, many patients have clinical complications that necessitate transfusion at higher counts. Therefore, the recommended indication for prophylactic transfusion is a platelet count of 10,000/μL. The usual dose of platelets is 1 apheresis unit or a pool of four to six concentrates from individual units of whole blood. The likelihood of bleeding is the same if half or double the usual dose is given, but half-dose transfusions must be given more often and double-dose transfusions less often than the standard dose. For patients with inherited defects of platelet function or acquired defects such as due to drugs or uremia, the platelet count is usually normal and prophylactic transfusion is not recommended. Transfusion may be helpful to treat serious bleeding. Patients undergoing cardiopulmonary bypass may be slightly thrombocytopenic but usually have platelet dysfunction. Transfusion is helpful to treat nonsurgical serious bleeding. In idiopathic thrombocytopenic purpura, platelet survival is short and transfusion is useful only for severe bleeding. © 2010 Elsevier Inc.


Masten A.S.,University of Minnesota
Child Development | Year: 2014

Global concerns about the consequences of disasters, political violence, disease, malnutrition, maltreatment, and other threats to human development and well-being have sparked a surge of international interest in resilience science. This article highlights progress and issues in research that aims to understand variations in human adaptation to adverse experiences. Two key questions are considered: Why is a new wave of global research on resilience important for developmental science? and Why is developmental science important for global resilience? The conclusion calls for developmental scientists to engage in international efforts to promote resilience. © 2013 Society for Research in Child Development, Inc.


Seaquist E.R.,University of Minnesota
Psychosomatic Medicine | Year: 2015

Diabetes alters cerebral metabolism, structure, and function. Both hyperglycemia and therapy-associated hypoglycemia are believed to have an impact on the brain, and this impact may depend on the age of the individual, their stage of neurological development, and whether they have Type 1 or Type 2 diabetes. Hypoglycemia in children with Type 1 has consistently been associated with a reduction in neurocognitive function, but such a finding has not been seen in adults with Type 1 diabetes. Both hypoglycemia and hyperglycemia have been linked with dementia in adults with Type 2 diabetes. In both Type 1 and Type 2 diabetes, recurrent episodes of treatment-associated hypoglycemia impair how well the brain can sense and respond to subsequent episodes of hypoglycemia. In this brief review, we will review how diabetes affects the brain with a focus on investigations done in our own laboratory. We have focused on using high magnetic field imaging and spectroscopy to identify subtle changes in brain structure and metabolism that may contribute to the long-term cerebral complications of diabetes. We have found evidence of microstructural changes in white matter regions, reduced gray matter density, and reduced activation of the thalamus in response to recurrent hypoglycemia in patients with Type 1 diabetes. © Lippincott Williams & Wilkins.


Iwen M.A.,University of Minnesota
Foundations of Computational Mathematics | Year: 2010

We study the problem of estimating the best k term Fourier representation for a given frequency sparse signal (i.e., vector) A of length N ≫ k. More explicitly, we investigate how to deterministically identify k of the largest magnitude frequencies of Â, and estimate their coefficients, in polynomial(k, log N) time. Randomized sublinear-time algorithms which have a small (controllable) probability of failure for each processed signal exist for solving this problem (Gilbert et al. in ACM STOC, pp. 152-161, 2002; Proceedings of SPIE Wavelets XI, 2005). In this paper we develop the first known deterministic sublinear-time sparse Fourier Transform algorithm which is guaranteed to produce accurate results. As an added bonus, a simple relaxation of our deterministic Fourier result leads to a new Monte Carlo Fourier algorithm with similar runtime/sampling bounds to the current best randomized Fourier method (Gilbert et al. in Proceedings of SPIE Wavelets XI, 2005). Finally, the Fourier algorithm we develop here implies a simpler optimized version of the deterministic compressed sensing method previously developed in (Iwen in Proc. of ACM-SIAM Symposium on Discrete Algorithms (SODA'08), 2008). © 2010 SFoCM.


A single fluorescently labeled protein generates a short burst of light whenever it passes through a tiny observation volume created within a biological cell. The average amplitude of the burst is related to the stoichiometry of the fluorescently labeled protein complex. Fluorescence fluctuation spectroscopy quantifies the burst amplitude by introducing the brightness parameter. Brightness provides a spectroscopic marker for observing protein interactions and their stoichiometry directly inside cells. Not all fluorescent proteins are suitable for brightness experiments. Here we discuss how brightness properties of the fluorophore influence brightness measurements and how to identify a well-behaved fluorescent protein. Protein interactions and stoichiometry are determined from a brightness titration. Experimental details of brightness titration measurements are described together with the necessary calibration and control experiments. Copyright 2010 Elsevier Inc. All rights reserved.


Matas A.J.,University of Minnesota
American Journal of Transplantation | Year: 2011

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Wei L.-N.,University of Minnesota
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2012

Retinoic acid (RA) acts by binding to nuclear RA receptors (RARs) to regulate a broad spectrum of downstream target genes in most cell types examined. In cytoplasm, RA binds specifically to cellular retinoic acid binding proteins I (CRABPI), and II. Although the function of CRABPI in animals remains the subject of debate, it is believed that CRABPI binding facilitates RA metabolism, thereby modulating the concentration of RA and the type of RA metabolites in cells. The basal promoter of the CrabpI gene is a housekeeping promoter that can be regulated by thyroid hormones (T3), DNA methylation, sphinganine, and ethanol acting on its upstream regulatory region. T3 regulation of CrabpI is mediated by the binding of thyroid hormone receptor (TR) to a TR response element (TRE) approximately 1 kb upstream of the basal promoter. Specifically, in the adipocyte differentiation process, T3 regulation is bimodal and closely associated with the cellular differentiation status: T3 activates CrabpI in predifferentiated cells (e.g., mesenchymal precursors or fibroblasts), but suppresses this gene once cells are committed to adipocyte differentiation. These disparate effects are functions of T3-triggered differential recruitment of coregulatory complexes in conjunction with chromatin looping/folding that alters the configuration of this genomic locus along adipocyte differentiation. Subsequent sliding, disassembly and reassembly of nucleosomes occur, resulting in specific changes in the conformation of the basal promoter chromatin at different stages of differentiation. This chapter summarizes studies illustrating the epigenetic regulation of CrabpI expression during adipocyte differentiation. Understanding the pathways regulating CrabpI in this specific context might help to illuminate the physiological role of CRABPI in vivo. This article is part of a special issue entitled: Retinoid and Lipid Metabolism. © 2011 Elsevier B.V.


Hassan N.R.,University of Minnesota
Communications of the Association for Information Systems | Year: 2014

This debate section article examines the notion of value or worth of IS research. It suggests that how others value the product of Information Systems (IS) research may be the underlying problem triggering various forms of anxiety discourses that are frequently recurring. The value of IS research is examined from the perspectives of ends-means, basic and applied research, and the significance of IS problems. The article also proposes ways of maintaining the value of IS research by emphasizing originality, being "active" and not "passive", and making evident what is not. The article argues that the value of IS research is found not in duplicating research already undertaken in management, computer science, psychology, economics or its other reference disciplines, but in asking questions that other disciplines are not asking or in addressing problems that others are incapable of addressing. © 2014 by the Association for Information Systems.


Hoffman M.C.,University of Minnesota
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Childhood cancer survivors (CCSs) are at risk for physical disability. The aim of this investigation was to characterize and compare physical performance among CCSs and a group of siblings age < 18 years and determine if diagnosis, treatment, and physical activity levels were associated with lower performance scores. CCSs ≥ 5 years from diagnosis and a sibling comparison group were recruited and evaluated for strength, mobility, and fitness. Physical performance measures were compared in regression models between survivors and siblings by diagnosis and among survivors by treatment exposures and physical activity levels. CCSs (n = 183; mean age ± standard deviation [SD], 13.5 ± 2.5 years; 53% male) scored lower than siblings (n = 147; mean age ± SD, 13.4 ± 2.4 years; 50% male) on lower-extremity strength testing, the timed up-and-go (TUG) test, and the 6-minute walk (6MW) test, despite reporting similar levels and types of habitual physical activity. The lowest scores were prevalent among survivors of CNS tumors and bone and soft tissue sarcomas on strength testing (score ± SD: CNS tumors, 76.5 ± 4.7; sarcoma 67.1 ± 7.2 v siblings, 87.3 ± 2.4 Newton-meters quadricep strength at 90° per second; P = .04 and .01, respectively) and among CNS tumor survivors on the TUG (score ± SD: 5.1 ± 0.1 v siblings, 4.4 ± 0.1 seconds; P < .001) and 6MW tests (score ± SD: 533.3 ± 15.6 v siblings, 594.1 ± 8.3 m; P < .001). CCSs may have underlying physiologic deficits that interfere with function that cannot be completely overcome by participation in regular physical activity. These survivors may need referral for specialized exercise interventions in addition to usual counseling to remain physically active.


Ramachandran G.,University of Minnesota
Journal of occupational and environmental hygiene | Year: 2011

This article describes a highly tailorable exposure assessment strategy for nanomaterials that enables effective and efficient exposure management (i.e., a strategy that can identify jobs or tasks that have clearly unacceptable exposures), while simultaneously requiring only a modest level of resources to conduct. The strategy is based on strategy general framework from AIHA® that is adapted for nanomaterials and seeks to ensure that the risks to workers handling nanomaterials are being managed properly. The strategy relies on a general framework as the basic foundation while building and elaborating on elements essential to an effective and efficient strategy to arrive at decisions based on collecting and interpreting available information. This article provides useful guidance on conducting workplace characterization; understanding exposure potential to nanomaterials; accounting methods for background aerosols; constructing SEGs; and selecting appropriate instrumentation for monitoring, providing appropriate choice of exposure limits, and describing criteria by which exposure management decisions should be made. The article is intended to be a practical guide for industrial hygienists for managing engineered nanomaterial risks in their workplaces.


Hecht S.S.,University of Minnesota
International Journal of Cancer | Year: 2012

Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This article discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers' lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year. Copyright © 2012 UICC.


Edmonds D.A.,University of Minnesota | Slingerland R.L.,Pennsylvania State University
Nature Geoscience | Year: 2010

The morphologies of the worlds deltas are thought to be determined by river discharge, tidal range and wave action. More recently, sea-level rise 2,3, and human engineering4 have been shown to shape delta evolution. The effects of factors such as sediment type and the overall amount of sediment carried by rivers are considered secondary4,6. In particular, the role of sediment cohesion, which is controlled by sediment size and type of vegetation, is unclear. Here we use a numerical flow and transport model7,10 to show that sediment cohesiveness also strongly influences the morphology of deltas. We find that, holding all other factors constant, highly cohesive sediments form birds-foot deltas with rugose shorelines and highly complex floodplains, whereas less cohesive sediments result in fan-like deltas with smooth shorelines and flat floodplains. In our simulations, sediment cohesiveness also controls the number of channels that form within the deltas, and the average angle of bifurcation of those channels. As vegetation generally acts as a cohesive agent, we suggest that deltas that formed before the expansion of land plants in the Devonian period should show fan-like characteristics, a finding consistent with the limited data from the sedimentological record11. © 2010 Macmillan Publishers Limited. All rights reserved.


Lu H.,University of Minnesota | Porte-Agel F.,Ecole Polytechnique Federale de Lausanne
Physics of Fluids | Year: 2011

When deployed as large arrays, wind turbines significantly interact among themselves and with the atmospheric boundary layer. In this study, we integrate a three-dimensional large-eddy simulation with an actuator line technique to examine the characteristics of wind-turbine wakes in an idealized wind farm inside a stable boundary layer (SBL). The wind turbines, with a rotor diameter of 112m and a tower height of 119m, were "immersed" in a well-known SBL case that bears a boundary layer height of approximately 175m. Two typical spacing setups were adopted in this investigation. The super-geostrophic low-level jet near the top of the boundary layer was eliminated owing to the energy extraction and the enhanced mixing of momentum. Non-axisymmetric wind-turbine wakes were observed in response to the non-uniform incoming turbulence, the Coriolis effect the rotational effects induced by blade motion. The Coriolis force caused a skewed spatial structure and drove a part of the turbulence energy away from the center of the wake. The SBL height was increased, while the magnitude of the surface momentum flux was reduced by more than 30% the magnitude of the surface buoyancy flux was reduced by more than 15%. The wind farm was also found to have a strong effect on vertical turbulent fluxes of momentum and heat, an outcome that highlights the potential impact of wind farms on local meteorology. © 2011 American Institute of Physics.


Msechu E.J.,Intel Corporation | Giannakis G.B.,University of Minnesota
IEEE Transactions on Signal Processing | Year: 2012

Consider a wireless sensor network (WSN) with a fusion center (FC) deployed to estimate signal parameters from noisy sensor measurements. If the WSN has a large number of low-cost, battery-operated sensor nodes with limited transmission bandwidth, then conservation of transmission resources (power and bandwidth) is paramount. To this end, the present paper develops a novel data reduction method which requires no inter-sensor collaboration and results in only a subset of the sensor measurements transmitted to the FC. Using interval censoring as a data-reduction method, each sensor decides separately whether to censor its acquired measurements based on a rule that promotes censoring of measurements with least impact on the estimator mean-square error (MSE). Leveraging the statistical distribution of sensor data, the censoring mechanism and the received uncensored data, FC-based estimators are derived for both deterministic (via maximum likelihood estimation) and random parameters (via maximum a posteriori probability estimation) for a linear-Gaussian model. Quantization of the uncensored measurements at the sensor nodes offers an additional degree of freedom in the resource conservation versus estimator MSE reduction tradeoff. Cramér-Rao bound analysis for the different censor-estimators and censor-quantizer estimators is also provided to benchmark and facilitate MSE-based performance comparisons. Numerical simulations corroborate the analytical findings and demonstrate that the proposed censoring-estimation approach performs competitively with alternative methods, under different sensing conditions, while having lower computational complexity. © 2006 IEEE.


Kondrath N.,University of Minnesota | Kazimierczuk M.K.,Wright State University
IEEE Transactions on Industrial Electronics | Year: 2012

Wide- (WF) and high-frequency (HF) small-signal models are presented for pulsewidth-modulated dc-dc buck converter power stage. An exact duty-ratio-to-inductor-current transfer function is derived using the WF model and compared to an approximate transfer function derived using the HF model for the buck converter power stage in continuous conduction mode. The theoretical results are validated using experimental results. © 2011 IEEE.


Goldfarb D.,Columbia University | Ma S.,University of Minnesota
SIAM Journal on Optimization | Year: 2012

We present in this paper two different classes of general multiple-splitting algorithms for solving finite-dimensional convex optimization problems. Under the assumption that the function being minimized can be written as the sum of K convex functions, each of which has a Lipschitz continuous gradient, we prove that the number of iterations needed by the first class of algorithms to obtain an ε-optimal solution is O((K -1)L/ε), where L is an upper bound on all of the Lipschitz constants. The algorithms in the second class are accelerated versions of those in the first class, where the complexity result is improved to O(√(K - 1)L/ε) while the computational effort required at each iteration is almost unchanged. To the best of our knowledge, the complexity results presented in this paper are the first ones of this type that have been given for splitting and alternating directiontype methods. Moreover, all algorithms proposed in this paper are parallelizable, which makes them particularly attractive for solving certain large-scale problems. © 2012 Society for Industrial and Applied Mathematics.


Systematic reviews of healthcare disparities suggest that clinicians diagnostic and therapeutic decision making varies by clinically irrelevant characteristics, such as patient race, and that this variation may contribute to healthcare disparities. However, there is little understanding of the particular features of the healthcare setting under which clinicians are most likely to be inappropriately influenced by these characteristics. This study delineates several hypotheses to stimulate future research in this area. It is posited that healthcare settings in which providers experience high levels of cognitive load will increase the likelihood of racial disparities via 2 pathways. First, providers who experience higher levels of cognitive load are hypothesized to make poorer medical decisions and provide poorer care for all patients, due to lower levels of controlled processing (H1). Second, under greater levels of cognitive load, it is hypothesized that healthcare providers medical decisions and interpersonal behaviors will be more likely to be influenced by racial stereotypes, leading to poorer processes and outcomes of care for racial minority patients (H2). It is further hypothesized that certain characteristics of healthcare settings will result in higher levels of cognitive load experienced by providers (H3). Finally, it is hypothesized that minority patients will be disproportionately likely to be treated in healthcare settings in which providers experience greater levels of cognitive load (H4a), which will result in racial disparities due to lower levels of controlled processing by providers (H4b) and the influence of racial stereotypes (H4c).The study concludes with implications for research and practice that flow from this framework.


Rothman A.J.,University of Minnesota
Biometrika | Year: 2012

Using convex optimization, we construct a sparse estimator of the covariance matrix that is positive definite and performs well in high-dimensional settings. A lasso-type penalty is used to encourage sparsity and a logarithmic barrier function is used to enforce positive definiteness. Consistency and convergence rate bounds are established as both the number of variables and sample size diverge. An efficient computational algorithm is developed and the merits of the approach are illustrated with simulations and a speech signal classification example. © 2012 Biometrika Trust.


Snell-Rood E.C.,University of Minnesota
Integrative and Comparative Biology | Year: 2012

Adaptive phenotypic plasticity, the ability of a genotype to develop a phenotype appropriate to the local environment, allows organisms to cope with environmental variation and has implications for predicting how organisms will respond to rapid, human-induced environmental change. This review focuses on the importance of developmental selection, broadly defined as a developmental process that involves the sampling of a range of phenotypes and feedback from the environment reinforcing high-performing phenotypes. I hypothesize that understanding the degree to which developmental selection underlies plasticity is key to predicting the costs, benefits, and consequences of plasticity. First, I review examples that illustrate that elements of developmental selection are common across the development of many different traits, from physiology and immunity to circulation and behavior. Second, I argue that developmental selection, relative to a fixed strategy or determinate (switch) mechanisms of plasticity, increases the probability that an individual will develop a phenotype best matched to the local environment. However, the exploration and environmental feedback associated with developmental selection is costly in terms of time, energy, and predation risk, resulting in major changes in life history such as increased duration of development and greater investment in individual offspring. Third, I discuss implications of developmental selection as a mechanism of plasticity, from predicting adaptive responses to novel environments to understanding conditions under which genetic assimilation may fuel diversification. Finally, I outline exciting areas of future research, in particular exploring costs of selective processes in the development of traits outside of behavior and modeling developmental selection and evolution in novel environments. © The Author 2012. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.


There is an understandable desire to use simple unpolarized infrared analysis of unoriented anisotropic samples to extract quantitative information, rather than using more demanding polarized techniques. Owing to the fact that unpolarized infrared absorbance in birefringent media deviates from the Beer-Lambert law, previous studies have either warned against using unpolarized spectroscopy for quantitative purposes, or have used flawed error analysis to justify using simple averages of integrated absorbance of multiple absorbance bands as a proxy for total integrated polarized absorbance in the principal spectra. It is shown here that unpolarized infrared absorbance is correctly calculated by averaging in the transmission domain. The errors in estimates of principal absorbance by averaging of unpolarized absorbance spectra are evaluated using correct theory of unpolarized infrared transmission. Correction schemes for integrated absorbance based on linear-absorbance error calculations are shown to be inappropriate. A theory is developed that allows the sum of the polarized principal absorbance spectra to be estimated from multiple unpolarized measurements of randomly oriented samples. The systematic errors that arise when averaging in the absorbance domain are avoided by use of exact theory rather than an approximation. Numerical simulation shows that applying the new procedure to 10 unpolarized measurements of OH stretching bands in olivine results in convergence of the estimated total integrated principal polarized absorbance to within 10% of the true value for a sample size of 10 measurements, but the technique is limited to spectral regions that do not contain absorption bands that are simultaneously intensely absorbing and strongly anisotropic.


The causality issue has become one of the key questions in the debate over the relationship between the built environment and travel behavior. To ascertain whether changes to the built environment are a cost-effective way to change travel behavior, it is necessary to determine the magnitude of the effect. Further, it is important to understand whether the observed influence of the built environment on travel behavior diminishes substantially once we control for self-selection. Using 1553 residents living in four traditional and four suburban neighborhoods in Northern California, this study explores the causal effect of neighborhood type on walking behavior and the relationship between this effect and the observed influence of neighborhood type on walking behavior. Specifically, propensity score stratification, which has been widely used to reduce selection bias, was applied. The results showed that, on average, the causal influences of neighborhood type are likely to be overstated by 64% for utilitarian walking frequency and 16% for recreational walking frequency, if residential self-selection is not controlled for. However, neighborhood type still plays a more important role in affecting walking behavior than does self-selection. This study also offers a basic tutorial for the propensity score stratification approach and discusses its strengths and weaknesses for applications in the field of land use and travel behavior. © 2010 Pion Ltd and its Licensors.


Goetz E.G.,University of Minnesota
Housing Studies | Year: 2010

Housing policy in the United States now serves an agenda defined by concerns over economic and racial segregation in older central city neighborhoods. HOPE VI, the main US initiative in this area, is aimed at the large-scale demolition of public housing projects and their replacement by smaller-scale, mixed-income developments. The logic model behind the effort to redevelop public housing and disperse subsidized housing residents anticipates benefits at both the individual and community level. Individuals are expected to progress in a range of economic, social and physical ways when freed of the negative area effects associated with high levels of income and racial segregation. Communities are expected to become more livable when rid of dysfunctional and outmoded public housing estates and their discouraging influence on private investment patterns. This paper examines the strengths and weaknesses of this model, assessing, in the process, the potential for achieving the policy goals set out by those advocating dispersal. © 2010 Taylor & Francis.


Markusen A.,University of Minnesota
Regional Studies | Year: 2010

Organizational complexity in the regional cultural economy, Regional Studies. Cultural industries offer a truncated understanding of the regional cultural economy, undercounting self-employed workers and others outside the for-profit sector. Commercial, public, non-profit, and unincorporated community sectors produce, present, train, organize, guide, and regulate elements of the cultural economy, each with distinctive structures, goals, and operational systems. Using survey and Census data on artists for two large California regions, inter-relationships among the sectors are explored. The size of the cultural economies of both regions would be underestimated if confined to for-profit cultural industries. In closing, policy implications for regional policy-makers are drawn out and avenues for further research are suggested. © 2010 Regional Studies Association.


Fernandes R.M.,University of Minnesota | Millis A.J.,Columbia University
Physical Review Letters | Year: 2013

In several families of iron-based superconducting materials, a d-wave pairing instability may compete with the leading s-wave instability. Here, we show that when both states have comparable free energies, superconducting and nematic degrees of freedom are strongly coupled. Whereas nematic order causes a sharp nonanalytic increase in Tc, nematic fluctuations can change the character of the s-wave to d-wave transition, favoring an intermediate state that does not break time-reversal symmetry but does break tetragonal symmetry. The coupling between superconductivity and nematicity is also manifested in the strong softening of the shear modulus across the superconducting transition. Our results show that nematicity can be used as a diagnostic tool to search for unconventional pairing states in iron pnictides and chalcogenides. © 2013 American Physical Society.


Baelde D.,University of Minnesota
ACM Transactions on Computational Logic | Year: 2012

The first-order theory of MALL (multiplicative, additive linear logic) over only equalities is a well-structured but weak logic since it cannot capture unbounded (infinite) behavior. Instead of accounting for unbounded behavior via the addition of the exponentials (! and ?), we add least and greatest fixed point operators. The resulting logic, which we call μMALL, satisfies two fundamental proof theoretic properties: we establish weak normalization for it, and we design a focused proof system that we prove complete with respect to the initial system. That second result provides a strong normal form for cut-free proof structures that can be used, for example, to help automate proof search. We show how these foundations can be applied to intuitionistic logic. © 2012 ACM.


Chen C.,University of Minnesota
Physical Review Letters | Year: 2013

We theoretically predict an exotic topological superfluid state with a spatially modulated pairing gap in one-dimensional spin-orbit-coupled Fermi gases. This inhomogeneous topological superfluidity is induced by applying simultaneously a perpendicular Zeeman magnetic field and an equally weighted Rashba and Dresselhaus spin-orbit coupling in one-dimensional optical lattices. Based on the self-consistent Bogoliubov-de Gennes theory, we confirm that this novel topological phase is a unique condensation of Cooper pairs, which manifests the interplay between the inhomogeneity of a superfluid and its nontrivial topological structure. The properties of the emergent Majorana bound states are investigated in detail by examining the associated Z2 topological number, the eigenenergy and density of states spectra, as well as the wave functions of the localized Majorana end modes. The experimental feasibility of observing this new topological state of matter is also discussed. © 2013 American Physical Society.


Voloshin M.B.,University of Minnesota | Voloshin M.B.,Institute of Theoretical and Experimental Physics
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

The amplitude of the diphoton decay of the Higgs boson is considered in an extension of the Standard Model involving heavy vectorlike fermions, which was recently suggested in the literature in order to explain a possible enhancement of the h→γγ decay rate. It is pointed out that generally in such models the decay amplitude acquires a sizable CP-odd contribution from the complex phases in the mass matrix of the new heavy fermions. The resulting CP violation in the diphoton decay can be studied experimentally when both photons are converted into e +e - pairs by measuring the distribution over the angle between the planes of the pairs. Such measurement, if feasible, would be of great interest on its own, regardless of specific models. © 2012 American Physical Society.


Redish A.D.,University of Minnesota
Nature Reviews Neuroscience | Year: 2016

When rats come to a decision point, they sometimes pause and look back and forth as if deliberating over the choice; at other times, they proceed as if they have already made their decision. In the 1930s, this pause-and-look behaviour was termed 'vicarious trial and error' (VTE), with the implication that the rat was 'thinking about the future'. The discovery in 2007 that the firing of hippocampal place cells gives rise to alternating representations of each of the potential path options in a serial manner during VTE suggested a possible neural mechanism that could underlie the representations of future outcomes. More-recent experiments examining VTE in rats suggest that there are direct parallels to human processes of deliberative decision making, working memory and mental time travel. © 2016 Macmillan Publishers Limited.


Freeman M.L.,University of Minnesota
Gastrointestinal Endoscopy Clinics of North America | Year: 2012

Endoscopic retrograde cholangiopancreatography (ERCP) is now almost exclusively a therapeutic modality for pancreatic as well as biliary disorders. ERCP alone or with associated pancreatic and biliary therapy can cause a spectrum of mild and severe complications, including pancreatitis, hemorrhage, perforation, and cardiopulmonary events. Understanding of complications of ERCP has progressed substantially in the past decade, including widespread adoption of standardized consensus-based definitions of complications, large multicenter multivariate studies that have permitted clearer understanding of patient and technique-related risk factors for complications, and introduction of new technical approaches to minimize risks of ERCP. © 2012 Elsevier Inc.


Brunstein C.G.,University of Minnesota
Cancer Control | Year: 2011

Background: The use of unrelated umbilical cord blood (UCB) has grown as an allogeneic source of hematopoietic cells for transplantation of patients with hematologic malignancies. As the number of UCB transplantation procedures has grown, an increasing number of publications have focused on disease-specifi c outcomes. Methods: This review focuses on the outcome data following UCB transplantation in subsets of hematologic malignancies in which experience with this graft source is greater. Results: Registry and single-institution reports regarding the outcomes of children and adults with acute leukemias after UCB transplantation include many patients, while data on the clinical outcomes of other leukemias are limited due in part to the small number of patients with these diseases. UCB is now routinely used as a source of hematopoietic stem cells (HSCs) in pediatric allogeneic transplantation when a suitable sibling donor is not available. Data also support the use of UCB as an alternative source of HSC for transplantation of patients with hematologic malignancies who lack a more conventional donor. Current data also support UCB for patients who require an allograft in the setting of prospective clinical trials. Conclusions: Along with safety and feasibility in UCB transplantation, continued study is needed that focuses on issues such as accelerating engraftment, extending access, ensuring quality, and examining outcomes in specifi c subgroups of patients.


Harrison A.K.,University of Minnesota
The Journal of the American Academy of Orthopaedic Surgeons | Year: 2011

Subacromial impingement syndrome (SIS) represents a spectrum of pathology ranging from subacromial bursitis to rotator cuff tendinopathy and full-thickness rotator cuff tears. The relationship between subacromial impingement and rotator cuff disease in the etiology of rotator cuff injury is a matter of debate. Both extrinsic compression and intrinsic degeneration may play a role. Management includes physical therapy, injections, and, for some patients, surgery. There remains a need for high-quality studies of the pathology, etiology, and management of SIS.


Kagawa-Singer M.,University of California at Los Angeles | Dadia A.V.,University of California at Los Angeles | Yu M.C.,University of Minnesota | Surbone A.,New York University
CA Cancer Journal for Clinicians | Year: 2010

Little progress has been made over the last 40 years to eliminate the racial/ethnic differences in incidence, morbidity, avoidable suffering, and mortality from cancer that result from factors beyond genetic differences. More effective strategies to promote equity in access and quality care are urgently needed because the changing demographics of the United States portend that this disparity will not only persist but significantly increase. Such suffering is avoidable. The authors posit that culture is a prime factor in the persistence of health disparities. However, this concept of culture is still poorly understood, inconsistently defined, and ineffectively used in practice and research. The role of culture in the causal pathway of disparities and the potential impact of culturally competent cancer care on improving cancer outcomes in ethnic minorities has, thus, been underestimated. In this article, the authors provide a comprehensive definition of culture and demonstrate how it can be used at each stage of the cancer care continuum to help reduce the unequal burden of cancer. The authors conclude with suggestions for clinical practice to eliminate the disconnection between evidence-based, quality, cancer care and its delivery to diverse population groups. ©2010 American Cancer Society, Inc.


Pine A.M.,University of Minnesota
Environment and Planning A | Year: 2010

In this analysis I examine how Dominican grocery-store owners (bodegueros) in Philadelphia gain the ability to operate corner stores in predominantly African American and Puerto Rican neighborhoods where they are often considered to be outsiders. A central element of the survival strategy of the grocers is to bend over backwards in order to serve their clients and 'perform' to the expectations of community residents. These actions disrupt discrete notions of community 'outsider' and 'insider' and suggest that urban citizenship is not a static positionality based solely on contest- ations with the state but, rather, an identity created by the interactions between the heterogenous elements of the modern city. I use the experience of the grocers to argue that our understanding of insurgent forms of citizenship must be attuned to this fluid definition of citizenship-one in which the relationships between different members of the polity is crucial. © 2010 Pion Ltd and its Licensors.


Aguirre C.I.,CICATA Legaria IPN | Reguera E.,CICATA Legaria IPN | Stein A.,University of Minnesota
Advanced Functional Materials | Year: 2010

Colloidal photonic crystals and materials derived from colloidal crystals can exhibit distinct structural colors that result from incomplete photonic band gaps. Through rational materials design, the colors of such photonic crystals can be tuned reversibly by external physical and chemical stimuli. Such stimuli include solvent and dye infiltration, applied electric or magnetic fields, mechanical deformation, light irradiation, temperature changes, changes in pH, and specific molecular interactions. Reversible color changes result from alterations in lattice spacings, filling fractions, and refractive index of system components. This review article highlights the different systems and mechanisms for achieving tunable color based on opaline materials with closepacked or non-close-packed structural elements and inverse opal photonic crystals. Inorganic and polymeric systems, such as hydrogels, metallopolymers, and elastomers are discussed. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Snyder P.K.,University of Minnesota
Earth Interactions | Year: 2010

Numerous studies have identified the regional-scale climate response to tropical deforestation through changes to water, energy, and momentum fluxes between the land surface and the atmosphere. There has been little research, however, on the role of tropical deforestation on the global climate. Previous studies have focused on the climate response in the extratropics with little analysis of the mechanisms responsible for propagating the signal out of the tropics. A climate modeling study is presented of the physical processes that are important in transmitting a deforestation signal out of the tropics to the Northern Hemisphere extratropics in boreal winter. Using the Community Climate System Model, version 3 Integrated Biosphere Simulator (CCM3-IBIS) climate model and by imposing an exaggerated land surface forcing of complete tropical forest removal, the thermodynamic and dynamical atmospheric response is evaluated regionally within the tropics, globally as the climate signal propagates to the Northern Hemisphere, and then regionally in Eurasia where land-atmosphere feedbacks contribute to amplifying the climate signal and warming the surface and lower troposphere by 1-4 K. Model results indicate that removal of the tropical forests causes weakening of deep tropical convection that excites a Rossby wave train emanating northeastward away from the South American continent. Changes in European storm-track activity cause an intensification and northward shift in the Ferrel cell that leads to anomalous adiabatic warming over a broad region of Eurasia. Regional-scale land-atmosphere feedbacks are found to amplify the warming. While hypothetical, this approach illustrates the atmospheric mechanisms linking the tropics with Eurasia that may otherwise not be detectable with more realistic land-use change simulations.


Clark M.J.,University of Minnesota
Journal of the American College of Nutrition | Year: 2013

Epidemiologic studies have shown that fiber intake is associated with a lower body weight. Satiety and energy intake are possible explanations for this effect. The purpose of this study was to recommend fiber types and doses that are effective in reducing appetite and energy intake. A systematic review was conducted using the American Dietetic Association's evidence analysis process as a guide. Studies were identified from PubMed and bibliographies of review articles. Studies measuring appetite, food and/or energy intake with a treatment period of ≤24 hours, a reported fiber type and amount, a low- or no-fiber control, and healthy human participants were included. Forty-four publications were identified, from which 107 treatments were analyzed. Thirty-eight fiber sources were identified. The percentage of treatments that significantly reduced subjective appetite rating compared with the control was 39%. The percentage that significantly reduced food or energy intake was 22%. The satiety-enhancing effects of β-glucan, lupin kernel fiber, rye bran, whole grain rye, or a mixed high-fiber diet were supported in more than one publication. Most fibers do not reduce appetite or energy intake in acute study designs. KEY TEACHING POINTS: • Dietary fiber intake is associated with lower body weight in epidemiologic studies. • Most acute fiber treatments (61%) did not enhance satiety. • Most acute fiber treatments (78%) did not reduce food intake. • Neither fiber type nor fiber dose were related to satiety response or food intake.


Kozak K.H.,University of Minnesota | Wiens J.J.,State University of New York at Stony Brook
American Naturalist | Year: 2010

Many biodiversity hotspots are in montane regions, and many plant and animal groups have their highest species richness at intermediate elevations. Yet, the explanation for this hump-shaped diversity pattern has remained unclear because no studies have addressed both the ecological and evolutionary causes. Here, we address these causes in North American plethodontid salamanders, using a near-comprehensive phylogeny and environmental data. We develop a null model for assessing the relationship between the time that an area has been occupied and its species richness, and we apply a new approach that tests whether clades exhibit long-term stasis in their climatic niches (niche conservatism). Evolutionary, the midelevation peak in species richness is explained by the time-for-speciation effect, with intermediate-elevation habitats seemingly being inhabited longest and accumulating more species. We find that this pattern is associated with evolutionary stasis in species' climatic niches, driving the midelevation peak by constraining the dispersal of lineages to environments at lower and higher elevations. These processes may help explain elevational diversity patterns in many montane regions around the world. The results also suggest that montane biotas may harbor high levels of'both species diversity and phylogenetic diversity but may be particularly susceptible to rapid climate change. © 2010 by The University of Chicago.


Gralnick J.A.,University of Minnesota
Biochemical Society Transactions | Year: 2012

Dissimilatory metal-reducing bacteria are able to conduct electrons from their cytoplasmic membrane across the periplasm and the outer membrane to redox proteins located on the surface of their cells. The Mtr respiratory pathway in Shewanella is the best-understood metal-reducing pathway to date. The core components of this pathway are well agreed upon, but are they sufficient? Could there be other components that we have yet to uncover? The present paper specifically considers the periplasm, its physical properties and organization. Two models are presented to explain how electrons could be conducted across this compartment in Shewanella. ©The Authors Journal compilation ©2012 Biochemical Society.


Wright R.,University of Minnesota
Genetics | Year: 2014

THE Genetics Society of America’s Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. Consistent with her philosophy of linking research and education, the 2014 Awardee Robin Wright includes undergraduate students in all of her research. She seeks to teach how to think like and to actually be a biologist, working in teams and looking at real-world problems. She emphasizes a learner-centered model of classroom work that promotes and enhances lifelong skills, and has transformed biology education at the University of Minnesota through several efforts including developing the interactive, stimulating Foundations of Biology course sequence, encouraging active learning and open-ended research; supporting the construction of Active Learning Classrooms; and establishing Student Learning Outcomes, standards that measure biology education. She serves as founding editor-in-chief of CourseSource, focusing national effort to collect learner-centered, outcomes-based teaching resources in undergraduate biology. © 2014 by the Genetics Society of America.


Carlson M.D.,University of Minnesota
Journal of cardiac failure | Year: 2013

Despite substantial improvements in treatment for chronic heart failure, morbidity and mortality for acute decompensated heart failure (ADHF) remain high. Treatment of ADHF is focused on controlling symptoms rather than improving long-term outcomes. The vasodilators nitroglycerin (NTG) and sodium nitroprusside (SNP) have been used in ADHF for decades, but, since the development of nesiritide 10 years ago, interest in new vasodilators has grown. Therapies that improve not only hemodynamics and symptoms but also long-term outcomes are in high demand, and numerous new vasodilatory agents have been investigated, including various natriuretic peptides, soluble guanylyl cyclase agents, renin-angiotensin-aldosterone system-modifying agents, and others. A review of the literature shows that few of them rise to the challenge set by NTG and SNP. Copyright © 2013 Elsevier Inc. All rights reserved.


Kozak K.H.,University of Minnesota | Wiens J.J.,State University of New York at Stony Brook
Ecology | Year: 2012

Many studies show that species richness is correlated with climate, especially among local sites within a region. However, few studies have addressed how these climate-diversity relationships actually arise. Only a few processes can directly change species richness (i.e., speciation, extinction, dispersal), and these processes may be best studied by incorporating a phylogenetic perspective. Here, we used a phylogenetic approach to address the causes of climate-diversity relationships in plethodontid salamanders by combining data on richness, climate, and phylogeny for 250 species. Our results suggest that species richness patterns in plethodontids are explained primarily by how long each region and climatic zone has been occupied, rather than by the effects of either area, species density (i.e., ecological limits), or climate on the rates of speciation or extinction. Across regions, diversity is related to time rather than climate. Within regions, significant climate-diversity relationships are also related to time, with higher richness in climatic regimes that have been occupied longer. Although some might think that phylogeny is unimportant at local scales and when climate and diversity are strongly correlated, we show that niche conservatism and phylogenetic history (time) combine to create species pools of different sizes in different habitats (climatic regimes), leading to variation in local species richness across these habitats within a region. © 2012 by the Ecological Society of America.


Koenig M.A.,University of Minnesota | Jaswal V.K.,University of Virginia
Child Development | Year: 2011

Do children expect an expert in one domain to also be an expert in an unrelated domain? In Study 1, 32 three- and four-year-olds learned that one informant was an expert about dogs relative to another informant. When presented with pictures of new dogs or of artifacts, children who could remember which informant was the dog expert preferred her over the novice as an informant about the names of dogs, but they had no preference when the informants presented artifact labels. In Study 2, 32 children learned that one informant was incompetent about dogs whereas another was neutral. In this case, children preferred the neutral speaker over the incompetent one about both dogs and artifacts. Taken together, these results suggest that for children, expertise is not subject to a "halo effect," but incompetence may be subject to a "pitchfork effect". © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.


The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model’s sodium kinetics to fourth order (m3 → m4). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 =14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the ratelimiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation. © 2015 the American Physiological Society.


Ozonder S.,University of Minnesota
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We consider a version of the McLerran-Venugopalan model by Lam and Mahlon where confinement is implemented via colored noise in the infrared. This model does not assume an infinite momentum frame, hence the boosted nuclei are not infinitely thin. Instead, the nuclei have a finite extension in the longitudinal direction and therefore depend on the longitudinal coordinate. In this fully three-dimensional framework an x dependence of the gluon distribution function emerges naturally. In order to fix the parameters of the model, we calculate the gluon distribution function and compare it with the JR09 parametrization of the data. We explore the parameter space of the model to attain a working framework that can be used to calculate the initial conditions in heavy ion collisions. Published by the American Physical Society.


Vanchurin V.,University of Minnesota
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We develop further a kinetic theory of strings and derive a transport equation for a network of cosmic strings with Nambu-Goto evolution, interactions, and background gravitational effects taken into account. We prove an H-theorem and obtain necessary and sufficient conditions for a thermodynamic equilibrium. At the lowest order, the equilibrium is estimated by the von Mises-Fisher distributions, parametrized by mean directions and dispersions of the right- and left-moving tangent vectors. Under assumption of a local equilibrium, we derive a complete set of hydrodynamic equations that govern the evolution of strings on large scales. We also argue that on small scales, the assumption of a local equilibrium would break down, so nonequilibrium steady states, described by the Sinai-Ruelle-Bowen distributions, should be used instead. © 2013 American Physical Society.


Shifman M.,University of Minnesota
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

I explain how conventional topological defects - the Abrikosov-Nielsen- Olesen string and domain walls - can acquire non-Abelian moduli localized on their world sheets. The setup is conceptually similar and generalizes that used by Witten for cosmic strings Witten. © 2013 American Physical Society.


Wang X.,Florida Atlantic University | Giannakis G.B.,University of Minnesota
IEEE Transactions on Information Theory | Year: 2011

Resource allocation issues are investigated in this paper for multiuser wireless transmissions based on orthogonal frequency division multiplexing (OFDM). Relying on convex and stochastic optimization tools, the novel approach to resource allocation includes: i) development of jointly optimal subcarrier, power, and rate allocation for weighted sum-average-rate maximization; ii) judicious formulation and derivation of the optimal resource allocation for maximizing the utility of average user rates; and iii) development of the stochastic resource allocation schemes, and rigorous proof of their convergence and optimality. Simulations are also provided to demonstrate the merits of the novel schemes. © 2011 IEEE.


Dehm S.M.,University of Minnesota
Clinical Cancer Research | Year: 2013

E7107 is a derivative of the pladienolide family of natural product spliceosome inhibitors, which targets the U2 small nuclear ribonucleoprotein (snRNP) subunit SF3b. The results of a first-in-human trial with E7107 have been reported, representing an important translational step toward the goal of modulating RNA splicing for cancer therapy. © 2013 American Association for Cancer Research.


Tilman D.,University of Minnesota
American Naturalist | Year: 2011

Competition theory predicts that multispecies coexistence requires that species have traits that fall on the same interspecific trade-off surface. Fossil records for mollusks,mammals, trees, and other taxa show that with rare exception, ecologically similar species have coexisted for a million years or more after interchange between formerly isolated realms. This coexistence suggests the possibility, termed the universal trade-off hypothesis, that ecologically similar species of different realms have been bound to the same interspecific trade-off surface despite millions of years of independent evolution. Such persistence fails to support the biogeographic superiority hypothesis, which posits that genetic drift, recombination, mutation, and selection would cause taxa of one realm to gain superiority over those of another realm during long periods of isolation. Analysis of the lengths of time that species have persisted once in contact suggests that the trade-off surfaces of realms differed by >0.1% at the time of interchange. This implies that macroevolutionary patterns of differentiation and speciation within and between realms were more likely the movement of traits on a common tradeoff surface rather than directional selection achieved without compensatory trade-offs and costs. The existence of transrealm tradeoffs, should further work support this possibility, has deep implications for ecology and evolution. © 2011 by The University of Chicago.


Voller V.R.,University of Minnesota
International Journal of Heat and Mass Transfer | Year: 2014

The solution of the classical one-dimensional Stefan problem predicts that in time t the melt front goes as s(t)∼t12. In the presence of heterogeneity, however, anomalous behavior can be observed where the time exponent n12. In such a case, it may be appropriate to write down the governing equations of the Stefan problem in terms of fractional order time (1≥β>0) and space (1≥α>0) derivatives. Here, we present sharp and diffuse interface models of fractional Stefan problems and discuss available analytical solutions. We illustrate that in the fractional time case (β<1), a solution of the diffuse interface model in the sharp interface limit will not coincide with the solution of the sharp interface counterpart; negating a well know result of integer derivative Stefan problems. The paper concludes with the development of an implicit time stepping numerical solution for the diffuse interface fractional Stefan model. Results from this solution are verified with available analytical solutions. © 2014 Elsevier Ltd. All rights reserved.


Snell-Rood E.C.,University of Minnesota
Animal Behaviour | Year: 2013

I outline how understanding the mechanism of behavioural plasticity is important for predicting how organisms will respond to rapidly changing and novel environments. I define two major forms of behavioural plasticity: developmental and activational. Developmental plasticity refers to the capacity of a genotype to adopt different developmental trajectories in different environments. Activational plasticity refers to differential activation of an underlying network in different environments such that an individual expresses various phenotypes throughout their lifetime. I suggest that the costs and benefits of these two forms of behavioural plasticity may differ: developmental plasticity is slow, but results in a wider range of more integrated responses. Furthermore, the neural costs associated with activational plasticity may be greater because large neural networks must be maintained past an initial sampling and learning phase. While the benefits of plasticity are realized in variable environments, I argue that fine-grained and coarse-grained variation may differentially select for activational and developmental plasticity, respectively. Because environmental variation experienced by an organism is largely determined by behaviour, developmental plasticity may still evolve in fine-grained environments if niche choice results in coarse-grained 'realized' variation. Behavioural plasticity should impact evolution in novel environments because it increases the chances of survival in these environments. Developmental behavioural plasticity may be particularly important for diversification in novel environments because it can impact not only survival, but also the development of signals and preferences important in mate choice. Future areas of research on behavioural plasticity and rapid environmental change include stress as a mechanism underlying rapid integrated responses and life history perspectives on predicting developmental versus evolutionary responses. © 2013 The Association for the Study of Animal Behaviour.


Seelig B.,University of Minnesota
Nature protocols | Year: 2011

The mRNA display technology enables the in vitro selection and directed evolution of functional proteins from libraries of more than 10(12) different mutants in a single test tube. The size of these libraries is well beyond the limit of screening technologies and of most in vivo and in vitro selection methods. The mRNA display technology has been used to select peptides and proteins that bind to a specific ligand, as well as novel enzymes. This protocol details the procedure to produce mRNA-displayed proteins (3 d) and to subject them to a selection and evolution of enzymes for bond-forming reactions (4-10 weeks). This method is demonstrated by the generation of new RNA ligase enzymes.


Mulla D.J.,University of Minnesota
Biosystems Engineering | Year: 2013

Precision agriculture dates back to the middle of the 1980's. Remote sensing applications in precision agriculture began with sensors for soil organic matter, and have quickly diversified to include satellite, aerial, and hand held or tractor mounted sensors. Wavelengths of electromagnetic radiation initially focused on a few key visible or near infrared bands. Today, electromagnetic wavelengths in use range from the ultraviolet to microwave portions of the spectrum, enabling advanced applications such as light detection and ranging (LiDAR), fluorescence spectroscopy, and thermal spectroscopy, along with more traditional applications in the visible and near infrared portions of the spectrum. Spectral bandwidth has decreased dramatically with the advent of hyperspectral remote sensing, allowing improved analysis of specific compounds, molecular interactions, crop stress, and crop biophysical or biochemical characteristics. A variety of spectral indices now exist for various precision agriculture applications, rather than a focus on only normalised difference vegetation indices. Spatial resolution of aerial and satellite remote sensing imagery has improved from 100's of m to sub-metre accuracy, allowing evaluation of soil and crop properties at fine spatial resolution at the expense of increased data storage and processing requirements. Temporal frequency of remote sensing imagery has also improved dramatically. At present there is considerable interest in collecting remote sensing data at multiple times in order to conduct near real time soil, crop and pest management. © 2012 IAgrE.


Ruden P.,University of Minnesota
Nature Materials | Year: 2011

A suitably chosen thin layer inserted between a ferromagnetic electrode and an organic semiconductor allows control over the polarization of the injected spins. Among the advantages that organic semiconductors possess over conventional inorganic semiconductors is the relative ease with which their electronic structure can be modified through well-developed methods of synthesis. The weakness of coupling mechanisms can be a strength when envisaging possible spintronic devices, but it also precludes certain experiments that could probe the spin polarization of the mobile charge carriers. To overcome the difficulty of directly determining the spin polarization of injected charge carriers in organic semiconductors, the team led by Alan Drew pioneered a complex but elegant technique of measuring the local internal magnetic field by implanting (positive) muons and measuring the direction and timing of the positrons emitted in their decay.


Young sexual minority males are among those at highest risk for HIV infection, yet we know relatively little about the impact of sexual identity development on HIV risk. This study used cross-sectional data to investigate factors associated with HIV-related sexual risk among a sample of sexual minority males (n = 156), ages 14 to 21 years, using an extended version of the information-motivation-behavioral skills (IMB) model tailored for this population. Path analysis results indicated that the extended model predicted a sizable amount of primary and secondary sexual risk (r2 = .35 and .42). In addition to increasing HIV prevention information and motivation and decreasing substance use, study findings suggest that interventions with young sexual minority males should focus on sexual identity development factors including youths' attitudes toward LBGT people, sex-centered versus identity-centered development, and with specific emphasis on youth with non-male exclusive sexual orientations. © 2012 Society for Public Health Education.


Sun C.C.,University of Minnesota
Journal of Adhesion Science and Technology | Year: 2011

Tabletability, the ability to make a tablet of adequate mechanical strength by powder compaction, is of paramount importance in the successful manufacture of tablet products. Poor tabletability is a persistent problem in the pharmaceutical industry. Tablet strength can be understood based on a qualitative model where contributions of bonding area and bonding strength are simultaneously considered. Formation and elimination of bonding area is related to compaction conditions, mechanical properties and particulate properties (such as particle size and shape). Plastic deformation emerges as the most important mechanism for creating a large bonding area among deformation mechanisms. Interfacial adhesion defines bonding strength and is dependent on the chemical nature of the materials involved. An analysis of how the chemical, mechanical and physical properties of a powder impact bonding strength and bonding areas leads to an understanding of their effects on powder tabletability. Appropriate use of this model can minimize empiricism in product development and facilitate the design of high quality tablets and robust manufacturing processes. © 2011 VSP.


Kane R.L.,University of Minnesota
Gerontologist | Year: 2015

This article argues for a fresh look at how we provide long-term care (LTC) for older persons. Essentially, LTC offers a compensatory service that responds to frailty. Policy debate around LTC centers on costs, but we are paying for something we really don't want. Building societal enthusiasm (or even support) for LTC will require re-inventing and re-branding. LTC has three basic components: personal care, housing, and health care (primarily chronic disease management). They can be delivered in a variety of settings. It is rare to find all three done well simultaneously. Personal care (PC) needs to be both competent and compassionate. Housing must provide at least minimal amenities and foster autonomy; when travel time for PC raises costs dramatically, some form of clustered housing may be needed. Health care must be proactive, aimed at preventing exacerbations of chronic disease and resultant hospitalizations. Enhancing preferences means allowing taking informed risks. Payment incentives should reward both quality of care and quality of life, but positive outcomes must be defined as slowing decline. Paying for services but not for housing under Medicaid would automatically level the playing field between nursing homes (NH) and community-based services. Regulations should achieve greater parity between NH and community care and include both positive and negative feedback. Providing post-acute care should be separate from LTC. Using the tripartite LTC framework, we can create innovative flexible approaches to providing needed services for frail older persons in formats that are both desirable and affordable. Such care will be more socially desirable and hence worth paying for. © The Author 2015.


Isaacson R.,University of Minnesota
Animal health research reviews / Conference of Research Workers in Animal Diseases | Year: 2012

The intestinal microbiome has been the subject of study for many decades because of its importance in the health and well being of animals. The bacterial components of the intestinal microbiome have closely evolved as animals have and in so doing contribute to the overall development and metabolic needs of the animal. The microbiome of the pig has been the subject of many investigations using culture-dependent methods and more recently using culture-independent techniques. A review of the literature is consistent with many of the ecologic principles put forth by Rene Dubos. Animals develop an intestinal microbiome over time and space. During the growth and development of the pig, the microbiome changes in composition in a process known as the microbial succession. There are clear and distinct differences in the composition of the pig intestinal microbiome moving from the proximal end of the intestinal tract to the distal end. The majority (>90%) of the bacteria in the pig intestinal microbiome are from two Phyla: Firmicutes and Bacteroidetes. However, the ileum has a high percentage of bacteria in the phylum Proteobacterium (up to 40%). Perturbations to the microbiome occur in response to many factors including stresses, treatment with antibiotics, and diet.


Borowsky I.W.,University of Minnesota
Academic Medicine | Year: 2011

Many young people who present to primary care providers (PCPs) have high levels of emotional distress and/or suicidal ideation. Therefore, PCPs are in an ideal position to recognize and respond to early symptoms and distress signals that accompany suicide warning signs, yet they underrecognize mood disorders and suicidality among youth. Medical school and residency programs typically provide inadequate training on pediatric mental health and adolescent suicide prevention. Thus, PCPs lack complete knowledge of risk factors and feel unprepared to handle mental health problems among youth.In this article, the authors provide an overview of the epidemiology of adolescent suicide and describe risk factors, protective factors, and warning signs. They propose that physician education represents a promising strategy to prevent adolescent suicide, and they establish the need for improved educational opportunities that would provide PCPs with the necessary skills and supports to identify and respond to psychosocial concerns that may increase suicide risk among youth. They recommend strategies, methods, and content areas for addressing educational gaps, as well as organizational approaches to support enhanced physician education. They also suggest areas for future research. Copyright © by the Association of American Medical College.


Woosley S.E.,University of California at Santa Cruz | Heger A.,University of Minnesota
Astrophysical Journal | Year: 2012

In the collapsar model for common gamma-ray bursts (GRBs), the formation of a centrifugally supported disk occurs during the first 10 s following the collapse of the iron core in a massive star. This only occurs in a small fraction of massive stellar deaths, however, and requires unusual conditions. A much more frequent occurrence could be the death of a star that makes a black hole and a weak or absent outgoing shock, but in a progenitor that only has enough angular momentum in its outermost layers to make a disk. We consider several cases where this is likely to occur - blue supergiants with low mass-loss rates, tidally interacting binaries involving either helium stars or giant stars, and the collapse to a black hole of very massive pair-instability supernovae. These events have in common the accretion of a solar mass or so of material through a disk over a period much longer than the duration of a common GRB. A broad range of powers is possible, 1047-1050erg s-1, and this brightness could be enhanced by beaming. Such events were probably more frequent in the early universe where mass-loss rates were lower. Indeed, this could be one of the most common forms of gamma-ray transients in the universe and could be used to study first generation stars. Several events could be active in the sky at any one time. Recent examples of this sort of event may have been the Swift transients Sw-1644+57, Sw-2058+0516, and GRB 101225A. © 2012. The American Astronomical Society. All rights reserved..


Seaquist E.R.,University of Minnesota
Diabetes Care | Year: 2015

This address was delivered by Elizabeth R. Seaquist, MD, President, Medicine & Science, of the American Diabetes Association (ADA) at the Association's 74th Scientific Sessions in San Francisco, CA, on 15 June 2014. Dr. Seaquist is a professor of medicine at the University of Minnesota in Minneapolis, where she holds the Pennock Family Chair in Diabetes Research. She has been an ADA volunteer since 1987 and has served on several national committees and chaired the Association's work-group on Hypoglycemia in Diabetes. At the local level, she served a 2-year term as cochair of the ADA EXPO in Minneapolis. Dr. Seaquist is a clinical investigator interested in the complications of diabetes. Her research focuses on the effect of diabetes on brain metabolism structure and function. She directs the University of Minnesota site for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) trials and has an active clinical practice. She was the 2009 recipient of the ADA's Distinguished Clinical Scientist Award. Dr. Seaquist holds a Bachelor of Arts degree from Vassar College in Poughkeepsie, NY, and a doctorate in medicine from the University of Minnesota. She is board certified in internal medicine and endocrinology, diabetes, and metabolism. The ADA and Diabetes Care thank Dr. Seaquist for her outstanding leadership and service to the Association. © 2015 by the American Diabetes Association.


Steinman B.A.,University of Minnesota | Mann M.E.,Pennsylvania State University | Miller S.K.,Pennsylvania State University
Science | Year: 2015

The recent slowdown in global warming has brought into question the reliability of climate model projections of future temperature change and has led to a vigorous debate over whether this slowdown is the result of naturally occurring, internal variability or forcing external to Earth's climate system. To address these issues, we applied a semi-empirical approach that combines climate observations and model simulations to estimate Atlantic- and Pacific-based internal multidecadal variability (termed "AMO" and "PMO," respectively). Using this method, the AMO and PMO are found to explain a large proportion of internal variability in Northern Hemisphere mean temperatures. Competition between a modest positive peak in the AMO and a substantially negative-trending PMO are seen to produce a slowdown or "false pause" in warming of the past decade. © 2015, American Association for the Advancement of Science. All rights reserved.


Southern P.J.,University of Minnesota
Trends in Microbiology | Year: 2013

Although unprotected heterosexual intercourse is recognized as the primary mechanism sustaining the global spread of HIV-1, many fundamental details surrounding transmission and establishment of primary HIV-1 infection remain unresolved. Unprotected intercourse induces widespread changes in female reproductive tissues linked to immediate removal of excess spermatozoa and preparation of the uterus for implantation. Concurrently, contact with semen may transiently increase susceptibility to HIV-1 by perturbing mucosal barrier function and triggering localized inflammation. In this manner, infectious HIV-1 in semen becomes an adventitious traveler on the pathway leading to normal human reproduction. This review summarizes key elements of male-to-female HIV-1 transmission and presents a rationalization for human-based studies to illuminate the biology of heterosexual HIV-1 transmission. © 2013 Elsevier Ltd.


Micheyl C.,University of Minnesota
The Journal of the Acoustical Society of America | Year: 2012

The "combined-stimulation advantage" refers to an improvement in speech recognition when cochlear-implant or vocoded stimulation is supplemented by low-frequency acoustic information. Previous studies have been interpreted as evidence for "super-additive" or "synergistic" effects in the combination of low-frequency and electric or vocoded speech information by human listeners. However, this conclusion was based on predictions of performance obtained using a suboptimal high-threshold model of information combination. The present study shows that a different model, based on Gaussian signal detection theory, can predict surprisingly large combined-stimulation advantages, even when performance with either information source alone is close to chance, without involving any synergistic interaction. A reanalysis of published data using this model reveals that previous results, which have been interpreted as evidence for super-additive effects in perception of combined speech stimuli, are actually consistent with a more parsimonious explanation, according to which the combined-stimulation advantage reflects an optimal combination of two independent sources of information. The present results do not rule out the possible existence of synergistic effects in combined stimulation; however, they emphasize the possibility that the combined-stimulation advantages observed in some studies can be explained simply by non-interactive combination of two information sources.


Seufert V.,McGill University | Ramankutty N.,McGill University | Foley J.A.,University of Minnesota
Nature | Year: 2012

Numerous reports have emphasized the need for major changes in the global food system: agriculture must meet the twin challenge of feeding a growing population, with rising demand for meat and high-calorie diets, while simultaneously minimizing its global environmental impacts. Organic farming-a system aimed at producing food with minimal harm to ecosystems, animals or humans-is often proposed as a solution. However, critics argue that organic agriculture may have lower yields and would therefore need more land to produce the same amount of food as conventional farms, resulting in more widespread deforestation and biodiversity loss, and thus undermining the environmental benefits of organic practices. Here we use a comprehensive meta-analysis to examine the relative yield performance of organic and conventional farming systems globally. Our analysis of available data shows that, overall, organic yields are typically lower than conventional yields. But these yield differences are highly contextual, depending on system and site characteristics, and range from 5% lower organic yields (rain-fed legumes and perennials on weak-acidic to weak-alkaline soils), 13% lower yields (when best organic practices are used), to 34% lower yields (when the conventional and organic systems are most comparable). Under certain conditions-that is, with good management practices, particular crop types and growing conditions-organic systems can thus nearly match conventional yields, whereas under others it at present cannot. To establish organic agriculture as an important tool in sustainable food production, the factors limiting organic yields need to be more fully understood, alongside assessments of the many social, environmental and economic benefits of organic farming systems. © 2012 Macmillan Publishers Limited. All rights reserved.


Katz J.,Johns Hopkins University | Sheng J.,University of Minnesota
Annual Review of Fluid Mechanics | Year: 2010

The quantification of three-dimensional (3D) flow structures and particle dynamics is crucial for unveiling complex interactions in turbulent flows. This review summarizes recent advances in volumetric particle detection and 3D flow velocimetry involving holography. We introduce the fundamental principle of holography and discuss the debilitating depth-of-focus problem, along with methods that have been implemented to circumvent it. The focus of this review is on recent advances in the development of in-line digital holography in general, and digital holographic microscopy in particular. A mathematical background for the numerical reconstruction of digital holograms is followed by a summary of recently introduced 3D particle tracking and velocity measurement techniques. The review concludes with sample applications, including 3D velocity measurements that fully resolve the flow in the inner part of a turbulent boundary layer, the diffusion of oil droplets in high-Reynolds number turbulence, and predator-prey interactions among swimming microorganisms in dense suspensions, as well as oceanic and atmospheric field experiments. Copyright © 2010 by Annual Reviews. All rights reserved.


Khoruts A.,University of Minnesota
Nature Reviews Gastroenterology and Hepatology | Year: 2014

Although the idea of faecal transplantation dates back many decades, only with advances in scientific technologies can we begin systematic development of this new class of therapeutics. The primary focus remains on treatment of Clostridium difficile infection-new applications are beginning to emerge, but a long journey remains ahead.


Multiple myeloma (MM), the second most common hematopoietic malignancy, remains an incurable plasma cell (PC) neoplasm. While the proteasome inhibitor, bortezomib (Bz) has increased patient survival, resistance represents a major treatment obstacle as most patients ultimately relapse becoming refractory to additional Bz therapy. Current tests fail to detect emerging resistance; by the time patients acquire resistance, their prognosis is often poor. To establish immunophenotypic signatures that predict Bz sensitivity, we utilized Bz-sensitive and -resistant cell lines derived from tumors of the Bcl-X(L)/Myc mouse model of PC malignancy. We identified significantly reduced expression of two markers (CD93, CD69) in "acquired" (Bz-selected) resistant cells. Using this phenotypic signature, we isolated a subpopulation of cells from a drug-naïve, Bz-sensitive culture that displayed "innate" resistance to Bz. Although these genes were identified as biomarkers, they may indicate a mechanism for Bz-resistance through the loss of PC maturation which may be induced and/or selected by Bz. Significantly, induction of PC maturation in both "acquired" and "innate" resistant cells restored Bz sensitivity suggesting a novel therapeutic approach for reversing Bz resistance in refractory MM.


Stinchfield R.,University of Minnesota
Psychology of Addictive Behaviors | Year: 2011

The specific aims of this study are twofold. First, measure 2007 rates of gambling and underage gambling among public school students. Second, compare rates of gambling, frequent gambling, and underage gambling from 1992 to 2007. The 2007 sample includes 40,605 male and 42,655 female Minnesota public school students enrolled in the 9th and 12th grades and similar sample sizes from 1992, 1995, 1998, 2001, and 2004. Students were administered the Minnesota Student Survey, a 126-item, anonymous, self-administered, paper-and-pencil questionnaire that inquires about multiple health-related content domains, including gambling behavior. In 2007, most students gambled at least once during the past year, however, most did not gamble frequently. Gambling participation has shown a gradual and consistent decline from 1992 to 2007 for both boys and girls. Underage gambling has also shown declines over time. Conversely, rates of frequent gambling (weekly or more often) have remained fairly stable over time. There have been two fluctuations of note, a peak in lottery play in 1998 and a peak in card playing in 2004 with subsequent declines in both. © 2011 American Psychological Association.


Arnold T.W.,University of Minnesota
Journal of Wildlife Management | Year: 2010

As use of Akaike's Information Criterion (AIC) for model selection has become increasingly common, so has a mistake involving interpretation of models that are within 2 AIC units (ΔAIC ≤ 2) of the top-supported model. Such models are <2 ΔAIC units because the penalty for one additional parameter is 2 AIC units, but model deviance is not reduced by an amount sufficient to overcome the 2-unit penalty and, hence, the additional parameter provides no net reduction in AIC. Simply put, the uninformative parameter does not explain enough variation to justify its inclusion in the model and it should not be interpreted as having any ecological effect. Models with uninformative parameters are frequently presented as being competitive in the Journal of Wildlife Management, including 72 of all AIC-based papers in 2008, and authors and readers need to be more aware of this problem and take appropriate steps to eliminate misinterpretation. I reviewed 5 potential solutions to this problem: 1) report all models but ignore or dismiss those with uninformative parameters, 2) use model averaging to ameliorate the effect of uninformative parameters, 3) use 95 confidence intervals to identify uninformative parameters, 4) perform all-possible subsets regression and use weight-of-evidence approaches to discriminate useful from uninformative parameters, or 5) adopt a methodological approach that allows models containing uninformative parameters to be culled from reported model sets. The first approach is preferable for small sets of a priori models, whereas the last 2 approaches should be used for large model sets or exploratory modeling. © 2010 The Wildlife Society.


Wu E.L.,University of Minnesota
Journal of Computational Chemistry | Year: 2010

The nonadiabatic quantum dynamics and Coriolis coupling effect in chemical reaction have been reviewed, with emphasis on recent progress in using the time-dependent wave packet approach to study the Coriolis coupling and nonadiabatic effects, which was done by K. L. Han and his group. Several typical chemical reactions, for example, H+D2, F+H2/D2/HD, D ++H2, O+H2, and He+H2 +, have been discussed. One can find that there is a significant role of Coriolis coupling in reaction dynamics for the ion-molecule collisions of D + +H2, Ne+H 2 +, and He+H2 + in both adiabatic and nonadiabatic context. © 2010 Wiley Periodicals, Inc.


Goldsmith S.R.,University of Minnesota
Journal of Cardiology | Year: 2016

Conventional therapies for acute decongestion have yielded uniformly poor results in patients with acute heart failure (AHF). The failure of current strategies may be due to advanced disease in hospitalized patients, incomplete therapy, inherent limitations to existing therapy, or some combination of all three factors. Loop diuretics are the mainstay of current therapy and are in theory not ideal since while producing immediate intravascular volume reduction and relief of symptoms they activate neurohormonal forces that are deleterious to both the heart and the kidney. Ultrafiltration is an alternative to loop diuretics but has not proved advantageous in the setting of renal dysfunction, and if not carefully applied may also aggravate neurohormonal imbalance. In theory decongestive therapy for AHF should remove large volumes of fluid quickly and safely and improve symptoms, particularly dyspnea, without aggravating renal dysfunction or causing neurohormonal activation. Several studies have now suggested that the use of aquaretics such as antagonists to the V2 receptor for arginine vasopressin may be useful as adjunctive therapy in AHF, particularly when renal dysfunction and/or hyponatremia are present. These agents leverage osmotic forces to produce tissue decongestion while causing a water diuresis. They do not adversely affect renal function or neurohormonal balance. Building on the current base of knowledge about outcomes in AHF together with the only study of vasopressin antagonists as short-term monotherapy in chronic heart failure, it would be reasonable to design a trial in AHF in which the use of loop diuretics was minimized in favor of these agents. © 2016 Japanese College of Cardiology.


Vollum M.J.,University of Minnesota
Computers in Human Behavior | Year: 2014

This paper did a review of the literature on social interaction in education, social media and social interaction, and the use of social media in personal/community health and physical education programs in order to set a research agenda for the use of social media in K-12 physical and health education. The findings were that social interaction can positively impact education and that social media can enhance the social interaction in the educational setting. It also showed how current health/wellness programs outside of the K-12 system are already using social media. There is a need for research on social media in K-12 settings in order to find if it can have an impact in creating healthy and informed decision makers in K-12 physical and health education. © 2014 Elsevier Ltd. All rights reserved.


Wolf S.M.,University of Minnesota
Annual Review of Genomics and Human Genetics | Year: 2013

The debate over return of individual research results and incidental findings to study participants is a key frontier in research ethics and practice. This is fundamentally a problem of translational science-a question of when information about an individual that is generated in research should be communicated for clinical attention, particularly as technologies such as whole-genome sequencing and whole-exome sequencing are increasingly used in clinical care. There is growing consensus that investigators should offer participants at least those individual findings of high clinical importance and actionability. Increasing attention to what information biobanks and secondary researchers owe people who provide data and specimens offers an opportunity to treat these source individuals as research partners. Cutting-edge issues include return of results in pediatric populations and return to kin and family, both before and after the death of the proband, as well as how to manage incidental findings in clinical sequencing. Progress will require an understanding of the continuum linking research and clinical care and developing standards and models for return. Copyright © 2013 by Annual Reviews. All rights reserved.


Goldstein S.M.,University of Minnesota | Iossifova A.R.,Slippery Rock University
Journal of Operations Management | Year: 2012

We investigate the long-term relationship between an organization's quality management practices and process-level performance. Further, we examine whether availability of organizational slack over the study interval interferes with the relationship between quality practices and process performance. Organizational slack consists of the available and accessible resources in an organization; we focus here on unabsorbed slack in the form of financial resources. We investigate the quality practices of U.S. general acute care hospitals, measured by their depth of implementation of practices characterizing a total quality management system, and use them to predict process performance related to four medical conditions. Analysis reveals differing effects that are dependent on hospital slack conditions. In hospitals with high slack, quality practices significantly predict three of four studied process performance measures. In contrast, in hospitals with low slack, quality practices predict only one of the four process performance measures, while other factors outweigh the effects of quality practices. This study lends support to management taking a long-term perspective related to implementation of quality management systems, and highlights the relevance of slack conditions in garnering the benefits of such systems. © 2011 Elsevier B.V. All rights reserved.


Santi P.A.,University of Minnesota
Journal of Histochemistry and Cytochemistry | Year: 2011

Light sheet fluorescence microscopy (LSFM) functions as a non-destructive microtome and microscope that uses a plane of light to optically section and view tissues with subcellular resolution. This method is well suited for imaging deep within transparent tissues or within whole organisms, and because tissues are exposed to only a thin plane of light, specimen photobleaching and phototoxicity are minimized compared to wide-field fluorescence, confocal, or multiphoton microscopy. LSFMs produce well-registered serial sections that are suitable for three-dimensional reconstruction of tissue structures. Because of a lack of a commercial LSFM microscope, numerous versions of light sheet microscopes have been constructed by different investigators. This review describes development of the technology, reviews existing devices, provides details of one LSFM device, and shows examples of images and three-dimensional reconstructions of tissues that were produced by LSFM. © The Author(s) 2011.


Sroufe L.A.,University of Minnesota
Development and Psychopathology | Year: 2013

Progress in the field of developmental psychopathology is appraised in general and with regard to the particular lens of our understanding of the development of disorder. In general, the outpouring of research on various features of disorder and underlying processes could not have even been imagined 25 years ago. The progress is dazzling. At the same time, work on the development of disorders, beginning with antecedent patterns of adaptation, pales in comparison with work on the correlates of disorder. However, progress has been made. It is well established that the brain develops in the context of experience and that organism and environment continually interact over time. Something is now known about pathways leading to certain disorders and what initiates and impels individuals along them. If developmental psychopathology is to completely fulfill its promise of offering new ways of conceptualizing disorder and new guidance for prevention and intervention, much more work on developmental processes and a new way of exploring the development of disorder will be needed. Such a path is suggested. © 2013 Cambridge University Press.


Causadias J.M.,University of Minnesota
Development and Psychopathology | Year: 2013

In this paper, I propose a roadmap for the integration of culture in developmental psychopathology. This integration is pressing because culture continues to be somewhat disconnected from theory, research, training, and interventions in developmental psychopathology, thus limiting our understanding of the epigenesis of mental health. I argue that in order to successfully integrate culture into developmental psychopathology, it is crucial to (a) study cultural development, (b) consider both individual-level and social-level cultural processes, (c) examine the interplay between culture and biology, and (d) promote improved and direct cultural assessment. I provide evidence in support of each of these guidelines, present alternative conceptual frameworks, and suggest new lines of research. Hopefully, that these directions will contribute to the emerging field of cultural development and psychopathology, which focuses on the elucidation of the cultural processes that initiate, maintain, or derail trajectories of normal and abnormal behavior. © 2013 Cambridge University Press.


Tiffin P.,University of Minnesota | Ross-Ibarra J.,University of California at Davis
Trends in Ecology and Evolution | Year: 2014

Local adaptation shapes species diversity, can be a stepping stone to ecological speciation, and can facilitate species range expansion. Population genetic analyses, which complement organismal approaches in advancing our understanding of local adaptation, have become widespread in recent years. We focus here on using population genetics to address some key questions in local adaptation: what traits are involved? What environmental variables are the most important? Does local adaptation target the same genes in related species? Do loci responsible for local adaptation exhibit trade-offs across environments? After discussing these questions we highlight important limitations to population genetic analyses including challenges with obtaining high-quality data, deciding which loci are targets of selection, and limits to identifying the genetic basis of local adaptation. © 2014 Elsevier Ltd.


Redden J.P.,University of Minnesota | Galak J.,Carnegie Mellon University
Journal of Experimental Psychology: General | Year: 2013

The traditional view of satiation is that repeated consumption produces an unavoidable decline in liking according to the quantity and recency of consumption. We challenge this deterministic view by showing that satiation is instead partially constructed in the moment based on contextual cues. More specifically, while satiation is a function of the actual amount consumed, it also depends on the subjective sense of how much one has recently consumed. We demonstrate the influence of this subjective sense of satiation and show that it is driven by metacognitive cues such as the ease of retrieval of past experiences (Experiments 1 and 2) and can also be directly manipulated by providing a normative standard for consumption quantity (Experiment 3). Our research demonstrates that satiety is not driven solely by the amount and timing of past consumption, thereby establishing the role of higher order metacognitive inferences in satiation and providing insight into how they underlie the construction of satiation. © 2012 American Psychological Association.


Hook K.P.,University of Minnesota
Seminars in Perinatology | Year: 2013

Vascular birthmarks can be difficult to diagnose in the perinatal period due to varied growth characteristics and similar initial appearances. Location and type of birthmark can provide signals that extracutaneous involvement may be a concern. This article provides a baseline framework that can help diagnose, define associations and guide workup and treatment in these neonates. © 2013 Elsevier Inc.


Fernandes R.M.,University of Minnesota | Chubukov A.V.,University of Wisconsin - Madison | Schmalian J.,Karlsruhe Institute of Technology
Nature Physics | Year: 2014

Although the existence of nematic order in iron-based superconductors is now a well-established experimental fact, its origin remains controversial. Nematic order breaks the discrete lattice rotational symmetry by making the x and y directions in the iron plane non-equivalent. This can happen because of a regular structural transition or as the result of an electronically driven instability-in particular, orbital order or spin-driven Ising-nematic order. The latter is a magnetic state that breaks rotational symmetry but preserves time-reversal symmetry. Symmetry dictates that the development of one of these orders immediately induces the other two, making the origin of nematicity a physics realization of the 'chicken and egg problem'. In this Review, we argue that the evidence strongly points to an electronic mechanism of nematicity, placing nematic order in the class of correlation-driven electronic instabilities, like superconductivity and density-wave transitions. We discuss different microscopic models for nematicity and link them to the properties of the magnetic and superconducting states, providing a unified perspective on the phase diagram of the iron pnictides. © 2014 Macmillan Publishers Limited.


Schwitzer G.,University of Minnesota
JAMA Internal Medicine | Year: 2014

From April 16, 2006, through May 30, 2013, a team of reviewers from HealthNewsReview.org, many of whom were physicians, evaluated the reporting by US news organizations on new medical treatments, tests, products, and procedures. After reviewing 1889 stories (approximately 43% newspaper articles, 30% wire or news services stories, 15% online pieces [including those by broadcast and magazine companies], and 12% network television stories), the reviewers graded most stories unsatisfactory on 5 of 10 review criteria: costs, benefits, harms, quality of the evidence, and comparison of the new approach with alternatives. Drugs, medical devices, and other interventions were usually portrayed positively; potential harms were minimized, and costs were ignored. Our findings can help journalists improve their news stories and help physicians and the public better understand the strengths and weaknesses of news media coverage of medical and health topics. Copyright 2014 American Medical Association. All rights reserved.


Bellemare M.F.,University of Minnesota
American Journal of Agricultural Economics | Year: 2015

Can food prices cause social unrest? Throughout history, riots have frequently broken out, ostensibly as a consequence of high food prices. Using monthly data at the international level, this article studies the impact of food prices-food price levels as well as food price volatility-on social unrest. Because food prices and social unrest are jointly determined, data on natural disasters are used to identify the causal relationship flowing from food price levels to social unrest. Results indicate that for the period 1990-2011, food price increases have led to increases in social unrest, whereas food price volatility has not been associated with increases in social unrest. These results are robust to alternative definitions of social unrest, to using real or nominal prices, to using commodity-specific price indices instead of aggregated price indices, to alternative definitions of the instrumental variable, to alternative definitions of volatility, and to controlling for non-food-related social unrest. © 2014 The Author.


Yu X.,University of Minnesota
Nanoscale Research Letters | Year: 2011

The fabrication of transparent, conductive, and uniform silver nanowire films using the scalable rod-coating technique is described in this study. Properties of the transparent conductive thin films are investigated, as well as the approaches to improve the performance of transparent silver nanowire electrodes. It is found that silver nanowires are oxidized during the coating process. Incubation in hydrogen chloride (HCl) vapor can eliminate oxidized surface, and consequently, reduce largely the resistivity of silver nanowire thin films. After HCl treatment, 175 Ω/sq and approximately 75% transmittance are achieved. The sheet resistivity drops remarkably with the rise of the film thickness or with the decrease of transparency. The thin film electrodes also demonstrated excellent flexible stability, showing < 2% resistance change after over 100 bending cycles. © 2011 Liu and Yu.


Wei L.-N.,University of Minnesota
Integrative Biology | Year: 2011

Neurons are highly polarized cells with extensive sub-cellular compartmentalization to accommodate diverse local needs. Information flows between the pre-synaptic (axon) and post-synaptic (dendrite) compartments, as well as between the soma and the nerve termini. It is critical that a neuron controls efficient molecular transfer/transport through its axon. But this is extremely challenging to study because of the long distance molecules must travel through axons and the apparent contextual difference in the axons' various local environments, which should not be examined in isolation. Understanding the action in neurons of drug-responsive neurotransmitter receptors such as opioid receptors has been hindered by the lack of information on the control of molecular flow between such various sub-cellular neuron compartments. Recent studies have uncovered new transport systems other than the classical vesicle transport in neurons, particularly those utilizing various granules containing certain RNAs including protein-coding mRNAs. Through integrated approaches exploiting various experimental systems, tools, and methodologies, studies have provided solid evidence for functional roles of specific RNA granules in several biological processes crucial for the survival and function of neurons. These include neurons' transport of molecules/information, stress response, and local axonal translation. By using the kappa opioid receptor (KOR) as a model, studies have also revealed a novel physiological function of KOR in mediating growth factor-stimulated neurite outgrowth during a critical period of development, which requires specific KOR mRNA untranslated sequences that direct spatially and temporally specific expression of KOR. © 2011 The Royal Society of Chemistry.


Newman E.A.,University of Minnesota
Journal of Cerebral Blood Flow and Metabolism | Year: 2013

The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed. © 2013 ISCBFM.


Potter L.R.,University of Minnesota
Cellular Signalling | Year: 2011

Nitric oxide, bicarbonate, natriuretic peptides (ANP, BNP and CNP), guanylins, uroguanylins and guanylyl cyclase activating proteins (GCAPs) activate a family of enzymes variously called guanyl, guanylyl or guanylate cyclases that catalyze the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP) and pyrophosphate. Intracellular cyclic GMP is a second messenger that modulates: platelet aggregation, neurotransmission, sexual arousal, gut peristalsis, blood pressure, long bone growth, intestinal fluid secretion, lipolysis, phototransduction, cardiac hypertrophy and oocyte maturation. This review briefly discusses the discovery of cGMP and guanylyl cyclases, then nitric oxide, nitric oxide synthase and soluble guanylyl cyclase are described in slightly greater detail. Finally, the structure, function, and regulation of the individual mammalian single membrane-spanning guanylyl cyclases GC-A, GC-B, GC-C, GC-D, GC-E, GC-F and GC-G are described in greatest detail as determined by biochemical, cell biological and gene-deletion studies. © 2011 Elsevier Inc.


Siemsen E.,University of Minnesota
Journal of Supply Chain Management | Year: 2011

Behavioral supply chain management emphasizes the use of controlled laboratory experiments as a valid research methodology. This article discusses control, efficiency and responsiveness as unique advantages of behavioral experiments. While often sacrificing external validity, laboratory experiments allow the clear temporal separation of cause and effect, as well as the exclusion of spurious causes through randomization. Further, they are efficient to run, requiring little cost and time compared with extensive field studies or multiple site surveys. This makes it easier to use observations made in experiments to change theoretical models, since modified predictions can be more easily tested on new data. © 2011 Institute for Supply Management, Inc.™.


Ballas S.K.,Thomas Jefferson University | Gupta K.,University of Minnesota | Adams-Graves P.,University of Tennessee Health Science Center
Blood | Year: 2012

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia, and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other nonsickle pain syndromes. © 2012 by The American Society of Hematology.


Background: Medical tourism companies play an important role in promoting transnational medical travel for elective, out-of-pocket medical procedures. Though researchers are paying increasing attention to the global phenomenon of medical tourism, to date websites of medical tourism companies have received limited scrutiny. This article analyzes websites of Canadian medical tourism companies that advertised international healthcare but ultimately exited the marketplace. Using content analysis of company websites as an investigative tool, the article provides a detailed account of medical tourism companies that were based in Canada but no longer send clients to international health care facilities.Methods: Internet searches, Google Alerts, searches on Google News Canada and ProQuest Newsstand, and searches of an Industry Canada database were used to locate medical tourism companies located in Canada. Once medical tourism companies were identified, the social science research method of content analysis was used to extract relevant information from company websites. Company websites were analyzed to determine: 1) where these businesses were based; 2) the destination countries and medical facilities that they promoted; 3) the health services they advertised; 4) core marketing messages; and 5) whether businesses marketed air travel, hotel accommodations, and holiday excursions in addition to medical procedures.Results: In total, 25 medical tourism companies that were based in Canada are now defunct. Given that an estimated 18 medical tourism companies and 7 regional, cross-border medical travel facilitators now operate in Canada, it appears that approximately half of all identifiable medical tourism companies in Canada are no longer in business. 13 of the previously operational companies were based in Ontario, 7 were located in British Columbia, 4 were situated in Quebec, and 1 was based in Alberta. 14 companies marketed medical procedures within a single country, 9 businesses marketed health care at 2 or more destination nations, and 2 companies did not specify particular health care destinations. 22 companies operated as "generalist" businesses marketing many different types of medical procedures. 3 medical tourism companies marketed "specialist" services restricted to dental procedures or organ transplants. In general, medical tourism companies marketed health services on the basis of access to affordable, timely, and high-quality care. 16 businesses offered to make travel arrangements, 20 companies offered to book hotel reservations, and 17 medical tourism companies advertised holiday excursions.Conclusions: This article provides a detailed empirical analysis of websites of medical tourism companies that were based in Canada but exited the marketplace and are now inoperative. The article identifies where these companies were located in Canada, what countries and health care facilities they selected as destination sites, the health services they advertised, how they marketed themselves in a competitive environment, and what travel-related services they promoted in addition to marketing health care. The paper reveals a fluid marketplace, with many medical tourism companies exiting this industry. In addition, by disclosing identities of companies, providing their websites, archiving these websites or print copies of websites for future studies, and analyzing content of medical tourism company websites, the article can serve as a useful resource for future studies. Citizens, health policy-makers, clinicians, and researchers can all benefit from increased insight into Canada's medical tourism industry. © 2011 Turner; licensee BioMed Central Ltd.


Nyman J.A.,University of Minnesota
Health Economics | Year: 2011

In previous work (Health Econ. 2004; 13: 417-427; Health Econ. 2006; 15: 319-322) has suggested that survivor consumption costs should be included in cost-utility analyses only if the corresponding utility gains are also included. Here, it is further argued that the welfare implications of survivor consumption are already known because unlike new medical treatments or interventions whose complex and uncertain outcomes and third-party purchasing make the welfare implications unclear, survivor consumption must have passed a private market welfare test. That is, the gains must have exceeded the costs in order for the survivor consumption to be purchased; therefore, survivor consumption is welfare increasing. The same would apply for survivor leisure forgone. Implications for cost-benefit analysis are clear, but are less so for cost-utility analysis. Moreover, as it is currently practiced, cost-utility analysis does not evaluate welfare because quality-adjusted life years (QALYs) do not meet all the criteria for representing utility. Therefore, rather than using QALYs to analyze welfare, cost-QALY analysis should be differentiated from cost-utility analysis. The former should continue to employ existing QALYs as a measure of health-focused effectiveness, but the latter should develop a new broader measure that meets the criteria for representing utility, and either this new measure or cost-benefit analysis should be used to evaluate welfare. Copyright © 2009 John Wiley & Sons, Ltd.


Schimmenti L.A.,University of Minnesota
European Journal of Human Genetics | Year: 2011

Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, frequently called optic nerve coloboma or morning glory anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst and pigmentary macular dysplasia. The kidney abnormalities consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than the normal number of glomeruli and these glomeruli are enlarged, a finding called oligomeganephronia. Consequences of the ocular malformations include decreased visual acuity and retinal detachment. Consequences of the renal hypodysplasia include hypertension, proteinuria and renal insufficiency that frequently progresses to end-stage kidney disease. High frequency hearing loss has been reported. Autosomal dominant mutations in PAX2 can be identified in nearly half of all patients with clinical findings suggestive of RCS, however, the majority of published cases have mutations in PAX2, thus biasing the known information about the phenotype. © 2011 Macmillan Publishers Limited All rights reserved.


Matas A.J.,University of Minnesota
American Journal of Transplantation | Year: 2012

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


LaPrade R.F.,University of Minnesota
The American journal of sports medicine | Year: 2010

BACKGROUND: The popliteus tendon has important dynamic and static stabilizing functions at the knee. Evaluation of its static role as the "fifth ligament" of the knee and a subsequent analysis of a popliteus tendon reconstruction has not been performed. HYPOTHESIS: In vitro knee stability can be restored to a popliteus tendon-deficient knee with an anatomic popliteus tendon reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Eleven nonpaired cadaveric knees were tested under the following popliteus tendon states: intact, sectioned, and reconstructed using an autogenous semitendinosus graft. Each knee was subjected to 10-N.m varus moments, 5-N.m external and internal torques, and 88-N anterior and posterior loads at flexion angles of 0 degrees , 20 degrees , 30 degrees , 60 degrees , and 90 degrees . A 6 degrees of freedom electromagnetic motion tracking system was used to assess motion changes of the tibia with respect to the femur. RESULTS: Significant increases in external rotation and small but significant increases in internal rotation, varus angulation, and anterior translation motion were found after sectioning the popliteus tendon compared to the intact state. Significant decreases in external rotation were found in the reconstructed state compared with the sectioned state at knee flexion angles of 20 degrees , 30 degrees , 60 degrees , and 90 degrees . Comparing the reconstructed state to the intact state, there were no significant differences at knee flexion angles of 0 degrees and 20 degrees , but significant decreases of external rotation were found at knee flexion angles of 30 degrees , 60 degrees , and 90 degrees . Additionally, there were small but significant differences between the reconstructed and intact state with respect to varus angulation at knee flexion angles of 20 degrees , 30 degrees , and 60 degrees ; anterior translation at 20 degrees and 30 degrees ; and internal rotation at all flexion angles. CONCLUSION: The popliteus tendon has important primary stabilization roles at the knee. The authors also found that an anatomic popliteus tendon reconstruction significantly reduced the increase in external rotation that occurred with sectioning the popliteus tendon; however, differences seen with respect to internal rotation, varus angulation, and anterior translation were not restored. CLINICAL SIGNIFICANCE: The popliteus tendon functions essentially as the fifth major ligament of the knee. An anatomic popliteus tendon reconstruction can restore external rotation stability to knees with popliteus tendon injury.


This study examines how independent living residents in Continuing Care Retirement Communities (CCRCs) work to maintain a healthy, active community. Specifically, this paper elucidates how independent living residents, who have high status in CCRCs but also face transitions to more advanced care, manage their daily lives to build a positive sense of community against the backdrop of potential health and social declines. The researcher supplemented four years of observation in one CCRC and two years of observation in another with qualitative interviews with thirty residents from both facilities. Results indicated that shared sentiments contrasting the active social world in independent living with other living units, norms of mutual support balanced with autonomy, social participation as a source of belonging (or isolation), and definitions of deviance surrounding functional health and manners framed residents' understandings of daily life by reaffirming independent living residents' privileged status in each facility. © 2011 Elsevier Inc.


Transgenic sickle mice expressing β(S) hemoglobin have activated vascular endothelium in multiple organs that exhibits enhanced expression of NF-KB and adhesion molecules and promotes microvascular stasis in sickle, but not normal, mice in response to hypoxia/reoxygenation (H/R), or heme. Induction of heme oxygenase-1 (HO-1) or administration of its products, carbon monoxide (CO) or biliverdin, inhibits microvascular stasis in sickle mice. Infusion of human hemoglobin conjugated with polyethylene glycol and saturated with CO (MP4CO) markedly induced hepatic HO-1 activity and inhibited NF-KB activation and H/R-induced microvascular stasis in sickle mice. These effects were mediated by CO; saline or MP4 saturated with O2 (MP4OX) had little to no effect on H/R-induced stasis, though unmodified oxyhemoglobin exacerbated stasis. The HO-1 inhibitor, tin protoporphyrin, blocked MP4CO protection, consistent with HO-1 involvement in the protection afforded by MP4CO. MP4CO also induced nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), an important transcriptional regulator of HO-1 and other antioxidant genes. In a heterozygous (hemoglobin-AS) sickle mouse model, intravenous hemin induced cardiovascular collapse and mortality within 120 minutes, which was significantly reduced by MP4CO, but not MP4OX. These data demonstrate that MP4CO induces cytoprotective Nrf2 and HO-1 and decreases NF-KB activation, microvascular stasis, and mortality in transgenic sickle mouse models.


Langley P.C.,University of Minnesota
Current Medical Research and Opinion | Year: 2011

Objectives: To report on the results of a recent large-scale, internet-based survey of the population, prevalence and attributes of pain experience in the United Kingdom (UK), France, Spain, Germany and Italy. Methods: The results reported here are taken from the internet-based, 2008 National Health and Wellness Survey (NHWS). In addition to detailing the prevalence of pain, the survey reports on the correlates of pain socio-demographic characteristics of respondents, health status and health related quality of life, pain associated comorbidities, satisfaction with care, employment and productivity and utilization of health care resources. In addition, the survey also captures treatment patterns, satisfaction with medications (both prescription and over the counter [OTC]) and adherence experience. Results: An estimated 49.7 million persons in these five countries reported pain by both its severity and frequency in the previous month. Of these, 11.2 million reported severe pain, 29.4 million reported moderate pain and 9.0 million reported mild pain. The population prevalence of daily pain is 8.85 with 3.47 reporting severe daily pain and 4.70 moderate daily pain. The cumulative burden of pain is demonstrated in terms of HRQoL, employment status and workforce activities as well as in healthcare resource utilization. The most striking impacts are seen in the impact of severe and frequent pain on HRQoL. Of the measures employed, the impact on the physical component score (PCS) of the SF-12 and the SF-6D absolute utility scores are substantial. The presence of severe and daily pain not only reduces the PCS score against that reported for the no pain population by over 20 points (or approximately 40) but the impact on the absolute utility score is to reduce it from a no pain average of 0.74 to a score of 0.54. As far as productivity losses to the community are concerned the impact of severe pain is equally dramatic. Conclusions: The reported prevalence of pain in these five countries represents a substantial burden to individuals, employers, healthcare systems and society in general. The fact that one in five of the adult population has experienced pain presents a major policy challenge. This would involve not only reducing the prevalence of pain where chronic pain may be considered a disease in its own right but to co-ordinate pain management programs across a range of disease states and socio-economic groups. © 2011 Informa UK Ltd All rights reserved.


Austin J.,University of Minnesota
Limnology and Oceanography | Year: 2013

Directly measured velocity data collected in Lake Superior between 2008 and 2011 show that currents in the open waters of the lake are dominated by near-inertial energy. The near-inertial signal is composed almost entirely of clockwise rotation, with vertical structure dominated by the first baroclinic mode, where waters above and below the thermocline are roughly 180° out of phase with each other. The strength of the oscillations is strongly related to the strength of the stratification; in periods of the year when the water column is well-mixed (typically late autumn and late spring) the near-inertial signal is very weak; when stratification exists, near-inertial oscillations can occur. Combining the velocity amplitudes with an estimate of the thermocline displacement allows estimation of the dominant direction and horizontal wavelength of the near-inertial field, showing that horizontal wavelengths are on the order of 50-100 km, and the direction of the waves veers counter-clockwise over the course of the season with a period of ~ 1 month. Observations of backscatter suggest that inertial oscillations may be responsible for re-suspension of bottom sediments, which could have significant ecological consequences. © 2013, by the Association for the Sciences of Limnology and Oceanography, Inc.


Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important role in the maintenance of peripheral tolerance. We explored the role of PD-1 ligands in regulating graft-versus-host disease (GVHD). Both PD-L1 and PD-L2 expression were upregulated in the spleen, liver, colon, and ileum of GVHD mice. Whereas PD-L2 expression was limited to hematopoietic cells, hematopoietic and endothelial cells expressed PD-L1. PD-1/PD-L1, but not PD-1/PD-L2, blockade markedly accelerated GVHD-induced lethality. Chimera studies suggest that PD-L1 expression on host parenchymal cells is more critical than hematopoietic cells in regulating acute GVHD. Rapid mortality onset in PD-L1-deficient hosts was associated with increased gut T-cell homing and loss of intestinal epithelial integrity, along with increased donor T-cell proliferation, activation, Th1 cytokine production, and reduced apoptosis. Bioenergetics profile analysis of proliferating alloreactive donor T-cells demonstrated increased aerobic glycolysis and oxidative phosphorylation in PD-L1-deficient hosts. Donor T-cells exhibited a hyperpolarized mitochondrial membrane potential, increased superoxide production, and increased expression of a glucose transporter in PD-L1-deficient hosts. Taken together, these data provide new insight into the differential roles of host PD-L1 and PD-L2 and their associated cellular and metabolic mechanisms controlling acute GVHD.


Fok A.S.L.,University of Minnesota
Dental Materials | Year: 2013

Objectives The aim of this paper is to develop a comprehensive mathematical model for shrinkage stress development in dental composites that can account for the combined effect of material properties, specimen geometry and external constraints. Methods A viscoelastic model that includes the composite's elastic, creep and shrinkage strains, and their interaction with the sample's dimensions and the external constraint is developed. The model contains two dimensionless parameters. The first one represents the compliance of the external constraint relative to that of the composite sample, and the second controls the rate of shrinkage stress decay through creep. The resulting differential equation is solved for two special cases: zero compliance and zero creep. Predictions for shrinkage stress measurements are then made using the analytical solutions for instruments with different compliances, samples with different thicknesses and composites with different filler fractions. Results The model correctly predicts how shrinkage stress increases with time, its dependence on the interaction between the entire system's compliance and the material properties, and the effect of the filler fraction on its maximum value. Comparisons with reported shrinkage stress measurements have provided very good agreement between theory and experiments. Significance The results provided by the model can help to resolve most, if not all, of the seemingly conflicting experimental observations reported in the literature. They can also provide some useful guidelines for optimizing the mechanical performance of dental composite restorations. The compliance ratio, a new parameter derived from the model, represents a fuller description of the constraints of the system. © 2013 Academy of Dental Materials.


During bacterial infection, hematopoietic stem and progenitor cells (HSPCs) differentiate into polymorphonuclear leukocytes (PMNs) in the bone marrow. We reported that HSPCs recruited to Staphylococcus aureus-infected skin wounds in mice undergo granulopoiesis, whereas other authors have demonstrated their differentiation in vitro after Toll-like receptor 2 (TLR2)/MyD88 stimulation. Here, we examined this pathway in HSPC trafficking and granulopoiesis within S aureus-infected wounds. Lineage- HSPCs from TLR2- or MyD88-deficient mice injected into infected wounds of wild-type (WT) mice exhibited impaired granulopoiesis. However, HSPCs from WT mice produced similar numbers of PMNs whether transferred into wounds of TLR2-, MyD88-deficient, or WT mice. Prostaglandin E2 (PGE2), which stimulates HSPC survival and proliferation, was produced by HSPCs after TLR2 stimulation, suggesting that TLR2/MyD88 activation promotes granulopoiesis in part by production and autocrine activity of PGE2. Pretreatment of TLR2- or MyD88-deficient HSPCs with PGE2 rescued granulocytic differentiation in vivo. Finally, we demonstrate that bone marrow-derived lin-/Sca-1+/c-kit+ cells produced PGE2 and underwent granulopoiesis after TLR2 stimulation. lin-/Sca-1+/c-kit+ cells deficient in TLR2 or MyD88 produced PMNs after PGE2 treatment when transferred into uninfected wounds. We conclude that granulopoiesis in S aureus-infected wounds is induced by TLR2/MyD88 activation of HSPCs through a mechanism that involves autocrine production and activity of PGE2.


Graft-versus-host disease (GVHD) is a critical complication after allogeneic bone marrow transplantation. During GVHD, donor T cells are activated by host antigen-presenting cells and differentiate into T-effector cells (Teffs) that migrate to GVHD target organs. However, local environmental factors influencing Teff differentiation and migration are largely unknown. Vitamin A metabolism within the intestine produces retinoic acid, which contributes to intestinal homeostasis and tolerance induction. Here, we show that the expression and function of vitamin A-metabolizing enzymes were increased in the intestine and mesenteric lymph nodes in mice with active GVHD. Moreover, transgenic donor T cells expressing a retinoic acid receptor (RAR) response element luciferase reporter responded to increased vitamin A metabolites in GVHD-affected organs. Increasing RAR signaling accelerated GVHD lethality, whereas donor T cells expressing a dominant-negative RARα (dnRARα) showed markedly diminished lethality. The dnRARα transgenic T cells showed reduced Th1 differentiation and α4β7 and CCR9 expression associated with poor intestinal migration, low GVHD pathology, and reduced intestinal permeability, primarily via CD4(+) T cells. The inhibition of RAR signaling augmented donor-induced Treg generation and expansion in vivo, while preserving graft-versus-leukemia effects. Together, these results suggested that reagents blunting donor T-cell RAR signaling may possess therapeutic anti-GVHD properties.


Vincent L.,University of Minnesota
Blood | Year: 2013

Sickle cell anemia (SCA) is an inherited disorder associated with severe lifelong pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood. We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease in granulocyte-macrophage colony-stimulating factor and white blood cells in transgenic sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pretreatment with the mast cell stabilizer cromolyn sodium improved analgesia following low doses of morphine that were otherwise ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain, and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA.


Oetting W.S.,University of Minnesota
Human Mutation | Year: 2010

The annual scientific meeting of the Human Genome Variation Society (HGVS) was held on the 20th of October, 2009, in Honolulu, Hawaii. The theme of this meeting was the "Impact of Next Generation Sequencing." Presenters spoke on issues ranging from advances in the technology of large-scale genome sequencing to how this information can be analyzed to uncover genetic variants associated with disease. Many of the challenges resulting from the implementation of these new technologies were presented, but possible solutions, or at least paths to the solutions, were also given. With the combined efforts of investigators using next-generation sequencing to help understand the impact of genetic variants on disease, the use of the personal genome in medicine will soon become a reality. © 2010 Wiley-Liss, Inc.


McCullough J.,University of Minnesota
Blood | Year: 2013

The report by Solomon et al in this issue of Blood is a welcome addition to understanding the clinical impact of prolonged red cell storage. Copyright 2011 by The American Society of Hematology.


Human interleukin (IL)-22-producing RORγt(+) innate lymphoid cells (ILC22) and conventional natural killer (cNK) cells are present in secondary lymphoid tissues. Both have an immunophenotype corresponding to stage III NK progenitors (CD56(+/-)CD117(high)CD94(-)). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD56(+)CD117(+)CD7(+/-)LFA-1(high) phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD56(+)CD117(high)CD94(-)CD7(-)LFA-1(-) fraction and produced IL-22, IL-8, and granulocyte macrophage colony stimulating factor. Although ILC22 cells expressed NKp44 and CD161, they lacked most other NK receptors and NK-associated transcription factors (T-bet and Eomes) and were incapable of interferon-γ production or cytotoxic responses. Most purified CD56(+)CD117(+)CD7(+/-)LFA-1(-) remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD34(+) cells showed a complete block in cNK differentiation and instead gave rise to a CD56(+) population of ILC22 cells. Conversely, in the absence of IL-7 and stem cell factor, cNK cells were generated but ILC22 cells showed minimal differentiation. Although human ILC22 cells and cNK progenitors have a phenotype that overlaps with stage III NK progenitors, they have unique cytokine requirements and can be distinguished by LFA-1 expression.


Marini J.J.,University of Minnesota
Critical care (London, England) | Year: 2013

The ability to compensate for life-threatening failure of respiratory function is perhaps the signature technology of intensive care medicine. Unchanging needs for providing effective life-support with minimized risk and optimized comfort have been, are now, and will be the principal objectives of providing mechanical ventilation. Important lessons acquired over nearly half-a-century of ICU care have brought us closer to meeting them, as technological advances in instrumentation now effectively put this hard-won knowledge into action. Rising demand in the face of economic constraints is likely to drive future innovations focused on reducing the need for user input, automating multi-element protocols, and carefully monitoring the patient for progress and complications.


Hinchcliffe E.H.,University of Minnesota
Cell Cycle | Year: 2011

In vertebrate somatic cells, the centrosome functions as the major microtubule- organizing center (MTOC), which splits and separates to form the poles of the mitotic spindle. However, the role of the centriole-containing centrosome in the formation of bipolar mitotic spindles continues to be controversial. Cells normally containing centrosomes are still able to build bipolar spindles after their centrioles have been removed or ablated. In naturally occurring cellular systems that lack centrioles, such as plant cells and many oocytes, bipolar spindles form in the complete absence of canonical centrosomes. These observations have led to the notion that centrosomes play no role during mitosis. However, recent work has re-examined spindle assembly in the absence of centrosomes, both in cells that naturally lack them and those that have had them experimentally removed. The results of these studies suggest that an appreciation of microtubule network organization, both before and after nuclear envelope breakdown (NEB), is the key to understanding the mechanisms that regulate spindle assembly and the generation of bipolarity. © 2011 Landes Bioscience.


Harned A.M.,University of Minnesota
Chemical Communications | Year: 2015

Density functional theory (DFT) has been used to investigate the α-alkylation of a chiral tricyclic ketone. These calculations reveal that torsional strain and a strong conformational preference, rather than steric influences, are responsible for the high levels of observed stereoselectivity and suggest a way by which alternative stereoisomers could be accessed. This journal is © The Royal Society of Chemistry 2015.


Buchwald H.,University of Minnesota
Obesity Surgery | Year: 2015

Revisional metabolic/bariatric surgery is a moral obligation; for not to perform revisional surgery is a denial of the precepts of our discipline and an abandonment of the underprivileged population who has placed its trust and future in our hands. © 2014, Springer Science+Business Media New York.


Yusubov M.S.,Siberian State Medical University | Zhdankin V.V.,University of Minnesota
Current Organic Synthesis | Year: 2012

Recent advances in the development of environmentally friendly recyclable reagents and catalytic systems based on hypervalent iodine are discussed. The review covers the following topics of active current research: polymer-supported iodine(III) and iodine(V) oxidants, recyclable monomeric hypervalent iodine(III) reagents, reactions of hypervalent iodine in solid state, application of water or recyclable organic solvents in these reactions, and catalytic systems based on hypervalent iodine compounds. These efficient and ecofriendly reagents and catalytic systems are now widely used in organic synthesis for various oxidative transformations of organic substrates. © 2012 Bentham Science Publishers.


Mogilner A.,University of California at Davis | Odde D.,University of Minnesota
Trends in Cell Biology | Year: 2011

Recent advances in photonic imaging and fluorescent protein technology offer unprecedented views of molecular space-time dynamics in living cells. At the same time, advances in computing hardware and software enable modeling of ever more complex systems, from global climate to cell division. As modeling and experiment become more closely integrated we must address the issue of modeling cellular processes in 3D. Here, we highlight recent advances related to 3D modeling in cell biology. While some processes require full 3D analysis, we suggest that others are more naturally described in 2D or 1D. Keeping the dimensionality as low as possible reduces computational time and makes models more intuitively comprehensible; however, the ability to test full 3D models will build greater confidence in models generally and remains an important emerging area of cell biological modeling. © 2011 Elsevier Ltd.


Langley P.C.,University of Minnesota
Journal of Medical Economics | Year: 2012

Objectives: The purpose of this paper is to estimate the impact of the severity and frequency of pain on health-related quality-of-life (HRQoL), self-reported health status, and direct medical costs in Germany. Methods: Data are from the internet-based 2010 National Health and Wellness Survey (NHWS). Estimates of the impact of pain experience are generated by a series of regression models. In the case of HRQoL the physical and mental summary scores from the SF-12, together with SF-6D utilities, are evaluated within an ordinary least squares framework. Health status is assessed through an ordered logit model. Direct medical costs are estimated through a semi-logarithmic healthcare cost function. Socioeconomic characteristics, health risk behaviors, and the Charlson Comorbidity Index (CCI) are introduced as control variables in all regressions. Results: An estimated 23.96% of the adult German population (16.39 million) reported experiencing pain in the last 30 days. Of these 13.16% reported severe pain. The experience of frequent severe and moderate pain has a significant deficit impact on HRQoL. For those experiencing severe daily pain, the deficit in the SF-12 physical component score (PCS) is -17.930 (95% CI: -18.720 to -17.140), the SF-12 mental component score (MCS) is -8.787 (05% CI: -9.857 to -7.716), and SF-6D absolute utilities -0.201 (95% CI: -0.214 to -0.188); with self-reported health status the deficit impact of severe daily pain is also substantial (O=29.000; 95% CI: 23.000-36.580). In the case of direct medical costs severe daily pain increases healthcare provider costs by 101.6% and total direct costs by 123.9%. Limitations: The NHWS is an internet survey. The principal limitation is that as a self-report there is no separate validation of pain severity or chronicity. Conclusions: The experience of pain has a substantial negative impact on HRQoL, health status, and resource utilization in Germany. If pain is considered as a disease in its own right, the experience of chronic pain presents policy-makers with a major challenge. © 2012 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.


Morrison V.A.,University of Minnesota
Best Practice and Research: Clinical Haematology | Year: 2010

Infectious complications continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukaemia (CLL). The pathogenesis of infections in these patients is multifactorial, related to inherent immune defects and therapy-related immunosuppression. Hypogammaglobulinaemia is an important predisposing factor for infection in all patients. The use of the purine analogues such as fludarabine, and monoclonal antibodies such as rituximab and alemtuzumab, has introduced a new spectrum of infectious complications caused by pathogens such as Pneumocystis, Listeria, mycobacteria, herpesviruses Candida and Aspergillus, related to the cellular immune suppression induced by these agents. This review focusses on the pathogenesis and risk factors for infections in patients with CLL, the spectrum of infectious complications and preventive approaches to infection in these patients, using antimicrobial and immunoglobulin prophylaxis and vaccination strategies. © 2010 Elsevier Ltd. All rights reserved.


Lutsey P.L.,University of Minnesota
American Journal of Epidemiology | Year: 2012

Recently, there has been interest in determining whether diet is associated with the risk of venous thromboembolism. The article by Varraso et al. (Am J Epidemiol. 2012;175(2):114-126) published in this issue of the Journal is an important contribution to this literature. In this commentary, the author discusses the findings of Varraso et al. within the context of the existing literature and posits epidemiologic explanations for why investigators might have failed to identify strong associations between diet and venous thromboembolism. © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.


Newman E.A.,University of Minnesota
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2015

Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. As reviewed in this article, Mu¨ ller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Mu¨ ller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca2þ-activated Kþ (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells.Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells. 2015 The Author(s) Published by the Royal Society. All rights reserved.


Hernandez L.E.,University of Minnesota
Cardiology in the Young | Year: 2014

Since Takotsubo cardiomyopathy was first described by Sato in 1990, multiple cases have been reported, but only few in children, among whom this type of cardiomyopathy is to some extent underappreciated. A series of children with this syndrome were therefore reviewed, drawing comparison with cases reported by others. The review addresses the current challenges in diagnosis, presentation, triggers, clinical course, management, and possible pathogenic mechanisms of the entity. © Cambridge University Press 2014.


Bottini N.,La Jolla Institute for Allergy and Immunology | Peterson E.J.,University of Minnesota
Annual Review of Immunology | Year: 2014

Inheritance of a coding variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is associated with increased susceptibility to autoimmunity and infection. Efforts to elucidate the mechanisms by which the PTPN22-C1858T variant modulates disease risk revealed that PTPN22 performs a signaling function in multiple biochemical pathways and cell types. Capable of both enzymatic activity and adaptor functions, PTPN22 modulates signaling through antigen and innate immune receptors. PTPN22 plays roles in lymphocyte development and activation, establishment of tolerance, and innate immune cell-mediated host defense and immunoregulation. The disease-Associated PTPN22-R620W variant protein is likely involved in multiple stages of the pathogenesis of autoimmunity. Establishment of a tolerant B cell repertoire is disrupted by PTPN22-R620W action during immature B cell selection, and PTPN22-R620W alters mature T cell responsiveness. However, after autoimmune attack has initiated tissue injury, PTPN22-R620W may foster inflammation through modulating the balance of myeloid cell-produced cytokines. © 2014 by Annual Reviews. All rights reserved.


Arbustini E.,Center for Inherited Cardiovascular Disease | Weidemann F.,University of Wurzburg | Hall J.L.,University of Minnesota
Journal of the American College of Cardiology | Year: 2014

Whether left ventricular noncompaction (LVNC) is a distinct cardiomyopathy or a morphologic trait shared by different cardiomyopathies remains controversial. Current guidelines from professional organizations recommend different strategies for diagnosing and treating patients with LVNC. This state-of-the-Art review discusses new insights into the basic mechanisms leading to LVNC, its clinical manifestations, treatment modalities, anatomy and pathology, embryology, genetics, epidemiology, and imaging. Three markers currently define LVNC: prominent left ventricular trabeculae, deep intertrabecular recesses, and a thin compacted layer. Although new genetic data from mice and humans supports LVNC as a distinct cardiomyopathy, evidence for LVNC as a shared morphological trait is not ruled out. Criteria supporting LVNC as a shared morphological trait may depend on consensus guidelines from the multiple professional organizations. Enhanced imaging and increased use of genetics are both predicted to significantly impact our overall understanding of the basic mechanisms causing LVNC and its optimal management. © 2014 American College of Cardiology Foundation.


Stinis P.,University of Minnesota
Journal of Computational Physics | Year: 2012

We present a reformulation of stochastic global optimization as a filtering problem. The motivation behind this reformulation comes from the fact that for many optimization problems we cannot evaluate exactly the objective function to be optimized. Similarly, we may not be able to evaluate exactly the functions involved in iterative optimization algorithms. For example, we may only have access to noisy measurements of the functions or statistical estimates provided through Monte Carlo sampling. This makes iterative optimization algorithms behave like stochastic maps. Naive global optimization amounts to evolving a collection of realizations of this stochastic map and picking the realization with the best properties. This motivates the use of filtering techniques to allow focusing on realizations that are more promising than others. In particular, we present a filtering reformulation of global optimization in terms of a special case of sequential importance sampling methods called particle filters. The increasing popularity of particle filters is based on the simplicity of their implementation and their flexibility. We utilize the flexibility of particle filters to construct a stochastic global optimization algorithm which can converge to the optimal solution appreciably faster than naive global optimization. Several examples of parametric exponential density estimation are provided to demonstrate the efficiency of the approach. © 2011 Elsevier Inc.


Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer. Published by Oxford University Press 2012.


Duprez D.,University of Minnesota
Expert Review of Cardiovascular Therapy | Year: 2012

Systolic hypertension is a major health economy problem within our aging society. Increased arterial stiffness is the vascular phenotype of systolic hypertension, especially of the large arteries. Elevated systolic blood pressure is even more associated with cardiovascular morbidity and mortality than diastolic blood pressure. Treatment of systolic hypertension in the elderly should be based on nonpharmacological measures and medical therapy if the systolic hypertension cannot be controlled by conservative therapy alone. The HYVET study provided evidence-based medicine data showing that, in the very elderly, lowering blood pressure to a level of 150/80 mmHg is still very beneficial. Antihypertensive therapy needs to be tailored in the elderly because of comorbid conditions, such as ischemic heart disease, heart failure, atrial fibrillation, renal insufficiency and diabetes. Angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers should be considered in combination with diuretics or with a dihydropyridine calcium antagonist. β-blockers seem to be less effective for cardiovascular disease protection in comparison with other antihypertensive drug classes, such as diuretics, dihydropyridines, angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers. Major effort is required to reduce the therapeutic inertia and increase therapeutic adherence for better blood pressure control in the elderly with systolic hypertension. © 2012 Expert Reviews Ltd.


Sayer N.A.,Center for Chronic Disease Outcomes Research | Sayer N.A.,University of Minnesota
Annual Review of Medicine | Year: 2012

The postSeptember 11, 2001 wars in and around Afghanistan and Iraq have increased awareness of traumatic brain injury (TBI), particularly blast-induced mild TBI. This article provides an overview of TBI and its neuropsychiatric sequelae in U.S. war veterans who participated in the current operations in and around Afghanistan and Iraq, with particular emphasis on blast-related mild TBI. Psychiatric disorders, particularly posttraumatic stress disorder, pain, and sensory impairments are prevalent in war veterans with TBI. Research is needed to more definitively characterize the epidemiology of TBI-related functional difficulties, the effects of blasts compared with other mechanisms of injury, recovery trajectories, and treatment outcomes in this population. © 2012 by Annual Reviews. All rights reserved.


Wu L.,Center for Clinical and Translational Science | Zhu J.,University of Minnesota
Human Reproduction | Year: 2015

STUDY QUESTION Is there an association between oral contraceptive (OC) use and thyroid cancer risk in females? SUMMARY ANSWER OC use is inversely associated with the risk of thyroid cancer in females. WHAT IS KNOWN ALREADY OC use may be relevant to the risk of thyroid cancer as suggested by some epidemiological studies. However, the findings are inconsistent regarding the effect direction and size. STUDY DESIGN, SIZE, DURATION This systematic review and meta-analysis included a total of 1906 patients from about 1.3 million individuals who had participated in 9 prospective cohort studies. The follow-up length ranged 7.5-15.9 years. PARTICIPANTS/MATERIALS, SETTING, METHODS PubMed (MEDLINE) was searched through to January 2015 for eligible studies. References of relevant review articles were also manually screened. Prospective cohort studies that evaluated the association between OC use and thyroid cancer risk were included. Study characteristics including patients' characteristics, length of the follow-up and risk estimates were extracted. The quality of the studies was also assessed. MAIN RESULTS AND THE ROLE OF CHANCE The included studies were of high methodological quality according to the Newcastle-Ottawa Quality Assessment Scale. After pooling risk estimates from all the studies, there was a significant inverse association between the longest versus shortest duration of OC use and the risk of thyroid cancer [relative risk (RR) = 0.84, 95% confidence interval (CI) 0.73-0.97], with no considerable heterogeneity (I2 = 26.1%). There was no significant publication bias. The significant association persisted in the subgroup of high-quality studies (RR = 0.84, 95% CI 0.72-0.97). By dose-response analysis, there was a linear relationship (P = 0.0001) between the duration of OC use and thyroid cancer risk. The summary RR for an increment of 1 year of OC use was 0.96 (95% CI 0.94-0.98), with no significant heterogeneity. LIMITATIONS, REASONS FOR CAUTION Individual patient data were unavailable for a more accurate estimation. WIDER IMPLICATIONS OF THE FINDINGS These results indicate that OC use may decrease the risk of thyroid cancer in females. This may have implications for women's decisions regarding the use of OC. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.


Shifman M.,University of Minnesota
Journal of Experimental and Theoretical Physics | Year: 2015

We discuss similarities and differences between the resurgence program in quantum mechanics and the operator product expansion in strongly coupled Yang-Mills theories. In N = 1 super-Yang-Mills theories, renormalons are peculiar and are not quite similar to renormalons in QCD. © 2015, Pleiades Publishing, Inc.


The gentrification that has transformed high-poverty neighbourhoods in US cities since the mid 1990s has been characterised by high levels of state reinvestment. Prominent among public-sector interventions has been the demolition of public housing and in some cases multimillion dollar redevelopment efforts. In this paper, the racial dimension of state-supported gentrification in large US cities is examined by looking at the direct and indirect displacement induced by public housing transformation. The data show a clear tendency towards the demolition of public housing projects with disproportionately high African American occupancy. The pattern of indirect displacement is more varied; public housing transformation has produced a number of paths of neighbourhood change. The most common, however, involve significant reductions in poverty, sometimes associated with Black to White racial turnover and sometimes not. The findings underscore the central importance of race in understanding the dynamics of gentrification in US cities. © 2010 Urban Studies Journal Limited.


Cadotte M.W.,University of Toronto | Dinnage R.,University of Toronto | Tilman D.,University of Minnesota
Ecology | Year: 2012

Ecosystem stability in variable environments depends on the diversity of form and function of the constituent species. Species phenotypes and ecologies are the product of evolution, and the evolutionary history represented by co-occurring species has been shown to be an important predictor of ecosystem function. If phylogenetic distance is a surrogate for ecological differences, then greater evolutionary diversity should buffer ecosystems against environmental variation and result in greater ecosystem stability. We calculated both abundance-weighted and unweighted phylogenetic measures of plant community diversity for a long-term biodiversity-ecosystem function experiment at Cedar Creek, Minnesota, USA. We calculated a detrended measure of stability in aboveground biomass production in experimental plots and showed that phylogenetic relatedness explained variation in stability. Our results indicate that communities where species are evenly and distantly related to one another are more stable compared to communities where phylogenetic relationships are more clumped. This result could be explained by a phylogenetic sampling effect, where some lineages show greater stability in productivity compared to other lineages, and greater evolutionary distances reduce the chance of sampling only unstable groups. However, we failed to find evidence for similar stabilities among closely related species. Alternatively, we found evidence that plot biomass variance declined with increasing phylogenetic distances, and greater evolutionary distances may represent species that are ecologically different (phylogenetic complementarity). Accounting for evolutionary relationships can reveal how diversity in form and function may affect stability. © 2012 by the Ecological Society of America.


Tolman W.B.,University of Minnesota
Angewandte Chemie - International Edition | Year: 2010

No laughing matter, nitrous oxide's role in stratospheric ozone depletion and as a greenhouse gas has stimulated great interest in developing and understanding its decomposition, particularly through the use of transition-metal promoters. Recent advances in our understanding of the reaction pathways for N2O reduction by metal ions in the gas phase and in heterogeneous, homogeneous, and biological catalytic systems have provided provocative ideas about the structure and properties of metal N2O adducts and derived intermediates. These ideas are likely to inform efforts to design more effective catalysts for N2O remediation. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA,.


Gorr S.-U.,University of Minnesota
Frontiers of Oral Biology | Year: 2012

The development of oral biofilms and the host response to biofilm bacteria and their toxins are important factors in the development of periodontal disease. An early component of the host response is the secretion of antimicrobial proteins and peptides (AMPs) by salivary glands, oral epithelial cells and neutrophils. Over 45 AMPs have been identified in the oral cavity. All are found in saliva and several are also present in gingival crevicular fluid. Of these, 13 are up regulated in periodontal disease while 11 are downregulated. However, the concentrations of most AMPs found in oral fluids are below the effective in vitro concentrations, suggesting that local concentrations must be higher for effect or that additional biological functions are important in the oral cavity. Thus, in addition to direct antibacterial activity (e.g. bactericidal activity, bacterial agglutination), AMPs may affect the course of periodontal disease by inactivating bacterial or host proteases (e.g. secretory leukoprotease inhibitor) or bind bacterial toxins, including lipopolysaccharides (e.g. LL-37). Several AMPs (e.g. defensins) also act as immune system alarmins, i.e. endogenous mediators that recruit and activate antigen-presenting cells to enhance innate and adaptive immune responses. The differential regulation of AMP expression in periodontal disease suggests that AMP panels, including up-and downregulated proteins, can be used in oral fluid diagnosis of periodontal disease and to monitor treatment outcome. Copyright © 2012 S. Karger AG, Basel.


Craddock S.,University of Minnesota
Health and Place | Year: 2012

Tuberculosis poses one of the biggest threats to individuals living with HIV in most low-income regions of the world, and the increase of multi-drug resistant tuberculosis (MDR-TB) in South Africa, Eastern Europe, and elsewhere makes this threat that much more critical. Despite the extent of the problem, new drugs for tuberculosis have not been developed for over four decades, largely because tuberculosis occurs primarily among the poor in low-income regions and the market for tuberculosis drugs is not lucrative enough to warrant time and resource commitments by pharmaceutical companies. In the wake of sustained global criticism of pharmaceutical-state practices, however, new partnerships for drug development (PDPs) are forming to address critical shortages of drugs for diseases like tuberculosis that have been termed 'neglected' precisely because they have not seen new treatments for so long. This paper examines some of these partnerships, tracing some of the dynamic developments as well as challenges in forging alternative pathways to new drug and vaccine production. © 2011 Elsevier Ltd.


Zhu Z.,University of Minnesota
Biomaterials | Year: 2013

This study systematically compares the effects of amphiphilic diblock copolymer (di-BCP) on stabilizing hydrophobic drug nanoparticles formed by flash nanoprecipitation (FNP), and provides a guideline on choosing suitable di-BCPs. Four widely used di-BCPs, i.e., polystyrene-block-poly(ethylene glycol) (PS-b-PEG), polycaprolactone-block-poly(ethylene glycol) (PCL-b-PEG), polylactide-block-poly(ethylene glycol) (PLA-b-PEG), and poly(lactic-co-glycolic acid) (PLGA-b-PEG), and β-carotene as a model drug were used. The study showed that PLGA-b-PEG was the most suitable one, whose hydrophobic block was biodegradable and noncrystallizable as well as had relatively high glass transition temperature (Tg) and a right solubility parameter (δ). The molecular weight of PLGA block over the range from 5k to 15k showed an insignificant effect on controlling the particle size. Amorphous drug particles with a high drug loading of over 83wt% can be achieved. Much remarkable evidence supported the nanoparticles with kinetically frozen and non-equilibrium packing structures of polymer chains rather than either the micelles or micellar nanoparticles with two well segregated polymer blocks. The thermodynamic effects of the drug and BCP on the particle stability, size and structures were discussed by using solubility parameters. © 2013 Elsevier Ltd.


Bass J.L.,University of Minnesota
Catheterization and Cardiovascular Interventions | Year: 2010

Objectives: This study assessed the feasibility and efficacy of implanting a new nitinol device in the left atrial appendage (LAA) in a canine model. Background: Left atrial thrombus occurs in the LAA in 90% of humans with nonvalvular atrial fibrillation (AF). Methods: The Amplatzer Left Atrial Appendage Occluder Device now known as the Amplatzer Cardiac Plug (Amplatzer Medical LLC, Plymouth MN) is a new transcatheter Nitinol device containing polyester fabric designed to seal the LAA. The device was implanted in 10 canines with immediate, ∼30 and ∼90-day follow-up by echocardiography, angiography, and final pathological examination. Results: The device was successfully implanted in all animals and found to be retrievable and repositionable. There was complete occlusion of the LAA in all cases without embolization. There was no thrombus formation on the device and no pericardial effusion or impingement on the circumflex coronary artery, mitral valve, or left pulmonary vein. A single instance of tiny left atrial mural thrombus at device end screw contact was attributed to the small canine left atrium. Conclusions: The success of this animal study confirms safety and feasibility of the Amplatzer Cardiac Plug. Human trials are warranted. © 2010 Wiley-Liss, Inc.


Kennedy J.,University of Minnesota
Journal of Interactive Online Learning | Year: 2014

This review of research explores characteristics associated with massive open online courses (MOOCs). Three key characteristics are revealed: varied definitions of openness, barriers to persistence, and a distinct structure that takes the form as one of two pedagogical approaches. The concept of openness shifts among different MOOCs, models, researchers, and facilitators. The high dropout rates show that the barriers to learning are a significant challenge. Research has focused on engagement, motivation, and presence to mitigate risks of learner isolation. The pedagogical structure of the connectivist MOOC model (cMOOC) incorporates a social, distributed, networked approach and significant learner autonomy that is geared towards adult lifelong learners interested in personal or professional development. This connectivist approach relates to situated and social learning theories such as social constructivism (Kop, 2011). By contrast, the design of the Stanford Artificial Intelligence (AI) model (xMOOC) uses conventional directed instruction in the context of formal postsecondary educational institutions. This traditional pedagogical approach is categorized as cognitive-behaviorist (Rodriguez, 2012). These two distinct MOOC models attract different audiences, use different learning approaches, and employ different teaching methods. The purpose of this review is to synthesize the research describing the phenomenon of MOOCs in informal and postsecondary online learning.


Wackett L.P.,University of Minnesota
Current Opinion in Biotechnology | Year: 2011

The current biofuels landscape is chaotic. It is controlled by the rules imposed by economic forces and driven by the necessity of finding new sources of energy, particularly motor fuels. The need is bringing forth great creativity in uncovering new candidate fuel molecules that can be made via metabolic engineering. These next generation fuels include long-chain alcohols, terpenoid hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic fuel-producing organism(s) or via intermediary biomass polymers that were previously derived from carbon dioxide. To use the latter economically, biomass depolymerization processes must improve and this is a very active area of research. There are competitive approaches with some groups using enzyme based methods and others using chemical catalysts. With the former, feedstock and end-product toxicity loom as major problems. Advances chiefly rest on the ability to manipulate biological systems. Computational and modular construction approaches are key. For example, novel metabolic networks have been constructed to make long-chain alcohols and hydrocarbons that have superior fuel properties over ethanol. A particularly exciting approach is to implement a direct utilization of solar energy to make a usable fuel. A number of approaches use the components of current biological systems, but re-engineer them for more direct, efficient production of fuels. © 2010 Elsevier Ltd.


Dunny G.M.,University of Minnesota
Annual Review of Genetics | Year: 2013

In Enterococcus faecalis, lateral transfer of conjugative plasmids that encode antibiotic resistance and virulence determinants can be induced by peptide sex pheromones. The tetracycline-resistance plasmid pCF10 represents a paradigm for illustrating important conserved features of a large family of pheromone-responsive enterococcal plasmids. The pheromone is released into the growth medium by plasmid-free recipient cells and sensed by plasmid-containing donors. The activity of the pheromone is antagonized by a plasmid-encoded inhibitor peptide that prevents conjugation in the absence of an inducing signal and is also required to return the system to the ground state following an induction cycle. The pheromone response involves multiple transcriptional and posttranscriptional mechanisms as well as bi-stable biological switch behavior. Multiple layers of regulation are essential for proper function, and evolution of this tight control system may have been favored by reduction of the fitness cost of plasmid maintenance to the host cell. © 2013 by Annual Reviews. All rights reserved.


Matsumoto K.,University of Minnesota | Yokoyama Y.,University of Tokyo
Global Biogeochemical Cycles | Year: 2013

A rapid reduction in the Atlantic meridional overturning circulation (AMOC) can significantly disrupt the global heat transport and likely triggered abrupt climate change during the last glacial cycle. A slowdown in AMOC has long been assumed to inhibit the exchange of carbon between the atmosphere and the deep ocean and thus cause radiocarbon (14C), which is produced in the atmosphere, to accumulate in the atmosphere. Indeed previous model studies have demonstrated that a reduction in AMOC leads to higher atmospheric 14C abundance (Δ14C). However, this seems inconsistent with the observed rise in atmospheric pCO2 during Heinrich 1 and the Younger Dryas stadial events and the emerging view that this CO2 rise resulted from the deep ocean venting "old" carbon. Using an Earth system model, we offer an alternative scenario that AMOC slowdown and an accompanying dynamical response in the south (i.e., the bipolar seesaw) can in fact lead to a decline in atmospheric Δ14C. This decline is realized in the model when the bipolar seesaw and thus the flux of old carbon from the Southern Ocean are sufficiently large so as to overcome the accumulation of 14C in the atmosphere as AMOC is reduced. The bipolar seesaw we describe invokes an oceanic teleconnection, whereby a freshwater perturbation in the North Atlantic drives a southern Δ14C response, but this does not necessarily preclude an atmospheric teleconnection. ©2013. American Geophysical Union. All Rights Reserved.


We have recently described a specialized subset of human natural killer (NK) cells with a CD56dimCD57+NKG2C+ phenotype that expand specifically in response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. We hypothesize that these cells mediate relapse protection and improve post-HCT outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated CMV had lower leukemia relapse (26% (17–35%), P=0.05) and superior disease-free survival (DFS) (55% (45–65%) P=0.04) 1 year after reduced intensity conditioning (RIC) compared with CMV seronegative recipients who experienced higher relapse rates (35% (27–43%)) and lower DFS (46% (38–54%)). This protective effect was independent of age and graft-vs-host disease and was not observed in recipients who received myeloablative regimens. Analysis of the reconstituting NK cells demonstrated that CMV reactivation is associated with both higher frequencies and greater absolute numbers of CD56dimCD57+NKG2C+ NK cells, particularly after RIC HCT. Furthermore, expansion of these cells at 6 months posttransplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on posttransplant relapse is in part driven by adaptive NK cell responses.Leukemia advance online publication, 27 October 2015; doi:10.1038/leu.2015.260. © 2015 Macmillan Publishers Limited


Simon J.A.,University of Minnesota | Kingston R.E.,Harvard University
Molecular Cell | Year: 2013

Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence key developmental regulators and are centrally integrated in the transcriptional circuitry of stem cells. PRC2 trimethylates histone H3 on lysine 27 (H3K27me3), and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs are deployed to select and silence genomic targets is the subject of intense investigation. We review advances on targeting, modulation, and functions of PRC1 and PRC2 and progress on defining the transcriptional steps they impact. Recent findings emphasize PRC1 targeting independent of H3K27me3, nonenzymatic PRC1-mediated compaction, and connections between PRCs and noncoding RNAs. Systematic analyses of Polycomb complexes and associated histone modifications during DNA replication and mitosis have also emerged. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell-cycle progression. © 2013 Elsevier Inc.


Springer N.M.,University of Minnesota
Trends in Genetics | Year: 2013

There is considerable excitement about the potential for epigenetic information to contribute to heritable variation in many species. Our understanding of the molecular mechanisms of epigenetic inheritance is rapidly growing, and it is now possible to profile the epigenome at high resolution. Epigenetic information plays a role in developmental gene regulation, response to the environment, and in natural variation of gene expression levels. Because of these central roles, there is the potential for epigenetics to play a role in crop improvement strategies including the selection for favorable epigenetic states, creation of novel epialleles, and regulation of transgene expression. In this review we consider the potential, and the limitations, of epigenetic variation in crop improvement. © 2012 Elsevier Ltd.


Sandoval Y.,Hennepin County Medical Center | Smith S.W.,Hennepin County Medical Center | Thordsen S.E.,Hennepin County Medical Center | Apple F.S.,University of Minnesota
Journal of the American College of Cardiology | Year: 2014

Supply/demand (type 2) myocardial infarction is a commonly encountered clinical challenge. It is anticipated that it will be detected more frequently once high-sensitivity cardiac troponin assays are approved for clinical use in the United States. We provide a perspective that is based on available data regarding the definition, epidemiology, etiology, pathophysiology, prognosis, management, and controversies regarding type 2 myocardial infarction. Understanding these basic concepts will facilitate the diagnosis and treatment of these patients as well as ongoing research efforts. © © 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.


Coleman R.A.,University of North Carolina at Chapel Hill | Mashek D.G.,University of Minnesota
Chemical Reviews | Year: 2011

An overview of TAG metabolism as a dynamic process that allows its lipid participants to play numerous inter-related roles within cells is presented. For most synthetic pathways each step is catalyzed by a single enzyme unless specific regulation is required. Yet, in the glycerol-3-phosphate pathway of TAG synthesis, investigators have confirmed four independent GPAT isoforms, three AGPAT isoforms, three PAP isoforms, and two DGAT isoforms. The non-backcrossed mice resist weight gain on a high-fat diet. Their subdermal fat depots are absent, and their gonadal and brown adipose fat pads and adipocytes are smaller. The differences in fat pad size are not solely due to absent GPAT4 activity within the tissue, because although NEM-sensitive GPAT activity in brown adipose is 50% lower than in wild-type brown adipose, gonadal NEM-sensitive GPAT activity is identical.


The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of overgeneralization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety. © 2012 Wiley Periodicals, Inc.


This article explores the use of the best interest standard in the context of third-party interventions in ongoing parent-child relationships. I start by examining the history of the best interest standard and show that it has had different meanings in different eras. I then address the nature of the family and the question of whether interests beyond those addressed in the child's best interest standard are a legitimate part of family decision-making. I conclude that ongoing families are entitled to at least a measure of deference in their decisions about their children. Third-party interventions, such as those of doctors or judges, should require something more than simply a difference of opinion about where the child's interests lie. Copyright © 2014 by the American Academy of Pediatrics.


Larson N.,University of Minnesota
Journal of the American Dietetic Association | Year: 2011

Given the widespread use of out-of-home child care and an all-time high prevalence of obesity among US preschool-aged children, it is imperative to consider the opportunities that child-care facilities may provide to reduce childhood obesity. This review examines the scientific literature on state regulations, practices and policies, and interventions for promoting healthy eating and physical activity, and for preventing obesity in preschool-aged children attending child care. Research published between January 2000 and July 2010 was identified by searching PubMed and MEDLINE databases, and by examining the bibliographies of relevant studies. Although the review focused on US child-care settings, interventions implemented in international settings were also included. In total, 42 studies were identified for inclusion in this review: four reviews of state regulations, 18 studies of child-care practices and policies that may influence eating or physical activity behaviors, two studies of parental perceptions and practices relevant to obesity prevention, and 18 evaluated interventions. Findings from this review reveal that most states lack strong regulations for child-care settings related to healthy eating and physical activity. Recent assessments of child-care settings suggest opportunities for improving the nutritional quality of food provided to children, the time children are engaged in physical activity, and caregivers' promotion of children's health behaviors and use of health education resources. A limited number of interventions have been designed to address these concerns, and only two interventions have successfully demonstrated an effect on child weight status. Recommendations are provided for future research addressing opportunities to prevent obesity in child-care settings. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.


Kim D.,University of Minnesota
Analytical chemistry | Year: 2011

This article reviews measurement of single cell exocytosis with microelectrodes, covering history, basic instrumentation, cell types investigated, and fundamental insight gained.


Voller V.R.,University of Minnesota
International Journal of Heat and Mass Transfer | Year: 2010

An anomalous diffusion version of a limit Stefan melting problem is posed. In this problem, the governing equation includes a fractional time derivative of order 0 < β ≤ 1 and a fractional space derivative for the flux of order 0 < α ≤ 1. Solution of this fractional Stefan problem predicts that the melt front advance as s=tγ,γ=βα+1. This result is consistent with fractional diffusion theory and through appropriate choice of the order of the time and space derivatives, is able to recover both sub-diffusion and super-diffusion behaviors for the melt front advance. © 2010 Elsevier Ltd. All rights reserved.


Yee D.,University of Minnesota
Journal of the National Cancer Institute | Year: 2012

The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed. © 2012 The Author.


Wang Y.,University of Wisconsin - Madison | Agterberg D.F.,University of Wisconsin - Milwaukee | Chubukov A.,University of Minnesota
Physical Review Letters | Year: 2015

We analyze incommensurate charge-density-wave (CDW) and pair-density-wave (PDW) orders with transferred momenta (±Q,0)/(0,±Q) in underdoped cuprates within the spin-fermion model. Both orders appear due to an exchange of spin fluctuations before magnetic order develops. We argue that the ordered state with the lowest energy has nonzero CDW and PDW components with the same momentum. Such a state breaks C4 lattice rotational symmetry, time-reversal symmetry, and mirror symmetries. We argue that the feedback from CDW/PDW order on fermionic dispersion is consistent with ARPES data. We discuss the interplay between the CDW/PDW order and dx2-y2 superconductivity and make specific predictions for experiments. © 2015 American Physical Society.


Davidson V.L.,University of Central Florida | Wilmot C.M.,University of Minnesota
Annual Review of Biochemistry | Year: 2013

Methylamine dehydrogenase (MADH) catalyzes the oxidative deamination of methylamine to formaldehyde and ammonia. Tryptophan tryptophylquinone (TTQ) is the protein-derived cofactor of MADH required for this catalytic activity. TTQ is biosynthesized through the posttranslational modification of two tryptophan residues within MADH, during which the indole rings of two tryptophan side chains are cross-linked and two oxygen atoms are inserted into one of the indole rings. MauG is a c-type diheme enzyme that catalyzes the final three reactions in TTQ formation. In total, this is a six-electron oxidation process requiring three cycles of MauG-dependent two-electron oxidation events using either H2O2 or O2. The MauG redox form responsible for the catalytic activity is an unprecedented bis-FeIV species. The amino acids of MADH that are modified are ∼40 Å from the site where MauG binds oxygen, and the reaction proceeds by a hole hopping electron transfer mechanism. This review addresses these highly unusual aspects of the long-range catalytic reaction mediated by MauG. © 2013 by Annual Reviews. All rights reserved.


Nelson S.H.,University of Minnesota
Antipode | Year: 2015

This paper brings autonomist Marxist analyses of post-Fordist transition together with the geographical literature on ecosystem services to argue that the rise of the ecosystem service economy was central to what Paolo Virno has called the neoliberal counterrevolution. By analyzing the discourse of environmental crisis in the 1960s and 1970s, I demonstrate that early efforts to account for the value of environmental functions were a response to the instabilities faced by globalized capital in the postwar era. The rise of the ecosystem service economy is central to what autonomist Marxists describe as a post-Fordist mode of production in which the activities of social (and, I argue, ecological) reproduction become direct sources of value. The paper suggests the need to revise the autonomist analysis to account for both the ecological dimensions of Fordist crisis, and the importance of the ecosystem service economy as a means whereby the counterrevolution was accomplished. © 2014 Antipode Foundation Ltd.


Dehm S.M.,University of Minnesota
Cancer Research | Year: 2013

Systemic cancer therapy has traditionally exploited vulnerabilities in cancer cells, a strategy which has become more precise with the identification and targeting of driver oncogenes. However, persistent tumor growth due to primary (de novo) or secondary (acquired) resistance limits therapeutic efficacy for many patients. Alternative splicing is important for increasing the diversity of the cellular proteome, and is a process frequently deregulated during cancer development and progression. In cancer cells, diverse splicing alterations have been identified that eliminate protein domains or enzymatic activities required for efficacy of cancer therapies, promote gain of novel signaling functions that circumvent cancer therapies, and uncouple signaling pathways from upstream regulatory points that are blocked by cancer therapies. The mechanisms underlying these splicing changes range from stable alterations in gene sequence/structure to deregulation of splicing regulatory factors. In this review, the role of splice variants in cancer therapy resistance will be discussed, with examples of how mechanistic understanding of these processes has led to the development of novel strategies for therapy resensitization. ©2013 AACR.


Cicchetti D.,University of Minnesota | Cicchetti D.,University of Rochester
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2013

Background: Through a process of probabilistic epigenesis, child maltreatment progressively contributes to compromised adaptation on a variety of developmental domains central to successful adjustment. These developmental failures pose significant risk for the emergence of psychopathology across the life course. In addition to the psychological consequences of maltreatment, a growing body of research has documented the deleterious effects of abuse and neglect on biological processes. Nonetheless, not all maltreated children develop maladaptively. Indeed, some percentage of maltreated children develops in a resilient fashion despite the significant adversity and stress they experience. Methods: The literature on the determinants of resilience in maltreated children is selectively reviewed and criteria for the inclusion of the studies are delineated. Results: The majority of the research on the contributors to resilient functioning has focused on a single level of analysis and on psychosocial processes. Multilevel investigations have begun to appear, resulting in several studies on the processes to resilient functioning that integrate biological/genetic and psychological domains. Conclusions: Much additional research on the determinants of resilient functioning must be completed before we possess adequate knowledge based on a multiple levels of analysis approach that is commensurate with the complexity inherent in this dynamic developmental process. Suggestions for future research on the development of resilient functioning in maltreated children are proffered and intervention implications are discussed. © 2012 The Author. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.


Garry M.G.,University of Minnesota
Exercise and Sport Sciences Reviews | Year: 2011

Abnormal cardiovascular responses to exercise in heart failure contribute significantly to the morbidity and mortality in the patient population. These abnormal responses may be the result of peripheral impairment in the skeletal muscle and the neurons that innervate the muscle. We present the current literature on the role of muscle afferents in regulating the cardiovascular responses to exercise in cardiomyopathy. © 2011 by the American College of Sports Medicine.


Rinehart A.,University of Minnesota
Clinical Journal of the American Society of Nephrology | Year: 2013

Futility is an ancient concept arising from Greekmythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician-patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association's clinical practice guideline Shared Decision- Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline. © 2013 by the American Society of Nephrology.


Jacobs Jr. D.R.,University of Minnesota
Journal of Nutrition | Year: 2014

This article summarizes background materials and presentations at a symposium that considered the issue of the role of foods and dietary patterns vs. nutrients in relation to chronic disease risk. A model of food synergy is presented as a basis for studying whole foods and dietary patterns. Findings from a series of studies of walnuts were presented and support the concept that walnuts are a healthy food, with specific benefits in a mouse model of breast cancer growth, reductions in cardiovascular disease risk factors in humans, and motor performance and in vitro, in vivo, and ex vivo cellular response to challenge in an aged-rat model. © 2014 American Society for Nutrition.


Berland A.,University of Minnesota
Urban Ecosystems | Year: 2012

Urban forestry can benefit from improved knowledge of urbanization's effects on tree canopy cover (TCC), a prominent urban forest indicator. This study examined changes in TCC over a long time frame, with respect to land cover (LC) changes, and across municipal boundaries. Specifically, I used air photos at 14 dates from 1937 to 2009 to develop an exceptionally long record of TCC change in Minnesota's Twin Cities Metropolitan Area. During the study period overall TCC nearly doubled from 17% to 33% while the proportion urban land cover rose by 47%, highlighting the opportunity for substantial TCC gains following urbanization in previously agricultural landscapes, even in regions that were forested prior to European settlement. Results demonstrate that more intensely developed sites generally had lower TCC, and older urban sites had higher TCC. Modern TCC was not adequately characterized by linear distance along the urban-rural gradient, but instead peaked near the center of the gradient where mature residential neighborhoods are prevalent. Compared to other land cover changes, urbanization events caused the highest rate of immediate TCC loss (9.6% of events), yet urban areas had the second highest TCC (>35%) in 2009, indicating that urban land gained TCC relatively efficiently following development. The results of this study provide new historical context for urban forest management across an urban-rural gradient, and emphasize the need to consider ecological legacies and temporal lags following land cover changes when considering TCC goals in urban settings. © 2012 Springer Science+Business Media, LLC.


Adams J.E.,University of Minnesota
Clinical Orthopaedics and Related Research | Year: 2014

Background: Thumb carpometacarpal (CMC) joint arthritis is a common problem in clinical practice with a variety of treatment options. Arthroscopic procedures can preserve all or part of the trapezium in the setting of treatment of basilar joint arthritis, and such procedures (even without stabilization or ligament reconstruction) have high reported success rates. However, little is documented about the limitations of these procedures in terms of patient selection, the optimal type of interposition, if any, and rehabilitation. Questions/purposes: A systematic review was performed to determine the influence of (1) interposition material (manufactured, biological, or none); and (2) patient-related factors (including metacarpophalangeal joint hyperextension, ligamentous laxity, and severity of arthritis) on pain, functional scores, and postoperative complications unique to each approach. Methods: A systematic review of the English language literature regarding thumb basilar joint arthritis and arthroscopic partial trapeziectomy or débridement was performed. Those procedures including ligament reconstruction or stabilization were excluded. Results: Biological materials and no interposition were both associated with satisfactory improvement and low rates of complications; complication rates with synthetic materials were higher. Eaton Stages I to III were treated successfully with this technique. The effect of scaphotrapeziotrapezoid (STT) changes was variably described across series. In most series, metacarpophalangeal hyperextension did not seem to have an adverse effect on outcomes, although these patients were excluded in some series. Conclusions: Arthroscopic débridement with or without interposition can be used for treatment of Eaton Stages I to III CMC osteoarthritis with satisfactory outcomes. Some series suggest satisfactory outcomes in the setting of STT changes and metacarpophalangeal hyperextension. © 2013 The Association of Bone and Joint Surgeons®.


Clinical trials are typically designed to test the effect of a specific treatment on a single diagnostic entity. However, because common internalizing disorders are highly correlated ('co-morbid'), we sought to establish a practical and parsimonious method to characterize and quantify changes in a broad spectrum of internalizing psychopathology targeted for treatment in a clinical trial contrasting two transdiagnostic psychosocial interventions. Alcohol dependence treatment patients who had any of several common internalizing disorders were randomized to a six-session cognitive-behavioral therapy (CBT) experimental treatment condition or a progressive muscle relaxation training (PMRT) comparison treatment condition. Internalizing psychopathology was characterized at baseline and 4 months following treatment in terms of the latent structure of six distinct internalizing symptom domain surveys. Exploratory structural equation modeling (ESEM) identified a two-factor solution at both baseline and the 4-month follow-up: Distress (measures of depression, trait anxiety and worry) and Fear (measures of panic anxiety, social anxiety and agoraphobia). Although confirmatory factor analysis (CFA) demonstrated measurement invariance between the time-points, structural models showed that the latent means of Fear and Distress decreased substantially from baseline to follow-up for both groups, with a small but statistically significant advantage for the CBT group in terms of Distress (but not Fear) reduction. The approach demonstrated in this study provides a practical solution to modeling co-morbidity in a clinical trial and is consistent with converging evidence pointing to the dimensional structure of internalizing psychopathology.


Perry J.,University of Minnesota
Landscape and Urban Planning | Year: 2015

Natural World Heritage (WH) sites are globally recognized as having universal value, providing society with critical ecosystem services like biodiversity, clean water, and recreational opportunity. Every natural WH site is at risk from climate change, but the scope and nature of that risk varies widely. Climate change adaptation is a wicked problem; that is, there are no clear-cut solutions and stakeholders at each site disagree on values, norms and first steps, making adaptation difficult. Yet, delaying action poses more risks than taking action under uncertainty. I synthesize the refereed literature relevant to climate adaptation for natural WH sites. I argue that adaptation should be ecosystem based. It should begin by understanding linkages among site attributes and the surrounding landscape, and asking how off-site and on-site practices might reduce risk of negative effects of climate change on those attributes. Adaptation responses are tiered. Fine-scale, on-site responses are less expensive and easier but will have less impact than coarse-scale responses involving the surrounding community. We cannot precisely predict future conditions so we must act adaptively, designing responses, acting, evaluating results, re-designing and trying again. Action is constrained by institutional mandates focused on preserving existing conditions rather than recognizing a dynamic future. Climate change adaptation at natural WH sites should be Adaptive, Participatory and Transformative, deployed through clumsy solutions. Such solutions will require strong leadership and excellent communication, drawing together widely disparate views and iterative practices focusing on resilience. That requirement establishes the need for capacity development for climate change adaptation. © 2014 Elsevier B.V.


Hobbie S.E.,University of Minnesota
Trends in Ecology and Evolution | Year: 2015

In a review published over two decades ago I asserted that, along soil fertility gradients, plant traits change in ways that reinforce patterns of soil fertility and net primary productivity (NPP). I reevaluate this assertion in light of recent research, focusing on feedbacks to NPP operating through litter decomposition. I conclude that mechanisms emerging since my previous review might weaken these positive feedbacks, such as negative effects of nitrogen on decomposition, while others might strengthen them, such as slower decomposition of roots compared to leaf litter. I further conclude that predictive understanding of plant species effects on nutrient cycling will require developing new frameworks that are broadened beyond litter decomposition to consider the full litter-soil organic matter (SOM) continuum. © 2015 Elsevier Ltd.


Zarkower D.,University of Minnesota
Current Topics in Developmental Biology | Year: 2013

Genes containing the DM domain DNA-binding motif regulate sex determination and sexual differentiation in a broad variety of metazoans, including nematodes, insects, and vertebrates. They can function in primary sex determination or downstream in sexual differentiation, and they can act either throughout the body or in highly restricted cell types. In vertebrates, several DM domain genes- DMRT genes-play critical roles in gonadal differentiation or gametogenesis. DMRT1 has the most prominent role and likely regulates testicular differentiation in all vertebrates. In the mammalian gonad, DMRT1 exerts both intrinsic and extrinsic control of gametogenesis; it is required for germ cell differentiation in males and regulates meiosis in both sexes, and it is required in supporting cells for the establishment and maintenance of male fate in the testis. These varied functions of DMRT1 serve to coordinate gonadal development and function. In other vertebrates, DMRT1 regulates gonadal differentiation, and it also appears to have played a central role in the evolution of new sex-determining mechanisms in at least three vertebrate clades. This chapter focuses on the regulation of vertebrate gametogenesis by DMRT1. © 2013 Elsevier Inc.


Rail transit has been touted as a way to enhance livability, quality of life or satisfaction with life (SWL). However, the connections between transit and SWL are mainly conceptual, and little empirical evidence is available in the literature. Using the Hiawatha line in Minneapolis as a case, this study develops structural equations models on a 2011 dataset to explore the impacts of light rail transit (LRT) on SWL. We corroborate that the Hiawatha LRT positively influences SWL through enhanced access to different activities, and through improved transit service, enhanced accessibility, and their impacts on satisfaction with travel. The size of the impacts is marginal. © 2013 Springer Science+Business Media New York.


Gross B.L.,University of Minnesota | Zhao Z.,Chinese Academy of Sciences
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Rice (Oryza sativa) is one of the most important cereal grains in the world today and serves as a staple food source for more than half of the world's population. Research into when, where, and how rice was brought into cultivation and eventually domesticated, along with its development into a staple food source, is thus essential. These questions have been a point of nearly continuous research in both archaeology and genetics, and new information has continually come to light as theory, data acquisition, and analytical techniques have advanced over time. Here, we review the broad history of our scientific understanding of the rice domestication process from both an archaeological and genetic perspective and examine in detail the information that has come to light in both of these fields in the last 10 y. Current findings from genetics and archaeology are consistent with the domestication of O. sativa japonica in the Yangtze River valley of southern China. Interestingly, although it appears rice was cultivated in the area by as early 8000 BP, the key domestication trait of nonshattering was not fixed for another 1,000 y or perhaps longer. Rice was also cultivated in India as early as 5000 BP, but the domesticated indica subspecies currently appears to be a product of the introgression of favorable alleles from japonica. These findings are reshaping our understanding of rice domestication and also have implications for understanding the complex evolutionary process of plant domestication.


Zhu T.X.,University of Minnesota
Geomorphology | Year: 2012

Although gully development is frequently observed to be associated with piping and tunnel erosion in many parts of the world, there is a lack of detailed studies on their spatial interactions. Such studies not only contribute to developing geomorphic theories on the evolution of both hillslopes and drainage networks but also are useful to design effective control measures of erosion. The present study aims to examine the interactions between gully development and tunnel erosion in the hilly Loess Plateau region of northern China. Firstly, gullies, tunnel inlets and mass movements in the 9.1km 2 Wangjiagou watershed were mapped through aerial photo interpretation and reconnaissance surveys. Secondly, detailed field studies were carried out to investigate the interactions between gully development and tunnel formation processes in the selected gullies. Thirdly, the physiographic variables of gullies, derived from GIS and field measurements, were analyzed to identify differences between tunneled and untunneled gullies.A total of 704 channels, 967 tunnel inlets and 547 mass movements were identified in the study watershed. On the basis of their location and morphology, all the channels were classified into four types: headwater gullies, hillside gullies, valleyside gullies and ephemeral river channels. Tunnels are associated with 79% of headwater gullies, 48% of hillside gullies, 3% of valleyside gullies and none of ephemeral river channels. Mass movements are dominated by falls in headwater gullies, falls and slides in hillside gullies, and soil creeps in ephemeral stream channels. Statistical tests indicate that there are significant differences in physiographic variables between tunneled and untunneled gullies. Tunnel formation in gullies is intricately affected by topographic conditions, land uses, knickpoint distribution, soil materials and mass movements. © 2012.


Leitner H.,University of Minnesota
Annals of the Association of American Geographers | Year: 2012

Small towns throughout the rural upper Midwest have been experiencing dramatic economic restructuring and an unprecedented influx of new immigrants of color, triggering conflicts and tension between almost exclusively white residents and the new immigrants. Analyzing the roots and content of white residents' responses to their encounters with new immigrants in a small town in rural Minnesota, the concept of spaces of encounters draws attention to the relational quality of identities and attitudes and the active role of emotions and spatiality in processes of Othering and racialization, as well as the potential of the encounter to disrupt preconceived boundaries and racial stereotypes. White residents racialize immigrants and space, although the specific form taken by processes of racialization is inflected by individuals' social positionality and place identities and by longer term and broader scale racial stereotypes and dominant discourses about immigration, race, and nation in the United States. The racialization of immigrants defends white privilege and culture; recovers an imagined idealized place, past, and future; and establishes that belonging to the national and local community is conditional on immigrants conforming to white American values and norms-an assimilationist imaginary that runs up against the multicultural and multiracial reality of the town. Residents' reflections on their own racial prejudice and different forms of racism, as well as intimate social relations they forge with individual migrants, hold promise for social relations that transcend differences across racial and cultural divides. © 2012 Copyright Taylor and Francis Group, LLC.


Iacono W.G.,University of Minnesota
Psychophysiology | Year: 2016

Achieving Research Domain Criteria (RDoC) goals depends in part on how well scientists can grasp its principles and execute studies within its framework. Ford provides an exemplary illustration of a research program that aligns with RDoC guidelines. The future success of RDoC depends not just on research like that of Ford and colleagues. RDoC also must inspire the development of reliable neurobehavioral measures with demonstrable clinical validity that produce replicable findings leading to the establishment of neurocircuit-based behavioral dimensions that inform clinical work. Large samples not typically attainable in a clinical neuroscience laboratory or easily imagined within the confines of the RDoC matrix will be required if RDoC is to develop the insights and tools needed to establish incremental value over the DSM. Innovation that goes beyond reliance on the RDoC matrix and measures of neurocircuitry can help facilitate achievement of RDoC's goal of developing a science of psychopathology based on neurobiological systems. © 2016 Society for Psychophysiological Research..


Human induced pluripotent stem cells (iPSCs) can be divided into a leukemia inhibitory factor (LIF)-dependent naïve type and a basic fibroblast growth factor (bFGF)-dependent primed type. Although the former are more undifferentiated than the latter, they require signal transduction inhibitors and sustained expression of the transgenes used for iPSC production. We used a transcriptionally enhanced version of OCT4 to establish LIF-dependent human iPSCs without the use of inhibitors and sustained transgene expression. These cells belong to the primed type of pluripotent stem cell, similar to bFGF-dependent iPSCs. Thus, the particular cytokine required for iPSC production does not necessarily define stem cell phenotypes as previously thought. It is likely that the bFGF and LIF signaling pathways converge on unidentified OCT4 target genes. These findings suggest that our LIF-dependent human iPSCs could provide a novel model to investigate the role of cytokine signaling in cellular reprogramming.


Dahlen H.M.,University of Minnesota
American Journal of Public Health | Year: 2015

Objectives: I examined how labor market and health insurance outcomes were affected by the loss of dependent coverage eligibility under the Patient Protection and Affordable Care Act (ACA). Methods: I used National Health Interview Survey (NHIS) data and regression discontinuity models to measure the percentage-point change in labor market and health insurance outcomes at age 26 years. My sample was restricted to unmarried individuals aged 24 to 28 years and to a period of time before the ACA's individual mandate (2011-2013). I ran models separately for men and women to determine if there were differences based on gender. Results: Aging out of this provision increased employment among men, employersponsored health insurance offers for women, and reports that health insurance coverage was worse than it was 1 year previously (overall and for young women). Uninsured rates did not increase at age 26 years, but there was an increase in the purchase of non-group health coverage, indicating interest in remaining insured after age 26 years. Conclusions: Many young adults will turn to state and federal health insurance marketplaces for information about health coverage. Because young adults (aged 18-29 years) regularly use social media sites, these sites could be used to advertise insurance to individuals reaching their 26th birthdays.