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Rochester, NY, United States

The University of Rochester is a private, nonsectarian, research university in Rochester, New York, United States. The university grants undergraduate and graduate degrees, including doctoral and professional degrees. The university has six schools and various interdisciplinary programs.The University of Rochester is noted for its Eastman School of Music. The university is also home to the Institute of Optics, founded in 1929, the nation's first educational program devoted exclusively to optics. Rochester's Laboratory for Laser Energetics is home to the second most energetic fusion laser in the world.In its history, five university alumni, two faculty, and one senior research associate at Strong Memorial Hospital have been awarded a Nobel Prize; eight alumni and four faculty members have won a Pulitzer Prize, and 19 faculty members have been awarded a Guggenheim Fellowship. Faculty and alumni of Rochester make up nearly one-quarter of the scientists on the board advising NASA in the development of the James Webb Space Telescope, which will replace the Hubble Space Telescope as of 2011. The departments of political science and economics have made a significant and consistent impact on positivist social science since the 1960s; the distinctive, mathematical approach pioneered at Rochester and closely affiliated departments is known as the Rochester school, and Rochester graduates and former affiliates are highly represented at faculties across top economics and political science departments. The University of Rochester, across all of its schools and campuses, enrolls approximately 5,600 undergraduates and 4,600 graduate students. Its 158 buildings house over 200 academic majors. Additionally, Rochester is the largest employer in the Greater Rochester area and the sixth largest employer in the New York. Wikipedia.

Wortman M.,University of Rochester
Journal of Minimally Invasive Gynecology | Year: 2010

Office-based surgery (OBS) provides many advantages for the patient, physician, operating room team, and health care system. Newer technologies provide an array of procedures appropriate to the office setting, and with careful preparation, many can be performed without compromising patient safety or comfort. Several states have specific regulatory requirements for OBS, although half of them provide neither guidelines nor regulation. The Federation of State Medical Boards provides current regulatory information across the United States; the American College of Obstetrics and Gynecology has recently issued guidelines that provide recommendations for instituting an OBS practice, and the American Medical Association and the American Society of Anesthesiologists provide guidelines that promote patient safety and comfort in the office setting. Many issues must be considered before instituting an OBS program. Practices that perform invasive procedures requiring more than minimal sedation are encouraged to seek formal accreditation because it assures patients of quality of care. Residency programs and professional societies are encouraged to provide training in OBS surgery and to develop programs to mentor the next generation of physicians. © 2010 AAGL.

Oberdorster G.,University of Rochester
Journal of Internal Medicine | Year: 2010

Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano-enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico-chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos-like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano-specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists. © 2009 Blackwell Publishing Ltd.

Wijesinghe T.,Monash University | Premaratne M.,Monash University | Agrawal G.P.,University of Rochester
Optics Express | Year: 2014

Active plasmonic waveguiding has become a key requirement for designing and implementing nanophotonic devices. We study theoretically the performance of an Au/GaSb-based, metal-insulator- semiconductor (MIS) structure acting as a hybrid electrically pumped waveguide with gain. The surface-plasmon polariton (SPP) mode supported by this configuration is analyzed in the third telecommunication window and discussed in detail. Changes in the effective mode index, confinement factor and effective mode area are illustrated for different core widths and layer thicknesses. Electrical behavior of the MIS junction is analyzed using a self-consistent numerical technique and used to study variations in the material and model gains within the semiconducting region of the device. Our results indicate the possibility of achieving low loss SPP propagation while maintaining a strong field confinement. © 2014 Optical Society of America.

Greenberg B.D.,Brown University | Rauch S.L.,Harvard University | Haber S.N.,University of Rochester
Neuropsychopharmacology | Year: 2010

Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first such approval for a psychiatric illness. Several factors explain the emergence of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress, are much enhanced. Here, we review modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use. © 2010 Nature Publishing Group All rights reserved.

Bren K.L.,University of Rochester
Interface Focus | Year: 2015

This review summarizes three different approaches to engineering systems for the solar-driven evolution of hydrogen fuel from water: molecular, nanomaterials and biomolecular. Molecular systems have the advantage of being highly amenable to modification and detailed study and have provided great insight into photophysics, electron transfer and catalytic mechanism. However, they tend to display poor stability. Systems based on nanomaterials are more robust but also are more difficult to synthesize in a controlled manner and to modify and study in detail. Biomolecular systems share many properties with molecular systems and have the advantage of displaying inherently high efficiencies for light absorption, electron–hole separation and catalysis. However, biological systems must be engineered to couple modules that capture and convert solar photons to modules that produce hydrogen fuel. Furthermore, biological systems are prone to degradation when employed in vitro. Advances that use combinations of these three tactics also are described. Multidisciplinary approaches to this problem allow scientists to take advantage of the best features of biological, molecular and nanomaterials systems provided that the components can be coupled for efficient function. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

The sharing of scientific data reinforces open scientific inquiry; it encourages diversity of analysis and opinion while promoting new research and facilitating the education of next generations of scientists. In this article, we present an initiative for the development of a repository containing continuous electrocardiographic information and their associated clinical information. This information is shared with the worldwide scientific community to improve quantitative electrocardiology and cardiac safety. First, we present the objectives of the initiative and its mission. Then, we describe the resources available in this initiative following 3 components: data, expertise, and tools. The data available in the Telemetric and Holter ECG Warehouse (THEW) includes continuous electrocardiogram signals and associated clinical information. The initiative attracted various academic and private partners whom expertise covers a large list of research arenas related to quantitative electrocardiography; their contribution to the THEW promotes cross-fertilization of scientific knowledge, resources, and ideas that will advance the field of quantitative electrocardiography. Finally, the tools of the THEW include software and servers to access and review the data available in the repository. To conclude, the THEW is an initiative developed to benefit the scientific community and to advance the field of quantitative electrocardiography and cardiac safety. It is a new repository designed to complement the existing ones such as Physionet, the American Heart Association - Beth Israel Hospital (AHA-BIH) arrhythmia database, and the Common Standard for Electrocardiography (CSE) database. The THEW hosts unique datasets from clinical trials and drug safety studies that, so far, were not available. © 2010 Elsevier Inc. All rights reserved.

Boyd R.W.,University of Ottawa | Boyd R.W.,University of Rochester
Journal of the Optical Society of America B: Optical Physics | Year: 2011

There are two standard methods for controlling the group velocity of light. One makes use of the dispersive properties associated with the resonance structure of a material medium. The other makes use of structural resonances, such as those that occur in photonic crystals. Both procedures have proved useful in a variety of situations. In this work we contrast these two approaches, especially in terms of issues such as the kinematics of energy flow though the system and the resulting implications for the behavior of nonlinear optical processes in these situations. Stated differently, this paper addresses the question of when nonlinear optical processes are enhanced through use of slow-light interactions and when they are not. © 2011 Optical Society of America.

Epstein R.M.,University of Rochester | Street Jr. R.L.,Baylor College of Medicine
Annals of Family Medicine | Year: 2011

In the context of serious illness, individuals usually rely on others to help them think and feel their way through difficult decisions. To help us to understand why, when, and how individuals involve trusted others in sharing information, deliberation, and decision making, we offer the concept of shared mind- ways in which new ideas and perspectives can emerge through the sharing of thoughts, feelings, perceptions, meanings, and intentions among 2 or more people. We consider how shared mind manifests in relationships and organizations in general, building on studies of collaborative cognition, attunement, and sensemaking. Then, we explore how shared mind might be promoted through communication, when appropriate, and the implications of shared mind for decision making and patient autonomy. Next, we consider a continuum of patient-centered approaches to patient-clinician interactions. At one end of the continuum, an interactional approach promotes knowing the patient as a person, tailoring information, constructing preferences, achieving consensus, and promoting relational autonomy. At the other end, a transactional approach focuses on knowledge about the patient, information-as-commodity, negotiation, consent, and individual autonomy. Finally, we propose that autonomy and decision making should consider not only the individual perspectives of patients, their families, and members of the health care team, but also the perspectives that emerge from the interactions among them. By drawing attention to shared mind, clinicians can observe in what ways they can promote it through bidirectional sharing of information and engaging in shared deliberation.

Haber S.N.,University of Rochester | Knutson B.,Stanford University
Neuropsychopharmacology | Year: 2010

Although cells in many brain regions respond to reward, the cortical-basal ganglia circuit is at the heart of the reward system. The key structures in this network are the anterior cingulate cortex, the orbital prefrontal cortex, the ventral striatum, the ventral pallidum, and the midbrain dopamine neurons. In addition, other structures, including the dorsal prefrontal cortex, amygdala, hippocampus, thalamus, and lateral habenular nucleus, and specific brainstem structures such as the pedunculopontine nucleus, and the raphe nucleus, are key components in regulating the reward circuit. Connectivity between these areas forms a complex neural network that mediates different aspects of reward processing. Advances in neuroimaging techniques allow better spatial and temporal resolution. These studies now demonstrate that human functional and structural imaging results map increasingly close to primate anatomy. © 2010 Nature Publishing Group All rights reserved.

Hadjiargyrou M.,New York Institute of Technology | O'Keefe R.J.,University of Rochester
Journal of Bone and Mineral Research | Year: 2014

The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine. © 2014 American Society for Bone and Mineral Research.

Novotny L.,University of Rochester | Van Hulst N.,Institute Of Ciencies Fotoniques | Van Hulst N.,Catalan Institution for Research and Advanced Studies
Nature Photonics | Year: 2011

Optical antennas are devices that convert freely propagating optical radiation into localized energy, and vice versa. They enable the control and manipulation of optical fields at the nanometre scale, and hold promise for enhancing the performance and efficiency of photodetection, light emission and sensing. Although many of the properties and parameters of optical antennas are similar to their radiowave and microwave counterparts, they have important differences resulting from their small size and the resonant properties of metal nanostructures. This Review summarizes the physical properties of optical antennas, provides a summary of some of the most important recent developments in the field, discusses the potential applications and identifies the future challenges and opportunities. © 2011 Macmillan Publishers Limited. All rights reserved.

Almudevar A.,University of Rochester | De Arruda E.F.,Federal University of Rio de Janeiro
IEEE Transactions on Automatic Control | Year: 2012

Many iterative algorithms employ operators which are difficult to evaluate exactly, but for which a graduated range of approximations exist. In such cases, coarse-to-fine algorithms are often used, in which a crude initial operator approximation is gradually refined with new iterations. In such algorithms, because the computational complexity increases over iterations, the algorithm's convergence rate is properly calculated with respect to cumulative computation time. This suggests the problem of determining an optimal rate of refinement for the operator approximation. This paper shows that, for linearly convergent algorithm, the optimal rate of refinement approaches the rate of convergence of the exact algorithm itself, regardless of the tolerance-complexity relationship. We illustrate this result with an analysis of coarse-to-fine grid algorithms for Markov decision processes with continuous state spaces. Using the methods proposed here we deduce an algorithm that presents optimal complexity results and consists solely of a non-adaptive schedule for the gradual decrease of grid size. © 1963-2012 IEEE.

Bowen W.H.,University of Rochester
Molecular Oral Microbiology | Year: 2015

Cavitation in teeth results from a pathogenic process termed dental caries that has occurred on the tooth surface for weeks or even years. Accumulation of dental plaque (biofilm) on the tooth is usually the first manifestation of the disease. Although acid production is the immediate and proximal cause of dissolution of teeth; it is the milieu within which the acid is formed that should be of primary concern. Focusing on the 'critical pH' has detracted attention from the more biological aspects (biofilm formation) of dental caries. Dental caries is unique; it is a biological process occurring on essentially an inert surface. Investigation of the multitude of interactions occurring in plaque ranging from enamel interfaces to surfaces of bacteria and matrices poses challenges worthy of the best scientific minds. The mouth clearly offers unique opportunities to investigate the multi facets of biofilm formation in vivo, generating data that have relevance way beyond the mouth. Prevention of this ubiquitous disease, dental caries, continues to present serious challenges. The public health benefits of fluoride delivered in its various formats are well recognized. Nevertheless, additional preventive approaches are required. Overcoming the rapid clearance of agents from the mouth is particularly challenging. Building on the polymerizing capacity of glucosyltransferases it may be possible to incorporate a therapeutic agent into the matrix plaque, thereby delivering therapeutic agents precisely to where they are needed. © 2015 John Wiley & Sons A/S.

Welte M.A.,University of Rochester
Current Biology | Year: 2015

Lipid droplets are the intracellular sites for neutral lipid storage. They are critical for lipid metabolism and energy homeostasis, and their dysfunction has been linked to many diseases. Accumulating evidence suggests that the roles lipid droplets play in biology are significantly broader than previously anticipated. Lipid droplets are the source of molecules important in the nucleus: they can sequester transcription factors and chromatin components and generate the lipid ligands for certain nuclear receptors. Lipid droplets have also emerged as important nodes for fatty acid trafficking, both inside the cell and between cells. In immunity, new roles for droplets, not directly linked to lipid metabolism, have been uncovered, with evidence that they act as assembly platforms for specific viruses and as reservoirs for proteins that fight intracellular pathogens. Until recently, knowledge about droplets in the nervous system has been minimal, but now there are multiple links between lipid droplets and neurodegeneration: many candidate genes for hereditary spastic paraplegia also have central roles in lipid-droplet formation and maintenance, and mitochondrial dysfunction in neurons can lead to transient accumulation of lipid droplets in neighboring glial cells, an event that may, in turn, contribute to neuronal damage. As the cell biology and biochemistry of lipid droplets become increasingly well understood, the next few years should yield many new mechanistic insights into these novel functions of lipid droplets. © 2015 Elsevier Ltd All rights reserved.

Patrick H.,U.S. National Cancer Institute | Williams G.C.,University of Rochester
International Journal of Behavioral Nutrition and Physical Activity | Year: 2012

Mounting evidence implicates health behaviors (e.g., nutrition, physical activity, tobacco abstinence) in various health outcomes. As the science of behavior change has emerged, increasing emphasis has been placed on the use of theory in developing and testing interventions. Self-determination theory (SDT)-a theoretical perspective-and motivational interviewing (MI)-a set of clinical techniques-have both been used in health behavior intervention contexts. Although developed for somewhat different purposes and in relatively different domains, there is a good deal of conceptual overlap between SDT and MI. Accordingly, SDT may offer the theoretical backing that historically has been missing from MI, and MI may offer SDT some specific direction with respect to particular clinical techniques that have not been fully borne out within the confines of health related applications of SDT. Research is needed to empirically test the overlap and distinctions between SDT and MI and to determine the extent to which these two perspectives can be combined or co-exist as somewhat distinct approaches. © 2012 Patrick and Williams; licensee BioMed Central Ltd.

Vansteenkiste M.,Ghent University | Ryan R.M.,University of Rochester
Journal of Psychotherapy Integration | Year: 2013

Humans have a potential for growth, integration, and well-being, while also being vulnerable to defensiveness, aggression, and ill-being. Self-determination theory (R. M. Ryan & E. L. Deci, 2000, Self-determination theory and the facilitation of intrinsic motivation, social development and well-being, American Psychologist, Vol. 55, pp. 68-78) argues that satisfaction of the basic psychological needs for autonomy, competence, and relatedness both fosters immediate well-being and strengthens inner resources contributing to subsequent resilience, whereas need frustration evokes illbeing and increased vulnerabilities for defensiveness and psychopathology. We briefly review recent research indicating how contextual need support and the experience of need satisfaction promote well-being and different growth manifestations (e.g., intrinsic motivation, internalization), as well as a rapidly growing body of work relating need thwarting and need frustration to ill-being, pursuit of need substitutes, and various forms of maladaptive functioning. Finally, we discuss research on differences in autonomous self-regulation and mindfulness, which serve as factors of resilience. © 2013 American Psychological Association.

Alonso M.A.,University of Rochester | Bandres M.A.,National Institute of Astrophysics, Optics and Electronics
Optics Express | Year: 2014

Accelerating beams are wave packets that preserve their shape while propagating along curved trajectories. Recent constructions of nonparaxial accelerating beams cannot span more than a semicircle. Here, we present a ray based analysis for nonparaxial accelerating fields and pulses in two dimensions. We also develop a simple geometric procedure for finding mirror shapes that convert collimated fields or fields emanating from a point source into accelerating fields tracing circular caustics that extend well beyond a semicircle. © 2014 Optical Society of America.

Randall T.D.,University of Rochester
Advances in Immunology | Year: 2010

Bronchus-associated lymphoid tissue (BALT) is a constitutive mucosal lymphoid tissue adjacent to major airways in some mammalian species, including rats and rabbits, but not humans or mice. A related tissue, inducible BALT (iBALT), is an ectopic lymphoid tissue that is formed upon inflammation or infection in both mice and humans and can be found throughout the lung. Both BALT and iBALT acquire antigens from the airways and initiate local immune responses and maintain memory cells in the lungs. Here, we discuss the development and function of BALT and iBALT in the context of pulmonary immunity to infectious agents, tumors, and allergens as well as autoimmunity and inflammatory diseases of the lung. © 2010 Elsevier Inc.

Jones W.D.,University of Rochester
Topics in Current Chemistry | Year: 2014

Organometallic compounds have been found to be of use in cleaving C–C bonds, as strong metal–carbon bonds can be formed to replace the bond that is broken. Studies of the mechanism of C–C cleavage can provide insight into how these bonds can be cleaved, and can give valuable information that can be used to develop new strategies for breaking C–C bonds and using the products in catalysis. In this chapter, we will examine a number of systems where mechanistic information has been obtained in C–C cleavage. ©Springer-Verlag Berlin Heidelberg 2013

Betancourt A.J.,University of Rochester
Journal of Molecular Evolution | Year: 2010

In previous work (Betancourt, Genetics 181:1535, 2009), I propagated three large laboratory populations of an RNA phage (MS2) as they adapted to a controlled laboratory environment. These populations were large enough so that evolution might be expected to be mostly repeatable, but they nevertheless fixed different suites of mutations over the course of the experiment. Here, I investigate one possible explanation for these results: epistasis, in which the effect of a mutation depends on its genetic background, may have prevented populations with different initial substitutions from fixing the same set of subsequent mutations. I show that two mutations that previously occurred in different genetic backgrounds are beneficial on either background. This result suggests that sign epistasis-in which a mutation is beneficial on one background, but deleterious on another-is not the cause of different evolutionary trajectories observed in the Betancourt (2009) experiment. However, they can be explained by either magnitude epistasis-in which mutations have stronger or weaker beneficial effects depending on the background-or by the simultaneous fixation of multiple beneficial mutations. Surprisingly, the large populations of the previous experiment showed less parallel evolution than the small populations of this experiment, which lends support to the fixation of multiple beneficial mutations contributing to the patterns seen in both experiments. © 2010 Springer Science+Business Media, LLC.

Dolgaleva K.,Kings College | Boyd R.W.,University of Ottawa | Boyd R.W.,University of Rochester
Advances in Optics and Photonics | Year: 2012

It is well known that the optical response of a medium depends on the local field acting on an individual emitter rather than on the macroscopic average field in the medium. The local field depends very sensitively on the microcopic environment in an optical medium. It is thus possible to achieve a significant control over the local field by intermixing homogeneous materials on a nanoscale to produce composite optical materials. A combination of local-field effects and nanostructuring provides new degrees of freedom for manipulating the optical properties of photonic materials. Especially interesting opportunities open up in the nonlinear optical regime where the material response depends on the local-field correction as a power law. The goal of this review is to present a conceptual overview of the influence of local-field effects on the optical properties of photonic materials, both homogeneous and composite. We also give a summary of recent achievements in controlling the optical properties by local-field effects and nanostructuring. © 2010 Optical Society of America.

Presgraves D.C.,Harvard University | Presgraves D.C.,University of Rochester
American Naturalist | Year: 2010

Darwin's Origin of Species is often criticized for having little to say about speciation. The complaint focuses in particular on Darwin's supposed failure to explain the evolution of the sterility and inviability of interspecific hybrids. But in his chapter on hybridism, Darwin, working without genetics, got as close to the modern understanding of the evolution of hybrid sterility and inviabilityas might reasonably be expected. In particular, after surveying whatwas then known about interspecific crosses and the resulting hybrids, he established two facts that, while now taken for granted, were at the time radical. First, the sterility barriers between species are neither specially endowed by a creator nor directly favored by natural selection but rather evolve as incidental by-products of interspecific divergence. Second, the sterility of species hybrids results when their development is "disturbed by two organizations having been compounded into one." Bateson, Dobzhansky, and Muller later put Mendelian detail to Darwin's inference that the species-specific factors controlling development (i.e., genes) are sometimes incompatible. In this article, I highlight the major developments in our understanding of these interspecific genetic incompatibilities-from Darwin toMuller to modern theory-and review comparative, genetic, and molecular rules that characterize the evolution of hybrid sterility and inviability. © 2010 by The University of Chicago.

Meiklejohn C.D.,University of Rochester | Tao Y.,Emory University
Trends in Ecology and Evolution | Year: 2010

Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed in the germline, the distribution of genes in the genome, and the evolution of hybrid sterility between species. © 2009 Elsevier Ltd. All rights reserved.

Khorana A.A.,University of Rochester
JNCCN Journal of the National Comprehensive Cancer Network | Year: 2011

The frequency of venous thromboembolism (VTE) is rising in patients with cancer. VTE contributes to mortality and morbidity, but the risk for VTE can vary widely between individual patients. Clinical risk factors for VTE in cancer include primary site of cancer, use of systemic therapy, surgery, and hospitalization. Biomarkers predictive of VTE include platelet and leukocyte counts, hemoglobin, D-dimer, and tissue factor. A recently validated risk model incorporates 5 easily available variables and can be used clinically to identify patients at increased risk of VTE. In high-risk settings, including surgery and hospitalization, thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins has been shown to be safe and effective. Recent studies have also suggested a potential benefit for thromboprophylaxis in the ambulatory setting, although criteria for selecting patients for prophylaxis are not currently well defined. This article focuses on recent and ongoing studies of risk assessment and prophylaxis in patients with cancer. © JNCCN-Journal of the National Comprehensive Cancer Network.

Knox R.S.,University of Rochester
Journal of Biomedical Optics | Year: 2012

After 65 years of increasing scrutiny and application, Theodor Förster's treatment of resonance excitation transfer is widely quoted and has acquired the acronym FRET, in which "F" originally and rather curiously stood for "fluorescence." In this brief and mostly qualitative survey, we review some of its history, mention its important limitations, and relate some personal encounters with Förster. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE).

Miano J.M.,University of Rochester
Journal of Biomedical Research | Year: 2015

Myocardin (MYOCD) is a potent transcriptional coactivator that functions primarily in cardiac muscle and smooth muscle through direct contacts with serum response factor (SRF) over cis elements known as CArG boxes found near a number of genes encoding for contractile, ion channel, cytoskeletal, and calcium handling proteins. Since its discovery more than 10 years ago, new insights have been obtained regarding the diverse isoforms of MYOCD expressed in cells as well as the regulation of MYOCD expression and activity through transcriptional, post-transcriptional, and post-translational processes. Curiously, there are a number of functions associated with MYOCD that appear to be independent of contractile gene expression and the CArG-SRF nucleoprotein complex. Further, perturbations in MYOCD gene expression are associated with an increasing number of diseases including heart failure, cancer, acute vessel disease, and diabetes. This review summarizes the various biological and pathological processes associated with MYOCD and offers perspectives to several challenges and future directions for further study of this formidable transcriptional coactivator. © 2015 by the Journal of Biomedical Research.

DiMasi J.A.,Tufts University | Grabowski H.G.,Duke University | Hansen R.W.,University of Rochester
Journal of Health Economics | Year: 2016

The research and development costs of 106 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per approved new compound is $1395 million (2013 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 10.5% yields a total pre-approval cost estimate of $2588 million (2013 dollars). When compared to the results of the previous study in this series, total capitalized costs were shown to have increased at an annual rate of 8.5% above general price inflation. Adding an estimate of post-approval R&D costs increases the cost estimate to $2870 million (2013 dollars). © 2016 Elsevier B.V.

Francone T.D.,University of Rochester | Champagne B.,Case Western Reserve University
Surgical Clinics of North America | Year: 2013

Total proctocolectomy with ileal pouch anal anastomosis (IPAA) preserves fecal continence as an alternative to permanent end ileostomy in select patients with ulcerative colitis and familial adenomatous polyposis. The procedure is technically demanding, and surgical complications may arise. This article outlines both the early and late complications that can occur after IPAA, as well as the workup and management of these potentially morbid conditions. © 2013 Elsevier Inc.

Hwang J.,Johns Hopkins University | Romanski L.M.,University of Rochester
Journal of Neuroscience | Year: 2015

During communication we combine auditory and visual information. Neurophysiological research in nonhuman primates has shown that single neurons in ventrolateral prefrontal cortex (VLPFC) exhibit multisensory responses to faces and vocalizations presented simultaneously. However, whether VLPFC is also involved in maintaining those communication stimuli in working memory or combining stored information across different modalities is unknown, although its human homolog, the inferior frontal gyrus, is known to be important in integrating verbal information from auditory and visual working memory. To address this question, we recorded from VLPFC while rhesus macaques (Macaca mulatta) performed an audiovisual working memory task. Unlike traditional match-to-sample/ nonmatch-to-sample paradigms, which use unimodal memoranda, our nonmatch-to-sample task used dynamic movies consisting of both facial gestures and the accompanying vocalizations. For the nonmatch conditions, a change in the auditory component (vocalization), the visual component (face), or both components was detected. Our results show that VLPFC neurons are activated by stimulus and task factors: while some neurons simply responded to a particular face or a vocalization regardless of the task period, others exhibited activity patterns typically related to working memory such as sustained delay activity and match enhancement/suppression. In addition, we found neurons that detected the component change during the nonmatch period. Interestingly, some of these neurons were sensitive to the change of both components and therefore combined information from auditory and visual working memory. These results suggest that VLPFC is not only involved in the perceptual processing of faces and vocalizations but also in their mnemonic processing. © 2015 the authors.

Morrell C.N.,University of Rochester
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Our appreciation of the roles that platelets play in vascular biology is constantly expanding. One of the major roles of platelets is in initiating and accelerating immune responses. Platelet transfusion may be associated with adverse inflammatory outcomes manifested as fever, discomfort, tachycardia, and respiratory issues. This may in part be due to immune mediators either expressed by activated platelets or released into the platelet media during platelet storage. This review will highlight some more recent knowledge gained regarding the platelet storage lesion and potential mediators of platelet transfusion reactions.

Bahk S.-W.,University of Rochester
Optics Express | Year: 2011

New algorithms for reconstructing wavefront from slopes data are developed, which exhibit high accuracy over broad spatial-frequency bandwidth. Analyzing wavefront reconstructors in the frequency domain lends new insight into ways to improve frequency response and to understand noise propagation. The mathematical tools required to analyze the frequency domain are first developed for discrete band-limited signals. These tools are shown to improve frequency response in either spatial-or frequency-domain reconstruction algorithms. A new spatial-domain iterative reconstruction algorithm based on the Simpson rule is presented. The local phase estimate is averaged over 8 neighboring points whereas the traditional reconstructors use 4 points. Analytic results and numerical simulations show that the Simpson-rule-based reconstructor provides high accuracy up to 85% of the bandwidth. The previously developed rectangular-geometry band-limited algorithm in frequency domain is adapted to hexagonal geometry, which adds flexibility when applying frequency-domain algorithms. Finally, a generalized analytic expression for error propagation coefficient is found for different reconstructors and compared with numerical simulations. © 2011 Optical Society of America.

Illig K.A.,University of Rochester
Journal of Vascular Surgery | Year: 2010

Transaxillary first rib excision, used for thoracic outlet decompression, requires that the patient be in the lateral decubitus position with the arm elevated. This is traditionally accomplished by a junior resident or medical student holding the arm in the air for the duration of the case. This technical note presents a simplified method of passive arm elevation using orthopedic techniques that provides superb exposure of this area with no appreciable patient morbidity. © 2010 Society for Vascular Surgery.

Olsson P.,Umea University | Teitel S.,University of Rochester
Physical Review Letters | Year: 2012

We consider the rheology of soft-core frictionless disks in two dimensions in the neighborhood of the athermal jamming transition. From numerical simulations of bidisperse, overdamped particles, we argue that the divergence of the viscosity below jamming is characteristic of the hard-core limit, independent of the particular soft-core interaction. We develop a mapping from soft-core to hard-core particles that recovers all the critical behavior found in earlier scaling analyses. Using this mapping we derive a relation that gives the exponent of the nonlinear Herschel-Bulkley rheology above jamming in terms of the exponent of the diverging viscosity below jamming. © 2012 American Physical Society.

Weix D.J.,University of Rochester
Accounts of Chemical Research | Year: 2015

ConspectusCross-electrophile coupling, the cross-coupling of two different electrophiles, avoids the need for preformed carbon nucleophiles, but development of general methods has lagged behind cross-coupling and C-H functionalization. A central reason for this slow development is the challenge of selectively coupling two substrates that are alike in reactivity. This Account describes the discovery of generally cross-selective reactions of aryl halides and acyl halides with alkyl halides, the mechanistic studies that illuminated the underlying principles of these reactions, and the use of these fundamental principles in the rational design of new cross-electrophile coupling reactions.Although the coupling of two different electrophiles under reducing conditions often leads primarily to symmetric dimers, the subtle differences in reactivity of aryl halides and alkyl halides with nickel catalysts allowed for generally cross-selective coupling reactions. These conditions could also be extended to the coupling of acyl halides with alkyl halides. These reactions are exceptionally functional group tolerant and can be assembled on the benchtop.A combination of stoichiometric and catalytic studies on the mechanism of these reactions revealed an unusual radical-chain mechanism and suggests that selectivity arises from (1) the preference of nickel(0) for oxidative addition to aryl halides and acyl halides over alkyl halides and (2) the greater propensity of alkyl halides to form free radicals. Bipyridine-ligated arylnickel intermediates react with alkyl radicals to efficiently form, after reductive elimination, new C-C bonds. Finally, the resulting nickel(I) species is proposed to regenerate an alkyl radical to carry the chain.Examples of new reactions designed using these principles include carbonylative coupling of aryl halides with alkyl halides to form ketones, arylation of epoxides to form β-aryl alcohols, and coupling of benzyl sulfonate esters with aryl halides to form diarylmethanes. Arylnickel(II) intermediates can insert carbon monoxide to form acylnickel(II) intermediates that react with alkyl halides to form ketones, demonstrating the connection between the mechanisms of reactions of aryl halides and acid chlorides with alkyl halides. The low reactivity of epoxides with nickel can be overcome by the use of either titanium or iodide cocatalysis to facilitate radical generation and this can also be extended to enantioselective arylation of meso-epoxides. The high reactivity of benzyl bromide with nickel, which leads to the formation of bibenzyl in attempted reactions with bromobenzene, can be overcome by using a benzyl mesylate along with cobalt phthalocyanine cocatalysis to convert the mesylate into an alkyl radical. © 2015 American Chemical Society.

Lui L.L.,Monash University | Pasternak T.,University of Rochester
Journal of Neurophysiology | Year: 2011

Visually guided behavior often involves decisions that are based on evaluating stimuli in the context of those observed previously. Such decisions are made by monkeys comparing two consecutive stimuli, sample and test, moving in the same or opposite directions. We examined whether responses in the motion processing area MT during the comparison phase of this task (test) are modulated by the direction of the preceding stimulus (sample). This modulation, termed comparison signal, was measured by comparing responses to identical test stimuli on trials when it was preceded by sample moving in the same direction (S-trials) with trials when it was preceded by sample moving in a different direction (D-trials). The test always appeared in the neuron's receptive field (RF), whereas sample could appear in the RF or in the contralateral visual field (remote sample). With sample in-RF, we found three types of modulation carried by different sets of neurons: early suppression on S-trials and late enhancement, one on S-trials, and the other on D-trials. Under these conditions, many neurons with and without comparison effects exhibited significant, choice-related activity. Response modulation was also present following the remote sample, even though the information about its direction could only reach MT indirectly via top-down influences. However, unlike on trials with in-RF sample, these signals were dominated by response suppression, shedding light on the contribution of top-down influences to the comparison effects. These results demonstrate that during the task requiring monkeys to compare two directions of motion, MT responses during the comparison phase of this task reflect similarities and differences between the two stimuli, suggesting participation in sensory comparisons. The nature of these signals provides insights into the operation of bottom-up and top-down influences involved in this process. © 2011 the American Physiological Society.

Zareba W.,University of Rochester
Kidney International | Year: 2015

Initiation of dialysis is associated with increased morbidity and mortality. However, a question could be asked whether these events are caused by initiation of dialysis or whether dialysis serves as a trigger unveiling or worsening underlying preexisting cardiovascular comorbidities that could be pre-treated. © 2015 International Society of Nephrology.

Egea S.C.,University of Miami | Dickerson I.M.,University of Rochester
Endocrinology | Year: 2012

Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling. Copyright © 2012 by The Endocrine Society.

Tilson D.,University of Rochester | Lyytinen K.,Case Western Reserve University | Sorensen C.,The London School of Economics and Political Science
Information Systems Research | Year: 2010

Since the inauguration of information systems research (ISR) two decades ago, the information systems (IS) field's attention has moved beyond administrative systems and individual tools. Millions of users log onto Facebook, download iPhone applications, and use mobile services to create decentralized work organizations. Understanding these new dynamics will necessitate the field paying attention to digital infrastructures as a category of IT artifacts. A state-of-the-art review of the literature reveals a growing interest in digital infrastructures but also confirms that the field has yet to put infrastructure at the centre of its research endeavor. To assist this shift we propose three new directions for IS research: (1) theories of the nature of digital infrastructure as a separate type of IT artifact, sui generis; (2) digital infrastructures as relational constructs shaping all traditional IS research areas; (3) paradoxes of change and control as salient IS phenomena. We conclude with suggestions for how to study longitudinal, large-scale sociotechnical phenomena while striving to remain attentive to the limitations of the traditional categories that have guided IS research. © 2010 INFORMS.

Blackman E.G.,University of Rochester
Astronomische Nachrichten | Year: 2010

The origin of large scale magnetic fields in astrophysical rotators, and the conversion of gravitational energy into radiation near stars and compact objects via accretion have been subjects of active research for a half century. Magnetohydrodynamic turbulence makes both problems highly nonlinear, so both subjects have benefitted from numerical simulations.However, understanding the key principles and practical modeling of observations warrants testable semi-analytic mean field theories that distill the essential physics. Mean field dynamo (MFD) theory and alpha-viscosity accretion disc theory exemplify this pursuit. That the latter is a mean field theory is not always made explicit but the combination of turbulence and global symmetry imply such. The more commonly explicit presentation of assumptions in 20th century textbook MFDT has exposed it to arguably more widespread criticism than incurred by 20th century alpha-accretion theory despite complementary weaknesses. In the 21st century however, MFDT has experienced a breakthrough with a dynamical saturation theory that consistently agrees with simulations. Such has not yet occurred in accretion disc theory, though progress is emerging. Ironically however, for accretion engines, MFDT and accretion theory are presently two artificially uncoupled pieces of what should be a single coupled theory. Large scale fields and accretion flows are dynamically intertwined because large scale fields likely play a key role in angular momentum transport. I discuss and synthesize aspects of recent progress in MFDT and accretion disc theory to suggest why the two likely conspire in a unified theory. © 2010 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim.

Minckley R.L.,University of Rochester
Insect Conservation and Diversity | Year: 2014

Anthropogenic changes to ecosystems typically result in decreased species richness and abundance relative to that of adjacent semi-pristine or pristine areas. Yet, there is debate about the generality of this result for bees given that most studies have included extremely disturbed areas and are from a limited set of biogeographical areas. Repeat sampling of an unusually specialised, species-rich bee community was done in the north-western Chihuahuan Desert, North America at sites in five habitats (riparian, mesquite forest, abandoned field, grassland, and desert scrub) that either had been intensely grazed by cattle in the previous year or not been grazed for 22+ years. Species density and species composition of bees did not change in response to grazing, abundance and proportion of singleton species (those represented by one specimen) did. In all habitats, other than the riparian, there was lower overall abundance and a greater proportion of singleton species at sites that had been recently grazed than at sites that had not been grazed since 1979. The proportion of singletons was greater in recently grazed than in long-term ungrazed areas, but pollen-specialist species did not respond more strongly than pollen generalists. The substantial variation in bee abundance and rarity was probably associated with differences in floral resources. Overall, lower bee abundance in grazed areas reflects the continuous removal by grazers of the flowers that bees use. Despite reduced bee abundance due to long-term grazing, species richness, and composition in this desert bee community remained high. © 2013 The Royal Entomological Society.

Bubar E.J.,University of Rochester | King J.R.,Clemson University
Astronomical Journal | Year: 2010

The concept of kinematic assemblages evolving from dispersed stellar clusters has remained contentious since Eggen's initial formulation of moving groups in the 1960s. With high-quality parallaxes from the Hipparcos space astrometry mission, distance measurements for thousands of nearby, seemingly isolated stars are currently available. With these distances, a high-resolution spectroscopic abundance analysis can be brought to bear on the alleged members of these moving groups. If a structure is a relic of an open cluster, the members can be expected to be monolithic in age and abundance in as much as homogeneity is observed in young open clusters. In this work, we have examined 34 putative members of the proposed Wolf 630 moving group using high-resolution stellar spectroscopy. The stars of the sample have been chemically tagged to determine abundance homogeneity and confirm the existence of a homogeneous subsample of 19 stars. Fitting the homogeneous subsample with Yale-Yonsei isochrones yields a single evolutionary sequence of ∼2.7 ± 0.5 Gyr. It is concluded that this 19 star subsample of the Wolf 630 moving group sample of 34 stars could represent a dispersed cluster with an ([Fe/H]} = -0.01±0.02 and an age of 2.7±0.5 Gyr. In addition, chemical abundances of Na and Al in giants are examined for indications of enhancements as observed in field giants of old open clusters; overexcitation/ionization effects are explored in the cooler dwarfs of the sample; and oxygen is derived from the infrared triplet and the forbidden line at A6300. © 2010. The American Astronomical Society. All rights reserved.

According to the generally accepted theory of mammalian cochlear mechanics, the fluid in the cochlear scalae interacts with the elastic cochlear partition to generate transversely oscillating displacement waves that propagate along the cochlear coil. Using a computational model of cochlear segments, a different type of propagating wave is reported, an elastic propagating wave that is independent of the fluid-structure interaction. The characteristics of the propagating wave observed in the model, such as the wavelength, speed, and phase lag, are similar to those observed in the living cochlea. Three conditions are required for the existence of the elastic propagating wave in the cochlear partition without fluid-interaction: 1), the stiffness gradient of the cochlear partition; 2), the elastic longitudinal coupling; and 3), the Y-shaped structure in the organ of Corti formed by the outer hair cell, the Deiters cell, and the Deiters cell phalangeal process. The elastic propagating waves in the cochlear partition disappeared without the push-pull action provided by the outer hair cell and Deiters cell phalangeal process. The results suggest that the mechanical feedback of outer hair cells, facilitated by the organ of Corti microstructure, can control the tuning and amplification by modulating the cochlear traveling wave. © 2014 The Authors.

Thiele R.G.,University of Rochester
Current Rheumatology Reports | Year: 2011

Imaging of gout with conventional radiography has been described since shortly after roentgenography was invented. Ultrasound (US) detects more erosions than conventional radiography in rheumatoid arthritis, and the same seems to be true for gout. MRI is being used to assess articular and periarticular masses, including gouty tophi. However, MRI findings in gout can lack specificity. Monosodium urate (MSU) tophi are very echogenic when US is used. Typical US features of gout include a double-contour sign or "urate icing." The double-contour consists of the hyperechoic bony contour and a parallel hyperechoic line of MSU crystals that deposit on the hypoechoic or anechoic hyaline cartilage. Tophi can have a "wet clumps of sugar" appearance, often surrounded by an anechoic halo. Tophi are closely related to the formation of erosions. If serum urate levels are lowered consistently below 6.0 mg/dL, the disappearance of MSU crystals can be observed sonographically. © 2011 Springer Science+Business Media, LLC.

Sellix M.T.,University of Rochester
Journal of Biological Rhythms | Year: 2015

Rhythmic events in the female reproductive system depend on the coordinated and synchronized activity of multiple neuroendocrine and endocrine tissues. This coordination is facilitated by the timing of gene expression and cellular physiology at each level of the hypothalamo-pituitary-ovarian (HPO) axis, including the basal hypothalamus and forebrain, the pituitary gland, and the ovary. Central to this pathway is the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) that, through its myriad outputs, provides a temporal framework for gonadotropin release and ovulation. The heart of the timing system, a transcription-based oscillator, imparts SCN pacemaker cells and a company of peripheral tissues with the capacity for daily oscillations of gene expression and cellular physiology. Although the SCN sits comfortably at the helm, peripheral oscillators (such as the ovary) have undefined but potentially critical roles. Each cell type of the ovary, including theca cells, granulosa cells, and oocytes, harbor a molecular clock implicated in the processes of follicular growth, steroid hormone synthesis, and ovulation. The ovarian clock is influenced by the reproductive cycle and diseases that perturb the cycle and/or follicular growth can disrupt the timing of clock gene expression in the ovary. Chronodisruption is known to negatively affect reproductive function and fertility in both rodent models and women exposed to shiftwork schedules. Thus, influencing clock function in the HPO axis with chronobiotics may represent a novel avenue for the treatment of common fertility disorders, particularly those resulting from chronic circadian disruption. © 2014 The Author(s).

Bukata S.V.,University of Rochester
Injury | Year: 2011

Pharmacologic agents that modulate bone formation and bone remodelling are in broad use and development for the treatment of osteoporosis and other disorders of bone fragility. There is significant interest into the effect these agents may have on bone repair and fracture healing and whether these agents may be beneficial or detrimental to bone repair. Bisphosphonates delay callus remodelling, but increased callus volume seen during endochondral bone repair with bisphosphonate use allows for equivalent biomechanical properties for the fractured bone. Teripartide stimulates bone formation and in bone repair appears to have the potential to accelerate fracture callus formation and remodelling, potentially accelerating fracture healing. Animal models of fracture healing have demonstrated accelerated healing with larger callus volume, more rapid remodelling to mature bone, and improved biomechanical properties of the fractured bone. Clinical data with teriparatide has shown mixed results for its ability to stimulate fracture healing. Wnt signalling is one of the major pathways through which cartilage and bone formation is regulated during development. This same pathway has been identified as one of the ways that teriparatide stimulates bone formation. Antibodies to downstream proteins in this pathway, Dkk-1 and sclerostin, show significant promise of accelerating even normal fracture healing in preclinical animal models. © 2011 Elsevier Ltd. All rights reserved.

Shuttleworth T.J.,University of Rochester
Journal of Physiology | Year: 2012

Abstract The field of agonist-activated Ca 2+ entry in non-excitable cells underwent a revolution some 5 years ago with the discovery of the Orai proteins as the essential pore-forming components of the low-conductance, highly Ca 2+-selective CRAC channels whose activation is dependent on depletion of intracellular stores. Mammals possess three distinct Orai proteins (Orai1, 2 and 3) of which Orai3 is unique to this class, apparently evolving from Orai1. However, the sequence of Orai3 shows marked differences from that of Orai1, particularly in those regions of the protein outside of the essential pore-forming domains. Correspondingly, studies from several different groups have indicated that the inclusion of Orai3 is associated with the appearance of conductances that display unique features in their gating, selectivity, regulation and mode of activation. In this Topical Review, these features are discussed with the purpose of proposing that the evolutionary appearance of Orai3 in mammals, and the consequent development of conductances displaying novel properties - whether formed by Orai3 alone or in conjunction with the other Orai proteins - is associated with the specific role of this member of the Orai family in a unique range of distinct cellular activities. © 2012 The Author. The Journal of Physiology © 2012 The Physiological Society.

Treanor J.J.,University of Rochester
American Journal of Preventive Medicine | Year: 2015

The development of vaccines that could provide broad protection against antigenically variant influenza viruses has long been the ultimate prize in influenza research. Recent developments have pushed us closer to this goal, and such vaccines may now be within reach. This brief review outlines the current approaches to broadly protective vaccines, and the probable hurdles and roadblocks to achieving this goal. © 2015 by American Journal of Preventive Medicine and Elsevier Ltd. All rights reserved.

Habenicht B.F.,Oak Ridge National Laboratory | Prezhdo O.V.,University of Rochester
Journal of the American Chemical Society | Year: 2012

Motivated by recent experiments (J. Am. Chem. Soc. 2011, 133, 17156), we used nonadiabatic (NA) molecular dynamics implemented within ab initio time-domain density functional theory to investigate the evolution of the excited electronic singlet and triplet states in the (6,4) carbon nanotube (CNT). The simulation simultaneously included the NA electron-phonon interaction and the spin-orbit (SO) interaction and focused on the intersystem crossing (ISC) from the first excited singlet state (S 1) to the triplet state (T 1) and subsequent relaxation to the ground electronic state (S 0). For the first time, the state-of-the-art methodology (Phys. Rev. Lett. 2005, 95, 163001; Phys. Rev. Lett. 2008, 100, 197402) has been advanced to include triplet states. The S 1-T 1 ISC was calculated to occur within tens of picoseconds, in agreement with the experimental data. This time scale is on the same order as the S 1-S 0 nonradiative decay time obtained previously for the (6,4) CNT. The homogeneous phosphorescence line width, which can be measured in single-molecule experiments, was predicted to be on the order of 10 meV at room temperature. This value is similar to the fluorescence line widths of CNTs suspended in air. The NA electron-phonon and SO couplings were found to be on the order of 1 meV; however, the former fluctuates much more than the latter, causing the ISC rate to be limited by the SO interaction rather than NA interaction. The electronic energy lost nonradiatively during ISC is deposited into high-frequency optical phonons of the CNT arising from C-C stretching motions. The calculations indicate that ISC can contribute to the nonradiative energy losses and low photoluminescence quantum yields observed in semiconducting CNTs. © 2012 American Chemical Society.

Rahman I.,University of Rochester
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Cigarette/tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress are intimately associated with the progression and exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, targeting systemic and local oxidative stress with antioxidants/redox modulating agents, or boosting the endogenous levels of antioxidants are likely to have beneficial effects in the treatment/management of COPD. Various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine), have been reported to modulate various cellular and biochemical aspects of COPD. These antioxidants have been found to scavenge and detoxify free radicals and oxidants, regulate of glutathione biosynthesis, control nuclear factor-kappaB (NF-kappaB) activation, and hence inhibiting inflammatory gene expression. Synthetic molecules, such as specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, iNOS and myeloperoxidase inhibitors, lipid peroxidation inhibitors/blockers edaravone, and lazaroids/tirilazad have also been shown to have beneficial effects by inhibiting cigarette smoke-induced inflammatory responses and other carbonyl/oxidative stress-induced cellular alterations. A variety of oxidants, free radicals, and carbonyls/aldehydes are implicated in the pathogenesis of COPD, it is therefore, possible that therapeutic administration or supplementation of multiple antioxidants and/or boosting the endogenous levels of antioxidants will be beneficial in the treatment of COPD. This review discusses various novel pharmacological approaches adopted to enhance lung antioxidant levels, and various emerging beneficial and/or prophylactic effects of antioxidant therapeutics in halting or intervening the progression of COPD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. © 2011 Elsevier B.V.

Park K.,University of Rochester
Monthly Notices of the Royal Astronomical Society | Year: 2013

To investigate the effect of energy and helicity on the growth of magnetic fields, helical kinetic forcing was applied to a magnetohydrodynamic (MHD) system that had a specific distribution of energy and helicity as initial conditions. Simulation results show that the saturation of a system is not influenced by the initial conditions, but the growth rate of the large-scale magnetic field is proportionally dependent on the initial large-scale magnetic energy and helicity. It is already known that the helical component of a small-scale magnetic field (i.e. current helicity (j. b)) quenches the growth of large-scale magnetic fields. However, (j. b) can also boost the growth of a large-scale magnetic field by changing its sign and magnitude. In addition, the simulation shows that a non-helical magnetic field can suppress the velocity field through the Lorentz force. Comparison of the profiles of evolving magnetic and kinetic energy indicates that the kinetic energy migrates backward when external energy flows into the three-dimensional MHD system, which means that the velocity field may play an important role in the very early MHD dynamo stage. © 2013 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Nordhaus J.,Rochester Institute of Technology | Nordhaus J.,University of Rochester | Spiegel D.S.,Institute for Advanced Study
Monthly Notices of the Royal Astronomical Society | Year: 2013

The ultimate fates of binary companions to stars (including whether the companion survives and the final orbit of the binary) are of interest in light of an increasing number of recently discovered, low-mass companions to white dwarfs (WDs). In this Letter, we study the evolution of a two-body system wherein the orbit adjusts due to structural changes in the primary, dissipation of orbital energy via tides, and mass-loss during the giant phases; previous studies have not incorporated changes in the primary's spin. For companions ranging from Jupiter's mass to ~0.3M and primaries ranging from 1 to 3M, we determine the minimum initial semimajor axis required for the companion to avoid engulfment by the primary during postmain- sequence evolution, and highlight the implications for the ultimate survival of the known exoplanets.We present regions in secondary mass and orbital period space where an engulfed companion might be expected to survive the common envelope phase (CEP), and compare with known M dwarf+WD short-period binaries. Finally, we note that engulfed Earth-like planets cannot survive a CEP. Detection of a first-generation terrestrial planet in the WD habitable zone requires scattering from a several au orbit to a high-eccentricity orbit (with a periastron of ~R) from which it is damped into a circular orbit via tidal friction, possibly rendering it an uninhabitable, charred ember. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Fiscella K.,University of Rochester | Franks P.,University of California at Davis
Annals of Family Medicine | Year: 2010

PURPOSE: Findings are conflicting about the relationship between vitamin D levels and cardiovascular mortality. We wanted to determine the contribution of vitamin D levels to black-white disparities in cardiovascular mortality. METHODS: We examined the association of serum 25(OH)D levels with cardiovascular mortality and its contribution to elevated risk among blacks through a retrospective cohort using baseline data from the third National Health and Nutrition Examination Survey 1988-1994 and cause-specific mortality through 2001 using the National Death Index. Using piecewise Poisson regression models, we examined the risk of cardiovascular death (coronary heart disease, heart failure, and stroke) by sample 25(OH)D quartile, adjusting for cardiovascular risk factors, and compared models of adjusted race-related cardiovascular mortality with and without further adjustment for 25(OH)D levels. RESULTS: Participants with 25(OH)D levels in the lowest quartile (mean = 13.9 ng/mL) compared with those in the 3 higher quartiles (mean = 21.6, 28.4, and 41.6 ng/mL) had higher adjusted risk of cardiovascular death (incident rate ratio [IRR] = 1.40; 95% confidence interval [CI], 1.16 -1.70). The higher age- and sex-adjusted cardiovascular mortality observed in blacks vs whites (IRR = 1.38; 95% CI, 1.13-1.70) was attenuated (IRR = 1.14; 95% CI, 0.91-1.44) by adjustment for 25(OH)D levels and fully eliminated with further adjustment for income (IRR = 1.01; 95% CI, 0.82-1.24). CONCLUSIONS: Low serum levels of 25(OH)D are associated with increased cardiovascular mortality in a nationally representative US sample. Black-white differences in 25(OH)D levels may contribute to excess cardiovascular mortality in blacks. Interventional trials among persons with low vitamin D levels are needed to determine whether oral supplementation improves cardiovascular outcomes.

Balakrishnan L.,University of Rochester | Milavetz B.,University of North Dakota
Critical Reviews in Biochemistry and Molecular Biology | Year: 2010

The molecular biology of histone H4 lysine 20 (H4K20) methylation, like many other post-translational modifications of histones, has been the subject of intensive interest in recent years. While there is an emerging consensus linking H4K20me1, H4K20me2, and H4K20me3 to transcription, repair, and constitutive heterochromatin, respectively, the specific details of these associations and the biological mechanisms by which the methylated histones are introduced and function are now the subject of active investigation. Although a large number of methylases capable of methylating H4K20 have been identified and characterized; there is no known demethylase of H4K20, though the search is ongoing. Additionally, many recent studies have been directed at understanding the role of methylated H4K20 and other histone modifications associated with different biological processes in the context of a combinatorial histone code. It seems likely that continued study of the methylation of H4K20 will yield extremely valuable insights concerning the regulation of histone modifications before and during cell division and the impact of these modifications on subsequent gene expression. © 2010 Informa Healthcare USA, Inc.

Robert J.,University of Rochester
Developmental and Comparative Immunology | Year: 2010

Despite intense study in mammals, the different roles played by the immune system in detecting (immunosurveillance), controlling and remodeling (immunoediting) neoplasia, and perhaps in metastasis are not fully understood. In this review, I will present evidence of neoplasia and invasive malignancy, as well as tumor immunity in invertebrates and nonmammalian vertebrates. I will also present a comparative and evolutionary view of the complex interactions between neoplasia and the host immune system. Overall, I wish to go beyond the too simplistic dichotomy between invertebrates with innate immunity that are only affected with benign neoplasia and vertebrates with adaptive immunity that are affected by metastatic malignancies or cancer. © 2010 Elsevier Ltd.

Fan Q.,University of Rochester
Journal of Mechanical Design, Transactions of the ASME | Year: 2010

Face-hobbing is a continuous generating process employed in manufacturing spiral bevel and hypoid gears. Due to machining dynamics and tolerances of machine tools, the exact tooth surface geometry may not be obtained from the machining process using theoretical machine tool settings. Repeatable tooth surface geometric errors may be observed. The tooth surface errors will cause unfavorable displacement of tooth contact and increased transmission errors, resulting in noisy operation and premature failure due to edge contact and highly concentrated stresses. In order to eliminate the tooth surface errors and ensure precision products, a corrective machine setting technique is employed to modify the theoretical machine tool settings, compensating for the surface errors. This paper describes a method of correcting tooth surface errors for spiral bevel and hypoid gears generated by the face-hobbing process using computer numerically controlled hypoid gear generators. Polynomial representation of the universal motions of machine tool settings is considered. The corrective universal motion coefficients are determined through an optimization process with the target of minimization of the tooth surface errors. The sensitivity of the changes of the tooth surface geometry to the changes of universal motion coefficients is investigated. A numerical example of a face-hobbed hypoid pinion is presented. Copyright © 2010 by ASME.

Katzman P.J.,University of Rochester
Seminars in Perinatology | Year: 2015

The chronic inflammatory lesions of the placenta often run in the shadows of the better-known acute inflammatory processes of the placenta, such as acute chorioamnionitis and acute funisitis. A heterogeneous population of T-cell lymphocytes, plasma cells, and macrophages is the primary player in chronic villitis, chronic chorioamnionitis, chronic deciduitis, and chronic intervillositis, and eosinophils are an added component of eosinophilic/T-cell chorionic vasculitis. The histologic appearance, sites of occurrence in the placenta, and pathogeneses of these entities are reviewed. © 2014 Elsevier Inc.

Calvi L.M.,University of Rochester | Link D.C.,University of Washington
Blood | Year: 2015

The bone marrow microenvironment contains a heterogeneous population of stromal cells organizedintoniches that support hematopoietic stem cells (HSCs) and other lineage-committed hematopoietic progenitors. The stem cell niche generates signals that regulateHSCself-renewal,quiescence, and differentiation. Here, we review recent studies that highlight the heterogeneity of the stromal cells that comprise stem cell niches and the complexity of the signals that they generate. We highlight emerging data that stem cell niches in the bone marrow are not static but instead are responsive to environmental stimuli. Finally,we review recent data showing that hematopoietic niches are altered in certain hematopoietic malignancies, and we discuss how these alterations might contribute to disease pathogenesis. © 2015 by The American Society of Hematology.

Pinquart M.,University of Marburg | Duberstein P.R.,University of Rochester
Critical Reviews in Oncology/Hematology | Year: 2010

This meta-analysis integrates results of 87 studies on the associations of perceived social support, network size, and marital status with cancer survival. In controlled studies, having high levels of perceived social support, larger social network, and being married were associated with decreases in relative risk for mortality of 25%, 20%, and 12%, respectively. Moderator analyses revealed that never married patients had higher mortality rates than widowed and divorced/separated patients. Associations of social network with mortality were stronger in younger patients, and associations of marital status with mortality were stronger in studies with shorter time intervals, and in early-stage cancer. Relationships varied by cancer site, with stronger associations of social support observed in studies of patients with leukemia and lymphomas and stronger associations of network size observed in studies of breast cancer. Further randomized intervention studies are needed to test causal hypotheses about the role of social support and social network for cancer mortality. © 2009 Elsevier Ireland Ltd.

Fehn U.,University of Rochester
Annual Review of Earth and Planetary Sciences | Year: 2012

The two cosmogenic isotopes 129I and 36Cl have half-lives and geochemical characteristics that make their application of interest in the tracing of crustal fluids, oil field brines, and geothermal fluids. The focus of this review is to compare 129I data from volcanic fluids with those from mud volcanoes and gas hydrate locations associated with the same subduction zone in order to demonstrate that fundamentally different hydrologic systems are present in active margins. Whereas 129II ratios in volcanic fluids are site dependent and show a relation to the ages of subducting marine sediments, ratios in fore arc fluids are similar in all sites investigated and are independent of the ages of the host sediments and the age of the subducting slab. Volcanic fluids contain iodine transported in sediments from the trench to the main volcanic zone, whereas iodine in fore arc fluids is derived from organic material stored in the upper plates of subduction zones. © 2012 by Annual Reviews. All rights reserved.

O'Keefe R.J.,University of Rochester | Mao J.,Columbia University
Tissue Engineering - Part B: Reviews | Year: 2011

A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © 2011, Mary Ann Liebert, Inc.

Bowers W.J.,University of Rochester | Breakefield X.O.,Harvard University | Sena-Esteves M.,University of Massachusetts Medical School
Human Molecular Genetics | Year: 2011

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state. © The Author 2011. Published by Oxford University Press. All rights reserved.

Friedman D.I.,University of Rochester
Headache | Year: 2010

Burning mouth syndrome is a chronic pain condition characterized by burning, painful sensations within the oral cavity. A patient developed symptoms of burning mouth syndrome after initiating topiramate treatment for headache prevention. The symptoms resolved when the medication was discontinued, and the association was replicated upon re-challenge of the drug. © 2010 American Headache Society.

Lahiri M.,University of Rochester
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We consider superposition of two states of light polarized along mutually orthogonal directions. We show that partial polarization of the superposed light may be interpreted as a manifestation of the wave-particle duality. © 2011 American Physical Society.

Pinquart M.,University of Marburg | Duberstein P.R.,University of Rochester
Psychological Medicine | Year: 2010

Background The goal of the present study was to analyze associations between depression and mortality of cancer patients and to test whether these associations would vary by study characteristics.Method Meta-analysis was used for integrating the results of 105 samples derived from 76 prospective studies.Results Depression diagnosis and higher levels of depressive symptoms predicted elevated mortality. This was true in studies that assessed depression before cancer diagnosis as well as in studies that assessed depression following cancer diagnosis. Associations between depression and mortality persisted after controlling for confounding medical variables. The depression-mortality association was weaker in studies that had longer intervals between assessments of depression and mortality, in younger samples and in studies that used the Beck Depression Inventory as compared with other depression scales.Conclusions Screening for depression should be routinely conducted in the cancer treatment setting. Referrals to mental health specialists should be considered. Research is needed on whether the treatment of depression could, beyond enhancing quality of life, extend survival of depressed cancer patients. © 2010 Cambridge University Press.

Thakur D.S.,University of Rochester
Finite Fields and their Applications | Year: 2015

We look at two analogs each for the well-known congruences of Fermat and Wilson in the case of polynomials over finite fields. When we look at them modulo higher powers of primes, we find interesting relations linking them together, as well as linking them with derivatives and zeta values. The link with the zeta value carries over to the number field case, with the zeta value at 1 being replaced by Euler's constant. © 2014 Elsevier Inc. All rights reserved.

Powers K.S.,University of Rochester
Pediatrics in Review | Year: 2015

• Maintenance, deficit, and ongoing fluid and electrolyte losses need to be calculated. • Based on strong research evidence, mild-to-moderate isonatremic dehydration can be treated effectively with oral rehydration solutions. (10) • Based on expert opinion, children with moderate-to-severe dehydration should have electrolytes measured to determine content and rate of fluid replacement. • Based on expert consensus opinion, children with altered perfusion should receive immediate fluid bolus(es) with normal saline. • Based on expert opinion and reasoning from first principles, in children with moderate-to-severe isonatremic dehydration, maintenance plus deficit fluid and electrolyte needs generally calculate to be 5% dextrose (D5) 1/3 normal saline (NS) + 40 mEq/L (40 mmol/L) potassium chloride (KCl). Because this is not a readily available fluid, D5 1/2 NS + 40 mEq/L (40 mmol/L) KCl can generally be safely substituted. Maintenance plus deficit volumes can be infused over 24 hours. • Based on expert opinion and reasoning from first principles, children with moderate-to-severe hyponatremic dehydration are most likely to need immediate circulatory support. Fluid and electrolyte maintenance and deficit needs usually calculate to be D5 1/2 NS + 40 mEq/L (40 mmol/L) KCl. Maintenance plus deficit volumes can be infused over 24 hours, with goal correction of sodium not to exceed 12 to 15 mEq/L (12 to 15 mmol/L) over the 24 hours. • Infants with moderate-to-severe hypernatremic dehydration are at highest risk for morbidity and mortality, including risk for cerebral hemorrhage, thrombus, or edema. Their intravascular volume is generally spared. Based on expert opinion and reasoning from first principles, fluid and electrolyte maintenance and deficit needs usually calculate to be D5 1/4 NS + 20 to 40 mEq/L (20 to 40 mmol/L) KCl. Deficit replacement should occur over 48 hours, with goal correction of sodium not to exceed 0.5 mEq/L (0.5 mmol/L) per hour. (15). © 2015, American Academy of Pediatrics. All rights reserved.

Hu S.X.,University of Rochester
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

By solving the three-dimensional, time-dependent Schrödinger equation, we have demonstrated that the ultrafast charge-transfer process in ion-atom collisions can be mapped out with attosecond extreme uv (xuv) pulses. During the dynamic-charge transfer from the target atom to the projectile ion, the electron coherently populates the two sites of both nuclei, which can be viewed as a "short-lived" molecular state. A probing attosecond xuv pulse can instantly unleash the delocalized electron from such a "transient molecule," so that the resulting photoelectron may exhibit a "double-slit" interference. On the contrary, either reduced or no photoelectron interference will occur if the attosecond xuv pulse strikes well before or after the collision. Therefore, by monitoring the photoelectron interference visibility, one can precisely time the ultrafast charge-transfer process in atomic collisions with time-delayed attosecond xuv pulses. © 2011 American Physical Society.

Mamajek E.E.,Cerro Tololo Inter American Observatory | Mamajek E.E.,University of Rochester
Astrophysical Journal Letters | Year: 2012

The nearby (d = 7.7pc) A3V star Fomalhaut is orbited by a resolved dusty debris disk and a controversial candidate extrasolar planet. The commonly cited age for the system (200 ± 100Myr) from Barrado y Navascues et al. relied on a combination of isochronal age plus youth indicators for the K4V common proper-motion system TW PsA. TW PsA is 196 away from Fomalhaut and was first proposed as a companion by Luyten, but the physicality of the binarity is worth testing with modern data. I demonstrate that TW PsA is unequivocally a physical stellar companion to Fomalhaut, with true separation 0.280+0.019 - 0.012pc (57.4+3.9 - 2.5kAU) and sharing velocities within 0.1±0.5kms-1 - consistent with being a bound system. Hence, TW PsA should be considered "FomalhautB." Combining modern H-R diagram constraints with four sets of evolutionary tracks, and assuming the star was born with protosolar composition, I estimate a new isochronal age for Fomalhaut of 450 ± 40Myr and mass of 1.92±0.02 M .Various stellar youth diagnostics are re-examined for TW PsA. The star's rotation, X-ray emission, and Li abundances are consistent with approximate ages of 410, 380, and 360Myr, respectively, yielding a weighted mean age of 400 ± 70Myr. Combining the independent ages, I estimate a mean age for the Fomalhaut-TW PsA binary of 440 ± 40Myr. The older age implies that substellar companions of a given mass are approximately 1mag fainter at IR wavelengths than previously assumed. © 2012. The American Astronomical Society. All rights reserved..

Epstein R.M.,University of Rochester
Patient Education and Counseling | Year: 2013

Objective: To review the theory, research evidence and ethical implications regarding "whole mind" and "shared mind" in clinical practice in the context of chronic and serious illnesses. Methods: Selective critical review of the intersection of classical and naturalistic decision-making theories, cognitive neuroscience, communication research and ethics as they apply to decision-making and autonomy. Results: Decision-making involves analytic thinking as well as affect and intuition (" whole mind") and sharing cognitive and affective schemas of two or more individuals (" shared mind"). Social relationships can help processing of complex information that otherwise would overwhelm individuals' cognitive capacities. Conclusions: Medical decision-making research, teaching and practice should consider both analytic and non-analytic cognitive processes. Further, research should consider that decisions emerge not only from the individual perspectives of patients, their families and clinicians, but also the perspectives that emerge from the interactions among them. Social interactions have the potential to enhance individual autonomy, as well as to promote relational autonomy based on shared frames of reference. Practice implications: Shared mind has the potential to result in wiser decisions, greater autonomy and self-determination; yet, clinicians and patients should be vigilant for the potential of hierarchical relationships to foster coercion or silencing of the patient's voice. © 2012 Elsevier Ireland Ltd.

Moss A.J.,University of Rochester
Circulation Journal | Year: 2010

Electrical device therapy began 50 years ago with the external defibrillator, and was followed subsequently with the introduction of implantable cardiac pacemakers, defibrillators, and resynchronization devices to prevent bradycardia, sudden arrhythmic death, and heart failure. During the past 20 years the Multicenter Automatic Defibrillator Implantation Trial (MADIT) research group has carried out a series of trials, including the MADIT-I, MADIT-II, and MADIT-III (MADIT-CRT), that have focused on improving the outcomes for patients with ischemic and nonischemic cardiac disease. The most recent MADIT-CRT trial showed that a cardiac resynchronization therapy device with defibrillator (CRT-D) was effective in reducing the risk of heart failure or death, whichever came first, in cardiac patients who were asymptomatic or minimally symptomatic (New York Heart Association class I or II) with reduced ejection fraction ≤0.30 and wide QRS complex ≥130 ms when compared with an implantable cardiac defibrillator (ICD) device. The family of MADIT ICD and CRT-D trials have provided a firm foundation for improving the clinical management of at-risk cardiac patients as the second decade of the 21st century begins.

Douglass D.H.,University of Rochester
Journal of Geophysical Research: Atmospheres | Year: 2010

The alternating warm/cold phenomena in the Pacific, known as El Nio-Southern Oscillation (ENSO), is characterized by large perturbations to the worldwide climate. Indices have been defined to characterize this phenomenon. However, the commonly used indices contain an unwanted effect from the annual cycle that can be reduced by digital filtering. Using a filtered ENSO index NL on data from 1856 to the present allows more accurate calculations of various quantities to be made. New results are (1) the distribution of positive values of NL is Gaussian. Thus, large-magnitude El Niño events come from the tail of this distribution and not from some rare external perturbation. (2) The probability of occurrence of an El Niño of any magnitude can be calculated. A 1997-1998 El Niño will occur once in approximately 70 20 years, while an El Nio 25% larger will occur once in approximately 700 200 years. (3) The distribution of negative values of N L deviates from Gaussian because of a deficiency of large La Nia events. (4) Examination of the 20 largest El Nio events since 1856 shows that there is no increase in the frequency of such events with time. Copyright 2010 by the American Geophysical Union.

Katritsis D.G.,Athens Euroclinic | Zareba W.,University of Rochester | Camm A.J.,St Georges, University of London
Journal of the American College of Cardiology | Year: 2012

Nonsustained ventricular tachycardia (NSVT) has been recorded in a wide range of conditions, from apparently healthy individuals to patients with significant heart disease. In the absence of heart disease, the prognostic significance of NSVT is debatable. When detected during exercise, and especially at recovery, NSVT indicates increased cardiovascular mortality within the next decades. In trained athletes, NSVT is considered benign when suppressed by exercise. In patients with non-ST-segment elevation acute coronary syndrome, NSVT occurring beyond 48 h after admission indicates an increased risk of cardiac and sudden death, especially when associated with myocardial ischemia. In acute myocardial infarction, in-hospital NSVT has an adverse prognostic significance when detected beyond the first 13 to 24 h. In patients with prior myocardial infarction treated with reperfusion and beta-blockers, NSVT is not an independent predictor of long-term mortality when other covariates such as left ventricular ejection fraction are taken into account. In patients with hypertrophic cardiomyopathy, and most probably genetic channelopathies, NSVT carries prognostic significance, whereas its independent prognostic ability in ischemic heart failure and dilated cardiomyopathy has not been established. The management of patients with NSVT is aimed at treating the underlying heart disease. © 2012 American College of Cardiology Foundation.

McCamant D.W.,University of Rochester
Journal of Physical Chemistry B | Year: 2011

This work presents a theoretical treatment of the vibrational line shape generated in a femtosecond stimulated Raman spectroscopy (FSRS) experiment under conditions in which the probed vibration undergoes a significant frequency shift during its free induction decay. This theory is applied to simulate the FSRS lineshapes previously observed in rhodopsin (Kukura et al. Science2005, 310, 1006). The previously determined relaxation times for formation of the trans-photoproduct of rhodopsin were calculated using an incorrect equation for the time dependence of the observed frequency shifts. Here the data are reanalyzed by calculation of the corrected frequency sweep occurring during the vibrational free induction decay. It is shown that the calculated frequency shifts and general conclusions of the original work are sound but that the coherent vibrational frequency shifts of the C10, C11, and C12 hydrogen-out-of-plane vibrations occur with a 140 fs time constant rather than the previously reported 325 fs time constant. This time constant provides an important constraint for models of the dynamics of the cis to trans isomerization process. © 2011 American Chemical Society.

Andersen J.P.,University of Toronto | Blosnich J.,University of Rochester
PLoS ONE | Year: 2013

Background: Adverse childhood experiences (e.g., physical, sexual and emotional abuse, neglect, exposure to domestic violence, parental discord, familial mental illness, incarceration and substance abuse) constitute a major public health problem in the United States. The Adverse Childhood Experiences (ACE) scale is a standardized measure that captures multiple developmental risk factors beyond sexual, physical and emotional abuse. Lesbian, gay, and bisexual (i.e., sexual minority) individuals may experience disproportionately higher prevalence of adverse childhood experiences. Purpose: To examine, using the ACE scale, prevalence of childhood physical, emotional, and sexual abuse and childhood household dysfunction among sexual minority and heterosexual adults. Methods: Analyses were conducted using a probability-based sample of data pooled from three U.S. states' Behavioral Risk Factor Surveillance System (BRFSS) surveys (Maine, Washington, Wisconsin) that administered the ACE scale and collected information on sexual identity (n = 22,071). Results: Compared with heterosexual respondents, gay/lesbian and bisexual individuals experienced increased odds of six of eight and seven of eight adverse childhood experiences, respectively. Sexual minority persons had higher rates of adverse childhood experiences (IRR = 1.66 gay/lesbian; 1.58 bisexual) compared to their heterosexual peers. Conclusions: Sexual minority individuals have increased exposure to multiple developmental risk factors beyond physical, sexual and emotional abuse. We recommend the use of the Adverse Childhood Experiences scale in future research examining health disparities among this minority population.

Fry J.D.,University of Rochester
Journal of Experimental Biology | Year: 2014

The decaying fruit in which Drosophila melanogaster feed and breed can contain ethanol in concentrations as high as 6-7%. In this cosmopolitan species, populations from temperate regions are consistently more resistant to ethanol poisoning than populations from the tropics, but little is known about the physiological basis of this difference. I show that when exposed to low levels of ethanol vapor, flies from a tropical African population accumulated 2-3 times more internal ethanol than flies from a European population, giving evidence that faster ethanol catabolism by European flies contributes to the resistance difference. Using lines differing only in the origin of their third chromosome, however, I show that faster ethanol elimination cannot fully explain the resistance difference, because relative to African third chromosomes, European third chromosomes confer substantially higher ethanol resistance, while having little effect on internal ethanol concentrations. European third chromosomes also confer higher resistance to acetic acid, a metabolic product of ethanol, than African third chromosomes, suggesting that the higher ethanol resistance conferred by the former might be due to increased resistance to deleterious effects of ethanol-derived acetic acid. In support of this hypothesis, when ethanol catabolism was blocked with an Alcohol dehydrogenase mutant, there was no difference in ethanol resistance between flies with European and African third chromosomes. © 2014. Published by The Company of Biologists Ltd.

Wolf E.,University of Rochester
Optics Communications | Year: 2010

It is shown that the concept of statistical similarity of light vibrations introduced in recent years provides a new insight into the physical meaning of coherence and of polarization of light and reveals a close analogy between the two phenomena. © 2010 Elsevier B.V. All rights reserved.

In the past year there has been remarkable activity and some important success in the development of B cell-targeted therapies for the treatment of systemic lupus erythematosus (SLE). The most promising studies were BLISS-52 and BLISS-76, large phase III studies that demonstrated measurable efficacy for belimumab, a monoclonal antibody against B cell-activating factor (BAFF). The moderate-sized phase IIIII trials EXPLORER and LUNAR that tested rituximab, an anti-CD20 monoclonal antibody, for treatment of non-renal and renal lupus, disappointed many investigators with anecdotal success in refractory patients. These rituximab trials were intended to detect a large clinical effect in patients with very active disease and this was not found. Nevertheless, arguments can be made for additional studies in targeted populations or with a change in design to detect smaller or longer-term effects. Epratuzumab, a monoclonal antibody against the B cell surface antigen CD22, and atacicept, a chimeric molecule formed by a receptor for BAFF and a proliferation-inducing ligand (APRIL) with immunoglobulin (Ig)-G, have both been promising in initial small trials and now larger clinical trials are underway. Thus, recent clinical trial data show that B cell-targeting therapies are beginning to fulfil their promise as treatments for SLE and there are good reasons to hope for further progress in the near future. © 2010 Adis Data Information BV. All rights reserved.

Fischer S.A.,University of Washington | Prezhdo O.V.,University of Rochester
Journal of Physical Chemistry C | Year: 2011

Doping has been critical to the realization of current semiconductor devices, allowing for control and tuning of the electronic properties. Whereas doping is now common in bulk, its extension to spatially confined materials has not been easy. Recently, suitable synthetic methods have been developed, and it has become vital to understand the changes doping affects in spatially confined materials. For this purpose, we performed high-level, ab initio quantum-chemical calculations on small boron- and phosphorusdoped Si clusters, and obtained optical absorption spectra and excited states properties over a broad energy range, including single and multiple excitons. We find that doping blue-shifts the optical absorption spectra and moves the onset of multiexciton configurations to significantly higher energies. The latter factor can be very important in photovoltaic applications. The effect of doping on the cluster properties is similar to that of charging. © 2011 American Chemical Society.

Lam A.P.,Northwestern University | Dean D.A.,University of Rochester
Gene Therapy | Year: 2010

The nuclear envelope represents a key barrier to successful nonviral transfection and gene therapy both in vitro and in vivo. Although the main purpose of the nuclear envelope is to partition the cell to maintain cytoplasmic components in the cytoplasm and nuclear components, most notably genomic DNA, in the nucleus, this function poses a problem for transfections in which exogenous DNA is delivered into the cytoplasm. After delivery to the cytoplasm, nucleic acids rapidly become complexed with cellular proteins that mediate interactions with the cellular machinery for trafficking. Thus, it is these proteins that, in essence, control the nuclear import of DNA, and we must also understand their activities in cells. In this review, we will discuss the principles of nuclear import of proteins and DNA-protein complexes, as well as the various approaches that investigators have used to improve nuclear targeting of plasmids. These approaches include complexation of plasmids with peptides, native and engineered proteins, ligands and polymers, as well as the inclusion of transcription factor-binding sites for general and cell-specific delivery. © 2010 Macmillan Publishers Limited All rights reserved.

Lukishova S.G.,University of Rochester
Molecular Crystals and Liquid Crystals | Year: 2012

This paper describes some of my results on liquid crystal investigations under unconventional, incident light powers: (1) under high-power laser irradiation both in free space and inside laser resonators, and (2) in single-photon source applications for quantum information technology. Several effects under high-power, nanosecond laser irradiation are outlined: athermal helical pitch dilation and unwinding of cholesteric mirrors, showing the limits for using them in laser physics; some pitfalls in measurements of thermal-density refractive nonlinearity and the first observation of thermal lens effects in liquid crystals under several nanosecond, low-pulse-repetition rate (2-10 Hz) laser irradiation in the presence of two-photon absorption; feedback-free kaleidoscope of patterns (hexagons, stripes, etc.) in dye-doped liquid crystals. At the single-photon level, definite linear and circular polarizations of single (antibunched) photons for quantum communications were obtained using single-emitter fluorescence in planar-aligned nematic and cholesteric hosts. Circular polarized cholesteric microcavity resonances were also observed under cw-excitation. In addition, using near-field optical microscopy and AFM, 2D-hexagonal arrays made of cholesteric oligomers were investigated. With progress of this technology, similar arrays can be used for fluorescence control of single emitters. Copyright © 2012 Taylor and Francis Group, LLC.

Aslin R.N.,University of Rochester
Infancy | Year: 2014

Acquiring knowledge about the underlying structures of the environment presents a number of challenges for a naive learner. These challenges include the absence of reinforcement to guide learning, the presence of numerous information sources from which only a select few are relevant, and the uncertainty about when an underlying structure may have undergone a change. A crucial implication of these challenges is that the naive learner must make implicit decisions about when to generalize to novel inputs and when to restrict generalization because there are multiple underlying structures. An historical perspective on these challenges is presented, and some potential solutions are proposed. © International Society on Infant Studies (ISIS).

Biteau B.,University of Rochester | Jasper H.,Buck Institute for Research on Aging
Cell Reports | Year: 2014

In order to maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here, we identify a signal from enteroendocrine cells (EEs) that controls lineage specification in the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2 receptor in intestinal stem cells (ISCs) that limits ISC commitment to theendocrine lineage, establishing negative feedback control of EE regeneration. Furthermore, we show that this lineage decision is made within ISCs and requires induction of the transcription factor Prospero in ISCs. Our work identifies a function for the conserved Slit/Robo pathway in the regulation of adult stem cells, establishing negative feedback control of ISC lineage specification as a critical strategy to preserve tissue homeostasis. Our results further amend the current understanding of cell fate commitment within the Drosophila ISC lineage. © 2014 The Authors.

Krause A.G.,California Institute of Technology | Winger M.,California Institute of Technology | Blasius T.D.,California Institute of Technology | Lin Q.,University of Rochester | Painter O.,California Institute of Technology
Nature Photonics | Year: 2012

The monitoring of acceleration is essential for a variety of applications ranging from inertial navigation to consumer electronics. Typical accelerometer operation involves the sensitive displacement measurement of a flexibly mounted test mass, which can be realized using capacitive, piezo-electric, tunnel-current or optical methods. Although optical detection provides superior displacement resolution, resilience to electromagnetic interference and long-range readout, current optical accelerometers either do not allow for chip-scale integration or utilize relatively bulky test mass sensors of low bandwidth. Here, we demonstrate an optomechanical accelerometer that makes use of ultrasensitive displacement readout using a photonic-crystal nanocavity monolithically integrated with a nanotethered test mass of high mechanical Q-factor. This device achieves an acceleration resolution of 10 μg Hz -1/2 with submilliwatt optical power, bandwidth greater than 20 kHz and a dynamic range of greater than 40 dB. Moreover, the nanogram test masses used here allow for strong optomechanical backaction, setting the stage for a new class of motional sensors. © 2012 Macmillan Publishers Limited. All rights reserved.

Kent O.A.,University of Toronto | McCall M.N.,University of Rochester | Cornish T.C.,Johns Hopkins University | Halushka M.K.,Johns Hopkins University
Nucleic Acids Research | Year: 2014

miR-143 and miR-145 are co-expressed microRNAs (miRNAs) that have been extensively studied as potential tumor suppressors. These miRNAs are highly expressed in the colon and are consistently reported as being downregulated in colorectal and other cancers. Through regulation of multiple targets, they elicit potent effects on cancer cell growth and tumorigenesis. Importantly, a recent discovery demonstrates that miR-143 and miR-145 are not expressed in colonic epithelial cells; rather, these two miRNAs are highly expressed in mesenchymal cells such as fibroblasts and smooth muscle cells. The expression patterns of miR-143 and miR-145 and other miRNAs were initially determined from tissue level data without consideration that multiple different cell types, each with their own unique miRNA expression patterns, make up each tissue. Herein, we discuss the early reports on the identification of dysregulated miR-143 and miR-145 expression in colorectal cancer and how lack of consideration of cellular composition of normal tissue led to the misconception that these miRNAs are downregulated in cancer. We evaluate mechanistic data from miR-143/145 studies in context of their cell type-restricted expression pattern and the potential of these miRNAs to be considered tumor suppressors. Further, we examine other examples of miRNAs being investigated in inappropriate cell types modulating pathways in a non-biological fashion. Our review highlights the importance of determining the cellular expression pattern of each miRNA, so that downstream studies are conducted in the appropriate cell type. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Smolyanskaya A.,Harvard University | Haefner R.M.,University of Rochester | Lomber S.G.,Brain and Mind Institute | Born R.T.,Harvard University
Neuron | Year: 2015

The activity of individual sensory neurons can be predictive of an animal's choices. These decision signals arise from network properties dependent on feedforward and feedback inputs; however, the relative contributions of these inputs are poorly understood. We determined the role of feedforward pathways to decision signals in MT by recording neuronal activity while monkeys performed motion and depth tasks. During each session, we reversibly inactivated V2 and V3, which provide feedforward input to MT that conveys more information about depth than motion. We thus monitored the choice-related activity of the same neuron both before and during V2/V3 inactivation. During inactivation, MT neurons became less predictive of decisions for the depth task but not the motion task, indicating that a feedforward pathway that gives rise to tuning preferences also contributes to decision signals. We show that our data are consistent with V2/V3 input conferring structured noise correlations onto the MT population. © 2015 Elsevier Inc.

Hasan F.M.,University of Virginia | Alsahli M.,University of Toronto | Gerich J.E.,University of Rochester
Diabetes Research and Clinical Practice | Year: 2014

The kidney plays an important role in glucose homeostasis via its production, utilization, and, most importantly, reabsorption of glucose from glomerular filtrate which is largely mediated via the sodium glucose co-transporter 2 (SGLT2). Pharmacological inhibition of SGLT2 increases urinary glucose excretion and decreases plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 represent a novel class of drugs, which has recently become available for treatment of type 2 diabetes. This article summarizes the rationale for use of these agents and reviews available clinical data on their efficacy, safety, and risks/benefits. © 2014 Elsevier Ireland Ltd.

Bulger M.,University of Rochester | Groudine M.,Fred Hutchinson Cancer Research Center
Developmental Biology | Year: 2010

Transcriptional control in mammals and Drosophila is often mediated by regulatory sequences located far from gene promoters. Different classes of such elements - particularly enhancers, but also locus control regions and insulators - have been defined by specific functional assays, although it is not always clear how these assays relate to the function of these elements within their native loci. Recent advances in genomics suggest, however, that such elements are highly abundant within the genome and may represent the primary mechanism by which cell- and developmental-specific gene expression is accomplished. In this review, we discuss the functional parameters of enhancers as defined by specific assays, along with the frequency with which they occur in the genome. In addition, we examine the available evidence for the mechanism by which such elements communicate or interact with the promoters they regulate. © 2010 Elsevier Inc. All rights reserved.

Doom J.R.,University of Minnesota | Cicchetti D.,University of Minnesota | Rogosch F.A.,University of Rochester
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014

Objective: Child maltreatment is associated with dysregulation of stress-mediating systems and an increased risk of mental and physical health problems. Specifically, disruptions in hypothalamic-pituitary-adrenal (HPA) axis regulation have been reported in maltreated children. The current study investigates whether increased cortisol variability is responsible for inconsistent patterns in the literature. Method: This study modeled cortisol activity over 20 weeks in 187 maltreated and 154 nonmaltreated children (mean = 8.4 years, SD = 1.8 years) in order to capture week-to-week cortisol patterns. Maltreatment was assessed through coding of Department of Human Services records. Children attended an after-school program 1 day per week for 20 weeks, where saliva was collected at the same time each day and subsequently assayed for cortisol. Results: Multiple-group growth curves indicated that maltreated and nonmaltreated children differ in longitudinal cortisol patterns. Maltreated children showed higher variance in the initial cortisol levels and slope over time compared to nonmaltreated children, indicating greater between-person variability in the maltreated group. Maltreated children with higher cortisol at the first assessment showed cortisol suppression over time, indicating potential HPA blunting after chronic high cortisol levels. The severity, timing, and number of subtypes of maltreatment predicted individuals' cortisol variability, and both maltreatment status and greater cortisol variability predicted more behavior problems. Conclusion: Interventions for maltreated children may benefit from pre- and post-intervention HPA assessments to determine a component of treatment efficacy. As maltreatment dimensions predicted differential cortisol regulation, assessment of maltreatment experiences is necessary to understand alterations in behavior and HPA regulation post-intervention. © 2014 American Academy of Child and Adolescent Psychiatry.

Glor R.E.,University of Rochester
Annual Review of Ecology, Evolution, and Systematics | Year: 2010

Adaptive radiation is a response to natural selection and ecological opportunity involving diversification of species and associated adaptations. Although evolutionary biologists have long speculated that adaptive radiation is responsible for most of life's diversity, persistent confusion and disagreement over some of its most fundamental questions have prevented it from assuming a central role in explaining the evolution of biological diversity. Today, answers to many of these questions are emerging from a new wave of integrative research that combines phylogenetic trees with a variety of other data and perspectives. In this review, I discuss how modern phylogenetic analyses are central to (a) defining and diagnosing adaptive radiation, (b)identifying the factors underlying the occurrence and scope of adaptive radiation, (c)diagnosing predictable patterns of ecological diversification during adaptive radiation, and (d) reconstructing the history of adaptive radiations. Copyright © 2010 by Annual Reviews. All rights reserved.

Holland P.L.,University of Rochester
Dalton Transactions | Year: 2010

Transition-metal complexes of O2 and N2 play an important role in the environment, chemical industry, and metalloenzymes. This Perspective compares and contrasts the binding modes, reduction levels, and electronic influences on the nature of the bound O2 or N2 group in these complexes. The charge distribution between the metal and the diatomic ligand is variable, and different models for describing the adducts have evolved. In some cases, single resonance structures (e.g. M-superoxide = M-O2 -) are accurate descriptions of the adducts. Recent studies have shown that the magnetic coupling in certain N2 2- complexes differs between resonance forms, and can be used to distinguish experimentally between resonance structures. On the other hand, many O2 and N2 complexes cannot be described well with a simple valence-bond model. Defining the situations where ambiguities occur is a fertile area for continued study. © 2010 The Royal Society of Chemistry.

Presgraves D.C.,University of Rochester
Nature Reviews Genetics | Year: 2010

All plant and animal species arise by speciation ĝ€" the evolutionary splitting of one species into two reproductively incompatible species. But until recently our understanding of the molecular genetic details of speciation was slow in coming and largely limited to Drosophila species. Here, I review progress in determining the molecular identities and evolutionary histories of several new 'speciation genes' that cause hybrid dysfunction between species of yeast, flies, mice and plants. The new work suggests that, surprisingly, the first steps in the evolution of hybrid dysfunction are not necessarily adaptive. © 2010 Macmillan Publishers Limited. All rights reserved.

Miano J.M.,University of Rochester
Laboratory Investigation | Year: 2010

Serum response factor (SRF) is a ubiquitously expressed transcription factor that binds to a DNA cis element known as the CArG box, which is found in the proximal regulatory regions of over 200 experimentally validated target genes. Genetic deletion of SRF is incompatible with life in a variety of animals from different phyla. In mice, loss of SRF throughout the early embryo results in gastrulation defects precluding analyses in individual organ systems. Genetic inactivation studies using conditional or inducible promoters directing the expression of the bacteriophage Cre recombinase have shown a vital role for SRF in such cellular processes as contractility, cell migration, synaptic activity, inflammation, and cell survival. A growing number of experimental and human diseases are associated with changes in SRF expression, suggesting that SRF has a role in the pathogenesis of disease. This review summarizes data from experimental model systems and human pathology where SRF expression is either deliberately or naturally altered. © 2010 USCAP, Inc All rights reserved.

Schlesinger N.,The New School | Thiele R.G.,University of Rochester
Annals of the Rheumatic Diseases | Year: 2010

The characteristic radiographic hallmarks of chronic gouty arthritis are the presence of macroscopic tophi and erosions with overhanging edges and relative preservation of the joint space. In recent years there has been more insight into the processes underlying the development of bone erosions in gouty arthritis. This review discusses the mechanical, pathological, cellular and immunological factors that may have a role in the pathogenesis of bone erosions in gouty arthritis. It highlights the evidence suggesting that monosodium urate crystal deposition is associated with the presence of underlying osteoarthritis and the important role of osteoclasts and the receptor for activation of nuclear factor κ;B (RANK) and RANK ligand (RANK-RANKL) pathway in the pathogenesis of gouty erosions. Gouty arthritis is primarily driven by interleukin 1β (IL-1β). IL-1β has been implicated in bone destruction and erosions in other inflammatory arthridities. Thus, future IL-1 inhibitors may prevent and treat erosion formation due to tophaceous gouty arthritis. This review discusses imaging modalities and highlights ultrasongraphic evidence suggesting a significant relationship between the presence of the gouty tophus and bone erosions as well as the frequent presence of persistent low-grade inflammation in asymptomatic chronic tophaceous gouty arthritis on high-resolution ultrasonography. It is the tophus eroding the underlying bone that is pivotal for the development of bone erosions in gouty arthritis.

Dyche L.,Yeshiva University | Epstein R.M.,University of Rochester
Medical Education | Year: 2011

Context For doctors, curiosity is fundamental to understanding each patient's unique experience of illness, building respectful relationships with patients, deepening self-awareness, supporting clinical reasoning, avoiding premature closure and encouraging lifelong learning. Yet, curiosity has received limited attention in medical education and research, and studies from the fields of cognitive psychology and education suggest that common practices in medical education may inadvertently suppress curiosity. Objectives This study aimed to identify common barriers to and facilitators of curiosity and related habits of mind in the education of doctors. Methods We conducted a theory-driven conceptual exploration and qualitative review of the literature. Results Curiosity is related to inquisitiveness, reflection and mindfulness. Instructional practices can suppress curiosity by confusing haste with efficiency, neglecting negative emotions, promoting overconfidence and using teaching approaches that encourage passive learning. Curiosity tends to flourish in educational environments that promote the student's responsibility for his or her own learning, multiple perspectives and mindful reflection on both the subject and the learning process. Specific educational strategies that can support curiosity in classroom and clinical settings include the mindful pacing of teaching, modelling effective management of emotions, confronting uncertainty and overconfidence, using inquiry-based learning, helping students see familiar situations as novel, simultaneously considering multiple perspectives, and maximising the value of small-group discussions. Instructor attributes that contribute to the development of student curiosity include patience, a habit of inquiry, emotional candour, intellectual humility, transparency and recognition of the benefits to be gained in learning from peers. Conclusions Curiosity, inquisitiveness and related habits of mind can be supported in medical education through specific, evidence-based instructional approaches. Medical educators should balance the teaching of facts, techniques and protocols with approaches that help students cultivate and sustain curiosity and wonder in the context-rich, often ambiguous world of clinical medicine. © Blackwell Publishing Ltd 2011.

Ballatori N.,University of Rochester
Digestive Diseases | Year: 2011

The heteromeric organic solute transporter alpha-beta (Ostα- Ostβ) is expressed at relatively high levels on the basolateral membrane of enterocytes, where it plays a critical role in the intestinal absorption of bile acids and the enterohepatic circulation. However, this transporter is also expressed in nearly all human tissues, including those that are not normally thought to be involved in bile acid homeostasis, indicating that Ostα-Ostβ may have additional roles beyond bile acid transport in these other tissues, or that bile acids and their derivatives are more pervasive than currently envisioned. Emerging data from different laboratories provide support for both of these hypotheses. In particular, recent studies indicate that tissues such as brain and ovary have the capacity to synthesize bile acids or bile acid precursors. In addition, studies examining Ostα-Ostβ substrate specificity have revealed that this transporter can also accept conjugated steroids, including some neurosteroids, and that the transporter is selectively expressed in steroidogenic cells of the brain and adrenal gland, suggesting a novel function for Ostα-Ostβ. The broad tissue expression of Ostα-Ostβ is also consistent with the emerging concept that bile acids and their derivatives act as signaling molecules in diverse tissues. Bile acids activate nuclear receptors such as the farnesoid X receptor (FXR/NR1H4), the pregnane X receptor and the vitamin D receptor, are ligands for a G-protein-coupled bile acid receptor (GPBAR1/TGR5), and can also activate protein kinases A and C as well as mitogen-activated protein kinase pathways. These signaling pathways are present in many tissues and regulate processes such as triglyceride, glucose and energy homeostasis. Note that although FXR and TGR5 are thought to function primarily as bile acid receptors, they are modulated by some other sterols and select lipid metabolites, and are also widely expressed in tissues, indicating a complex interplay among diverse regulatory networks that impact critical cell and organ functions. The present report summarizes the evidence for a pleiotropic role of Ostα-Ostβ in different tissues. Copyright © 2011 S. Karger AG, Basel.

Olsson P.,Umea University | Teitel S.,University of Rochester
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2011

We perform numerical simulations to determine the shear stress and pressure of steady-state shear flow in a soft-disk model in two dimensions at zero temperature in the vicinity of the jamming transition Ï•J. We use critical point scaling analyses to determine the critical behavior at jamming, and we find that it is crucial to include corrections to scaling for a reliable analysis. We find that the relative size of these corrections are much smaller for pressure than for shear stress. We furthermore find a superlinear behavior for pressure and shear stress above Ï•J, both from the scaling analysis and from a direct analysis of pressure data extrapolated to the limit of vanishing shear rate. © 2011 American Physical Society.

O'Donnell K.J.,McGill University | Glover V.,Imperial College London | Barker E.D.,Birkbeck, University of London | O'Connor T.G.,University of Rochester
Development and Psychopathology | Year: 2014

Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre-and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis. Copyright © 2014 Cambridge University Press.

Hu S.X.,University of Rochester
Physical Review Letters | Year: 2013

Electron correlation plays an essential role in a wide range of fundamentally important many-body phenomena in modern physics and chemistry. An example is the importance of electron-electron correlation in multiple ionization of multielectron atoms and molecules exposed to intense laser pulses. Manipulating the dynamic electron correlation in such photoinduced processes is a crucial step toward the coherent control of chemical reactions and photobiological processes. The generation of an attosecond extreme ultraviolet (EUV) pulse may enable such controls. Here, we show for the first time, from full-dimensional ab initio calculations of double ionization of helium in intense laser pulses (λ=780 nm), that the electron-electron interactions can be instantaneously tuned using a time-delayed attosecond EUV pulse. Consequently, the probability of producing energetic electrons from excessive photoabsorption can be enhanced by an order of magnitude, by the attosecond control of electron-electron correlation. © 2013 American Physical Society.

Khorana A.A.,University of Rochester
American Journal of Hematology | Year: 2012

Thromboembolism, including both venous and arterial events, occurs commonly amongst patients with cancer. The occurrence of thromboembolism has significant consequences for cancer patients, including direct and indirect associations with mortality, morbidity, requirement for long-term anticoagulant therapy and consumption of healthcare resources. Recent studies have resulted in a better understanding of clinical risk factors and biomarkers of cancer-associated thrombosis, and a risk assessment model incorporating both has now been validated in multiple settings. Thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins (LMWHs) has been shown to be safe and effective in high-risk settings such as hospitalization for medical illness and the postsurgical period. Emerging new data from randomized studies have focused on outpatient prophylaxis, suggesting potential benefits in this setting as well. Treatment of cancer-associated thrombosis requires long-term anticoagulation with LMWH. Results from ongoing and planned trials of novel anticoagulants in the cancer setting are awaited. © 2012 Wiley Periodicals, Inc.

Luhman K.L.,Pennsylvania State University | Mamajek E.E.,Cerro Tololo Inter American Observatory | Mamajek E.E.,University of Rochester
Astrophysical Journal | Year: 2012

We present photometry at 3-24 μm for all known members of the Upper Scorpius association (τ ∼ 11 Myr) based on all images of these objects obtained with the Spitzer Space Telescope and the Wide-field Infrared Survey Explorer. We have used these data to identify the members that exhibit excess emission from circumstellar disks and estimate the evolutionary stages of these disks. Through this analysis, we have found ∼50 new candidates for transitional, evolved, and debris disks. The fraction of members harboring inner primordial disks is ≲ 10% for B-G stars (M > 1.2 M ⊙) and increases with later types to a value of ∼25% at ≳M5 (M ≲ 0.2 ≲ M Odot;), in agreement with the results of previous disk surveys of smaller samples of Upper Sco members. These data indicate that the lifetimes of disks are longer at lower stellar masses and that a significant fraction of disks of low-mass stars survive for at least ∼10 Myr. Finally, we demonstrate that the distribution of excess sizes in Upper Sco and the much younger Taurus star-forming region (τ ∼ 1 Myr) is consistent with the same, brief timescale for clearing of inner disks. © 2012. The American Astronomical Society. All rights reserved.

The aim was to systematically review genetic testing guidelines in the evaluation of children with autism spectrum disorders (ASDs). The Clinical Report published by the American Academy of Pediatrics (AAP) 1 recommended individualizing the workup, including karyotype and specific DNA testing for fragile X syndrome. A recent publication reported higher rates of abnormalities on CGH microarray (CMA) testing on children with ASD. 2 The medical records of 507 children seen through the Kirch Developmental Services Center were abstracted for genetic testing and factors associated with this testing. Abnormalities were found on karyotype in 2.3% and in DNA for fragile X in 0.04%. The author concludes that the diagnostic yield of the genetic testing was low in this population. Furthermore, their findings support the theory that CMA can be considered as part of the initial genetic screening in children with ASD in most situations. Future studies will need to be done prospectively to evaluate children in a standard fashion. © The Author(s) 2011.

Zhu A.X.,Harvard University | Hezel A.F.,University of Rochester
Hepatology | Year: 2011

Biliary tract cancers (BTCs), which encompass intra- and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic chemotherapy approaches are emerging, the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early-stage clinical trials with targeted therapies appear promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here we summarize the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC. © 2010 American Association for the Study of Liver Diseases.

Kenworthy M.A.,Leiden University | Mamajek E.E.,University of Rochester
Astrophysical Journal | Year: 2015

The light curve of 1SWASP J140747.93-394542.6, a 16 Myr old star in the Sco-Cen OB association, underwent a complex series of deep eclipses that lasted 56 days, centered on 2007 April. This light curve is interpreted as the transit of a giant ring system that is filling up a fraction of the Hill sphere of an unseen secondary companion, J1407b. We fit the light curve with a model of an azimuthally symmetric ring system, including spatial scales down to the temporal limit set by the star's diameter and relative velocity. The best ring model has 37 rings and extends out to a radius of 0.6 AU (9 × 107 km), and the rings have an estimated total mass on the order of 100 M Moon. The ring system has one clearly defined gap at 0.4 AU (6.1 × 107 km), which, we hypothesize, is being cleared out by a <0.8 M ⊕ exosatellite orbiting around J1407b. This eclipse and model imply that we are seeing a circumplanetary disk undergoing a dynamic transition to an exosatellite-sculpted ring structure, which is one of the first seen outside our solar system. © 2015. The American Astronomical Society. All rights reserved.

Hofmann A.P.,Queens University | Gerber S.A.,University of Rochester | Croy B.A.,Queens University
Molecular Human Reproduction | Year: 2014

Pregnancy involves progressive relationship changes between conceptus-derived trophoblasts and maternal decidual vessels and leukocytes. Uterine natural killer (uNK) cells, the dominant leukocytes in early human and mouse decidua, have late gestational cardio-protective roles through mid-gestational initiation of decidual spiral arterial modification. The earlier gestational functions of uNK cells are unknown. Comparisons of gestation days (GD) 6.5-9.5 implant sites from allogeneically mated alymphoid or normal BALB/c mice (Rag2-/-Il2rg-/-; NK-T-B- versus +/+) by whole mount immunohistochemistry revealed delays in Rag2-/-Il2rg-/- uterine lumen closure, trophoblast invasion and conceptus development. Also delayed were onset of mesometrial angiogenesis and pruning of neo-vascular networks in decidua basalis. This phenotype was fully reversed in BALB/c-Rag2-/-Il2rg-/- pregnancies that followed adoptive Rag2-/- (NK+B-T-) marrow transfer. These data suggest that uNK cells coordinate GD-appropriate phases of decidual angiogenesis, which in turn paces progressive changes in early implant sites that support normal fetal growth. Similar roles for human CD56bright decidual NK cells could explain the importance of CD56bright decidual NK cell activation to pregnancy success. © The Author 2013.

Senior A.E.,University of Rochester
The Journal of biological chemistry | Year: 2012

In this article, I reflect on research on two ATPases. The first is F(1)F(0)-ATPase, also known as ATP synthase. It is the terminal enzyme in oxidative phosphorylation and famous as a nanomotor. Early work on mitochondrial enzyme involved purification in large amount, followed by deduction of subunit composition and stoichiometry and determination of molecular sizes of holoenzyme and individual subunits. Later work on Escherichia coli enzyme utilized mutagenesis and optical probes to reveal the molecular mechanism of ATP hydrolysis and detailed facets of catalysis. The second ATPase is P-glycoprotein, which confers multidrug resistance, notably to anticancer drugs, in mammalian cells. Purification of the protein in large quantity allowed detailed characterization of catalysis, formulation of an alternating sites mechanism, and recently, advances in structural characterization.

This paper reviews the development of therapy for acute myelogenous leukemia that in 1973 led to the regimen of 7. days of continuous intravenous arabinosylcytosine (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given the nickname "7. +. 3." The state of leukemia treatment in the 1950s, 1960s and early 1970s is reviewed, the discovery of the two drugs in question described, and the introduction of clinical trials to reach an optimal regimen for their use delineated. During the 1950s, following World War Two and after a period of civil reconstitution, a national effort, facilitated by the U.S. Congress and federal investments in the National Cancer Institute, was initiated to enhance cancer therapy in the United States. The development of mouse models of leukemia and advances in understanding the structure and function of DNA and RNA and the process of cell proliferation provided new targets for drug development and new concepts for their use. The year, 2013, marks the 40th year that this protocol, 7. +. 3, is the method of induction of remission for most patients with acute myelogenous leukemia. Its inadequacies also are made clear. Many patients with the disease die soon after diagnosis, and patients who have more unfavorable oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance to therapy make up the vast majority of the affected and few are cured. It is evident to all that new paradigms are needed if acute myelogenous leukemia is to be subdued in most patients with the disease. © 2012 Elsevier Inc.

Miller B.L.,University of Rochester
Topics in Current Chemistry | Year: 2012

Nucleic acids were one of the first biological targets explored with DCC, and research into the application has continued to yield novel and useful structures for sequence- and structure-selective recognition of oligonucleotides. This chapter reviews major developments in DNA- and RNA-targeted DCC, including methods under development for the conversion of DCC-derived lead compounds into probe molecules suitable for studies in vitro and in vivo. Innovative applications of DCC for the discovery of new materials based on nucleic acids and new methods for the modification of nucleic acid structure and function are also discussed. © 2011 Springer-Verlag Berlin Heidelberg.

Ketz J.,University of Rochester | Sanders R.,Florida Orthopaedic Institute
Journal of Orthopaedic Trauma | Year: 2012

OBJECTIVE: Obtaining an accurate reduction of the posterior malleolar fragment in high-energy pilon fractures can be difficult through standard anterior or medial incisions, resulting in a less than optimal articular reduction. The purpose of this study was to report on our results using a direct approach with posterior malleolar plating in combination with staged anterior fixation in high-energy pilon fractures. DESIGN: Prospective clinical cohort. SETTING: A Level I trauma and tertiary referral center. PATIENTS/PARTICIPANTS: From January 1, 2005, to December 31, 2008, 19 Orthopaedic Trauma Association 43C pilon fractures (16 C3 and 3 C2) with a separate, displaced, posterior malleolar fragment were treated by the authors. Nine patients were treated with posterior plating of the tibia (PL) through a posterolateral approach followed by a staged direct anterior approach. Ten patients with similar fracture patterns were treated using standard anterior or anteromedial incisions (A) with indirect reduction of the posterior fragment. All 19 patients were available for follow-up at an average of 40 months (range, 28-54 months). INTERVENTION: All patients were treated with open reduction and internal fixation for their pilon fractures. MAIN OUTCOME MEASUREMENTS: Quality of reduction was assessed using postoperative plain radiographs and computed tomography. Serial radiographs were taken during the postoperative course to assess the progression of healing and the development of joint arthrosis. Clinical follow-up included physical examination and evaluation of the ankle using the American Orthopaedic Foot and Ankle Society Ankle & Hindfoot score, Maryland Foot Score as well as noting all complications. RESULTS: There were no differences in injury pattern or time to surgery between groups. Of the 10 patients who were in the A group, 4 (40%) had more than 2 mm of joint incongruity at the posterior articular fracture edge as compared with no patients in the PL group as measured on postoperative computed tomography scans. At latest follow-up, 7 (70%) patients in the A group had radiographic evidence of joint space narrowing compared with 3 (33%) in the PL group. Ankle range of motion for the A group was 35.8°versus 34.2 for the PL group (nonsignificant). There were 2 delayed wound healing complications in the A group with one deep infection in the PL group. Two patients in the A group required arthrodesis procedures resulting from posttraumatic arthrosis compared with none in the PL group. No significant difference was seen in postoperative complications across both groups. The average Maryland Foot Score and American Orthopaedic Foot and Ankle Society/Ankle & Hindfoot score for the PL group was 86.4/85.2 compared with 69.4/76.4 for the A group. CONCLUSIONS: The addition of a posterior lateral approach offers direct visualization for reduction of the posterior distal fragment of the tibial pilon. Although the joint surface itself cannot be visualized, this reduction allows the anterior components to be secured to a stable posterior fragment at a later date. This technique improved our ability to subsequently obtain an anatomic articular reduction based on computed tomography scans and preservation of the tibiotalar joint space at a minimum 1-year follow-up. Furthermore, it correlated with an improvement in clinical outcomes with increases in Maryland Foot Score and Ankle & Hindfoot score for the posterior plating group. Although promising, continued follow-up will be needed to determine the long-term outcome using this technique for treating tibial pilon fractures. Copyright © 2012 by Lippincott Williams &Wilkins.

Florian Jaeger T.,University of Rochester
Cognitive Psychology | Year: 2010

A principle of efficient language production based on information theoretic considerations is proposed: Uniform Information Density predicts that language production is affected by a preference to distribute information uniformly across the linguistic signal. This prediction is tested against data from syntactic reduction. A single multilevel logit model analysis of naturally distributed data from a corpus of spontaneous speech is used to assess the effect of information density on complementizer that-mentioning, while simultaneously evaluating the predictions of several influential alternative accounts: availability, ambiguity avoidance, and dependency processing accounts. Information density emerges as an important predictor of speakers' preferences during production. As information is defined in terms of probabilities, it follows that production is probability-sensitive, in that speakers' preferences are affected by the contextual probability of syntactic structures. The merits of a corpus-based approach to the study of language production are discussed as well. © 2010 Elsevier Inc. All rights reserved.

Parker K.J.,University of Rochester
Physics in Medicine and Biology | Year: 2014

A number of advances, including imaging of tissue displacements, have increased our ability to make measurements of tissue elastic properties of animal and human tissues. Accordingly, the question is increasingly asked, 'should our data be fit to a viscoelastic model, and if so which one?' In this paper we focus solely on soft tissues in a functional (non-pathological) state, and develop a model of elastic behavior that is based on the flow of viscous fluids through the extensive network of tissue microchannels in response to applied stress. This behavior can be captured in a 2-parameter model, and the model appears to predict the stress-relaxation behavior and the dispersive shear wave behavior of bovine liver specimens and other soft tissues and phantoms. The relationship of the microchannel flow model to more traditional models is also examined. © 2014 Institute of Physics and Engineering in Medicine.

Mathews D.H.,University of Rochester
Current Protocols in Bioinformatics | Year: 2014

The structures of many non-coding RNA (ncRNA) are conserved by evolution to a greater extent than their sequences. By predicting the conserved structure of two or more homologous sequences, the accuracy of secondary structure prediction can be improved as compared to structure prediction for a single sequence. This unit provides protocols for the use of four programs in the RNAstructure suite for prediction of conserved structures, Multilign, TurboFold, Dynalign, and PARTS. These programs can be run via Web servers, on the command line, or with graphical interfaces. © 2014 by John Wiley & Sons, Inc.

Tieu K.,University of Rochester
Cold Spring Harbor perspectives in medicine | Year: 2011

Parkinson's disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway.

Lawrence B.P.,University of Rochester | Vorderstrasse B.A.,Washington State University
Seminars in Immunopathology | Year: 2013

The host response to infection is known to be influenced by many factors, including genetics, nutritional status, age, as well as drug and chemical exposures. Recent advances reveal that the aryl hydrocarbon receptor (AhR) modulates aspects of the innate and adaptive immune response to viral, bacterial, and parasitic organisms. Although many of these observations were made using the high affinity but poorly metabolized AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), not all of the effects are detrimental to the host. Sometimes AhR activation, even with TCDD, was beneficial and improved host resistance and survival. A similar dichotomy is observed in infected AhR-deficient mice, wherein absence of functional AhR sometimes, but not always, alters host resistance. When examined in their totality, current data indicate that AhR controls multiple regulatory pathways that converge with infection-associated signals and depending on the context (e.g., type of pathogen, site of infection), lead to distinct outcomes. This creates numerous exciting opportunities to harness the immunomodulatory action of AhR to transform host responses to infection. Moreover, since many of the mechanisms cued in response to infectious agents are pivotal in the context of other diseases, there is much to be learned about AhR's cellular targets and molecular mechanisms of action. © 2013 Springer-Verlag Berlin Heidelberg.

Chandra A.,University of Rochester
Journal of Vascular Surgery | Year: 2013

The concurrent problems of research sustainability and decreased clinician involvement with medical device development can be jointly addressed through a novel, multidisciplinary solution. The University of Rochester Cardiovascular Device Design Program is a sustainable program in medical device design supported through a collaboration between the Schools of Medicine and Engineering. This article provides a detailed description of the motivation for starting the program, the current structure of the program, the methods of financial sustainability, and the direct impact it intends to have on the national vascular surgery community. The further expansion of this program and encouragement for development of similar programs throughout the country aims to address many of our current challenges in both research funding and device development education. © 2013 Society for Vascular Surgery.

Wyman P.A.,University of Rochester
American Journal of Preventive Medicine | Year: 2014

The 2012 National Strategy for Suicide Prevention expands the current suicide prevention paradigm by including a strategic direction aimed at promoting healthy populations. Childhood and adolescence are key suicide prevention window periods, yet knowledge of suicide prevention pathways through universal interventions is limited (Aspirational Goal 11). Epidemiologic evidence suggests that prevention programs in normative social systems such as schools are needed for broad suicide prevention impact. Prevention trial results show that current universal prevention programs for children and young adolescents are effective in reducing adolescent emotional and behavioral problems that are risk factors for suicidal behavior, and in the case of the Good Behavior Game, suicide attempts. A developmentally sequenced upstream suicide prevention approach is proposed: (1) childhood programs to strengthen a broad set of self-regulation skills through family and school-based programs, followed by (2) adolescent programs that leverage social influences to prevent emerging risk behaviors such as substance abuse and strengthen relationships and skills. Key knowledge breakthroughs needed are evidence linking specific intervention strategies to reduced suicidal behaviors and mortality and their mechanisms of action. Short- and long-term objectives to achieve these breakthroughs include combining evidence from completed prevention trials, increasing motivators for prevention researchers to assess suicide-related outcome, and conducting new trials of upstream interventions in populations using efficient designs acceptable to communities. In conclusion, effective upstream prevention programs have been identified that modify risk and protective factors for adolescent suicide, and key knowledge breakthroughs can jump-start progress in realizing the suicide prevention potential of specific strategies. © 2014 American Journal of Preventive Medicine.

Choe R.,University of Rochester | Durduran T.,ICFO - Institute of Photonic Sciences
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2012

Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic, and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-the-art diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict, and personalize neoadjuvant breast cancer therapies. © 2012 IEEE.

McNaught K.S.P.,Medical and Scientific Programs | Mink J.W.,University of Rochester
Nature Reviews Neurology | Year: 2011

Tourette syndrome is a hereditary, childhood-onset neurodevelopmental disorder that was first clearly described in France in 1885. This disorder is characterized by sudden, rapid, recurrent, nonrhythmic movements (motor tics) or sounds (vocal or phonic tics), often preceded by premonitory sensations or urges. Some individuals also have psychiatric comorbidities, notably attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Tourette syndrome occurs worldwide, in all races and ethnicities, in both sexes and in children as well as in adults. Estimates of its prevalence in children vary, with rates of up to 1% being reported, but rates of 0.3-0.8% are thought to accurately reflect the occurrence of the disorder. Research has led to progress in many aspects of Tourette syndrome, although many questions and unmet needs remain. For example, except for rare cases, the genetic basis remains elusive. The anatomical and neuronal changes in the brain that underlie Tourette syndrome are also unclear, although the evidence increasingly implicates alterations in basal ganglia function. Treatment is often unnecessary for individuals with mild tics, but for those with moderate to severe forms of the syndrome, some drugs are available, albeit frequently ineffective. Behavioral and surgical therapies, in particular deep brain stimulation, are currently undergoing development and show promising results. This Review examines the history of Tourette syndrome and describes its clinical presentation. The article also provides an overview of the epidemiology and pathophysiology of this disorder. Current treatment strategies and potential future therapies are also discussed. © 2011 Macmillan Publishers Limited. All rights reserved.

Andolina J.R.,University of Rochester | Neudorf S.M.,Childrens Hospital of Orange County | Corey S.J.,Northwestern University
Blood | Year: 2012

Chronic myeloid leukemia (CML) is composed of 3% of pediatric leukemias, making evidence-based recommendations difficult. Imatinib has revolutionized the treatment for adult CML by eliminating allogeneic stem cell transplantation for almost all patients in chronic phase. Shown effective in pediatric CML, imatinib and successive tyrosine kinase inhibitors (TKI) have provided more therapeutic options. Because stem cell transplantation has been better tolerated in children and adolescents, the decision to treat by either TKI or transplantation is controversial. We present a recent case of a 12-month-old boy diagnosed with BCR-ABL + CML to highlight the controversies in treatment recommendations. We review the pediatric stem cell transplantation outcomes as well as the pediatric experience with imatinib and other TKIs. Finally, we compare the side effects as well as costs associated with allogeneic stem cell transplantation versus TKI therapy. We recommend that frontline therapy for pediatric CMLin chronic phase is TKI therapy without transplantation. Patients in accelerated or blast crisis or who fail to reach landmarks on TKIs either because of intolerance or resistance should pursue stem cell transplantation. Although we recommend adopting adult clinical experience to guide therapeutic decisionmaking, the issues of infant CML, drug formulation, pharmacokinetics, and adolescent compliance merit clinical investigation. © 2012 by The American Society of Hematology.

Chaudron L.H.,University of Rochester
American Journal of Psychiatry | Year: 2013

The treatment of depression during pregnancy can be challenging for patients and providers alike. An increasing attention to perinatal mood disorders has led to an expanding literature that is often difficult for providers to navigate. It can be a challenge for providers to feel comfortable reviewing the broad scope of the risks and benefits of treatments in the context of the limitations of the literature. Women who are depressed during pregnancy have been found to have an elevated risk of poor obstetrical outcomes, although studies of the relationship between depression and outcomes are limited. Women who are treated with antidepressants during pregnancy are also at risk for a host of poor obstetrical and fetal outcomes. The risks for these outcomes are often confused by confounding facors and study design limitations. Understanding the current data and their limitations will allow providers to guide their patients in choosing treatment options. Consistent and simple strategies should be used when discussing the risk-benefit analysis with the patient.

Anolik J.H.,University of Rochester
Lupus | Year: 2013

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody- independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence. © The Author(s), 2013. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav.

Parker K.J.,University of Rochester
Journal of the Acoustical Society of America | Year: 2014

Hysteresis is a phenomenon that has been observed across many different materials and situations. Under small-amplitude cyclical motion, classical hysteresis designates a constant loss per cycle over a wide range of frequencies. This is also consistent with an increase in losses or attenuation with frequency that is strictly proportional to the first power of frequency. Unfortunately, the classical (and simple) frequency domain description of hysteresis does not result in a real and causal impulse response, and therefore is not useful for predicting laboratory results. This problem has led to many errors as well as other more fruitful approaches over the years. The frequency domain requirements for hysteresis are re-examined and it is demonstrated that there is a family of solutions that provide real and causal impulse responses over some extended frequency range. The family is conveniently divided into highpass, lowpass, and bandpass causal systems. These are populated by closed form analytical solutions which can be applied to the prediction of motion and waves in hysteretic materials and systems. © 2014 Acoustical Society of America.

Kavey R.-E.W.,University of Rochester
Current Hypertension Reports | Year: 2013

Left ventricular hypertrophy is an independent predictor of cardiovascular morbidity and mortality in adults. In children, the primary correlate of left ventricular mass (LVM) is lean body mass, but fat mass, gender and systolic blood pressure are also contributors. LVM can be estimated from echocardiographic measurements, and by indexing this allometrically to height to the 2.7 power, the left ventricular mass index (LVMI) can be calculated. LVMI optimizes detection of left ventricular hypertrophy with established normal curves for children from birth to 18 years. In children with sustained hypertension, 8-41 % have LVMI above the 95th percentile and in 10-15.5 % of these, LVMI is elevated above levels associated with increased mortality in adults. The presence of obesity is associated with higher LVMI than is found in children with hypertension alone. In children with chronic kidney disease, left ventricular hypertrophy develops relatively early and becomes more prevalent as kidney function decreases. In summary, left ventricular hypertrophy is a sensitive marker of target organ damage in children with BP elevation, obesity and chronic kidney disease providing important management information. © Springer Science+Business Media New York 2013.

Coca A.,University of Rochester | Sanz I.,Emory University
Current Opinion in Rheumatology | Year: 2012

PURPOSE OF REVIEW: Last year was marked by important clinical and mechanistic studies that improved our understanding of B-cell immunotherapy for systemic lupus erythematosus (SLE) and Sjogren's syndrome. Here, we will highlight the most relevant studies published in the last 18 months. RECENT FINDINGS: The highlight of the year was the approval of belimumab on the basis of two major trials. On the flip side, the disappointing results of rituximab in lupus nephritis provided a clinical and mechanistic counterpoint in SLE. Still, major limitations in the LUpus Nephritis Assessment with Rituximab (LUNAR) trial, positive subset analysis and new open studies and registries continue to provide hope for and major insights into the use of B-cell depletion. In Sjogren's syndrome, the role of B-cell depletion has been further investigated, both for glandular and extraglandular manifestations of the disease with mixed results in a disease in which outcomes are notoriously hard to measure. SUMMARY: The approval of anti-B cell activating factor therapy and an increasing body of open studies with rituximab as well as subset studies and secondary analysis of the Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus (EXPLORER) and LUNAR trials provide hope for B-cell immunotherapy and significant insight into its mechanisms of action and utilization in a selected subset of patients. Ongoing clinical trials of other B-cell targeting agents are eagerly anticipated. © Lippincott Williams & Wilkins.

Spyropoulos A.C.,University of Rochester | Douketis J.D.,McMaster University
Blood | Year: 2012

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of highquality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management. © 2012 by The American Society of Hematology.

Khorana A.A.,University of Rochester
Thrombosis Research | Year: 2010

Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. © 2010 Elsevier Ltd. All rights reserved.

Fellinger J.,11 Health | Fellinger J.,Medical University of Vienna | Holzinger D.,11 Health | Holzinger D.,University of Graz | Pollard R.,University of Rochester
The Lancet | Year: 2012

Deafness is a heterogeneous condition with far-reaching effects on social, emotional, and cognitive development. Onset before language has been established happens in about seven per 10 000 people. Increased rates of mental health problems are reported in deaf people. Many regard themselves as members of a cultural minority who use sign language. In this Review, we describe discrepancies between a high burden of common mental health disorders and barriers to health care. About a quarter of deaf individuals have additional disabilities and a high probability of complex mental health needs. Research into factors affecting mental health of deaf children shows that early access to effective communication with family members and peers is desirable. Improved access to health and mental health care can be achieved by provision of specialist services with professionals trained to directly communicate with deaf people and with sign-language interpreters. © 2012 Elsevier Ltd.

Mathews D.H.,University of Rochester
Current Protocols in Bioinformatics | Year: 2014

RNAstructure is a user-friendly program for the prediction and analysis of RNA secondary structure. It is available as a Web server, as a program with a graphical user interface, or as a set of command-line tools. The programs are available for Microsoft Windows, Macintosh OS X, or Linux. This unit provides protocols for RNA secondary structure prediction (using theWeb server or the graphical user interface) and prediction of high-affinity oligonucleotide biding sites to a structured RNA target (using the graphical user interface). © 2014 by John Wiley & Sons, Inc.

Moss W.N.,University of Rochester
Methods in Enzymology | Year: 2013

The purpose of this section is to detail methods for the computational prediction of RNA secondary structure. This protocol is intended to provide an easy entry into the field of RNA structure prediction for those wishing to utilize it in their research and to suggest 'best practices' for going from sequence to secondary structure depending on the available data. © 2013 Elsevier Inc.

Diehl M.M.,University of Puerto Rico at San Juan | Romanski L.M.,University of Rochester
Journal of Neuroscience | Year: 2014

Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. © 2014 the authors.

Bowen W.H.,University of Rochester
Odontology | Year: 2013

The Stephan Curve has played a dominant role in caries research over the past several decades. What is so remarkable about the Stephan Curve is the plethora of interactions it illustrates and yet acid production remains the dominant focus. Using sophisticated technology, it is possible to measure pH changes in plaque; however, these observations may carry a false sense of accuracy. Recent observations have shown that there may be multiple pH values within the plaque matrix, thus emphasizing the importance of the milieu within which acid is formed. Although acid production is indeed the immediate proximate cause of tooth dissolution, the influence of alkali production within plaque has received relative scant attention. Excessive reliance on Stephan Curve leads to describing foods as "safe" if they do not lower the pH below the so-called "critical pH" at which point it is postulated enamel dissolves. Acid production is just one of many biological processes that occur within plaque when exposed to sugar. Exploration of methods to enhance alkali production could produce rich research dividends. © 2012 The Society of The Nippon Dental University.

Dean D.A.,University of Rochester
Journal of Membrane Biology | Year: 2013

The use of electroporation to facilitate gene transfer is an extremely powerful and useful method for both in vitro and in vivo applications. One of its great strengths is that it induces functional destabilization and permeabilization of cell membranes throughout a tissue leading to widespread gene transfer to multiple cells and cell types within the electric field. While this is a strength, it can also be a limitation in terms of cell-specific gene delivery. The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, since ectopic expression of a transgene could lead to deleterious host inflammatory responses or dysregulation of normal cellular functions. At present, there are relatively few ways to obtain cell-specific targeting of nonviral vectors, molecular probes, small molecules, and imaging agents. We have developed a novel means of restricting gene delivery to desired cell types based on the ability to control the transport of plasmids into the nuclei of desired cell types. In this article, we discuss the mechanisms of this approach and several applications in living animals to demonstrate the benefits of the combination of electroporation and selective nuclear import of plasmids for cell-specific gene delivery. © 2013 Springer Science+Business Media New York.

Korshunov V.A.,University of Rochester
Clinical Science | Year: 2012

Axl is a receptor tyrosine kinase that was originally cloned from cancer cells. Axl belongs to the TAM (Tyro3, Axl and Mertk) family of receptor tyrosine kinases. Gas6 (growth-arrest-specific protein 6) is a ligand for Axl. Activation of Axl protects cells from apoptosis, and increases migration, aggregation and growth through multiple downstream pathways. Up-regulation of the Gas6/Axl pathway is more evident in pathological conditions compared with normal physiology. Recent advances in Axl receptor biology are summarized in the present review. The emphasis is given to translational aspects of Axl-dependent signalling under pathological conditions. In particular, inhibition of Axl reduces tumorigenesis and prevents metastasis as well. Axl-dependent signals are important for the progression of cardiovascular diseases. In contrast, deficiency of Axl in innate immune cells contributes to the pathogenesis of autoimmune disorders. Current challenges in Axl biology are related to the functional interactions of Axl with other members of the TAM family or other tyrosine kinases, mechanisms of ligand-independent activation, inactivation of the receptor and cell-cell interactions (with respect to immune cells) in chronic diseases. © The Authors Journal compilation © 2012 Biochemical Society.

Lammers J.C.,University of Rochester
Learning, Media and Technology | Year: 2013

Videogames, such as The Sims, are a digital media passion drawing adolescents to online spaces where they create and share content. This article explores how discourses and expectations are taught in one online, videogame-related fan site of adolescents who read and write Sims fan fiction. Using Bernstein's pedagogic discourse theory, data from a 2-year virtual ethnography are analyzed to study pedagogic interactions between moderators and members within The Sims Writers' Hangout, an online discussion forum. Findings point to the dominance of regulative discourse and how discourses relocated from other media sites serve as pedagogic discourse in this informal digital literacy learning space. This article contributes to our understanding of digital literacy and learning in online environments by focusing on the pedagogy used to teach expectations. The analysis also points to the utility of Bernstein's theory for studying informal online learning. © 2013 Taylor & Francis.

Brown T.M.,University of Rochester | Fee E.,National Library of Medicine
Annual Review of Public Health | Year: 2014

Most public health practitioners know that public health has relied on biomedical advances and administrative improvements, but it is less commonly understood that social movements in health have also been sources of motivation for population health advances. This review considers the impacts of social movements focused on urban conditions and health, on the health of children, and on behavioral and substance-related determinants of health and illustrates how these movements have significantly influenced public health activities and programs. We hope this review will motivate public health workers to make common cause with social activists and to encourage social activists to ally with public health professionals. ©2014 by Annual Reviews. All rights reserved.

Gene expression profiling has had a major impact on our understanding of the biology and heterogeneity of diffuse large B-cell lymphoma (DLBCL). Using this technology, investigators can identify biologic subgroups of DLBCL that provide unique targets for rational therapeutic intervention. This review summarizes these potential targets and updates the progress of clinical development of exciting novel agents for the treatment of DLBCL. Results of ongoing studies suggest that in the near future, we will be able to use gene expression profiling, or an accurate surrogate, to define the best therapeutic approach for individual patients with DLBCL. ©2011 AACR.

Emmert-Streib F.,Center for Cancer Research and Cell Biology | Glazko G.V.,University of Rochester
Wiley Interdisciplinary Reviews: Systems Biology and Medicine | Year: 2011

In this paper we discuss the dualism of gene networks and their role in systems biology. We argue that gene networks (1) can serve as a conceptual framework, forming a fundamental level of a phenomenological description, and (2) are a means to represent and analyze data. The latter point does not only allow a systems analysis but is even amenable for a direct approach to study biological function. Here we focus on the clarity of our main arguments and conceptual meaning of gene networks, rather than the causal inference of gene networks from data. © 2010 John Wiley & Sons, Inc.

Ivanov A.I.,University of Rochester
Advances in experimental medicine and biology | Year: 2012

Intestinal epithelium serves as a key interface between internal body compartments and the gut lumen. The epithelial layer forms a physical barrier that protects the body from the harmful environment of the lumen and also mediates vectorial fluxes of fluids, nutrients and waste. Increased permeability of the epithelial barrier is a common manifestation of different gastrointestinal diseases that enhances body exposure to external pathogens thereby exaggerating mucosal inflammation. Barrier properties of the intestinal epithelium are regulated by specialized adhesive plasma membrane structures known as tight junctions (TJs). It is gengrally believed that disease-related increase in intestinal permeability is caused by defects in TJ structure and functions. This chapter describes the molecular composition of intestinal epithelial TJs, basic mechanisms that regulate TJ functions in healthy gut mucosa as well as molecular events that contribute to increased mucosal permeability during intestinal inflammation. The chapter outlines our current understanding of TJ structure and dynamics and highlights several unresolved questions regarding regulation of this junctional complex under normal conditions and in gastroenterological diseases.

Dickerson I.M.,University of Rochester
Current Protein and Peptide Science | Year: 2013

The receptor for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) requires an intracellular peripheral membrane protein named CGRP-receptor component protein (RCP) for signaling. RCP is required for CGRP and AM receptor signaling, and it has recently been discovered that RCP enables signaling by binding directly to the receptor. RCP is present in most immortalized cell lines, but in vivo RCP expression is limited to specific subsets of cells, usually co-localizing with CGRP-containing neurons. RCP protein expression correlates with CGRP efficacy in vivo, suggesting that RCP regulates CGRP signaling in vivo as it does in cell culture. RCP is usually identified in cytoplasm or membranes of cells, but recently has been observed in nucleus of neurons, suggesting an additional transcriptional role for RCP in cell function. Together, these data support an essential role for RCP in CGRP and AM receptor function, in which RCP expression enhances signaling of the CGRP or AM receptor, and therefore increases the efficacy of CGRP and AM in vivo. © 2013 Bentham Science Publishers.

Internet-mediated research has offered substantial advantages over traditional laboratory-based research in terms of efficiently and affordably allowing for the recruitment of large samples of participants for psychology studies. Core technical, ethical, and methodological issues have been addressed in recent years, but the important issue of participant dropout has received surprisingly little attention. Specifically, web-based psychology studies often involve undergraduates completing lengthy and time-consuming batteries of online personality questionnaires, but no known published studies to date have closely examined the natural course of participant dropout during attempted completion of these studies. The present investigation examined participant dropout among 1,963 undergraduates completing one of six web-based survey studies relatively representative of those conducted in university settings. Results indicated that 10% of participants could be expected to drop out of these studies nearly instantaneously, with an additional 2% dropping out per 100 survey items included in the study. For individual project investigators, these findings hold ramifications for study design considerations, such as conducting a priori power analyses. The present results also have broader ethical implications for understanding and improving voluntary participation in research involving human subjects. Nonetheless, the generalizability of these conclusions may be limited to studies involving similar design or survey content. Copyright 2010, Mary Ann Liebert, Inc.

O'Brien S.R.,University of Rochester
Journal of Neurologic Physical Therapy | Year: 2010

Background and Purpose: The purpose of this systematic review was to examine quality care indicators for inpatient stroke rehabilitation, trends for length of stay (LOS), functional outcomes, and discharge destination. In order to examine the influence of the prospective payment system (PPS), which was instituted in 2002, particular attention was paid to the pre-PPS to post-PPS period. This is the first review of literature to examine the quality of stroke care provided in inpatient rehabilitation facilities in the United States. Methods: A search of Ovid Medline and Ovid Cumulative Index of Nursing and Allied Health databases was performed for articles published between 1990 and 2007. Search terms included treatment outcome, outcome assessment, activities of daily living, exercise, rehabilitation, cerebrovascular accident, LOS, and rehabilitation centers. Results: Twelve articles met the criteria for review. A trend for shorter LOS was evident in the literature up until the time of implementation of PPS. An insufficient amount of literature was available to confirm whether this trend continued after the implantation of PPS. The most recent data indicated that average LOS in inpatient rehabilitation facilities for stroke was <20 days. Functional Independence Measure (FIM) discharge scores remained stable through the 1990s. After the implementation of PPS, discharge FIM scores may be decreasing, but revisions to the FIM tool may confound interpretation of post-PPS findings. Data for discharge to noninstitutional settings after stroke rehabilitation were inconclusive pre-PPS. There may be indications that discharges to institutional settings are increasing post-PPS. Conclusions: The impact of PPS on quality care indicators for inpatient stroke rehabilitation, trends for LOS, and trends for functional outcomes are insufficiently documented in the medical literature. Further research is needed to understand the influence of LOS on functional outcomes and discharge destination. More information is needed on post-PPS outcomes to substantiate the benefit of inpatient rehabilitation for individuals with stroke. Copyright © 2010 Neurology Section, APTA.

Kieburtz K.,University of Rochester
Movement Disorders | Year: 2011

To compare the safety and efficacy of low dosages of pramipexole given twice daily (bid) in early Parkinson's disease (PD) with those of a standard 3 times daily (tid) regimen in a randomized, double-blind, placebo controlled trial involving 311 early PD patients not receiving dopaminergic treatment. Subjects were randomly assigned and followed on assigned treatment for 12 weeks with pramipexole at dosages of 0.5 mg bid, 0.75 mg bid, or 0.5 mg tid, or matching placebo. All subjects were dosed 3 times daily, with placebo if necessary, to maintain blinding. The primary outcome was the change from baseline to Week 12 in the Unified Parkinson Disease Rating Scale (UPDRS) total score (Parts I-III). All active dosages had similar antiparkinson efficacy showing reductions of 4-5 UPDRS points relative to placebo (p < 0.0001) for each comparison. Somnolence, fatigue, nausea, constipation, and peripheral edema were more common in the active treatment groups than in the placebo group, but their frequency did not vary by dosage. In this fixed dosage, randomized study pramipexole administered twice daily at a total daily dosage of 1.0-1.5 mg daily was of comparable efficacy and tolerability to a dosage of 0.5 mg tid over a 12-week treatment period in early PD. © 2010 Movement Disorder Society.

O'Reilly Zwald F.,Emory University | Brown M.,University of Rochester
Journal of the American Academy of Dermatology | Year: 2011

The management of skin cancer in solid organ transplant recipients is a challenge to both the dermatologist and transplant physician. Part II of this continuing medical education review offers an approach to the management of this increasing problem. The importance of specialty dermatology clinics providing access to transplant patients, frequent skin cancer screening, patient education, and multidisciplinary care is discussed. The management of low risk squamous cell carcinoma with topical therapies, photodynamic therapy, systemic retinoids, and capecitabine is reviewed. Revision of immunosuppression in the management of high-risk patients is discussed in association with the potential role of sentinel lymph node biopsy for aggressive disease. Finally, management of in-transit and metastatic squamous cell carcinoma is reviewed, with a discussion of the role of more recent innovative therapies, including epidermal growth factor receptor inhibitors in advanced squamous cell carcinoma in solid organ transplant recipients. © 2010 by the American Academy of Dermatology, Inc.

IMPORTANCE Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials. OBJECTIVE To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS). DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013. EXPOSURE Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion. MAIN OUTCOMES AND MEASURES Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years. RESULTS Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95%CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups. CONCLUSIONS AND RELEVANCE Using these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion. © 2016 American Medical Association.

O'Reilly Zwald F.,Emory University | Brown M.,University of Rochester
Journal of the American Academy of Dermatology | Year: 2011

Skin cancer is the most frequent malignancy in organ transplant recipients, 95% of which are nonmelanoma skin cancer, especially squamous cell and basal cell carcinomas. This paper also discusses the incidence of other tumors (eg, melanoma, Merkel cell carcinoma, and Kaposi sarcoma) that are also increased in organ transplant patients compared to the general population. Part I of this two-part series describes the latest data concerning the epidemiologic and pathogenic aspects of nonmelanoma skin cancer development in solid organ transplant recipients. This review also highlights the concept of "field cancerization," represented by extensive areas of actinic damage and epidermal dysplasia, which accounts for increased risk of aggressive skin cancer development in susceptible patients. © 2010 by the American Academy of Dermatology, Inc.

Parker K.J.,University of Rochester
Journal of the Acoustical Society of America | Year: 2012

A number of imaging systems exhibit speckle, which is caused by the interaction of a coherent pulse reflecting off of random reflectors. The limitations of these systems are quite serious because the speckle phenomenon creates a pattern of nulls and peaks from subresolvable scatterers or targets that are difficult to interpret. Another limitation of these pulse-echo imaging systems is that their resolution is dependent on the full spatial extent of the propagating pulse, usually several wavelengths in the axial or propagating dimension and typically longer in the transverse direction. This limits the spatial resolution to many multiples of the wavelength. This paper focuses on the particular case of ultrasound B-scan imaging and develops an inverse filter solution that eliminates both the speckle phenomenon and the poor resolution dependency on the pulse length and width to produce super-resolution ultrasound (SURUS) images. The key to the inverse filter is the creation of pulse shapes that have stable inverses. This is derived by use of the standard Z-transform and related properties. Although the focus of this paper is on examples from ultrasound imaging systems, the results are applicable to other pulse-echo imaging systems that also can exhibit speckle statistics. © 2012 Acoustical Society of America.

Fienup J.R.,University of Rochester
Applied Optics | Year: 2013

This paper gives the reader a personal tour through the field of phase retrieval and related works that lead up to or cited the paper "Phase Retrieval Algorithms: a Comparison," [Appl. Opt. 21, 2758 (1982)]. © 2012 Optical Society of America.

Khorana A.A.,University of Rochester
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

Emerging data have enhanced our understanding of cancer-associated thrombosis, a major cause of morbidity and mortality in patients with cancer. This update will focus on recent findings, including the phenomenon of incidental venous thromboembolism (VTE), novel approaches to risk assessment, and the results of randomized clinical trials focusing on prophylaxis of cancer outpatients. Incidental VTE is an important contributor to rates of cancer-associated VTE and, in terms of outcomes, appears to be as consequential for patients as symptomatic VTE. Multiple biomarkers have been studied, with the highest level of evidence for prechemotherapy elevated platelet counts, elevated leukocyte counts, and low hemoglobin. Other candidate biomarkers, including D-dimer and tissue factor, are currently being evaluated. A recently validated risk score for chemotherapy-associated VTE has now been evaluated in more than 10 000 cancer patients in a variety of clinical settings and trials and is ready for clinical use (Level 1 clinical decision rule). Several randomized clinical trials in solid-tumor patients with low-molecular-weight heparins and semuloparin, an ultra-low-molecular-weight heparin, demonstrate clearly that outpatient thromboprophylaxis is feasible, safe, and effective. Selecting the appropriate patients for prophylaxis, however, continues to be a matter of controversy.

Dorrer C.,University of Rochester
Journal of Lightwave Technology | Year: 2013

Optical pulse replicators generatemultiple replicas of an optical waveform that are averaged to increase the signal-tonoise ratio of single-shot, high-bandwidth temporal measurements. Processing a replicated waveform requires that the delayed realizations of the waveform under test be retimed properly before averaging. Delay miscalibration significantly reduces the measurement bandwidth. Processing algorithms based on edge alignment, centroid matching, and minimization of the distance between replicas decrease the impact of the detrimental bandwidth reduction, and a global distance minimization, simultaneously taking into account the distance between all pairs of retimed replicas, has the best performance, even in the presence of significant measurement noise. The general impact of chromatic dispersion on the averaged waveformis derived in the framework of the temporal transport-of-intensity equation, and the measurement error is quantified for various optical signals. © 2012 IEEE.

Schoenberg D.R.,Ohio State University | Maquat L.E.,University of Rochester
Nature Reviews Genetics | Year: 2012

Discoveries made over the past 20 years highlight the importance of mRNA decay as a means of modulating gene expression and thereby protein production. Up until recently, studies largely focused on identifying cis-acting sequences that serve as mRNA stability or instability elements, the proteins that bind these elements, how the process of translation influences mRNA decay and the ribonucleases that catalyse decay. Now, current studies have begun to elucidate how the decay process is regulated. This Review examines our current understanding of how mammalian cell mRNA decay is controlled by different signalling pathways and lays out a framework for future research. © 2012 Macmillan Publishers Limited. All rights reserved.

Mink J.W.,University of Rochester
Annals of the New York Academy of Sciences | Year: 2013

A common problem faced by neurologists is the existence of disorders that present with neurological symptoms but do not have identifiable neurological bases. Conversion disorder is the most common of these disorders. In some situations, members of a cohesive social group will develop the same or similar symptoms. This review discusses conversion disorder in children, with an emphasis on function movement disorders. It also reviews a recent occurrence of mass psychogenic illness in New York State with discussion of the key features of mass psychogenic illness. © 2013 New York Academy of Sciences.

Javed F.,Karolinska Institutet | Romanos G.E.,University of Rochester
Journal of Dentistry | Year: 2010

Objectives: To assess the role of primary stability for successful immediate loading (IL) of dental implants. Data: Original articles studying the role of primary stability for successful immediate loading of dental implants were included. The reference lists of potentially relevant review articles were also sought. Sources: The MEDLINE-PubMed databases were searched for appropriate articles addressing the objectives of the present study. Databases were searched from 1979 up to and including April 2010. The search was performed using a variety of keywords in different combinations. Articles published only in English language were included. Letters to the Editor, historical reviews and unpublished articles were not sought. Conclusions: There is a significant biological response by the hard and soft tissues to IL of dental implants. Within the limitations of the present literature review, it is evident that the core issue to observe during IL is the establishment of a good implant primary stability. There is sufficient evidence to suggest that the degree of achieved primary stability during IL protocols is dependent on several factors including bone density and quality, implant shape, design and surface characteristics and surgical technique. Further research is required in situations, such as poor bone quality and quantity and multiple implants or augmentation procedures, which may challenge the attainment of primary stability during IL.

Yang H.,University of Rochester
Angewandte Chemie - International Edition | Year: 2011

The core of the problem: Electrocatalysts need to be highly active and durable under harsh reactive environments in order to meet the requirements for future automotive applications. Platinum-group-metal-based core-shell and core-shell-like nanostructures have great potential in the design of multifunctional catalysts for the oxygen reduction reaction (ORR; see picture). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Yamakuchi M.,University of Rochester
Frontiers in Physiology | Year: 2012

SIRT1 is an NAD-dependent deacetylase that regulates stress response pathways. By deacetylating transcription factors and co-factors, SIRT1 modulates metabolism, inflammation, hypoxic responses, circadian rhythms, cell survival, and longevity. Since SIRT1 plays a key role in regulating pathways involved in cardiovascular diseases and metabolic diseases cancer, the regulation of SIRT1 has received intense scrutiny. The post-transcriptional regulation of SIRT1 is mediated by two classes of molecules, RNA-binding proteins (RBPs) and non-coding small RNAs. MicroRNAs (miRNAs) are short non-coding RNAs that regulate target gene expression in a post-transcriptional manner. More than 16 miRNAs modulate SIRT1 expression, including miR-34a. miR-34a induces colon cancer apoptosis through SIRT1, and miR-34a also promotes senescence in endothelial cells via SIRT1. This review describes the impact of miRNAs on SIRT1. The background of SIRT1 and miRNAs will be summarized, followed by the mechanism by which several key miRNAs alter SIRT1 levels, and how the RBP HuR regulates SIRT1. MicroRNA regulation of SIRT1 might affect a wide variety of pathways in humans, from metabolic diseases such as diabetes to cardiovascular diseases and cancer. © 2012 Yamakuchi.

Objectives - The aim of this study was to evaluate the feasibility of sonography as a tool to measure the hyomental distance ratio and tongue size in obese patients with a large neck circumference. The hyomental distance ratio is a predictor of difficult laryngoscopy that may result in difficult intubation. Methods - Five obese and 7 morbidly obese adult patients with a history of either difficult or easy intubation had a submandibular sonographic examination performed in the supine position. The hyomental distance was measured while the head was placed in the neutral position and then in a hyperextended position, and the ratio of two distances (hyomental distance ratio) was calculated. Their tongue volumes were derived from multiplication of the midsagittal cross-sectional area of the tongue by its width obtained from transverse sonograms. Results - The mean hyomental distance ratios ± SD in 6 patients with difficult intubation and 6 with easy intubation were 1.02 ± 0.01 and 1.14 ± 0.02 (P < .002), respectively. Tongue volumes did not differ statistically between the two groups: 137 ± 29 cm3 (difficult intubation) and 168 ± 34 cm3 (easy intubation). The mean body mass indices were 36.3 ± 6.0 and 43.2 ± 7.2 kg/m2 in the difficult and easy intubation groups. The mean neck circumferences were 44.5 ± 7.4 and 46.8 ± 7.0 cm in the difficult and easy intubation groups. Conclusions - Sonography allows bedside measurements of the hyomental distance ratio and tongue size in morbidly obese patients. Preoperative assessment of the hyomental distance ratio may predict difficult laryngoscopy resulting in difficult intubation. © 2012 by the American Institute of Ultrasound in Medicine.

Gendelman H.E.,85880 Nebraska Medical Center | Gelbard H.A.,University of Rochester
Current Opinion in HIV and AIDS | Year: 2014

Purpose of review We are pleased to review current and future strategies being developed to modulate neuroinflammation while reducing residual viral burden in the central nervous system. This has been realized by targeted longacting antiretroviral nano and adjunctive therapies being developed for HIV-infected people. Our ultimate goal is to eliminate virus from its central nervous system reservoirs and, in so doing, reverse the cognitive and motor dysfunctions. Recent findings Herein, we highlight our laboratories' development of adjunctive and nanomedicine therapies for HIVassociated neurocognitive disorders. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory proinflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HIV-associated neurocognitive disorders. Symptoms, although reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication, inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir-targeted nanoformulated antiretroviral therapy. The translation of these inventions from animals to humans is the focus of this review. Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Hyeon-Deuk K.,Kyoto University | Prezhdo O.V.,University of Rochester
Journal of Physics Condensed Matter | Year: 2012

Photoexcited dynamics of electrons and holes in semiconductor quantum dots (QD), including phonon-induced relaxation, multiple exciton generation, fission and recombination (MEG, MEF and MER), were simulated by combining abinitio time-dependent density functional theory and non-adiabatic molecular dynamics. These nonequilibrium phenomena govern the optical properties and photoexcited dynamics of QDs, determining the branching between electronic processes and thermal energy losses. Our approach accounts for QD size and shape as well as defects, core-shell distribution, surface ligands and charge trapping, which significantly influence the properties of photoexcited QDs. The method creates an explicit time-domain representation of photoinduced processes and describes various kinetic regimes owing to the non-perturbative treatment of quantum dynamics. QDs of different sizes and materials, with and without ligands, are considered. The simulations provide direct evidence that the high-frequency ligand modes on the QD surface play a pivotal role in the electron-phonon relaxation, MEG, MEF and MER. The insights reported here suggest novel routes for controlling the photoinduced processes in semiconductor QDs and lead to new design principles for increasing the efficiencies of photovoltaic devices. © 2012 IOP Publishing Ltd.

Glantz J.C.,University of Rochester
Obstetrics and Gynecology | Year: 2010

Objective: To determine whether changing the definition of the group to which induction is being compared (ie, noninduced delivering during the same week as those induced compared with two definitions of expectant management) changes the association of labor induction and increased cesarean risk. Methods: A New York State birth-certificate database was used to estimate odds ratios for cesarean delivery associated with labor induction at term. The analyses used three definitions of controls: cesarean delivery after induction compared with after spontaneous labor by week (week-to-week), induction at a given gestation age compared with expectant management of all other women after gestational age (all above), or induction at a given gestational age compared with expectant management of all other women at or after that gestational age (at or above). Chi-square logistic regression was used for comparisons and adjustment for possible confounders. Results: All variations of comparison groups were associated with increased unadjusted cesarean risk after induction, although not after 39 weeks in the all-above group. After adjustment, increased risk persisted from 37 to 41 weeks using the week-to-week group and from 38 to 41 weeks in the at-or-above group (odds ratios 1.24 to 1.45) but was no longer significant in the all-above group. The excess cesarean delivery risk associated with labor induction is between 1 and 2 per 25 inductions. CONCLUSION: Labor induction is associated with increased cesarean risk whether using a week-to-week comparison group or an expectant group that includes women the same week or beyond that of the index induction, even after adjustment for parity, high-risk factors, and demographic variables. Although the magnitude of increased risk for a given woman undergoing induction is not large, women nonetheless should be informed of this increased risk. © 2009 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Okishev A.V.,University of Rochester
Optics Letters | Year: 2012

A room-temperature, diode-pumped, pulsed Yb:YAG ceramic free-running laser with a 78% slope efficiency has been demonstrated. It has been shown that fine tuning of the mode diameter to the diameter of the pumped volume with a ratio of the pump to the mode diameter of 0.6 is important for achieving maximum laser efficiency with a Gaussian-like beam profile. A regenerative Yb:YAG ceramic amplifier with a maximum output energy of 14.5 mJ and a super-Gaussian beam profile is demonstrated. © 2012 Optical Society of America.

Cook P.C.,University of Rochester
Pediatric Clinics of North America | Year: 2014

Transient synovitis, septic hip, and Legg-Calvé-Perthes disease are common conditions in children. Distinguishing between these disorders can be a diagnostic challenge. Similar presentations, in an age group difficult to examine, coupled with literature that is confusing creates difficulty. It is important to make the correct diagnosis of septic hip in a timely fashion to avoid serious and potentially crippling consequences. As there is no single test for discriminating between these conditions, knowledge of the nuances of clinical presentation, physical examination, laboratory investigations, and imaging is essential. Judicious use of clinical algorithms can complement clinical acumen. © 2014 Elsevier Inc.

Adler D.H.,University of Rochester
Current HIV research | Year: 2010

PURPOSE OF REVIEW: highly active antiretroviral therapy (HAART) has had an unequivocally positive impact on morbidity and mortality in HIV-infected individuals. These benefits have clearly extended to some HIV-related malignancies, including Kaposi's sarcoma and non-Hodgkin's lymphoma. The impact of HAART on cervical cancer, however, remains uncertain. The objective of this review is to summarize the last ten years of registry-based and clinical research into the impact of HAART on human papillomavirus (HPV) related cervical disease. RELEVANT FINDINGS: compared to their HIV-uninfected counterparts, HIV-infected women have an increased prevalence of HPV infection, increased risk of progression of HPV-related cervical disease, and an increased risk of invasive cervical cancer. While the partial immune reconstitution afforded by HAART might be expected to decrease susceptibility to HPV infection and cervical disease, the local effects of improved immunosurveillance on the cervix are uncertain and the increased longevity of patients on HAART may increase risk of exposure to HPV and provide the time required for progression of cervical disease. Registry-based evidence has been consistent in identifying the lack of decrease in cervical cancer incidence in the HAART era. Clinical research on the subject, however, has produced conflicting evidence with regards to both the effect of HAART on HPV infection and its impact on cervical disease progression/regression. SUMMARY: the incidence of cervical cancer has not decreased in the HAART-era. Furthermore, clinical research has not shown a clear benefit of HAART in decreasing HPV-related cervical disease in HIV-infected women. A better understanding of this subject will have an impact on cervical disease surveillance practices.

Dodds-Ashley E.,University of Rochester
Pharmacotherapy | Year: 2010

Azole antifungal agents are frequently used in hematopoietic stem cell and solid organ transplant recipients for prevention or treatment of invasive fungal infections. However, because of metabolism by or substrate activity for various isoenzymes of the cytochrome P450 system and/or P-glycoprotein, azole antifungals have the potential to interact with many of the drugs commonly used in these patient populations. Thus, to identify drug interactions that may result between azole antifungals and other drugs, we conducted a literature search of the MEDLINE database (1966-December 2009) for English-language articles on drug interaction studies involving the azole antifungal agents fluconazole, itraconazole, voriconazole, and posaconazole. Another literature search between each of the azoles and the immunosuppressants cyclosporine, tacrolimus, and sirolimus, as well as the corticosteroids methylprednisolone, dexamethasone, prednisolone, and prednisone, was also conducted. Concomitant administration of azoles and immunosuppressive agents may cause clinically significant drug interactions resulting in extreme immunosuppression or toxicity. The magnitude and duration of an interaction between azoles and immunosuppressants are not class effects of the azoles, but differ between drug combinations and are subject to interpatient variability. Drug interactions in the transplant recipient receiving azole therapy may also occur with antibiotics, chemotherapeutic agents, and acid-suppressive therapies, among other drugs. Initiation of an azole antifungal in transplant recipients nearly ensures a drug-drug interaction, but often these drugs are required. Management of these interactions first involves knowledge of the potential drug interaction, appropriate dosage adjustments when necessary, and therapeutic or clinical monitoring at an appropriate point in therapy to assess the drug-drug interaction (e.g., immunosuppressive drug concentrations, signs and symptoms of toxicity). These aspects of drug interaction management are essential not only at the initiation of azole antifungal therapy, but also when these agents are removed from the regimen.

Unckless R.L.,University of Rochester
PLoS ONE | Year: 2011

Little is known about the viruses infecting most species. Even in groups as well-studied as Drosophila, only a handful of viruses have been well-characterized. A viral metagenomic approach was used to explore viral diversity in 83 wild-caught Drosophila innubila, a mushroom feeding member of the quinaria group. A single fly that was injected with, and died from, Drosophila C Virus (DCV) was added to the sample as a control. Two-thirds of reads in the infected sample had DCV as the best BLAST hit, suggesting that the protocol developed is highly sensitive. In addition to the DCV hits, several sequences had Oryctes rhinoceros Nudivirus, a double-stranded DNA virus, as a best BLAST hit. The virus associated with these sequences was termed Drosophila innubila Nudivirus (DiNV). PCR screens of natural populations showed that DiNV was both common and widespread taxonomically and geographically. Electron microscopy confirms the presence of virions in fly fecal material similar in structure to other described Nudiviruses. In 2 species, D. innubila and D. falleni, the virus is associated with a severe (~80-90%) loss of fecundity and significantly decreased lifespan. © 2011 Robert L. Unckless.

Petrie R.J.,U.S. National Institutes of Health | Koo H.,U.S. National Institutes of Health | Koo H.,University of Rochester | Koo H.,University of Pennsylvania | Yamada K.M.,U.S. National Institutes of Health
Science | Year: 2014

Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration.

Alonso M.A.,University of Rochester | Bandres M.A.,National Institute of Astrophysics, Optics and Electronics
Optics Letters | Year: 2012

We introduce nonparaxial spatially accelerating waves whose two-dimensional transverse profiles propagate along semicircular trajectories while approximately preserving their shape. We derive these waves by considering imaginary displacements on spherical fields, leading to simple closed-form expressions. The structure of these waves also allows the closed-form description of pulses. © 2012 Optical Society of America.

Rukhlenko I.D.,Monash University | Premaratne M.,Monash University | Agrawal G.P.,University of Rochester
Optics Letters | Year: 2012

We revisit the problem of the optimization of a silicon-nanocrystal (Si-NC) waveguide, aiming to attain the maximum field confinement inside its nonlinear core and to ensure optimal waveguide performance for a given mode power. Using a Si-NC=SiO2 slot waveguide as an example, we show that the common definition of the effective mode area may lead to significant errors in estimation of optical intensity governing the nonlinear optical response and, as a result, to poor strength evaluation of the associated nonlinear effects. A simple and physically meaningful definition of the effective mode area is given to relate the total mode power to the average field intensity inside the nonlinear region and is employed to study the optimal parameters of Si-NC slot waveguides. © 2012 Optical Society of America.

Scott S.,Kings College London | O'Connor T.G.,University of Rochester
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2012

Background: The concept of differential susceptibility has challenged the potential meaning of personal traits such as poor ability to regulate emotions. Under the traditional model of diathesis/stress, personal characteristics such as liability to angry outbursts are seen as essentially disadvantageous, emerging under duress in a way that is maladaptive. In contrast, with differential susceptibility, there is the same poorer functioning under adverse conditions but, under favorable conditions, individuals with the trait function better than those without it. To date, there have been limited studies on response under positive environments. We used the experimental power of an intervention trial to test the differential susceptibility hypothesis that children with emotional dysregulation would show greater response to an experimentally induced improvement in their parenting environment. Methods: Data were from the SPOKES trial (ISRCTN 77566446), a randomized controlled trial of 112 school children who were 5-6-years old, screened for elevated levels of oppositionality, randomized to parenting groups or control; 109 (97%) were followed-up a year later. Using DSM-IV oppositional-defiant symptoms, children were divided into an Emotionally-Dysregulated type (ED, n = 68) and a Headstrong type (n = 44). The parenting intervention was the Incredible Years program supplemented by positive strategies to use when reading with children. Assessment of conduct problems and parenting was by semistructured interviews. Results: At follow-up, parents of Emotionally-Dysregulated and Headstrong children allocated to the intervention showed significant improvements in their parenting strategies to an equal extent compared to parents in the control group. However, the Emotionally-Dysregulated children showed a significantly greater decrease in conduct problems between intervention and control groups (treatment effect-size 0.84 standard deviations) than the Headstrong (es 0.20 SD), p = 0.04. Conclusions: Using the power of a controlled experiment, this study showed that children who exhibited Emotionally-Dysregulated behavior pretreatment were more responsive to improvements in parental care that were experimentally induced. The findings extend prior work on differential sensitivity in suggesting that children exhibiting irascibility and emotionality may show greater susceptibility to the caregiving environment, and may identify a subset of children who respond better to existing treatments. © 2012 Association for Child and Adolescent Mental Health.

O'Connor T.G.,University of Rochester | Monk C.,Columbia University | Fitelson E.M.,Columbia University
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2014

Background The empirical base suggesting a link between prenatal maternal anxiety, stress or depression and cognitive, behavioral, and biological outcomes in the infant and child has increased dramatically in the past 10 years. Methods In this review, we consider the relevance of prenatal maternal mood for child mental health practitioners; the empirical base for a likely causal impact of the link between prenatal anxiety, depression, or stress and child outcomes; the degree to which the available evidence is sufficient for informing or altering clinical practice; and the possible role of prenatal interventions for promoting child health and development. A selective review of PubMed, Cochrane Library and other sources was undertaken. Findings Clinically significant links between maternal prenatal distress and child behavioral and cognitive outcomes have been reported; predictions to stress physiology, immunology, and neurodevelopment have been reported but the effect sizes and clinical significance is less clear. Several candidate mechanisms have been proposed, with some supporting evidence. Many behavioral treatments for prenatal maternal distress exist, but their application to promoting child health is largely unknown. Conclusions Research on maternal prenatal distress is a good example of translational research and offers a strong paradigm for promoting interdisciplinary clinical research on child health and development. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Scott G.,University of Rochester
Journal of Investigative Dermatology | Year: 2012

The process of melanosome transfer has fascinated pigment cell biologists for decades. Whole-organelle transfer is a unique property of melanocytes, suggesting that the biologic underpinnings of the process reflect melanocyte- and keratinocyte-specific proteins and pathways. Although several mechanisms of melanosome transfer are likely to occur in the skin, Ando et al. focused on a new mechanism of melanosome transfer that involves release of melanosome-containing globules, similar to shedding vesicles into the extracellular space, followed by uptake by keratinocytes. This model adds further complexity to the process of melanosome transfer in the skin. © 2012 The Society for Investigative Dermatology.

Sanada T.M.,National Institute for Physiological science | DeAngelis G.C.,University of Rochester
Journal of Neuroscience | Year: 2014

Neural processing of 2D visual motion has been studied extensively, but relatively little is known about how visual cortical neurons represent visual motion trajectories that include a component toward or away from the observer (motion in depth). Psychophysical studies have demonstrated that humans perceive motion in depth based on both changes in binocular disparity over time (CD cue) and interocular velocity differences (IOVD cue). However, evidence for neurons that represent motion in depth has been limited, especially in primates, and it is unknown whether such neurons make use of CD or IOVD cues. We show that approximately one-half of neurons in macaque area MT are selective for the direction of motion in depth, and that this selectivity is driven primarily by IOVD cues, with a small contribution from the CD cue. Our results establish that area MT, a central hub of the primate visual motion processing system, contains a 3D representation of visual motion. © 2014 the authors.

Friedberg J.W.,University of Rochester
Journal of Clinical Oncology | Year: 2012

A 72-year-old previously healthy woman presented with acute abdominal pain and a 10-lb weight loss. Positron emission tomography demonstrated [ 18F]fluorodeoxyglucose-avid mesenteric lymphadenopathy, with evidence of bowel compression near a 3 X 3 cm lymph node. Biopsy of this node revealed diffuse large B-cell lymphoma (DLBCL), CD10+, with Ki-67 staining 80% of malignant cells (Figs 1A to 1D). BCL2 immunostaining was positive; MYC immunostaining was not performed. Fluorescent in situ hybridization revealed evidence of a t(14;18) BCL2 translocation and evidence of an MYC gene rearrangement that was not t(8;14) (Figs 2A and 2B). Bone marrow biopsy was negative, and serum lactate dehydrogenase was minimally elevated. The patient is now referred to you to discuss the prognosis and management of stage IIa DLBCL, International Prognostic Index score of 2, with double-hit genetic features. Copyright © 2012 American Society of Clinical Oncology. All rights reserved.

Yamakuchi M.,University of Rochester
International Journal of Vascular Medicine | Year: 2012

Vascular inflammation is an important component of the pathophysiology of cardiovascular diseases, such as hypertension, atherosclerosis, and aneurysms. All vascular cells, including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and infiltrating cells, such as macrophages, orchestrate a series of pathological events. Despite dramatic improvements in the treatment of atherosclerosis, the molecular basis of vascular inflammation is not well understood. In the last decade, microRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Each miRNAs suppresses a set of genes, forming complex regulatory network. This paper provides an overview of current advances that have been made in revealing the roles of miRNAs during vascular inflammation. Recent studies show that miRNAs not only exist inside cells but also circulate in blood. These circulating miRNAs are useful biomarkers for diagnosis of cardiovascular diseases. Furthermore, recent studies demonstrate that circulating miRNAs are delivered into certain recipient cells and act as messengers. These studies suggest that miRNAs provide new therapeutic opportunities. © 2012 Munekazu Yamakuchi.

Sagare A.P.,University of Southern California | Deane R.,University of Rochester | Zlokovic B.V.,University of Southern California
Pharmacology and Therapeutics | Year: 2012

Low-density lipoprotein receptor-related protein-1 (LRP1) is the main cell surface receptor involved in brain and systemic clearance of the Alzheimer's disease (AD) toxin amyloid-beta (Aβ). In plasma, a soluble form of LRP1 (sLRP1) is the major transport protein for peripheral Aβ. LRP1 in brain endothelium and mural cells mediates Aβ efflux from brain by providing a transport mechanism for Aβ across the blood-brain barrier (BBB). sLRP1 maintains a plasma 'sink' activity for Aβ through binding of peripheral Aβ which in turn inhibits re-entry of free plasma Aβ into the brain. LRP1 in the liver mediates systemic clearance of Aβ. In AD, LRP1 expression at the BBB is reduced and Aβ binding to circulating sLRP1 is compromised by oxidation. Cell surface LRP1 and circulating sLRP1 represent druggable targets which can be therapeutically modified to restore the physiological mechanisms of brain Aβ homeostasis. In this review, we discuss how increasing LRP1 expression at the BBB and liver with lifestyle changes, statins, plant-based active principles and/or gene therapy on one hand, and how replacing dysfunctional plasma sLRP1 on the other regulate Aβ clearance from brain ultimately controlling the onset and/or progression of AD. © 2012 Elsevier Inc.

Shoulson I.,University of Rochester
Movement Disorders | Year: 2010

The focus on disease-modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi-center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow-up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype-phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. © 2010 Movement Disorder Society.

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.

Holland P.L.,University of Rochester
Angewandte Chemie - International Edition | Year: 2011

M-M bonds meet two-coordination: Systems with metal-metal bonds are of great interest in inorganic chemistry. A recent report describes the first example of a metal-metal bond to a two-coordinate transition-metal center (see structure, Fe orange, O red, C gray). The metal-metal bond in this "xenophilic complex" is best described as a dative bond. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Finley S.,University of Rochester
Cognitive Science | Year: 2012

Traditional flat-structured bigram and trigram models of phonotactics are useful because they capture a large number of facts about phonological processes. Additionally, these models predict that local interactions should be easier to learn than long-distance ones because long-distance dependencies are difficult to capture with these models. Long-distance phonotactic patterns have been observed by linguists in many languages, who have proposed different kinds of models, including feature-based bigram and trigram models, as well as precedence models. Contrary to flat-structured bigram and trigram models, these alternatives capture unbounded dependencies because at an abstract level of representation, the relevant elements are locally dependent, even if they are not adjacent at the observable level. Using an artificial grammar learning paradigm, we provide additional support for these alternative models of phonotactics. Participants in two experiments were exposed to a long-distance consonant-harmony pattern in which the first consonant of a five-syllable word was [s] or [∫] ("sh") and triggered a suffix that was either [-su] or [-∫u] depending on the sibilant quality of this first consonant. Participants learned this pattern, despite the large distance between the trigger and the target, suggesting that when participants learn long-distance phonological patterns, that pattern is learned without specific reference to distance. © 2012 Cognitive Science Society, Inc.

Yang F.,University of Kentucky | Li J.C.M.,University of Rochester
Materials Science and Engineering R: Reports | Year: 2013

Indentation test using a cylindrical indenter with a flat end is now known as impression test. The advantage is its capability to reach a steady state for creep test at constant load and it is possible to compare with the conventional tensile or compression tests. The test is simple and all the temperature and strain rate dependences can be obtained locally from one sample avoiding the sample to sample variations. It became very popular in the last decade. The literature is reviewed here. © 2013 Elsevier B.V.

Prostate specific antigen (PSA) is a serine protease that is exclusively produced in the prostate, and its detection is the only laboratory test available for screening men for prostate cancer (PC). The interpretation of the assay is difficult since it is specific for prostate tissue and cellular growth, but not for PC. Pharmacologic therapy for hyperlipidemia, such as statins, may influence prostate cellular growth and subsequently PSA levels in patients. Dysregulated cellular growth in the prostate is mediated by inhibiting the rate-limiting pathway step in cholesterol synthesis, thereby decreasing isoprenylate intermediates, decreasing cholesterol rich cellular membrane domains, and down-regulating androgen and estrogen receptors. Statins, with variable efficacy, have been previously shown to inhibit cellular inflammation, angiogenesis, proliferation, migration/adhesion, and invasion, while promoting apoptosis in prostate cells by inhibiting the conversion of HMG-CoA to mevalonate. An individual statin's molecular structure, need for enzymatic conversion, bioavailability, and peripheral tissue concentration may partially account for differing properties. By inhibiting prostatic cellular growth and promoting apoptosis, statins may subsequently decrease PSA levels, an effect recently observed in cohorts. There is scientific and clinical evidence supporting the observations that statins are associated with an overall reduction in serum PSA in men, when used for greater than 6 months, and especially when used for greater than 2 years. © 2010 IUBMB.

A total of 622 suicides were reported among students attending 645 distinct campuses from 2004-2005 through 2008-2009. Adjusting for gender in the population at risk of 14.9 million student-years and for the source of these data, the student suicide rate of 7.0 was significantly and substantially lower than for a matched national sample. Suicide rates by firearm were significantly and substantially lower for both female and male students. Hanging was significantly and substantially lower for male students, less prominently so for female students. It is principally the ninefold decrease in the availability of firearms on campuses (vs. homes) and secondarily other features of the campus environment that are the bases for lower student suicide rates. © 2011 The American Association of Suicidology.

Weiss B.,University of Rochester
Journal of the Neurological Sciences | Year: 2011

Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. © 2011 Elsevier B.V. All rights reserved.

Trivedi D.J.,University of Rochester | Wang L.,University of Southern California | Prezhdo O.V.,University of Southern California
Nano Letters | Year: 2015

By slowing down electron-phonon relaxation in nanoscale materials, one can increase efficiencies of solar energy conversion via hot electron extraction, multiple exciton generation, and elimination of exciton trapping. The elusive phonon bottleneck is hard to achieve, in particular, due to Auger-type energy exchange between electrons and holes. The Auger channel can be suppressed by hole trapping. Using time-domain ab initio simulation, we show that deep hole traps cannot fully eliminate the Auger channel. The simulations show that the hole-mediated electron relaxation is slowed down only by about 30%, which is in agreement with the recent experiments. The Auger energy exchange and hole relaxation to the trap state occur on similar time scales. Hole trapping is slow, because holes themselves experience a weak bottleneck effect. The study establishes the fundamental mechanisms of the electron and hole relaxation processes with and without hole traps. It shows that more sophisticated hole trapping strategies, for example, involving shell layers, are required in order to achieve the phonon bottleneck and to reduce electronic energy losses. © 2015 American Chemical Society.

Goldman S.A.,University of Rochester
Archives of Neurology | Year: 2011

The childhood leukodystrophies are characterized by neonatal or childhood deficiencies in myelin production or maintenance; these may be due to hereditary defects in genes for myelin maintenance, as in Pelizaeus-Merzbacher disease, or to enzymatic deficiencies resulting in substrate misaccumulation or misprocessing, as in the lysosomal storage disorders. Regardless of their respective etiologies, these disorders are essentially all manifested by a profound deterioration in neurological function with age. A congenital deficit in forebrain myelination is also noted in children with the periventricular leukomalacia of cerebral palsy, which yields a more static morbidity. In light of the wide range of disorders to which congenital hypomyelination or postnatal demyelination may contribute, and the relative homogeneity of oligodendrocytes and their progenitors, the leukodystrophies may be especially attractive targets for cell-based therapeutic strategies. As a result, glial progenitor cells, which can give rise to new myelinogenic oligodendrocytes, have become of great interest as potential vectors for the restoration of myelin to the dysmyelinated brain and spinal cord. In addition, by distributing throughout the neuraxis after perinatal graft, and giving rise to astrocytes as well as oligodendrocytes, glial progenitor cells may be of great utility in rectifying the dysmyelination-associated enzymatic deficiencies of the lysosomal storage disorders. ©2011 American Medical Association. All rights reserved.

Grossfield A.,University of Rochester
Biochimica et Biophysica Acta - Biomembranes | Year: 2011

G protein-coupled receptors (GPCRs) are a large, biomedically important family of proteins, and the recent explosion of new high-resolution structural information about them has provided an enormous opportunity for computational modeling to make major contributions. In particular, molecular dynamics simulations have become a driving factor in many areas of GPCR biophysics, improving our understanding of lipid-protein interaction, activation mechanisms, and internal hydration. Given that computers will continue to get faster and more structures will be solved, the importance of computational methods will only continue to grow, particularly as simulation research is more closely coupled to experiment. © 2011 Elsevier B.V. All rights reserved.

Schor N.F.,University of Rochester
Neurology | Year: 2012

As it is currently configured, completion of child neurology residency requires performance of 12 months of training in adult neurology. Exploration of whether or not this duration of training in adult neurology is appropriate for what child neurology is today must take into account the initial reasons for this requirement and the goals of adult neurology training during child neurology residency. Copyright © 2012 by AAN Enterprises, Inc.

Liu J.,University of Rochester | Prezhdo O.V.,University of Southern California
Journal of Physical Chemistry Letters | Year: 2015

Rapid development in lead halide perovskites has led to solution-processable thin film solar cells with power conversion efficiencies close to 20%. Nonradiative electron-hole recombination within perovskites has been identified as the main pathway of energy losses, competing with charge transport and limiting the efficiency. Using nonadiabatic (NA) molecular dynamics, combined with time-domain density functional theory, we show that nonradiative recombination happens faster than radiative recombination and long-range charge transfer to an acceptor material. Doping of lead iodide perovskites with chlorine atoms reduces charge recombination. On the one hand, chlorines decrease the NA coupling because they contribute little to the wave functions of the valence and conduction band edges. On the other hand, chlorines shorten coherence time because they are lighter than iodines and introduce high-frequency modes. Both factors favor longer excited-state lifetimes. The simulation shows good agreement with the available experimental data and contributes to the comprehensive understanding of electronic and vibrational dynamics in perovskites. The generated insights into design of higher-efficiency solar cells range from fundamental scientific principles, such as the role of electron-vibrational coupling and quantum coherence, to practical guidelines, such as specific suggestions for chemical doping. © 2015 American Chemical Society.

Schiavenato M.,University of Rochester | Craig K.D.,University of British Columbia
Clinical Journal of Pain | Year: 2010

Pain assessment conventionally has been viewed hierarchically with self-report as its "gold-standard." Recent attempts to improve pain management have focused on the importance of assessment, for example, the initiative to include pain as the "fifth vital sign." We question the focus in the conceptualization of pain assessment upon a "vital sign," not in terms of the importance of assessment, but in terms of the application of self-report as a mechanistic index akin to a biologic measure such as heart rate and blood pressure. We synthesize current inclusive models of pain and pain assessment and propose a more comprehensive conceptualization of pain assessment as a transaction based on an organismic interplay between the patient and clinician. © 2010 by Lippincott Williams & Wilkins.

Getty A.L.,University of South Dakota | Getty A.L.,University of Rochester | Pearce D.A.,University of South Dakota
Cellular and Molecular Life Sciences | Year: 2011

Neuronal ceroid lipofuscinoses (NCL) are caused by mutations in eight different genes, are characterized by lysosomal accumulation of autofluorescent storage material, and result in a disease that causes degeneration of the central nervous system (CNS). Although functions are defined for some of the soluble proteins that are defective in NCL (cathepsin D, PPT1, and TPP1), the primary function of the other proteins defective in NCLs (CLN3, CLN5, CLN6, CLN7, and CLN8) remain poorly defined. Understanding the localization and network of interactions for these proteins can offer clues as to the function of the NCL proteins and also the pathways that will be disrupted in their absence. Here, we present a review of the current understanding of the localization, interactions, and function of the proteins associated with NCL. © 2010 Springer Basel AG.

Domb B.G.,Hinsdale Orthopaedics | Philippon M.J.,Steadman Clinic | Giordano B.D.,University of Rochester
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2013

Purpose: The purpose of this systematic review was to critically evaluate the available literature exploring the role of the hip joint capsule in the normal state (stable) and pathologic states (instability or stiffness). Furthermore, we examined the various ways that arthroscopic hip surgeons address the capsule intraoperatively: (1) capsulotomy or capsulectomy without closure, (2) capsulotomy with closure, and (3) capsular plication. Methods: Two independent reviewers (B.D.G. and B.G.D.) performed a systematic review of the literature using PubMed and the reference lists of related articles by means of defined search terms. Relevant studies were included if these criteria were met: (1) written in English, (2) Levels of Evidence I to V, (3) focus on capsule and its role in hip stability, and (4) human studies and reviews. Articles were excluded if they evaluated (1) total hip arthroplasty constructs using bony procedures or prosthetic revision, (2) developmental dysplasia of the hip where reorientation osteotomies were used, (3) syndromic instability, and (4) traumatic instability with associated bony injury. Results: By use of the search method described, 5,085 publications were reviewed, of which 47 met appropriate criteria for inclusion in this review. Within this selection group, there were multiple publications that specifically addressed more than 1 of the inclusion criteria. Relevant literature was organized into the following areas: (1) capsular anatomy, biomechanics, and physiology; (2) the role of the capsule in total hip arthroplasty stability; (3) the role of the capsule in native hip stability; and (4) atraumatic instability and capsulorrhaphy. Conclusions: As the capsuloligamentous stabilizers of the hip continue to be studied, and their role defined, arthroscopic hip surgeons should become facile with arthroscopic repair or plication techniques to restore proper capsular integrity and tension when indicated. Level of Evidence: Level IV, systematic review. © 2013 by the Arthroscopy Association of North America.

Bi X.,University of Rochester
IUBMB Life | Year: 2014

The eukaryotic genome can be roughly divided into euchromatin and heterochromatin domains that are structurally and functionally distinct. Heterochromatin is characterized by its high compactness and its inhibitory effect on DNA transactions such as gene expression. Formation of heterochromatin involves special histone modifications and the recruitment and spread of silencing complexes and causes changes in the primary and higher order structures of chromatin. The past two decades have seen dramatic advances in dissecting the molecular aspects of heterochromatin because of the identification of the histone code for heterochromatin as well as its writers and erasers (histone-modifying enzymes) and readers (silencing factors recognizing histone modifications). How heterochromatic histone modifications and silencing factors contribute to the special primary and higher order structures of heterochromatin has begun to be understood. The budding yeast Saccharomyces cerevisiae has long been used as a model organism for heterochromatin studies. Results from these studies have contributed significantly to the elucidation of the general principles governing the formation, maintenance, and function of heterochromatin. This review is focused on investigations into the structural aspects of heterochromatin in S. cerevisiae. Current understanding of other aspects of heterochromatin including how it promotes gene silencing and its epigenetic inheritance is briefly summarized. © 2014 IUBMB Life.

Ritchlin C.T.,University of Rochester
Journal of Rheumatology | Year: 2014

The enthesis, attachment site of ligaments, tendons, and joint capsules to bone, has emerged as a complex structure or entheseal organ that dissipates stress to maintain homeostasis. Entheses are also anatomically and functionally integrated with adjacent bursa, fibrocartilage, and synovium in a synovial entheseal complex that may trigger inflammation in response to biomechanical stress. Recent studies have suggested that inflammation in psoriatic arthritis (PsA) arises in the enthesis based on imaging and anatomical data. In this review, the anatomy of the enthesis from a functional perspective is discussed, and the data that support a central role for enthesitis in PsA are outlined. In addition, new animal models that implicate Th17 and tumor necrosis factor pathways in enthesitis are highlighted along with new data that question the primacy of the enthesis in the early stages of PsA. Finally, future studies that incorporate new technologies are outlined. Those studies may address the contribution of entheseal inflammation to initiation and perpetuation of key pathophysiologic pathways in the psoriatic joint.

Bulger M.,University of Rochester | Groudine M.,Fred Hutchinson Cancer Research Center | Groudine M.,University of Washington
Cell | Year: 2011

Biological differences among metazoans and between cell types in a given organism arise in large part due to differences in gene expression patterns. Gene-distal enhancers are key contributors to these expression patterns, exhibiting both sequence diversity and cell type specificity. Studies of long-range interactions indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. However, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. © 2011 Elsevier Inc.

Xue Y.,University of Rochester
International Journal of Nursing Studies | Year: 2015

Background: Understanding minority nurses' job satisfaction is a critical first step to inform strategies designed to retain minority nurses and improve institutional climate to ensure sustained diversity. Yet, empirical evidence is limited in this regard, especially comparisons across racial and ethnic groups in a national sample in the U.S. Objectives: To determine minority nurses' job satisfaction across racial and ethnic groups relative to White nurses using a national representative sample. Methods: A retrospective cross-sectional analysis was conducted using the 2008 National Sample Survey of Registered Nurses. The sample includes registered nurses who were primarily employed in nursing in the U.S. Job satisfaction was measured by a single survey item. Racial and ethnic minority status was defined as self-identified membership in a group other than White non-Hispanic, including Hispanic and non-Hispanic Black, Asian, Native Hawaiian/Pacific Islander, American Indian/Alaska Native, and Multiracial. Multinomial logistic regression was performed to compare job satisfaction across racial and ethnic groups while adjusting for individual and job-related characteristics. Results: The majority of nurses were satisfied with their job. The nurse group that had the highest proportion of being satisfied with their job was Native Hawaiian/Pacific Islander (88.8%), followed by White (81.6%), Asian (81%), Hispanic (78.9%), Black (76%), Multiracial (75.7%), and American Indian/Alaska Native (74.3%). Adjusting for individual and job-related characteristics, evidence indicated the potential for lower job satisfaction among Black, American Indian/Alaska Native, and Multiracial nurses compared to White nurses. Asian nurses reported the highest levels of neutral (versus dissatisfaction) compared to White nurses. There was no evidence indicating a clear difference in job satisfaction between Hispanic, Native Hawaiian/Pacific Islander, and White nurses. Conclusions: Moderate differences in job satisfaction were observed across racial and ethnic groups. More research is needed to understand factors underlying these differences, so that nursing and hospital administrators can develop effective strategies to improve job satisfaction and retain minority nurses. © 2014 Elsevier Ltd.

Chapman B.P.,University of Rochester | Hampson S.,Oregon Research Institute | Clarkin J.,New York Medical College
Developmental Psychology | Year: 2014

We describe 2 frameworks in which personality dimensions relevant to health, such as Conscientiousness, can be used to inform interventions designed to promote health aging. First, contemporary data and theory do not suggest that personality is "immutable," but instead focus on questions of who changes, in what way, why, when, and how. In fact, the notion that personality could be changed was part and parcel of many schools of psychotherapy, which suggested that long-term and meaningful change in symptoms could not be achieved without change in relevant aspects of personality. We review intervention research documenting change in personality. On the basis of an integrative view of personality as a complex system, we describe a bottom-up model of change in which interventions to change basic personality processes eventuate in changes at the trait level. A 2nd framework leverages the descriptive and predictive power of personality to tailor individual risk prediction and treatment, as well as refine public health programs, to the relevant dispositional characteristics of the target population. These methods dovetail with, and add a systematic and rigorous psychosocial dimension to, the personalized medicine and patient-centeredness movements in medicine. In addition to improving health through earlier intervention and increased fit between treatments and persons, cost-effectiveness improvements can be realized by more accurate resource allocation. Numerous examples from the personality, health, and aging literature on Conscientiousness and other traits are provided throughout, and we conclude with a series of recommendations for research in these emerging areas. © 2012 American Psychological Association.

Schieber M.H.,University of Rochester
Journal of Physiology | Year: 2011

During closed-loop control of a brain-computer interface, neurons in the primary motor cortex can be intensely active even though the subject may be making no detectable movement or muscle contraction. How can neural activity in the primary motor cortex become dissociated from the movements and muscles of the native limb that it normally controls? Here we examine circumstances in which motor cortex activity is known to dissociate from movement - including mental imagery, visuo-motor dissociation and instructed delay. Many such motor cortex neurons may be related to muscle activity only indirectly. Furthermore, the integration of thousands of synaptic inputs by individual α-motoneurons means that under certain circumstances even cortico-motoneuronal cells, which make monosynaptic connections to α-motoneurons, can become dissociated from muscle activity. The natural ability of motor cortex neurons under voluntarily control to become dissociated from bodily movement may underlie the utility of this cortical area for controlling brain-computer interfaces. © 2011 The Author. Journal compilation © 2011 The Physiological Society.

Pigeon W.R.,University of Rochester
Indian Journal of Medical Research | Year: 2010

Insomnia is a highly prevalent sleep disorder that frequently occurs in its acute form and occurs at a rate of approximately 10 per cent in its chronic form in many countries. There is a high prevalence of insomnia in a variety of medical and psychiatric conditions for which insomnia often serves as a risk factor. The aetiology and pathophysiology of insomnia is such that several factors may predispose individuals for or precipitate and/or perpetuate the condition. Both sedative-hypnotic and cognitive-behavioural interventions exist for insomnia and each type of intervention have substantial levels of empirical support for their efficacy.

Eberly J.H.,University of Rochester
Contemporary Physics | Year: 2015

The classical theory of polarisation coherence is briefly summarised and then extended. The extension is motivated by the recognition that the traditional theory of two-point coherence provides only what we identify as ‘diagonal’ correlation functions and their associated two-point coherence matrices. It is pointed out that a wider focus is possible when taking account of the three-sector vector space underlying all two-point coherences in classical optics. This reveals the possibility of observing a new type of ‘off-diagonal’ correlations that arise when the correlation functions under investigation are associated with points in two distinct vector spaces, pairs of points that are not analogous to the pairs of space points or time points that underlie traditional measures of spatial and temporal coherence. Quantum theory has experience with correlations engaging such ‘cross-sector’ coherences, for example in tests of Bell inequalities, and the quantum formulations are shown to be easily adopted by classical theory without incorporating quantum features in the optical signals. The familiar theory of classical coherence that is associated with the pioneering work of Emil Wolf is extended in conformance with three criteria advanced by Abner Shimony to obtain formulas for correlation functions and for the Bell measure (Formula presented.) of coherence. Values of (Formula presented.) greater than the standard upper limit (Formula presented.) are predicted for certain classical Shimony–Wolf fields, indicating strong cross-sector coherence, but only when standard measures of coherence such as degree of polarisation (Formula presented.) are minimised. Experimental results confirming the predictions for cross-sector coherence are exhibited. © 2015 Taylor & Francis.

Douglass D.H.,University of Rochester
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2011

The Pacific sea surface temperature data contains two components: NL, a signal that exhibits the familiar El Niño/La Niña phenomenon and NH, a signal of one-year period. Analysis reveals: (1) The existence of an annual solar forcing FS; (2) NH is phase locked directly to FS while NL is frequently phase locked to the 2nd or 3rd subharmonic of FS. At least ten distinct subharmonic time segments of NL since 1870 are found. The beginning or end dates of these segments have a near one-to-one correspondence with the abrupt climate changes previously reported. Limited predictability is possible. © 2011 Elsevier B.V. All rights reserved.

Kim-Spoon J.,Virginia Polytechnic Institute and State University | Cicchetti D.,University of Minnesota | Rogosch F.A.,University of Rochester
Child Development | Year: 2013

The longitudinal contributions of emotion regulation and emotion lability-negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that for both maltreated and nonmaltreated children, emotion regulation was a mediator between emotion lability-negativity and internalizing symptomatology, whereas emotion lability-negativity was not a mediator between emotion regulation and internalizing symptomatology. Early maltreatment was associated with high emotion lability-negativity (age 7) that contributed to poor emotion regulation (age 8), which in turn was predictive of increases in internalizing symptomatology (from age 8 to 9). The results imply important roles of emotion regulation in the development of internalizing symptomatology, especially for children with high emotion lability-negativity. © 2012 Society for Research in Child Development, Inc.

Lambert J.D.,University of Rochester
Current Biology | Year: 2010

At least five animal phyla exhibit spiralian development, which is characterized by striking similarities in the geometry of the early cleavage pattern and the fate map of the blastula, along with similarities in larval morphology. Recent advances in reconstructing the phylogeny of spiralians and their relatives suggest that the common ancestor of a large clade of protostome phyla known as the Lophotrochozoa had spiralian development. In this minireview, I describe characteristics of spiralian development and some recent insights into its mechanisms and evolution. © 2010 Elsevier Ltd. All rights reserved.

Yoo B.-K.,University of Rochester
Journal of Preventive Medicine and Public Health | Year: 2011

Annual epidemics of seasonal influenza occur during autumn and winter in temperate regions and have imposed substantial public health and economic burdens. At the global level, these epidemics cause about 3 - 5 million severe cases of illness and about 0.25-0.5 million deaths each year. Although annual vaccination is the most effective way to prevent the disease and its severe outcomes, influenza vaccination coverage rates have been at suboptimal levels in many countries. For instance, the coverage rates among the elderly in 20 developed nations in 2008 ranged from 21% to 78% (median 65%). In the U.S., influenza vaccination levels among elderly population appeared to reach a "plateau" of about 70% after the late 1990s, and levels among child populations have remained at less than 50%. In addition, disparities in the coverage rates across subpopulations within a country present another important public health issue. New approaches are needed for countries striving both to improve their overall coverage rates and to eliminate disparities. This review article aims to describe a broad conceptual framework of vaccination, and to illustrate four potential determinants of influenza vaccination based on empirical analyses of U.S. nationally representative populations. These determinants include the ongoing influenza epidemic level, mass media reporting on influenza-related topics, reimbursement rate for providers to administer influenza vaccination, and vaccine supply. It additionally proposes specific policy implications, derived from these empirical analyses, to improve the influenza vaccination coverage rate and associated disparities in the U.S., which could be generalizable to other countries.

Javed F.,University of Rochester | Warnakulasuriya S.,Kings College London
Critical Reviews in Oncology/Hematology | Year: 2016

Oral cancer (OC) is known to have a multi-factorial etiology; tobacco, alcohol and betel quid being the major risk factors. Tooth loss and periodontal disease (PD) have been implicated to increase the risk of developing various cancers. The aim of this systematic review was to assess any possible association between PD and OC. Indexed databases were searched using different combinations of the following key words: "oral cancer", "periodontal disease", "tooth loss", "squamous cell carcinoma", "missing teeth" "alveolar bone loss", "clinical attachment loss" and "periodontitis". PRISMA criteria were followed to accrue data and databases were searched from 1984 up to and including June 2015. In total, 12 case-control studies were selected from the published literature. Results: Nine studies reported a 2-5 fold increase in the risk of OC among patients with PD as compared to those without PD. Three studies reported no association between PD and OC. In one study, an increased risk of tongue cancer was associated with each millimeter of alveolar bone loss and in two studies clinical attachment loss of more than 1.5. mm was associated with an increased risk of OC. In studies reporting significant findings these associations persisted after adjusting for major risk factors. PD is associated with a small but significant increase in risk for OC. In several reported studies this association was attenuated following adjustment for tobacco and alcohol use. © 2015 Elsevier Ireland Ltd.

Ryan J.L.,University of Rochester
Journal of Investigative Dermatology | Year: 2012

Skin changes caused by ionizing radiation have been scientifically documented since 1902. Ionizing radiation is a widely accepted form of treatment for various types of cancer. Despite the technological advances, radiation skin injury remains a significant problem. This injury, often referred to as radiation dermatitis, occurs in about 95% of patients receiving radiation therapy for cancer, and ranges in severity from mild erythema to moist desquamation and ulceration. Ionizing radiation is not only a concern for cancer patients, but also a public health concern because of the potential for and reality of a nuclear and/or radiological event. Recently, the United States has increased efforts to develop medical countermeasures to protect against radiation toxicities from acts of bioterrorism, as well as cancer treatment. Management of radiation dermatitis would improve the therapeutic benefit of radiation therapy for cancer and potentially the mortality expected in any dirty bomb attack. Currently, there is no effective treatment to prevent or mitigate radiation skin injury. This review summarizes the good, the bad, and the ugly of current and evolving knowledge regarding mechanisms of and treatments for radiation skin injury. © 2012 The Society for Investigative Dermatology.

Malygin E.G.,Institute of Molecular Biology | Hattman S.,University of Rochester
Critical Reviews in Biochemistry and Molecular Biology | Year: 2012

The sequence-specific transfer of methyl groups from donor S-adenosyl-L-methionine (AdoMet) to certain positions of DNA-adenine or-cytosine residues by DNA methyltransferases (MTases) is a major form of epigenetic modification. It is virtually ubiquitous, except for some notable exceptions. Site-specific methylation can be regarded as a means to increase DNA information capacity and is involved in a large spectrum of biological processes. The importance of these functions necessitates a deeper understanding of the enzymatic mechanism(s) of DNA methylation. DNA MTases fall into one of two general classes; viz. amino-MTases and [C5-cytosine]-MTases. Amino-MTases, common in prokaryotes and lower eukaryotes, catalyze methylation of the exocyclic amino group of adenine ([N6-adenine]-MTase) or cytosine ([N4-cytosine]-MTase). In contrast, [C5-cytosine]-MTases methylate the cyclic carbon-5 atom of cytosine. Characteristics of DNA MTases are highly variable, differing in their affinity to their substrates or reaction products, their kinetic parameters, or other characteristics (order of substrate binding, rate limiting step in the overall reaction). It is not possible to present a unifying account of the published kinetic analyses of DNA methylation because different authors have used different substrate DNAs and/or reaction conditions. Nevertheless, it would be useful to describe those kinetic data and the mechanistic models that have been derived from them. Thus, this review considers in turn studies carried out with the most consistently and extensively investigated [N6-adenine]-, [N4-cytosine]-and [C5-cytosine]-DNA MTases. © 2012 Informa Healthcare USA, Inc.

Alonso M.A.,University of Rochester
Advances in Optics and Photonics | Year: 2011

This tutorial gives an overview of the use of the Wigner function as a tool for modeling optical field propagation. Particular emphasis is placed on the spatial propagation of stationary fields, as well as on the propagation of pulses through dispersive media. In the first case, the Wigner function gives a representation of the field that is similar to a radiance or weight distribution for all the rays in the system, since its arguments are both position and direction. In cases in which the field is paraxial and where the system is described by a simple linear relation in the ray regime, the Wigner function is constant under propagation along rays. An equivalent property holds for optical pulse propagation in dispersive media under analogous assumptions. Several properties and applications of the Wigner function in these contexts are discussed, as is its connection with other common phase-space distributions like the ambiguity function, the spectrogram, and the Husimi, P, Q, and Kirkwood-Rihaczek functions. Also discussed are modifications to the definition of the Wigner function that allow extending the property of conservation along paths to a wider range of problems, including nonparaxial field propagation and pulse propagation within general transparent dispersive media. © 2010 Optical Society of America.

Khorana A.A.,University of Rochester
Thrombosis Research | Year: 2012

Venous thromboembolism (VTE) is an increasingly frequent complication of cancer and its treatments. One in five cancer patients are estimated to develop venous and arterial events during the natural history of their illness. However, the risk for VTE varies widely between various subgroups of cancer patients and even in the same cancer patient over time. This narrative review focuses on risk factors, biomarkers and risk assessment tools and attempts to clarify approaches to risk stratification. Clinical risk factors include primary site of cancer, chemotherapy, anti-angiogenic therapy, surgery and hospitalization. Predictive and candidate biomarkers include platelet and leukocyte counts, hemoglobin, D-dimer and tissue factor. However, single risk factors or biomarkers have not, in general, been able to identify sufficiently high-risk populations. A clinical risk score, incorporating 5 simple clinical and laboratory variables, has now been studied in over 10,000 patients and can successfully categorize patients at low- and high-risk for VTE. Recent trials have shown that outpatient prophylactic anticoagulation is both safe and effective, but event rates have been highly variable. Targeted thromboprophylaxis provides an optimal risk-benefit ratio and the best opportunity to reduce the burden of VTE and its consequences for patients with cancer. © 2012 Elsevier Ltd.

Ritchlin C.T.,University of Rochester
Journal of Rheumatology | Year: 2012

Psoriatic disease includes psoriasis and associated comorbidities (arthritis, uveitis, inflammatory bowel disease, cardiovascular disease, metabolic syndrome, and anxiety/depression) and is remarkably diverse in disease presentation and course. The marked heterogeneity of musculoskeletal involvement in psoriatic arthritis (PsA) presents major challenges to clinicians regarding diagnosis, risk stratification, and management. Members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have begun collaborative efforts to develop biomarkers that can assist in the diagnosis and management of patients with psoriasis and related comorbidities. This brief review provides a rationale for biomarker research in PsA, consideration of types and sources of biomarkers, and examples of important biomarker studies in PsA, followed by a review of trial designs for biomarker research and a discussion of potential funding sources. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Smith H.C.,University of Rochester
Trends in Biochemical Sciences | Year: 2011

APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild-type Vif targets A3G for proteasomal degradation and when this happens, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In this article, I suggest that it is time to recognize that A3G has the potential to act as a double agent. Future research should focus on understanding how cellular and viral regulatory mechanisms enable the antiviral function of A3G, and on the development of novel research reagents to explore these pathways. © 2010 Elsevier Ltd.

Matthiesen C.,University of Cambridge | Vamivakas A.N.,University of Cambridge | Vamivakas A.N.,University of Rochester | Atature M.,University of Cambridge
Physical Review Letters | Year: 2012

The observation of quantum-dot resonance fluorescence enabled a new solid-state approach to generating single photons with a bandwidth approaching the natural linewidth of a quantum-dot transition. Here, we operate in the small Rabi frequency limit of resonance fluorescence-the Heitler regime-to generate subnatural linewidth and high-coherence quantum light from a single quantum dot. The measured single-photon coherence is 30 times longer than the lifetime of the quantum-dot transition, and the single photons exhibit a linewidth which is inherited from the excitation laser. In contrast, intensity-correlation measurements reveal that this photon source maintains a high degree of antibunching behavior on the order of the transition lifetime with vanishing two-photon scattering probability. Generating decoherence-free phase-locked single photons from multiple quantum systems will be feasible with our approach. © 2012 American Physical Society.

Allen Orr H.,University of Rochester
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

The population genetic study of advantageous mutations has lagged behind that of deleterious and neutral mutations. But over the past two decades, a number of significant developments, both theor-etical and empirical, have occurred. Here, I review two of these developments: the attempt to determine the distribution of fitness effects among beneficial mutations and the attempt to deter-mine their average dominance. Considering both theory and data, I conclude that, while considerable theoretical progress has been made, we still lack sufficient data to draw confident conclusions about the distribution of effects or the dominance of beneficial mutations. © 2010 The Royal Society.

Meiklejohn C.D.,University of Rochester | Coolon J.D.,University of Michigan | Hartl D.L.,Harvard University | Wittkopp P.J.,University of Michigan
Genome Research | Year: 2014

Evolutionary changes in gene expression underlie many aspects of phenotypic diversity within and among species. Understanding the genetic basis for evolved changes in gene expression is therefore an important component of a comprehensive understanding of the genetic basis of phenotypic evolution. Using interspecific introgression hybrids, we examined the genetic basis for divergence in genome-wide patterns of gene expression between Drosophila simulans and Drosophila mauritiana. We find that cis-regulatory and trans-regulatory divergences differ significantly in patterns of genetic architecture and evolution. The effects of cis-regulatory divergence are approximately additive in heterozygotes, quantitatively different between males and females, and well predicted by expression differences between the two parental species. In contrast, the effects of trans-regulatory divergence are associated with largely dominant introgressed alleles, have similar effects in the two sexes, and generate expression levels in hybrids outside the range of expression in both parental species. Although the effects of introgressed trans-regulatory alleles are similar in males and females, expression levels of the genes they regulate are sexually dimorphic between the parental D. simulans and D. mauritiana strains, suggesting that purespecies genotypes carry unlinked modifier alleles that increase sexual dimorphism in expression. Our results suggest that independent effects of cis-regulatory substitutions in males and females may favor their role in the evolution of sexually dimorphic phenotypes, and that trans-regulatory divergence is an important source of regulatory incompatibilities. © 2014 Meiklejohn et al.

Shuttleworth T.J.,University of Rochester
Frontiers in Bioscience | Year: 2012

The ARC channel is a small conductance, highly Ca2+-selective ion channel whose activation is specifically dependent on low concentrations of arachidonic acid acting at an intracellular site. They are widely distributed in diverse cell types where they provide an alternative, storeindependent pathway for agonist-activated Ca2+ entry. Although biophysically similar to the store-operated CRAC channels, these two conductances function under distinct conditions of agonist stimulation, with the ARC channels providing the predominant route of Ca2+ entry during the oscillatory signals generated at low agonist concentrations. Despite these differences in function, like the CRAC channel, activation of the ARC channels is dependent on STIM1, but it is the pool of STIM1 that constitutively resides in the plasma membrane that is responsible. Similarly, both channels are formed by Orai proteins but, whilst the CRAC channel pore is a tetrameric assembly of Orai1 subunits, the ARC channel pore is formed by a heteropentameric assembly of three Orai1 subunits and two Orai3 subunits. There is increasing evidence that the activity of these channels plays a critical role a variety of different cellular activities.

Kierzek R.,Polish Academy of Sciences | Turner D.H.,University of Rochester | Kierzek E.,Polish Academy of Sciences
Nucleic Acids Research | Year: 2015

Oligonucleotide microarrays are widely used in various biological studies. In this review, application of oligonucleotide microarrays for identifying binding sites and probing structure of RNAs is described. Deep sequencing allows fast determination of DNA and RNA sequence. High-throughput methods for determination of secondary structures of RNAs have also been developed. Those methods, however, do not reveal binding sites for oligonucleotides. In contrast, microarrays directly determine binding sites while also providing structural insights. Microarray mapping can be used over a wide range of experimental conditions, including temperature, pH, various cations at different concentrations and the presence of other molecules. Moreover, it is possible to make universal microarrays suitable for investigations of many different RNAs, and readout of results is rapid. Thus, microarrays are used to provide insight into oligonucleotide sequences potentially able to interfere with biological function. Better understanding of structure-function relationships of RNA can be facilitated by using microarrays to find RNA regions capable to bind oligonucleotides. That information is extremely important to design optimal sequences for antisense oligonucleotides and siRNA because both bind to single-stranded regions of target RNAs. © 2015 The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Long R.,University College Dublin | Prezhdo O.V.,University of Rochester
Nano Letters | Year: 2014

To achieve a high photon-to-charge conversion efficiency, the electron-hole pair generated by photon absorption in organic photovoltaic systems must overcome the Coulomb attraction, which often results in voltage loss. Bearing this in mind, we performed ab initio time-domain simulations of the charge separation and energy relaxation across an interface formed by poly(3-hexylthiophene) (P3HT) and a single-walled carbon nanotube (CNT). The dynamics of the positive and negative charges showed strong asymmetry. Photoexcitation of the polymer leads to a 100 fs electron transfer, in agreement with the experiment, followed by a loss of 0.6 eV of energy within 0.5 ps. Photoexcitation of the CNT leads to hole transfer, which requires nearly 2 ps, but loses only 0.3 eV of energy. The strong disparity arises due to the differences in the localization of the photoexcited donor states, the number densities of the acceptor states, and the phonon modes involved. Used as a chromophore, P3HT produces faster charge separation but leads to larger energy losses and cannot harvest light in the red region of the solar spectrum. In contrast, CNT absorbs a broader range of photons and reduces energy losses but gives a less efficient charge separation. The complementary properties of the two chromophores can be utilized to improve the performance of solar cells by optimizing simultaneously light harvesting, charge separation, and energy relaxation, which affect the photovoltaic yield, current, and voltage. © 2014 American Chemical Society.

Novotny L.,University of Rochester
American Journal of Physics | Year: 2010

Strongly interacting quantum systems are at the heart of many physical processes, ranging from photosynthesis to quantum information. We demonstrate that many characteristic features of strongly coupled systems can be derived classically for a simple coupled harmonic oscillator. This model system is used to derive frequency splittings and to analyze adiabatic and diabatic transitions between the coupled states. A classical analog of the Landau-Zener formula is derived. The classical analysis is intuitive and well suited for introducing students to the basic concepts of strongly interacting systems. © 2010 American Association of Physics Teachers.

Haydon P.G.,Tufts University | Nedergaard M.,University of Rochester
Cold Spring Harbor Perspectives in Biology | Year: 2015

Work over the past 20 years has implicated electrically nonexcitable astrocytes in complex neural functions. Despite controversies, it is increasingly clear that many, if not all, neural processes involve astrocytes. This review critically examines past work to identify the commonalities among the many published studies of neuroglia signaling. Although several studies have shown that astrocytes can impact short-term and long-term synaptic plasticity, further work is required to determine the requirement for astrocytic Ca2 þ and other second messengers in these processes. One of the roadblocks to the field advancing at a rapid pace has been technical. We predict that the novel experimental tools that have emerged in recent years will accelerate the field and likely disclose an entirely novel path of neuroglia signaling within the near future. © 2015 Cold Spring Harbor Laboratory Press. All rights reserved.

Lichtman M.A.,University of Rochester
Oncologist | Year: 2010

The aggregate of epidemiological studies indicates a significantly elevated risk for cancer in people with a high body mass index (BMI); a "dose-response" effect exists with increasing risk as BMI increases from the normal to overweight to obese categories. Successful sustained weight loss decreases future risk. The relationship of being overweight to the risk for leukemia in the aggregate has been supported in several large cohort studies and two meta-analyses of cohort and case-control studies. One meta-analysis found an elevated risk for each of the four major subtypes of leukemia. A significant association between the risk for non-Hodgkin's lymphoma and elevated BMI was supported by a meta-analysis of 13 cohort and nine case- control studies. The risk for diffuse large B-cell lymphoma may be especially significant. A high BMI increases the risk for myeloma, as judged by a meta-analysis of 11 cohort and four case-control studies. The biological relationship of obesity to the risk for cancer (biological plausibility) is unresolved. The two major causal final pathways could be "inductive" or "selective." The metabolic, endocrinologic, immunologic, and inflammatory like changes resulting from obesity may increase the cell mutation rate, dysregulate gene function, disturb DNA repair, or induce epigenetic changes, favoring the induction of neoplastic transformation (inductive). Alternatively, obesity may create an environment in which pre-existing clones that are dormant are permitted (selected) to emerge. © AlphaMed Press.

Turner D.H.,University of Rochester
Biopolymers | Year: 2013

Interpreting the tsunami of sequence information for RNA would be facilitated by an understanding of all the physical principles determining RNA structure. In principle, a complete understanding would make it computationally possible to find RNA sequences that fold for function and to predict their three-dimensional structure. It would, thus, also facilitate discovery of new principles relating structure to function. This review covers some of the progress in understanding RNA over roughly the preceding 40 years and suggests progress still to be made. Copyright © 2013 Wiley Periodicals, Inc.

Palis J.,University of Rochester
Blood | Year: 2014

In this issue of Blood, An et al provide human and murine transcriptome data revealing significant stage- and species-specific differences in gene expression during erythroblast maturation. © 2014 by The American Society of Hematology.

Berryman D.R.,University of Rochester
Medical Reference Services Quarterly | Year: 2012

Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries. © 2012 Copyright Taylor and Francis Group, LLC.

Ritchlin C.T.,University of Rochester
Journal of Rheumatology | Year: 2012

At the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), 24 trainees (rheumatology fellows and dermatology residents) engaged in research in psoriatic disease were invited to present their work at the Trainees Symposium, which preceded the GRAPPA meeting and was also attended by GRAPPA members and invited guests. Nineteen posters and 6 oral presentations were presented by the trainees, all of which are summarized here. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Tafen D.N.,U.S. National Energy Technology Laboratory | Tafen D.N.,URS Corporation | Long R.,University College Dublin | Prezhdo O.V.,University of Rochester
Nano Letters | Year: 2014

Assumptions about electron transfer (ET) mechanisms guide design of catalytic, photovoltaic, and electronic systems. We demonstrate that the mechanism of ET from a CdSe quantum dot (QD) into nanoscale TiO2 depends on TiO2 dimensionality. The injection into a TiO2 QD is adiabatic due to strong donor-acceptor coupling, arising from unsaturated chemical bonds on the QD surface, and low density of acceptor states. In contrast, the injection into a TiO2 nanobelt (NB) is nonadiabatic, because the state density is high, the donor-acceptor coupling is weak, and multiple phonons accommodate changes in the electronic energy. The CdSe adsorbant breaks symmetry of delocalized TiO2 NB states, relaxing coupling selection rules, and generating more ET channels. Both mechanisms can give efficient ultrafast injection. However, the dependence on system properties is very different for the two mechanisms, demonstrating that the fundamental principles leading to efficient charge separation depend strongly on the type of nanoscale material. © 2014 American Chemical Society.

Doyley M.M.,University of Rochester
Physics in Medicine and Biology | Year: 2012

Elastography is emerging as an imaging modality that can distinguish normal versus diseased tissues via their biomechanical properties. This paper reviews current approaches to elastography in three areasquasi-static, harmonic and transientand describes inversion schemes for each elastographic imaging approach. Approaches include first-order approximation methods; direct and iterative inversion schemes for linear elastic; isotropic materials and advanced reconstruction methods for recovering parameters that characterize complex mechanical behavior. The paper's objective is to document efforts to develop elastography within the framework of solving an inverse problem, so that elastography may provide reliable estimates of shear modulus and other mechanical parameters. We discuss issues that must be addressed if model-based elastography is to become the prevailing approach to quasi-static, harmonic and transient elastography: (1) developing practical techniques to transform the ill-posed problem with a well-posed one; (2) devising better forward models to capture the complex mechanical behavior of soft tissues and (3) developing better test procedures to evaluate the performance of modulus elastograms. © 2012 Institute of Physics and Engineering in Medicine.

Aslin R.N.,University of Rochester
Infancy | Year: 2012

Eye-trackers suitable for use with infants are now marketed by several commercial vendors. As eye-trackers become more prevalent in infancy research, there is the potential for users to be unaware of dangers lurking "under the hood" if they assume the eye-tracker introduces no errors in measuring infants' gaze. Moreover, the influx of voluminous data sets from eye-trackers requires users to think hard about what they are measuring and what these measures mean for making inferences about underlying cognitive processes. The present commentary highlights these concerns, both technical and interpretive, and reviews the five articles that comprise this Special Issue. © International Society on Infant Studies (ISIS).

Parker K.J.,University of Rochester
Ultrasound in Medicine and Biology | Year: 2015

For nearly 100y in the study of cyclical motion in materials, a particular phenomenon called "linear hysteresis" or "ideal hysteretic damping" has been widely observed. More recently in the field of shear wave elastography, the basic mechanisms underlying shear wave losses in soft tissues are in question. Could linear hysteresis play a role? An underlying theoretical question must be answered: Is there a real and causal physical model that is capable of producing linear hysteresis over a band of shear wave frequencies used in diagnostic imaging schemes? One model that can approximately produce classic linear hysteresis behavior, by examining a generalized Maxwell model with a specific power law relaxation spectrum, is described here. This provides a theoretical plausibility for the phenomenon as a candidate for models of tissue behavior. © 2015 World Federation for Ultrasound in Medicine & Biology.

Marie-Mitchell A.,Loma Linda University | O'Connor T.G.,University of Rochester
Academic Pediatrics | Year: 2013

Objective: To pilot test a tool to screen for adverse childhood experiences (ACE), and to explore the ability of this tool to distinguish early child outcomes among lower- and higher-risk children. Methods: This cross-sectional study used data collected of 102 children between the ages of 4 and 5 years presenting for well-child visits at an urban federally qualified health center. Logistic regression analyses adjusted for child sex, ethnicity, and birth weight were used to test the association between each dichotomized child outcome and risk exposure based on a 6-item (maltreatment suspected, domestic violence, substance use, mental illness, criminal behavior, single parent) and 7-item (plus maternal education) Child ACE tool. Results: Effect sizes were generally similar for the 6-item and 7-item Child ACE tools, with the exception of 2 subscales measuring development. The adjusted odds of behavior problems was higher for children with a higher compared to a lower 7-item Child ACE score (adjusted odds ratio [aOR] 3.12, 95% confidence interval [CI] 1.34-7.22), as was the odds of developmental delay (aOR 3.66, 95% CI 1.10-12.17), and injury visits (aOR 5.65, 95% CI 1.13-28.24), but lower for obesity (aOR 0.32, 95% CI 0.11-0.92). Conclusions: Brief tools can be used to screen for ACE and identify specific early child outcomes associated with ACE. We suggest that follow-up studies test the incorporation of the 7-item Child ACE tool into practice and track rates of child behavior problems, developmental delays, and injuries. © 2013 by Academic Pediatric Association.

Pedram A.,University of California at Irvine | Razandi M.,Long Beach | Lewis M.,Baylor College of Medicine | Hammes S.,University of Rochester | Levin E.R.,University of California at Irvine
Developmental Cell | Year: 2014

Steroid receptors are found in discrete cellular locations, but it is unknown whether extranuclear pools are necessary for normal organ development. To assess this, we developed a point mutant estrogen receptor α (ERα) knockin mouse (C451A) that precludes palmitoylation and membrane trafficking of the steroid receptor in all organs. Homozygous knockin female mice (nuclear-only ERα [NOER]) show loss of rapid signaling that occurs from membrane ERα in wild-type mice. Multiple developmental abnormalities were found, including infertility, relatively hypoplastic uteri, abnormal ovaries, stunted mammary gland ductal development, and abnormal pituitary hormone regulation in NOER mice. These abnormalities were rescued in heterozygous NOER mice that were comparable to wild-type mice. mRNAs implicated in organ development were often poorly stimulated by estrogen only in homozygous NOER mice. We conclude that many organs require membrane ERα and resulting signal transduction to collaborate with nuclear ERα for normal development and function. © 2014 Elsevier Inc.

Eisenberg R.,University of Rochester
Coordination Chemistry Reviews | Year: 2011

The discovery of trigonal prismatic (TP) coordination in tris(dithiolene) complexes is recounted. The research was stimulated by the efforts of Gray, Schrauzer, Holm and Davison in the 1960s on the chemistry of dithiolene complexes that showed multiple reversible electron transfer processes and challenged conventional oxidation state assignments. The structures of Re(S 2C 2Ph 2) 3, V(S 2C 2Ph 2) 3 and Mo(S 2C 2H 2) 3 were reported at that time. Bonding pictures based on semiempirical molecular orbital calculations were presented and the basis for stability of TP coordination was put forward based on partial oxidation of the unsaturated 1,2-dithiolate ligands. The structures of M(L) 3 n complexes for M=Groups 5-7 and n=0, -1, -2, -3 from the Cambridge structural database are tabulated. The results show that for any M(L) 3 system as the magnitude of n increases, the coordination geometry twists to intermediate between TP and octahedral. The notion of redox-non-innocence in the dithiolene ligands is revisited through the recent work of Wieghardt including two studies that focus on the molecular and electronic structures of Re(L) 3 n and V(L) 3 n complexes. New experimental work is briefly summarized and the bonding in these systems is reanalyzed. A comparison is given between the early studies of the 1960s and the experimentally and computationally more complete studies recently published. © 2010 Elsevier B.V.

Menton C.,University of Rochester
Theory of Computing Systems | Year: 2013

We study the behavior of Range Voting and Normalized Range Voting with respect to electoral control. Electoral control encompasses attempts from an election chair to alter the participation or structure of an election in order to change the outcome. We show that a voting system resists a case of control by proving that performing that case of control is computationally hard. Range Voting is a natural extension of approval voting, and Normalized Range Voting is a simple variant which alters each vote to maximize the potential impact of each voter. We show that Normalized Range Voting has among the largest known number of control resistances among natural voting systems. © 2012 Springer Science+Business Media New York.

Phizicky E.M.,University of Rochester | Hopper A.K.,Ohio State University
Genes and Development | Year: 2010

tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis. © 2010 by Cold Spring Harbor Laboratory Press.

Sanchez R.,CSIC - Institute of Materials Science | Sothmann B.,University of Geneva | Jordan A.N.,University of Rochester | Jordan A.N.,Chapman University
Physical Review Letters | Year: 2015

The thermoelectric properties of a three-terminal quantum Hall conductor are investigated. We identify a contribution to the thermoelectric response that relies on the chirality of the carrier motion rather than on spatial asymmetries. The Onsager matrix becomes maximally asymmetric with configurations where either the Seebeck or the Peltier coefficients are zero while the other one remains finite. Reversing the magnetic field direction exchanges these effects, which originate from the chiral nature of the quantum Hall edge states. The possibility to generate spin-polarized currents in quantum spin Hall samples is discussed. © 2015 American Physical Society.

Gao Y.,University of Rochester
Materials Science and Engineering R: Reports | Year: 2010

Surface and interface analytical studies have generated critical insight of the fundamental processes at interfaces involving organic semiconductors. I will review surface analytical studies of interface formation of organic semiconductors with different materials. Metal/organic interface is a focus of both device engineering and basic science, since it is a key factor in nearly all important aspects of device performances, including operation voltages, degradation, and efficiency. I will discuss metal-organic interface dipole formation, charge transfer, chemical reaction, energy level alignment, in-diffusion, quenching of luminescence and possible recovery of it. The effect of the insertion of ultra-thin interlayers such as LiF and doping by alkali metals will also be discussed. In organic/organic interface, the energy offset between the two dissimilar organic materials is vitally important to efficient device operation of organic light emitting diodes (OLED), as well as change separation at donor-acceptor interface in organic photovoltaic devices (OPV). I will discuss the interface energy level alignment, band bending, Debye screening, and charge separation dynamics as observed in surface analytical studies, and the implications to OLED and OPV. The interfaces of OSCs with other inorganic materials are also important. For organic thin film transistors (OTFT), the electronic properties of the interface formed between the organic and the dielectric strongly influences the current-voltage characteristics, as the electronic activity has been shown to occur primarily at the interface between the dielectric and the organic materials. I will review the interface formation of OSCs with dielectric materials and with indium-tin-oxide (ITO), a material whose transparency and conductivity make it indispensable for a number of opto-electronic applications and whose electronic properties and energy level alignment with organics have proven dramatically altered by surface treatments. © 2010 Elsevier B.V. All rights reserved.

Illig K.A.,University of Rochester
Seminars in Vascular Surgery | Year: 2011

The failure of an autogenous or prosthetic arteriovenous hemodialysis access is usually related to the failure of the venous outflow resulting from a stenosis somewhere in the venous system, commonly at the venous anastomosis for a prosthetic access or within the central veins. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines state that percutaneous transluminal venoplasty with or without stenting is the preferred initial treatment for a central venous stenosis, but the results of these therapies have been have relatively disappointing when analyzed as a whole. Although endoluminal intervention works well (and is, indeed, the primary option) for treating areas of stenosis surrounded by soft tissue, we believe stenoses occurring at the costoclavicular junction are caused by extrinsic bony compression and, therefore, should be considered dialysis-associated venous thoracic outlet syndrome. The treatment of venous thoracic outlet syndrome, based on decades of experience, generally requires bony decompression for long-term patency. In the last 2 years, we have treated 12 patients with dialysis-associated venous thoracic outlet syndrome with surgical decompression of the thoracic outlet. Functional patency was achieved in 75% of patients at a mean follow-up of 8 months. We would contend that not all central vein stenoses are equivalent and that an individualized approach is most appropriate based on the extent and anatomic location of the lesion. © 2011 Elsevier Inc.

Ritchlin C.,University of Rochester
Journal of Rheumatology | Year: 2012

Biomarkers can provide insights into disease pathogenesis and assist clinicians in screening patients with psoriasis for arthritis. They can also help to stratify patients who are at risk for progression to bone destruction or ankylosis. Biomarkers in psoriatic disease are still in the discovery phase, but the field is advancing at a rapid pace. This review discusses definitions of the different types of biomarkers and the development of markers that reflect preclinical and early psoriatic arthritis along with those that may be able to predict disease severity and response to anti-tumor necrosis factor agents. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Thiele R.G.,University of Rochester
Rheumatic Disease Clinics of North America | Year: 2012

Ultrasonography is an elegant tool for the detection of tenosynovitis, synovitis, and erosions very early in rheumatoid arthritis, and the presence of a power Doppler signal is one of the best predictors of joint damage. Although clinical scores remain the mainstay of disease activity assessment, ultrasonography has proved to be a remarkably robust tool for reliable assessment of changes in rheumatoid arthritis. There is no evidence to suggest that problems with operator dependence would be greater than with other imaging modalities or physical examination, if performed by trained providers. © 2012 Elsevier Inc.

Eisenberg R.,University of Rochester | Gray H.B.,California Institute of Technology
Inorganic Chemistry | Year: 2011

Noninnocence in inorganic chemistry traces its roots back half a century to work that was done on metal complexes containing unsaturated dithiolate ligands. In a flurry of activity in the early 1960s by three different research groups, homoleptic bis and tris complexes of these ligands, which came to be known as dithiolenes, were synthesized, and their structural, electrochemical, spectroscopic, and magnetic properties were investigated. The complexes were notable for facile one-electron transfers and intense colors in solution, and conventional oxidation-state descriptions could not account for their electronic structures. The bis complexes were, in general, found to be square-planar, including the first examples of this geometry for paramagnetic complexes and different formal d n configurations. Several of the neutral and monoanionic tris complexes were found to have trigonal-prismatic coordination, the first time that this geometry had been observed in molecular metal complexes. Electronic structural calculations employing extended Hückel and other semiempirical computational methods revealed extensive ligand-metal mixing in the frontier orbitals of these systems, including the observation of structures in which filled metal-based orbitals were more stable than ligand-based orbitals of the same type, suggesting that the one-electron changes upon oxidation or reduction were occurring on the ligand rather than on the metal center. A summary of this early work is followed with a brief section on the current interpretations of these systems based on more advanced spectroscopic and computational methods. The take home message is that the early work did indeed provide a solid foundation for what was to follow in investigations of metal complexes containing redox-active ligands. © 2011 American Chemical Society.

Gerich J.,University of Rochester
Diabetes Research and Clinical Practice | Year: 2010

Attenuation of the prandial incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), contributes to hyperglycemia in type 2 diabetes mellitus (T2DM). Since the launch of sitagliptin in 2006, a compelling body of evidence has accumulated showing that dipeptidyl peptidase-4 (DPP-4) inhibitors, which augment endogenous GLP-1 and GIP levels, represent an important advance in the management of T2DM. Currently, three DPP-4 inhibitors - sitagliptin, vildagliptin and saxagliptin - have been approved in various countries worldwide. Several other DPP-4 inhibitors, including linagliptin and alogliptin, are currently in clinical development. As understanding of, and experience with, the growing number of DPP-4 inhibitors broadens, increasing evidence suggests that the class may offer advantages over other antidiabetic drugs in particular patient populations. The expanding evidence base also suggests that certain differences between DPP-4 inhibitors may prove to be clinically significant. This therapeutic diversity should help clinicians tailor treatment to the individual patient, thereby increasing the proportion that safely attain target HbA1c levels, and reducing morbidity and mortality. This review offers an overview of DPP-4 inhibitors in T2DM and suggests some characteristics that may provide clinically relevant differentiators within this class. © 2010 Elsevier Ireland Ltd.

Chapman B.P.,University of Rochester
American Journal of Epidemiology | Year: 2013

In this issue of the Journal, Jokela et al. (Am J Epidemiol. 2013;178(5):667-675) scrutinize the association between personality phenotype and all-cause mortality in remarkable detail by using an "individual- participant meta-analysis" design. Across 7 large cohorts varying in demographics and methods of personality measurement, they find varying prospective associations for 4 dimensions of the five-factor (or "Big Five") model of personality, but robust and consistent prospective associations for Big Five dimension of "conscientiousness." Jokela et al. place an important exclamation point on a long era of study of this topic and hint directly and indirectly at new avenues for this line of research. I consider the following 3 areas particularly rife for further inquiry: the role of genetics in personality and health studies; the role of personality in social inequalities in health; and the health policy and clinical implications of work like that of Jokela et al., including the potential role of personality phenotype in the evolution of personalized medicine. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

Smrcka A.V.,University of Rochester
Science Signaling | Year: 2015

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) control a wide diversity of cellular responses throughout biology. Each GPCR couples to a distinct array of members of the G protein family to control the specificity and diversity of these responses and ultimately determines the therapeutic efficacy of drugs that target these receptors. In this issue of Science Signaling, Masuho et al. developed an approach to broadly defining these GPCR coupling fingerprints.