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Irvine, CA, United States

The University of California, Irvine , is a public research university located in Irvine, California, and one of the 10 general campuses in the University of California system. UCI has over 30,000 students, 1,100 faculty members and 9,000 staff. Times Higher Education in 2013 ranked UC Irvine 1st among all US universities and 5th among the top 100 global universities under 50 years old.UC Irvine is considered a Public Ivy and offers 80 undergraduate degrees and 98 graduate and professional degrees. The university is designated as having very high research activity in the Carnegie Classification of Institutions of Higher Education, and in fiscal year 2012 had $350 million in research and development expenditures according to the National Science Foundation. UC Irvine became a member of the Association of American Universities in 1996, and is the youngest university to hold membership. The university also administers the UC Irvine Medical Center, a large teaching hospital, and its affiliated health science system in the city of Orange; the University of California, Irvine, Arboretum; and a portion of the University of California Natural Reserve System.UCI was one of three new UC campuses established in the 1960s to accommodate growing enrollments across the UC system. A site in Orange County was identified in 1959, and in the following year the Irvine Company sold the University of California 1,000 acres of land for one dollar to establish the new campus. President Lyndon B. Johnson dedicated the campus in 1964.The UC Irvine Anteaters compete in 18 men's and women's sports in the NCAA Division I as members of the Big West Conference and the Mountain Pacific Sports Federation. The Anteaters have won 28 national championships in nine different team sports, 64 Anteaters have won individual national championships, and 53 Anteaters have competed in the Olympics. Wikipedia.


Lakes K.D.,University of California at Irvine
Psychological Assessment | Year: 2013

One factor that affects the reliability of observed scores is restriction of range on the construct measured for a particular group of study participants. This study illustrates how researchers can use generalizability theory to evaluate the impact of restriction of range in particular sample characteristics on the generalizability of test scores and to estimate how changes in measurement design could improve the generalizability of the test scores. An observer-rated measure of child self-regulation (Response to Challenge Scale; Lakes, 2011) is used to examine scores for 198 children (Grades K through 5) within the generalizability theory (GT) framework. The generalizability of ratings within relatively developmentally homogeneous samples is examined and illustrates the effect of reduced variance among ratees on generalizability. Forecasts for g coefficients of various D study designs demonstrate how higher generalizability could be achieved by increasing the number of raters or items. In summary, the research presented illustrates the importance of and procedures for evaluating the generalizability of a set of scores in a particular research context. © 2012 American Psychological Association.


Luong G.,Max Planck Institute for Human Development | Charles S.T.,University of California at Irvine
Developmental Psychology | Year: 2014

Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults' differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict avoidance/de-escalation, self-distraction) during a controlled negative social interaction may explain age differences in affective and cardiovascular responses to the conflict discussion. Participants (N = 159; 80 younger adults, 79 older adults) discussed hypothetical dilemmas with disagreeable confederates. Throughout the laboratory session, participants' subjective emotional experience, blood pressure, and pulse rate were assessed. Older adults generally exhibited less reactivity (negative affect reactivity, diastolic blood pressure reactivity, and pulse rate reactivity) to the task and more pronounced positive and negative affect recovery following the task than did younger adults. Older adults appraised the task as more enjoyable and the confederate as more likeable and more strongly endorsed goals to perform well on the task, which mediated age differences in negative affect reactivity, pulse rate reactivity, and positive affect recovery (i.e., increases in posttask positive affect), respectively. In addition, younger adults showed increased negative affect reactivity with greater use of self-distraction, whereas older adults did not. Together, findings suggest that older adults respond less negatively to unpleasant social interactions than younger adults, and these responses are explained in part by older adults' pursuit of different motivational goals, less threatening appraisals of the social interaction, and more effective use of self-distraction, compared with younger adults. © 2014 American Psychological Association.


Zoccola P.M.,Ohio University | Dickerson S.S.,University of California at Irvine
Journal of Psychosomatic Research | Year: 2012

Objective and methods: For individuals who ruminate, or mentally rehearse past stressful events, the physiological effects of a stressor may be longer lasting. This is well-supported within the cardiovascular domain. In the context of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol, the results are inconsistent. This review summarizes key theoretical and methodological issues that contribute to these mixed findings among the 15 studies to date that have examined the association between rumination and cortisol. Results: State measures of rumination were consistently linked to increased cortisol concentrations. Stress-related rumination questionnaires were often positively associated with cortisol, whereas depression-related rumination scales predicted lower cortisol concentrations or were unrelated to cortisol. Rumination manipulations in the laboratory (e.g., ruminative self-focused writing tasks compared to distraction writing tasks) influenced cortisol concentrations, but often did not increase cortisol relative to baseline values. Studies that utilized social-evaluative stressor tasks to examine the relationship between rumination and cortisol levels generally showed that rumination predicted greater cortisol reactivity or delayed recovery. Results from studies examining rumination and basal cortisol or the cortisol awakening response were inconsistent. Conclusion: The ways in which researchers conceptualize and assess rumination and the associated cortisol response influences the association between rumination and cortisol. Suggestions for future studies in this area of research are provided. © 2012 Elsevier Inc.


Yu Y.,University of California at Irvine
Statistics and Computing | Year: 2011

A fast new algorithm is proposed for numerical computation of (approximate) D-optimal designs. This cocktail algorithm extends the well-known vertex direction method (VDM; Fedorov in Theory of Optimal Experiments, 1972) and the multiplicative algorithm (Silvey et al. in Commun. Stat. Theory Methods 14:1379-1389, 1978), and shares their simplicity and monotonic convergence properties. Numerical examples show that the cocktail algorithm can lead to dramatically improved speed, sometimes by orders of magnitude, relative to either the multiplicative algorithm or the vertex exchange method (a variant of VDM). Key to the improved speed is a new nearest neighbor exchange strategy, which acts locally and complements the global effect of the multiplicative algorithm. Possible extensions to related problems such as nonparametric maximum likelihood estimation are mentioned. © 2010 The Author(s).


Kleinfelder S.A.,University of California at Irvine
IEEE Transactions on Nuclear Science | Year: 2013

The ARIANNA experiment will observe high-energy cosmogenic neutrino signatures via a large array of autonomous radio listening stations dispersed on the Ross Ice Shelf in Antarctica. Each station in the projected array of 900 stations will contain RF antennas, amplifiers, digitization, real-time triggering circuitry, a CPU with solid-state data storage, and redundant remote communications paths. Power is provided by both sun and wind. Two prototype stations have been installed, with a hexagonal array of seven stations, with each positioned 1 km apart, due for deployment over the next two seasons. The station's core data acquisition system includes four channels of analog sampling circuits that operate at 2 GHz and achieve over 11 bits of dynamic range. These circuits sample continuously over a 128-sample circular analog storage array. The circuits use a phase-locked loop to generate the 2 GHz internal sample clocking from a {\sim} 30 MHz external clock. Unlike most previous such designs, the high-speed sample clocking is completely synchronous and has very high timing stability, with about 1 ppm RMS jitter. The sampling circuits include the ability to produce a real-time trigger based on pattern-matching of the incoming waveform. Up to 72 patterns can be searched for in parallel, and each pattern looks at 8 consecutive samples, requiring that any or all of the samples be above a high threshold, below a separate low threshold, in-between the two thresholds, or a 'don't care' condition. Each station also includes computing and solid-state event storage, environmental monitoring of voltage and power consumption, wind and temperature conditions, and both long-distance wireless to McMurdo Station and Iridium satellite communications. For the 2011-2012 austral season, about 1.4 million events were acquired between the second station's installation on December 21, 2011 and March 15, 2012. © 1963-2012 IEEE.


Xu G.,University of California at Irvine
Proceedings of the Conference on Object-Oriented Programming Systems, Languages, and Applications, OOPSLA | Year: 2012

A big source of run-time performance problems in largescale, object-oriented applications is the frequent creation of data structures (by the same allocation site) whose lifetimes are disjoint, and whose shapes and data content are always the same. Constructing these data structures and computing the same data values many times is expensive; significant performance improvements can be achieved by reusing their instances, shapes, and/or data values rather than reconstructing them. This paper presents a run-time technique that can be used to help programmers find allocation sites that create such data structures to improve performance. At the heart of the technique are three reusability definitions and novel summarization approaches that compute summaries for data structures based on these definitions. The computed summaries are used subsequently to find data structures that have disjoint lifetimes, and/or that have the same shapes and content. We have implemented this technique in the Jikes RVM and performed extensive studies on large-scale, real-world programs. We describe our experience using six case studies, in which we have achieved large performance gains by fixing problems reported by our tool.


Cadigan K.M.,University of Michigan | Waterman M.L.,University of California at Irvine
Cold Spring Harbor Perspectives in Biology | Year: 2012

T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors are the major end point mediators of Wnt/Wingless signaling throughout metazoans. TCF/LEFs are multifunctional proteins that use their sequence-specific DNA-binding and context-dependent interactions to specify which genes will be regulated by Wnts. Much of the work to define their actions has focused on their ability to repress target gene expression when Wnt signals are absent and to recruit β-catenin to target genes for activation when Wnts are present. Recent advances have highlighted how these on/off actions are regulated by Wnt signals and stabilized β-catenin. In contrast to invertebrates, which typically contain one TCF/LEF protein that can both activate and repress Wnt targets, gene duplication and isoform complexity of the family in vertebrates have led to specialization, in which individual TCF/LEF isoforms have distinct activities. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.


Frebel A.,Massachusetts Institute of Technology | Simon J.D.,Carnegie Institution of Washington | Kirby E.N.,University of California at Irvine
Astrophysical Journal | Year: 2014

We present Magellan/MIKE and Keck/HIRES high-resolution spectra of six red giant stars in the dwarf galaxy Segue 1. Including one additional Segue 1 star observed by Norris et al., high-resolution spectra have now been obtained for every red giant in Segue 1. Remarkably, three of these seven stars have metallicities below [Fe/H] = -3.5, suggesting that Segue 1 is the least chemically evolved galaxy known. We confirm previous medium-resolution analyses demonstrating that Segue 1 stars span a metallicity range of more than 2 dex, from [Fe/H] = -1.4 to [Fe/H] = -3.8. All of the Segue 1 stars are α-enhanced, with [α/Fe] ∼ 0.5. High α-element abundances are typical for metal-poor stars, but in every previously studied galaxy [α/Fe] declines for more metal-rich stars, which is typically interpreted as iron enrichment from supernova Ia. The absence of this signature in Segue 1 indicates that it was enriched exclusively by massive stars. Other light element abundance ratios in Segue 1, including carbon enhancement in the three most metal-poor stars, closely resemble those of metal-poor halo stars. Finally, we classify the most metal-rich star as a CH star given its large overabundances of carbon and s-process elements. The other six stars show remarkably low neutron-capture element abundances of [Sr/H] < -4.9 and [Ba/H] < -4.2, which are comparable to the lowest levels ever detected in halo stars. This suggests minimal neutron-capture enrichment, perhaps limited to a single r-process or weak s-process synthesizing event. Altogether, the chemical abundances of Segue 1 indicate no substantial chemical evolution, supporting the idea that it may be a surviving first galaxy that experienced only one burst of star formation. © 2014. The American Astronomical Society. All rights reserved..


Heidbrink W.W.,University of California at Irvine
Review of Scientific Instruments | Year: 2010

The fast-ion Dα (FIDA) diagnostic is an application of charge-exchange recombination spectroscopy. Fast ions that neutralize in an injected neutral beam emit Balmer- α light with a large Doppler shift. The spectral shift is exploited to distinguish the FIDA emission from other bright sources of Dα light. Background subtraction is the main technical challenge. A spectroscopic diagnostic typically achieves temporal, energy, and transverse spatial resolution of ∼1 ms, ∼10 keV, and ∼2 cm, respectively. Installations that use narrow-band filters achieve high spatial and temporal resolution at the expense of spectral information. For high temporal resolution, the bandpass-filtered light goes directly to a photomultiplier, allowing detection of ∼50 kHz oscillations in FIDA signal. For two-dimensional spatial profiles, the bandpass-filtered light goes to a charge-coupled device camera; detailed images of fast-ion redistribution at instabilities are obtained. Qualitative and quantitative models relate the measured FIDA signals to the fast-ion distribution function. The first quantitative comparisons between theory and experiment found excellent agreement in beam-heated magnetohydrodynamics (MHD)-quiescent plasmas. FIDA diagnostics are now in operation at magnetic-fusion facilities worldwide. They are used to study fast-ion acceleration by ion cyclotron heating, to detect fast-ion transport by MHD modes and microturbulence, and to study fast-ion driven instabilities. © 2010 American Institute of Physics.


Vaziri N.D.,University of California at Irvine
American Journal of Kidney Diseases | Year: 2013

Although judicious use of intravenous iron preparations is an indispensable part of anemia treatment in hemodialysis patients, their excessive and indiscriminate use can have insidious but serious adverse consequences. With recent implementation of the bundling reimbursement policy, use of intravenous iron preparations in the hemodialysis population has markedly increased. Excessive use of these agents potentially can exacerbate oxidative stress, inflammation, endothelial dysfunction, cardiovascular disease, and immune deficiency and potentially increases the risk of microbial infections in this population. Most of these adverse effects are mediated by iron-catalyzed generation of reactive oxygen species and the resultant cell injury and dysfunction. This review is intended to provide an overview of the nature and mechanisms of the adverse effects of iron overload and call for the judicious use of these vitally important products. © 2013 National Kidney Foundation, Inc.


Hayes W.,University of California at Irvine | Sun K.,Imperial College London | Przulj N.,Imperial College London
Bioinformatics | Year: 2013

Motivation: Large amounts of biological network data exist for many species. Analogous to sequence comparison, network comparison aims to provide biological insight. Graphlet-based methods are proving to be useful in this respect. Recently some doubt has arisen concerning the applicability of graphlet-based measures to low edge density networks-in particular that the methods are 'unstable'-and further that no existing network model matches the structure found in real biological networks.Results: We demonstrate that it is the model networks themselves that are 'unstable' at low edge density and that graphlet-based measures correctly reflect this instability. Furthermore, while model network topology is unstable at low edge density, biological network topology is stable. In particular, one must distinguish between average density and local density. While model networks of low average edge densities also have low local edge density, that is not the case with protein-protein interaction (PPI) networks: real PPI networks have low average edge density, but high local edge densities, and hence, they (and thus graphlet-based measures) are stable on these networks. Finally, we use a recently devised non-parametric statistical test to demonstrate that PPI networks of many species are well-fit by several models not previously tested. In addition, we model several viral PPI networks for the first time and demonstrate an exceptionally good fit between the data and theoretical models. © 2013 The Author.


Matthew R.,University of California at Irvine
Climatic Change | Year: 2014

Peacebuilding countries are concentrated in areas of heightened vulnerability to climate change impacts, and almost certainly lack the capacity to manage these impacts. In spite of this overlap, climate change adaptation and mitigation projects are typically excluded from peacebuilding activities. This is particularly alarming given that many analysts believe climate change will trigger, amplify or perpetuate humanitarian crises, population displacement, political extremism and violent conflict in the regions in which most peacebuilding operations take place. This paper investigates opportunities for integrating climate change into peacebuilding. It identifies three obstacles to this integration-the lack of climate change tools and policies that can be easily introduced into typical peacebuilding programming; the skepticism and complacency of the donor community; and tensions between the objectives and timeframes of peacebuilding and those of climate change response. The paper then examines opportunities to integrate climate change into four principal programmatic areas of peacebuilding-socio-economic recovery, politics and governance, security and rule of law, and human rights-and concludes that more attention needs to be given to these opportunities in order to build resilience and reduce the likelihood of more daunting and costly challenges in the future. © 2013 Springer Science+Business Media Dordrecht.


Chu C.,Stanford University | Spitale R.C.,Stanford University | Spitale R.C.,University of California at Irvine | Chang H.Y.,Stanford University | Chang H.Y.,Howard Hughes Medical Institute
Nature Structural and Molecular Biology | Year: 2015

Thousands of long noncoding RNAs (lncRNAs) have been discovered, but their functional characterization has been slowed by a limited set of research tools. Here we review emerging RNA-centric methods to interrogate the intrinsic structure of lncRNAs as well as their genomic localization and biochemical partners. Understanding these technologies, including their advantages and caveats, and developing them in the future will be essential to progress from description to comprehension of the myriad roles of lncRNAs. © 2015 Nature America, Inc. All rights reserved.


Duncan G.J.,University of California at Irvine
Child Development | Year: 2012

As with any discipline, the field of child development progresses by both deepening and broadening its conceptual and empirical perspective. The rewards to refinement are impressive, but there is little need for encouragement in this area, since existing disciplines, universities, and funding agencies reward depth. The current study makes the case for breadth: for combining insights from different disciplines and methods in synergistic ways. Examples include influences of family poverty on children, inequality and child development, and methods for assessing impacts of policies. Drawing together disparate ideas from different research traditions can be not only time consuming and frustrating but also deeply rewarding, both scientifically and personally. The study closes with thoughts about how departments, universities, funding agencies, and Society for Research in Child Development itself might promote interdisciplinary inquiry. © 2012 The Author. Child Development © 2012 Society for Research in Child Development, Inc.


Chernyshev A.L.,University of California at Irvine
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We discuss threshold field dependence of the decay rate of the uniform magnon mode in yttrium iron garnet (YIG) thin films. We demonstrate that decays must cease to exist in YIG films of thickness less than 1μm, the length scale defined by the exchange length. We show that due to the symmetry of the three-magnon coupling, the decay rate is linear in ΔH=(H c-H) in the vicinity of the threshold field H c instead of the steplike Γ k=0ΘΔH expected from the two-dimensional character of magnon excitations in such films. For thicker films, the decay rate should exhibit multiple steps due to thresholds for decays into a sequence of the two-dimensional magnon bands. For yet thicker films, such thresholds merge and crossover to the three-dimensional single-mode behavior: Γ k=0 |ΔH |3 /2. © 2012 American Physical Society.


Paydar K.Z.,University of California at Irvine
Plastic and Reconstructive Surgery | Year: 2010

Background: Free flap success depends on rapid identification and subsequent salvage of failing flaps. Conventional free flap monitoring techniques require an external component, whereas an implantable monitor readily indicates changes in free flap perfusion, especially in buried flaps used in head and neck reconstruction. Methods: This is a retrospective review of 169 consecutive head and neck free flaps reconstructed mostly for oncologic surgical defects in 155 patients from April of 2000 to December of 2006, all of which were monitored by an implantable venous Doppler device. Results: There were 25 buried flaps, representing 14.8 percent of 169 flaps. Flap ischemia caused by thrombosis (n = 16), hematoma (n = 2), or tight closure (n = 1) occurred in 11.2 percent of the cases. The Doppler probe detected all of the failing free flaps, and we were able to salvage 18 of 19 ischemic flaps (94.7 percent). All Doppler-detected ischemic nonburied flaps (100 percent) and three of the four buried free flaps were salvaged (75 percent). There were 33 total complications (19.5 percent), with thrombosis occurring in 9.5 percent of the flaps, whereas 12 flaps required reoperation for vascular revision (7.1 percent). The mortality rate was less than 1 percent (0.6 percent). The overall success rate using the implantable Doppler probe was 98.2 percent, which was similar to that of the most recent reported cases of all free flaps in the literature, with significant improvement in the salvage rate for both buried and nonburied head and neck free flaps. Conclusion: The implantable Doppler probe is a useful monitoring device in buried free flaps and should be considered for use in head and neck reconstruction. Copyright © 2010 by the American Society of Plastic Surgeons.


Kim H.,University of California at Irvine
Sociology of Health and Illness | Year: 2013

Germinated brown rice (GBR) is a functional food, whose benefits for chronic diseases have been demonstrated by scientific research on a single constituent of GBR, gamma aminobutyric acid. This article examines the processes through which the emphasis on biomedical rationality made during the production and consumption of functional foods is embedded in the complicated social contexts of the post-1990s. In the case of GBR, the Korean government, food scientists, mass media and consumers have added cultural accounts to the biomedical understanding of foods. In particular, consumers have transformed their households and online communities into a place for surveillance medicine. Functional foods are embedded in multiple actors' perspectives on what healthy foods mean and how and where the risks of chronic diseases should be managed. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/JohnWiley & Sons Ltd.


Wang Y.,University of California at Irvine
Electrochimica Acta | Year: 2012

Lithium-air batteries show a great promise in electrochemical energy storage with their theoretical specific energy comparable to gasoline. Discharge products such as Li 2O 2 or Li 2CO 3 are insoluble in several major nonaqueous electrolytes, and consequently precipitate at the reaction sites. These materials are also low in electric conductivity. As a result, the reduced pore space and electrode passiviation increase the reaction resistance and consequently reduce discharge voltage and capability. This work presents a modeling study of discharge product precipitation and effects for lithium-air batteries. Theoretical analysis is also performed to evaluate the variations of important quantities including temperature, species concentrations, and electric potentials. Precipitation growth modes on planar, cylindrical and spherical surfaces are discussed. A new approach, following the study of ice formation in PEM fuel cells, is proposed. Validation is carried out against experimental data in terms of discharge voltage loss. © 2012 Elsevier Ltd. All rights reserved.


Kwon Y.J.,University of California at Irvine
Accounts of Chemical Research | Year: 2012

Silencing the expression of a target gene by RNA interference (RNAi) shows promise as a potentially revolutionizing strategy for manipulating biological (pathological) pathways at the translational level. However, the lack of reliable, efficient, versatile, and safe means for the delivery of small interfering RNA (siRNA) molecules, which are large in molecular weight, negatively charged, and subject to degradation, has impeded their use in basic research and therapy. Polyplexes of siRNA and polymers are the predominant mode of siRNA delivery, but innovative synthetic strategies are needed to further evolve them to generate the desired biological and therapeutic effects. This Account focuses on the design of polymeric vehicles for siRNA delivery based on an understanding of the molecular interactions between siRNA and cationic polymers. Ideal siRNA/polymer polyplexes should address an inherent design dilemma for successful gene silencing: (1) Cationic polymers must form tight complexes with siRNA via attractive electrostatic interactions during circulation and cellular internalization and (2) siRNA must dissociate from its cationic carrier in the cytoplasm before they are loaded into RNA-induced silencing complex (RISC) and initiate gene silencing. The physicochemical properties of polymers, which dictate their molecular affinity to siRNA, can be programmed to be altered by intracellular stimuli, such as acidic pH in the endosome and cytosolic reducers, subsequently inducing the siRNA/polymer polyplex to disassemble. Specific design goals include the reduction of the cationic density and the molecular weight, the loss of branched structure, and changes in the hydrophilicity/hydrophobicity of the polymeric siRNA carriers, via acid-responsive degradation and protonation processes within the endosome and glutathione (GSH)-mediated reduction in the cytoplasm, possibly in combination with gradual stimuli-independent hydrolysis. Acetals/ketals are acid-cleavable linkages that have been incorporated into polymeric materials for stimuli-responsive gene and drug delivery. Tailoring the ketalization ratio and the molecular weight of ketalized branched PEI (K-BPEI) offers molecular control of the intracellular trafficking of siRNA/polymer polyplexes and, therefore, the gene silencing efficiency. The ketalization of linear PEI (K-LPEI) enhances gene silencing in vitro and in vivo by improving siRNA complexation with the polymer during circulation and cellular internalization, supplementing proton buffering efficiency of the polymer in the endosome, and facilitating siRNA dissociation from the polymer in the cytoplasm, in a serum-resistant manner. Spermine polymerization via ketalization and esterification for multistep intracellular degradations provides an additional polymeric platform for improved siRNA delivery and highly biocompatible gene silencing. The chemistry presented in this Account will help lay the foundation for the development of innovative and strategic approaches that advance RNAi technology. © 2011 American Chemical Society.


Webb C.H.,University of California at Irvine
RNA biology | Year: 2011

HDV ribozymes catalyze their own scission from the transcript during rolling circle replication of the hepatitis delta virus. In vitro selection of self-cleaving ribozymes from a human genomic library revealed an HDV-like ribozyme in the second intron of the human CPEB3 gene and recent results suggest that this RNA affects episodic memory performance. Bioinformatic searches based on the secondary structure of the HDV/CPEB3 fold yielded numerous functional ribozymes in a wide variety of organisms. Genomic mapping of these RNAs suggested several biological roles, one of which is the 5' processing of non-LTR retrotransposons. The family of HDV-like ribozymes thus continues to grow in numbers and biological importance.


Thompson W.C.,University of California at Irvine
Australian Journal of Forensic Sciences | Year: 2011

Concern about contextual bias has led some authorities to recommend that forensic scientists know as little as possible about the facts of the underlying case when interpreting physical evidence; but concern about contextual ignorance has led other authorities to recommend, to the contrary, that forensic scientists know as much as possible in order to frame questions properly. This article recommends a case manager model that addresses both concerns. This article also responds to standard objections to the use of blind procedures in forensic science, explaining why contextual bias cannot be conquered through willpower; why use of domain-irrelevant contextual facts undermines the value of forensic evidence; how a well-known cognitive illusion (the 'introspection illusion') can mislead forensic scientists into thinking they can control their biases, when they cannot; and how a paradoxical feature of forensic inference (the 'criminalist's paradox') can mislead analysts into thinking they should rely on contextual facts, when they should not. © 2011 Australian Academy of Forensic Sciences.


Lee R.H.,University of California at Irvine
World Journal of Gastroenterology | Year: 2013

Quality colonoscopy is defined by the detection of adenomatous polyps at least 25% of the time in men and 15% of the time in women. Recent studies highlight the importance of key aspects of high quality colonoscopy. These include the amount of time spent examining the mucosa or withdrawal time, the quality of withdrawal technique and new technologies which seek to maximize the detection of colonic neoplasia. This review summarizes the latest evidence regarding the role of time, technique and technology in shaping the quality of colonoscopy. © 2013 Baishideng. All rights reserved.


Wodarz D.,University of California at Irvine
Ecology and Evolution | Year: 2013

Giant viruses contain large genomes, encode many proteins atypical for viruses, replicate in large viral factories, and tend to infect protists. The giant virus replication factories can in turn be infected by so called virophages, which are smaller viruses that negatively impact giant virus replication. An example is Mimiviruses that infect the protist Acanthamoeba and that are themselves infected by the virophage Sputnik. This study examines the evolutionary dynamics of this system, using mathematical models. While the models suggest that the virophage population will evolve to increasing degrees of giant virus inhibition, it further suggests that this renders the virophage population prone to extinction due to dynamic instabilities over wide parameter ranges. Implications and conditions required to avoid extinction are discussed. Another interesting result is that virophage presence can fundamentally alter the evolutionary course of the giant virus. While the giant virus is predicted to evolve toward increasing its basic reproductive ratio in the absence of the virophage, the opposite is true in its presence. Therefore, virophages can not only benefit the host population directly by inhibiting the giant viruses but also indirectly by causing giant viruses to evolve toward weaker phenotypes. Experimental tests for this model are suggested. © 2013 The Authors. Ecology and Evolution.


Turney K.,University of California at Irvine
Journal of Health and Social Behavior | Year: 2014

Stress proliferation theory suggests that parental incarceration may have deleterious intergenerational health consequences. In this study, I use data from the 2011–2012 National Survey of Children’s Health (NSCH) to estimate the relationship between parental incarceration and children’s fair or poor overall health, a range of physical and mental health conditions, activity limitations, and chronic school absence. Descriptive statistics show that children of incarcerated parents are a vulnerable population who experience disadvantages across an array of health outcomes. After adjusting for demographic, socioeconomic, and familial characteristics, I find that parental incarceration is independently associated with learning disabilities, attention deficit disorder and attention deficit hyperactivity disorder, behavioral or conduct problems, developmental delays, and speech or language problems. Taken together, results suggest that children’s health disadvantages are an overlooked and unintended consequence of mass incarceration and that incarceration, given its unequal distribution across the population, may have implications for population-level racial-ethnic and social class inequalities in children’s health. © American Sociological Association 2014.


Leslie F.M.,University of California at Irvine
BMC Medicine | Year: 2013

A recent preclinical study has shown that not only maternal smoking but also grandmaternal smoking is associated with elevated pediatric asthma risk. Using a well-established rat model of in utero nicotine exposure, Rehan et al. have now demonstrated multigenerational effects of nicotine that could explain this 'grandmother effect'. F1 offspring of nicotine-treated pregnant rats exhibited asthma-like changes to lung function and associated epigenetic changes to DNA and histones in both lungs and gonads. These alterations were blocked by co-administration of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, implicating downregulation of this receptor in the nicotine effects. F2 offspring of F1 mated animals exhibited similar changes in lung function to that of their parents, even though they had never been exposed to nicotine. Thus epigenetic mechanisms appear to underlie the multigenerational transmission of a nicotine-induced asthma-like phenotype. These findings emphasize the need for more effective smoking cessation strategies during pregnancy, and cast further doubt on the safety of using nicotine replacement therapy to reduce tobacco use in pregnant women.Please see related article: http://www.biomedcentral.com/1741-7015/10/129. © 2013 Leslie; licensee BioMed Central Ltd.


Alicea J.,University of California at Irvine
Reports on Progress in Physics | Year: 2012

The 1937 theoretical discovery of Majorana fermions - whose defining property is that they are their own anti-particles - has since impacted diverse problems ranging from neutrino physics and dark matter searches to the fractional quantum Hall effect and superconductivity. Despite this long history the unambiguous observation of Majorana fermions nevertheless remains an outstanding goal. This review paper highlights recent advances in the condensed matter search for Majorana that have led many in the field to believe that this quest may soon bear fruit. We begin by introducing in some detail exotic topological one- and two-dimensional superconductors that support Majorana fermions at their boundaries and at vortices. We then turn to one of the key insights that arose during the past few years; namely, that it is possible to engineer such exotic superconductors in the laboratory by forming appropriate heterostructures with ordinary s-wave superconductors. Numerous proposals of this type are discussed, based on diverse materials such as topological insulators, conventional semiconductors, ferromagnetic metals and many others. The all-important question of how one experimentally detects Majorana fermions in these setups is then addressed. We focus on three classes of measurements that provide smoking-gun Majorana signatures: tunneling, Josephson effects and interferometry. Finally, we discuss the most remarkable properties of condensed matter Majorana fermions - the non-Abelian exchange statistics that they generate and their associated potential for quantum computation. © 2012 IOP Publishing Ltd.


Reinkensmeyer D.J.,University of California at Irvine
Journal of neuroengineering and rehabilitation | Year: 2012

Mobility technologies, including wheelchairs, prostheses, joint replacements, assistive devices, and therapeutic exercise equipment help millions of people participate in desired life activities. Yet, these technologies are not yet fully transformative because many desired activities cannot be pursued or are difficult to pursue for the millions of individuals with mobility related impairments. This WTEC study, initiated and funded by the National Science Foundation, was designed to gather information on European innovations and trends in technology that might lead to greater mobility for a wider range of people. What might these transformative technologies be and how might they arise? Based on visits to leading mobility technology research labs in western Europe, the WTEC panel identified eight major trends in mobility technology research. This commentary summarizes these trends, which are then described in detail in companion papers appearing in this special issue.


Rafelski S.M.,University of California at Irvine
BMC Biology | Year: 2013

The morphology of mitochondrial networks is complex and highly varied, yet vital to cell function. The first step toward an integrative understanding of how mitochondrial morphology is generated and regulated is to define the interdependent geometrical features and their dynamics that together generate the morphology of a mitochondrial network within a cell. Distinct aspects of the size, shape, position, and dynamics of mitochondrial networks are described and examples of how these features depend on one another discussed. © 2013 Rafelski; licensee BioMed Central Ltd.


Middlebrooks J.C.,University of California at Irvine
Handbook of Clinical Neurology | Year: 2015

The auditory system derives locations of sound sources from spatial cues provided by the interaction of sound with the head and external ears. Those cues are analyzed in specific brainstem pathways and then integrated as cortical representation of locations. The principal cues for horizontal localization are interaural time differences (ITDs) and interaural differences in sound level (ILDs). Vertical and front/back localization rely on spectral-shape cues derived from direction-dependent filtering properties of the external ears. The likely first sites of analysis of these cues are the medial superior olive (MSO) for ITDs, lateral superior olive (LSO) for ILDs, and dorsal cochlear nucleus (DCN) for spectral-shape cues. Localization in distance is much less accurate than that in horizontal and vertical dimensions, and interpretation of the basic cues is influenced by additional factors, including acoustics of the surroundings and familiarity of source spectra and levels. Listeners are quite sensitive to sound motion, but it remains unclear whether that reflects specific motion detection mechanisms or simply detection of changes in static location. Intact auditory cortex is essential for normal sound localization. Cortical representation of sound locations is highly distributed, with no evidence for point-to-point topography. Spatial representation is strictly contralateral in laboratory animals that have been studied, whereas humans show a prominent right-hemisphere dominance. © 2015 Elsevier B.V.


Escayg A.,Emory University | Goldin A.L.,University of California at Irvine
Epilepsia | Year: 2010

Mutations in a number of genes encoding voltage-gated sodium channels cause a variety of epilepsy syndromes in humans, including genetic (generalized) epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS, severe myoclonic epilepsy of infancy). Most of these mutations are in the SCN1A gene, and all are dominantly inherited. Most of the mutations that cause DS result in loss of function, whereas all of the known mutations that cause GEFS+ are missense, presumably altering channel activity. Family members with the same GEFS+ mutation often display a wide range of seizure types and severities, and at least part of this variability likely results from variation in other genes. Many different biophysical effects of SCN1A-GEFS+ mutations have been observed in heterologous expression systems, consistent with both gain and loss of channel activity. However, results from mouse models suggest that the primary effect of both GEFS+ and DS mutations is to decrease the activity of GABAergic inhibitory neurons. Decreased activity of the inhibitory circuitry is thus likely to be a major factor contributing to seizure generation in patients with GEFS+ and DS, and may be a general consequence of SCN1A mutations. © 2010 International League Against Epilepsy.


Longhurst J.,University of California at Irvine
Medical Acupuncture | Year: 2013

Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system. © 2013, Mary Ann Liebert, Inc.


Kalantar-Zadeh K.,University of California at Irvine
Patient Preference and Adherence | Year: 2013

Objectives: This review explores the challenges and solutions in educating patients with chronic kidney disease (CKD) to lower serum phosphorus while avoiding protein insufficiency and hypercalcemia. Methods: A literature search including terms "hyperphosphatemia," "patient education," "food fatigue," "hypercalcemia," and "phosphorus-protein ratio" was undertaken using PubMed. Results: Hyperphosphatemia is a strong predictor of mortality in advanced CKD and is remediated via diet, phosphorus binders, and dialysis. Dietary counseling should encourage the consumption of foods with the least amount of inorganic or absorbable phosphorus, low phosphorus-to-protein ratios, and adequate protein content, and discourage excessive calcium intake in high-risk patients. Emerging educational initiatives include food labeling using a "traffic light" scheme, motivational interviewing techniques, and the Phosphate Education Program - whereby patients no longer have to memorize the phosphorus content of each individual food component, but only a "phosphorus unit" value for a limited number of food groups. Phosphorus binders are associated with a clear survival advantage in CKD patients, overcome the limitations associated with dietary phosphorus restriction, and permit a more flexible approach to achieving normalization of phosphorus levels. Conclusion: Patient education on phosphorus and calcium management can improve concordance and adherence and empower patients to collaborate actively for optimal control of mineral metabolism. © 2013 Kalantar-Zadeh, publisher and licensee Dove Medical Press Ltd.


Weinberger N.M.,University of California at Irvine
Handbook of Clinical Neurology | Year: 2015

Primary ("early") sensory cortices have been viewed as stimulus analyzers devoid of function in learning, memory, and cognition. However, studies combining sensory neurophysiology and learning protocols have revealed that associative learning systematically modifies the encoding of stimulus dimensions in the primary auditory cortex (A1) to accentuate behaviorally important sounds. This "representational plasticity" (RP) is manifest at different levels. The sensitivity and selectivity of signal tones increase near threshold, tuning above threshold shifts toward the frequency of acoustic signals, and their area of representation can increase within the tonotopic map of A1. The magnitude of area gain encodes the leanalyzers devoid of function in learningvel of behavioral stimulus importance and serves as a substrate of memory strength. RP has the same characteristics as behavioral memory: it is associative, specific, develops rapidly, consolidates, and can last indefinitely. Pairing tone with stimulation of the cholinergic nucleus basalis induces RP and implants specific behavioral memory, while directly increasing the representational area of a tone in A1 produces matching behavioral memory. Thus, RP satisfies key criteria for serving as a substrate of auditory memory. The findings suggest a basis for posttraumatic stress disorder in abnormally augmented cortical representations and emphasize the need for a new model of the cerebral cortex. © 2015 Elsevier B.V.


Yel L.,University of California at Irvine
Journal of Clinical Immunology | Year: 2010

Introduction: Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. IgA and Its Functions: Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. Pathogenesis: In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. Conclusion: The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency.


Lott I.T.,University of California at Irvine | Dierssen M.,CIBER ISCIII
The Lancet Neurology | Year: 2010

Improvements in medical interventions for people with Down's syndrome have led to a substantial increase in their longevity. Diagnosis and treatment of neurological complications are important in maintaining optimal cognitive functioning. The cognitive phenotype in Down's syndrome is characterised by impairments in morphosyntax, verbal short-term memory, and explicit long-term memory. However, visuospatial short-term memory, associative learning, and implicit long-term memory functions are preserved. Seizures are associated with cognitive decline and seem to cause additional decline in cognitive functioning, particularly in people with Down's syndrome and comorbid disorders such as autism. Vision and hearing disorders as well as hypothyroidism can negatively impact cognitive functioning in people with Down's syndrome. Dementia that resembles Alzheimer's disease is common in adults with Down's syndrome. Early-onset dementia in adults with Down's syndrome does not seem to be associated with atherosclerotic complications. © 2010 Elsevier Ltd. All rights reserved.


Cupisti A.,University of Pisa | Kalantar-Zadeh K.,University of California at Irvine
Seminars in Nephrology | Year: 2013

Phosphorus retention occurs from higher dietary phosphorus intake relative to its renal excretion or dialysis removal. In the gastrointestinal tract the naturally existing organic phosphorus is only partially (̃60%) absorbable; however, this absorption varies widely and is lower for plant-based phosphorus including phytate (<40%) and higher for foods enhanced with inorganic phosphorus-containing preservatives (>80%). The latter phosphorus often remains unrecognized by patients and health care professionals, even though it is widely used in contemporary diets, in particular, low-cost foods. In a nonenhanced mixed diet, digestible phosphorus correlates closely with total protein content, making protein-rich foods a main source of natural phosphorus. Phosphorus burden is limited more appropriately in predialysis patients who are on a low-protein diet (̃0.6 g/kg/d), whereas dialysis patients who require higher protein intake (̃1.2 g/kg/d) are subject to a higher dietary phosphorus load. An effective and patient-friendly approach to reduce phosphorus intake without depriving patients of adequate proteins is to educate patients to avoid foods with high phosphorus relative to protein such as egg yolk and those with high amounts of phosphorus-based preservatives such as certain soft drinks and enhanced cheese and meat. Phosphorus rich foods should be prepared by boiling, which reduces phosphorus as well as sodium and potassium content, or by other types of cooking-induced demineralization. The dose of phosphorus-binding therapy should be adjusted separately for the amount and absorbability of phosphorus in each meal. Dietician counseling to address the emerging aspects of dietary phosphorus management is instrumental for achieving a reduction of phosphorus load. © 2013 Elsevier Inc.


Nasr R.,University of California at Irvine
Journal of chemical information and modeling | Year: 2010

In many large chemoinformatics database systems, molecules are represented by long binary fingerprint vectors whose components record the presence or absence of particular functional groups or combinatorial features. To speed up database searches, we propose to add to each fingerprint a short signature integer vector of length M. For a given fingerprint, the i component of the signature vector counts the number of 1-bits in the fingerprint that fall on components congruent to i modulo M. Given two signatures, we show how one can rapidly compute a bound on the Jaccard-Tanimoto similarity measure of the two corresponding fingerprints, using the intersection bound. Thus, these signatures allow one to significantly prune the search space by discarding molecules associated with unfavorable bounds. Analytical methods are developed to predict the resulting amount of pruning as a function of M. Data structures combining different values of M are also developed together with methods for predicting the optimal values of M for a given implementation. Simulations using a particular implementation show that the proposed approach leads to a 1 order of magnitude speedup over a linear search and a 3-fold speedup over a previous implementation. All theoretical results and predictions are corroborated by large-scale simulations using molecules from the ChemDB. Several possible algorithmic extensions are discussed.


Feig S.A.,University of California at Irvine
Academic Radiology | Year: 2015

Long-term follow-up of randomized trials provide the most accurate estimates of overdiagnosis. Estimates from follow-up of service screening studies are almost as accurate if there is sufficient adjustment for lead time and risk status. When properly analyzed data from both of these types of trials indicate that the rate of overdiagnosis at screening mammography is clinically negligible: 0-5%. Population trend studies are a potentially highly inaccurate means to estimate overdiagnosis. Most cases of DCIS detected at screening are medium and high grade with substantial potential to become an invasive disease. To avoid overtreatment, clinicians need to tailor their treatment of DCIS to the histologic and molecular characteristics of each case. © 2015 AUR.


Fruman D.A.,University of California at Irvine | Rommel C.,Intellikine
Cancer Discovery | Year: 2011

Several phosphoinositide 3-kinase (PI3K) inhibitors are in the clinic and many more are in preclinical development. CAL-101, a selective inhibitor of the PI3Kδ isoform, has shown remarkable success in certain hematologic malignancies. Although PI3Kδ signaling plays a central role in lymphocyte biology, the degree of single-agent therapeutic activity of CAL-101 during early-phase development has been somewhat unexpected. CAL-101 works in part by blocking signals from the microenvironment that normally sustain leukemia and lymphoma cells in a protective niche. As PI3Ks enter the arena of molecular-targeted therapies, CAL-101 provides proof of principle that isoform-selective compounds can be effective in selected cancer types and patient populations. Significance: A key question is whether compounds targeting a single PI3K catalytic isoform can provide meaningful single agent efficacy in cancer cells that express multiple isoforms. Clinical studies of the drug CAL-101 have provided a significant advance by showing that selective targeting of PI3Kδ achieves efficacy in chronic lymphocytic leukemia, in part through targeting the tumor microenvironment. © 2011 American Association for Cancer Research.


Beiko G.,McMaster University | Steinert R.,University of California at Irvine
Journal of Cataract and Refractive Surgery | Year: 2013

The original technique for scleral fixation of an intraocular lens using fibrin glue requires an assistant to grasp and hold an externalized haptic with forceps. We present a modification of the technique in which the externalized haptic is maintained by a silicone "tire" without the aid of an assistant. Financial Disclosure: Drs. Beiko and Steinert are consultants to Abbott Medical Optics, Inc., Milpitas, CA, USA. Neither has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS Published by Elsevier Inc.


AghaKouchak A.,University of California at Irvine
Hydrology and Earth System Sciences | Year: 2014

The 2012 drought was one of the most extensive drought events in half a century, resulting in over USD 12 billion in economic loss in the United States and substantial indirect impacts on global food security and commodity prices. An important feature of the 2012 drought was rapid development and intensification in late spring/early summer, a critical time for crop development and investment planning. Drought prediction remains a major challenge because dynamical precipitation forecasts are highly uncertain, and their prediction skill is low. Using a probabilistic framework for drought forecasting based on the persistence property of accumulated soil moisture, this paper shows that the US drought of summer 2012 was predictable several months in advance. The presented drought forecasting framework provides the probability occurrence of drought based on climatology and near-past observations of soil moisture. The results indicate that soil moisture exhibits higher persistence than precipitation, and hence improves drought predictability. © Author(s) 2014.


Chiang Y.-S.,University of California at Irvine
Evolution and Human Behavior | Year: 2010

The theory of biological markets and competitive altruism contends that competitive partner selection is favorable to the selection of prosocial behaviors in social evolution. The current study provides an empirical assessment of this theory based on a laboratory experiment with human subjects using the Ultimatum game. The experimental results show that more generous proposers and more tolerant responders are preferred as partners. This indicates that subjects tend to choose partners in a manner that coincides with their own interests. In competitive partner selection, partner preferences driven by self-interest nevertheless generate an assortative pairing structure that prompts players to behave fairly in the game. The study shows that a free market of partner selection, plus the type of partner preferences driven by self-interests, can facilitate the emergence of fairness in social exchange. © 2010.


Lee M.D.,University of California at Irvine
Behavioral and Brain Sciences | Year: 2011

Jones & Love (J&L) should have given more attention to Agnostic uses of Bayesian methods for the statistical analysis of models and data. Reliance on the frequentist analysis of Bayesian models has retarded their development and prevented their full evaluation. The Ecumenical integration of Bayesian statistics to analyze Bayesian models offers a better way to test their inferential and predictive capabilities. © 2011 Cambridge University Press.


Widgerow A.D.,University of California at Irvine
Annals of Plastic Surgery | Year: 2014

ABSTRACT: Ischemia-reperfusion injury forms the basis of tissue damage and cellular apoptosis in many pathologic and traumatic processes. The tissue damage follows a natural progression of cellular and metabolic events initiated by an ischemic episode. Ischemia causes intracellular/extracellular changes principally resulting in increased intracellular calcium, pH changes, and adenosine triphosphate depletion that end in cell death if the process is not interrupted. This interruption takes the form of reperfusion, characterized by a "flushing" of tissues with toxic metabolites, principally reactive oxygen species. The immediate effect is mitochondrial pore permeability, complement activation, cytochrome release, cytokine activation, inflammation, edema, neutrophil platelet adhesion, capillary plugging, and thrombosis. This sets the stage for the long recognized "no-reflow" phenomenon and progressive tissue death. Current recognition of cellular "cross-talk" and molecular events have introduced new logical strategies to sequentially combat the events occurring in relation to ischemia-reperfusion injury. These include mechanical preconditioning and pharmacological preconditioning and postconditioning strategies. It is likely that success in reversing or limiting tissue damage will be found in a sequential multitargeted approach using a combination of these strategies - clinical trials in this regard are sorely needed. Copyright © 2012 by Lippincott Williams & Wilkins.


Xu K.,University of California at Irvine
IEEE Transactions on Electron Devices | Year: 2014

In this paper, the switching characteristics as associated with p+n gated MOSFET silicon LED are reviewed. By employing the insulated-gate terminal, which allows the adjustment of P+ source/drain to N-substrate junction breakdown voltage, it is demonstrated that the electro-optical modulation in the Si-PMOSFET device operates as gate-controlled diodes. The PMOSFET device can operate as a Si-diode LED or an Si gate-controlled diode LED. The main features of switching transitions of Si-diode LED and Si gate-controlled diode LED are characterized, and a model is developed to explain the modulation speed, which is then reviewed. The upper limit derived value for the expected maximum modulation of the device could be in the range of a few hundred GHz. According to the best of my knowledge, despite the low efficiency, the Si-PMOSFET light-emitting device will be a potentially key component for silicon photonic integrated circuits for future computing I/O applications. © 1963-2012 IEEE.


Bromiley P.,University of California at Irvine | Rau D.,Northern Illinois University
Journal of Operations Management | Year: 2016

This paper evaluates the usefulness of the resource-based view (RBV) to the field of operations management. Based on the seminal RBV articles, we argue that using the RBV does not align with the objectives and activities of operations management researchers in several ways. First, the dependent variable in the RBV is sustained competitive advantage. Using sustained competitive advantage as a dependent variable implies that scholars focus on explaining the differences between the relatively few firms with sustained competitive advantage and all the other firms, ignoring performance variations within the great mass of firms. In addition, competitive advantage exists at the level of the business or the firm and does not directly translate into the normal level of operations management research. Measuring sustained competitive advantage also presents difficulties. Second, the explanatory variables in the RBV are resources that must be rare, valuable and hard or impossible to imitate. Measuring valuable resources or factors firms cannot imitate poses serious problems both in demonstrating value independent of the factor's impact on performance (i.e.; avoiding tautology) and in measuring unique or nearly unique entities. Third, under the RBV, prescription is problematic; you cannot prescribe things that firms can readily implement because such things can be imitated. We present the practice-based view (PBV) as a simpler and better alternative for operations management where scholars attempt to explain the entire range of firm and unit performance based on transferable practices. © 2015 Elsevier B.V. All rights reserved.


Buchmueller T.,University of Michigan | Carpenter C.S.,University of California at Irvine
American Journal of Public Health | Year: 2010

Objectives. We used data from the Behavioral Risk Factor Surveillance System to compare health insurance coverage, access to care, and women's cancer screenings for individuals in same-sex versus different-sex relationships. Methods. We estimated logistic regression models by using data on 5265 individuals in same-sex relationships and 802659 individuals in different-sex relationships. Results. Compared with women in different-sex relationships, women in same-sex relationships were significantly less likely to have health insurance coverage, were less likely to have had a checkup within the past year, were more likely to report unmet medical needs, and were less likely to have had a recent mammogram or Pap test. Compared with men in different-sex relationships, men in same-sex relationships were significantly less likely to have health insurance coverage and were more likely to report unmet medical needs, although they were more likely to have had a checkup in the past year. Conclusions. In the largest and most recent nationally representative sample, we found important differences in health insurance coverage and access to care between individuals in same-sex relationships and those in different-sex relationships for both men and women.


Cardarelli F.,University of California at Irvine
Biophysical journal | Year: 2011

No methods proposed thus far have the sensitivity to measure the transport of single molecules through single nuclear pore complexes (NPCs) in intact cells. Here we demonstrate that fluorescence correlation spectroscopy (FCS) combined with real-time tracking of the center of mass of single NPCs in live, unperturbed cells allows us to detect the transport of single molecules in a reference system of a pore with high temporal (millisecond) and spatial (limited by diffraction) resolution. We find that the transport of the classical receptor karyopherin-β1 (Kapβ1) is regulated so as to produce a peculiar distribution of characteristic times at the NPC. This regulation, which is spatially restricted to the pore, depends on the properties and metabolic energy of Kapβ1. As such, this method provides a powerful tool for studying nucleocytoplasmic shuttling at the nanometer scale under physiological conditions. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.


Enayati M.H.,Isfahan University of Technology | Mohamed F.A.,University of California at Irvine
International Materials Reviews | Year: 2014

Mechanical alloying (MA) and mechanical milling (MM) techniques have been widely utilised over the past two decades for synthesis of various alloys and composites with equilibrium or metastable structure at room temperature. One of the most interesting features of MA/MM is the ability to produce nanocrystalline and amorphous materials. Several mechanisms for formation of nanocrystalline and amorphous structures have been introduced based on experimental findings and similarity of MA/MM to other solid-state processing routes. In this paper, the recent experimental observations reported on development of nanocrystalline and amorphous structures using ball mill technique are selectively examined and critically reviewed to provide further insight into the key issues related to this solid-state technique. The review includes four major parts. It begins with a brief introduction to MA/MM and the principles of ball milling process for synthesis of materials. The second part is devoted to the formation of nanocrystalline structure by ball milling process. The earlier studies are summarised with special emphasis on the minimum grain size obtainable by ball milling, besides the recent progresses on the prediction of minimum grain size based on dislocation models are analysed and discussed in detail. The third part deals with the amorphisation reaction induced by ball milling. This section includes the thermodynamic and kinetic aspects, the criteria developed for amorphisation reaction and microstructural evolution of powders during MA leading to the amorphisation reaction. The last part is devoted to the bulk amorphous/nanocrystalline alloys produced from precursor powder. © 2014 Institute of Materials, Minerals and Mining and ASM International.


Freeman F.,University of California at Irvine
Chemical Communications | Year: 2014

The density functionals B3LYP, B3PW91, M062X, and CAM-B3LYP with the 6-311+G(d,p) basis set predict the cysteine sulfenic acid O-sulfenylation of the s-cis-ketoenol tautomer of 1,3-cyclohexanedione proceeds through a cyclic 14-membered transition state structure containing three water molecules. This journal is © the Partner Organisations 2014.


Sirignano W.A.,University of California at Irvine
Progress in Energy and Combustion Science | Year: 2014

A review of research on the subject of the vaporization and burning of fuel droplets configured in a prescribed array is presented, including both classical works and research over the past decade or two. Droplet arrays and groups and the relation to sprays are discussed. The classical works are reviewed. Recent research on transient burning and vaporization of finite arrays with Stefan convection but without forced convection is presented, including extensions to non-unitary Lewis number and multi-component, liquid fuels. Recent results on transient, convective burning of droplets in arrays are also examined. In particular, transient convective burning of infinite (single-layer periodic and double-layer periodic) and finite droplet arrays are discussed; attention is given to the effects of droplet deceleration due to aerodynamic drag, diameter decrease due to vaporization, internal liquid circulation, and arrays with moving droplets in tandem and staggered configurations. Flame structure is examined as a function of spacing between neighboring droplets and Damköhler number: individual droplet flames versus group flames and wake flames versus envelope flames. Based on existing knowledge of laminar droplet array and spray combustion theory, experimental evidence, and turbulent studies for non-vaporizing and non-reacting two-phase flows, comments are made on the needs and implications for the study of turbulent spray and array combustion. © 2014 Elsevier Ltd. All rights reserved.


Holman E.A.,University of California at Irvine
Journal of Traumatic Stress | Year: 2012

Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress. © 2012 International Society for Traumatic Stress Studies.


Shapiro J.,University of California at Irvine
Medical Humanities | Year: 2011

Several scholarly trends, such as narrative medicine, patient-centered and relationship-centered care, have long advocated for the value of the patient's voice in the practice of medicine. As theories of textual analysis are applied to the understanding of stories of illness, doctors and scholars have the opportunity to develop more nuanced and multifaceted appreciation for these accounts. We realize, for example, that a patient's story is rarely "just a story," but is rather the conscious and unconscious representation and performance of intricate personal motives and dominant meta-narrative influences. Overall, this complexifying of narrative is beneficial as it reduces readers' and listeners' nai{dotless}̈ve assumptions about reliability and authenticity. However, the growing body of scholarship contesting various aspects of personal narratives may have the unintended effect of de-legitimizing the patient's voice because of concerns regarding its trustworthiness. Further, the academy's recent focus on transgressive, boundary-violating counternarratives, while meant to right the balance of what constitutes acceptable, even valuable stories in medicine, may inadvertently trivialize more conventional, conformist stories as inauthentic. While acknowledging the not inconsiderable pitfalls awaiting the interpreter of illness narratives, I argue that ultimately, physicians and scholars should approach patient stories with an attitude of narrative humility, despite inevitable limits on reliability and authenticity. While critical inquiry is an essential part of both good clinical practice and scholarship, first and foremost both types of professionals should respect that patients tell the stories they need to tell.


Tajima T.,University of California at Irvine
European Physical Journal: Special Topics | Year: 2014

With newly available compact laser technology [1] we are capable of producing 100 PW-class laser pulses with a single-cycle duration on the femtosecond timescale. With this fs intense laser we can produce a coherent X-ray pulse that is also compressed, well into the hard X-ray regime (∼10 keV) and with a power up to as much as 10 Exawatts. We suggest utilizing these coherent X-rays to drive the acceleration of particles. Such X-rays are focusable far beyond the diffraction limit of the original laser wavelength and when injected into a crystal it forms a metallic-density electron plasma ideally suited for laser wakefield acceleration. If the X-ray field is limited by the Schwinger field at the focal size of ∼100 nm, the achievable energy is 1 PeV over 50 m. (If the X-rays are focused further, much higher energies beyond this are possible). These processes are not limited to only electron acceleration, and if ions are pre-accelerated to beyond GeV they are capable of being further accelerated using a LWFA scheme [2] to similar energies as electrons over the same distance-scales. Such high energy proton (and ion) beams can induce copious neutrons, which can also give rise to intense compact muon beams and neutrino beams that may be portable. High-energy gamma rays can also be efficiently emitted with a bril- liance many orders of magnitude above the brightest X-ray sources by this accelerating process, from both the betatron radiation as well as the dominant radiative-damping dynamics. With the exceptional conditions enabled by this technology we envision a whole scope of new physical phenomena, including: the possibility of laser self-focus in the vacuum, neutron manipulation by the beat of such lasers, zeptosecond spectroscopy of nuclei, etc. Further, we now introduce along with the idea of vacuum as a nonlinear medium, the Schwinger Fiber Accelerator. This is a self-organized vacuum fiber acceleration concept, in which the repeated process of self-focusing and defocusing for the X-ray pulse in vacuum forms a modulated fiber that guides the intense X-rays. © 2014 EDP Sciences and Springer.


Dewan S.,University of California at Irvine | Ramaprasad J.,McGill University
MIS Quarterly: Management Information Systems | Year: 2014

Motivated by the growing importance of social media, this paper examines the relationship between new media, old media, and sales in the context of the music industry. In particular, we study the interplay between blog buzz, radio play, and music sales at both the album and song levels of analysis. We employ the panel vector autoregression (PVAR) methodology, an extension of vector autoregression to panel data. We find that radio play is consistently and positively related to future sales at both the song and album levels. Blog buzz, however, is not related to album sales and negatively related to song sales, suggesting that sales displacement due to free online sampling dominates any positive word-of-mouth effects of song buzz on sales. Further, the negative relationship between song buzz and sales is stronger for niche music relative to mainstream music, and for less popular songs within albums. We discuss the implications of these results for both research and practice regarding the role of new media in the music industry.


LaFerla F.M.,University of California at Irvine
Biochemical Society Transactions | Year: 2010

Aβ (amyloid β-peptide) and tau are the main proteins that misfold and accumulate in amyloid plaques and NFTs (neurofibrillary tangles) of Alzheimer's disease and other neurological disorders. Historically, because plaques and NFTs accumulate in diverse cellular compartments, i.e. mainly extracellularly for plaques and intracellularly for NFTs, it was long presumed that the constituent proteins formed these lesions via unrelated pathways. Animal and cell studies over the last decade, however, have provided convincing evidence to show that Aβ can facilitate the development of tau pathology by altering several cell-dependent and -independent mechanisms. In the present article, results are reviewed from several laboratories that show that modulating Aβ pathology can directly affect the development of tau pathology, which has significant implications for the treatment of Alzheimer's disease. ©The Authors.


Steffan J.S.,University of California at Irvine
Cell Cycle | Year: 2010

The accumulation of protein aggregates in neurons appears to be a basic feature of neurodegenerative disease. In Huntington disease (HD), a progressive and ultimately fatal neurodegenerative disorder caused by an expansion of the polyglutamine repeat within the protein Huntingtin (Htt), the immediate proximal cause of disease is well understood. However, the cellular mechanisms which modulate the rate at which fragments of Htt containing polyglutamine accumulate in neurons is a central issue in the development of approaches to modulate the rate and extent of neuronal loss in this disease. We have recently found that Htt is phosphorylated by the kinase IKK on serine (S) 13, activating its phosphorylation on S16 and its acetylation and poly-SUMOylation, modifications that modulate its clearance by the proteasome and lysosome in cells.1 In the discussion here I suggest that Htt may have a normal function in the lysosomal mechanism of selective macroautophagy involved in its own degradation which may share some similarity with the yeast cytoplasm to vacuole targeting (Cvt) pathway. Pharmacologic activation of this pathway may be useful early in disease progression to treat HD and other neurodegenerative diseases characterized by the accumulation of disease proteins. © 2010 Landes Bioscience.


Poulos T.L.,University of California at Irvine
Chemical Reviews | Year: 2014

The review focuses on those enzymes that catalyze oxidation reactions and those for which crystal structures are available. There are two broad classes of heme enzyme oxidants: oxygenases that use O2 to oxidize, oxygenate, substrates and peroxidases that use 2O2 to oxidize. The review demonstrates that out of the oxidants molecular oxygen is the most unusual, as O2 is not a reactive molecule despite the oxidation of nearly all biological molecules by O2 being a thermodynamically favorable process. The reason is that there is a large kinetic barrier to these reactions owing to O2 being a paramagnetic molecule so that the reaction between a majority of biological molecules that have paired spins is a spin forbidden process.


Xu K.,University of California at Irvine
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2014

The fabrication and performance of a MOSFET-like silicon light source that is able to monolithically integrate with silicon photo-detector in standard 3-μm CMOS process technology is introduced. The relation between gate voltage Vg and the breakdown voltage BV of the p-n junction in the gate-controlled diode is simulated to show that the modulation of light intensity can be reasonably explained by the decrease in BV, since the reverse-bias of the junction is fixed and the relation between the reverse current flowing through the p-n junction and the light intensity is linear. Based on such linearity, the paper attempts to explain the physical mechanisms responsible for the light emission in Si as a function of hot-carrier distribution functions. In order to further investigate the optical properties, measurement of photon emission and reverse current in silicon gate-controlled diode in avalanche breakdown has been made using electrical and near-infrared microscopy. © 1995-2012 IEEE.


Masoomi H.,University of California at Irvine
Diseases of the colon and rectum | Year: 2012

Information about adenosquamous carcinoma of the colon and rectum is scarce because of its extremely low incidence. The aim of this study was to examine the prognostic significance of a histological diagnosis of adenosquamous carcinoma in comparison with adenocarcinoma of the colon and rectum. This study was retrospective in design. California Cancer Registry data from 1994 through 2004 with follow-up through 2008 were analyzed. Patients were included whose cancer of the colon and rectum, excluding the anus with a tumor histology of adenocarcinoma and adenosquamous carcinoma, was surgically treated. The primary outcomes measured were histology-specific survival analyses (with the use of the Kaplan-Meier method), and overall and colorectal-specific mortality (with the use of multivariable Cox proportional hazards regression analyses). A total of 111,263 adenocarcinoma and adenosquamous carcinoma of colon and rectal cancer cases were identified (adenocarcinoma, 99.91%; adenosquamous carcinoma, 0.09%). There was no significant difference in sex, age, race, and socioeconomic status between the 2 groups. The most common location of adenocarcinoma and adenosquamous carcinoma was the right and transverse colon. The adenosquamous carcinoma group was significantly associated with a higher rate of metastasis at the time of operation (adenosquamous carcinoma, 36.56% vs adenocarcinoma, 13.92%) and with poorly differentiated tumor grade (adenosquamous carcinoma, 65.96% vs adenocarcinoma, 19.74%) in comparison with the adenocarcinoma group. The median overall survival time was significantly greater in the adenocarcinoma group (82.4 months) in comparison with the adenosquamous carcinoma group (35.3 months). With the use of multivariable hazard regression analyses, adenosquamous carcinoma histology was independently associated with increased overall mortality (hazard ratio, 1.67) and colorectal-specific mortality (hazard ratio, 1.69) in comparison with adenocarcinoma. This is one of the largest studies of adenosquamous carcinoma of the colon and rectum to date. This uncommon colorectal cancer subtype was associated with higher overall and colorectal-specific mortality in comparison with adenocarcinoma. Among colorectal cancer cases, adenosquamous carcinoma histology should be considered a poor prognostic feature.


Turner J.,University of California at Irvine
Operations Research | Year: 2012

As targeted advertising becomes prevalent in a wide variety of media vehicles, planning models become increasingly important to ad networks that need to match ads to appropriate audience segments, provide a high quality of service (meet advertisers' goals), and ensure that ad serving opportunities are not wasted. We define Guaranteed Targeted Display Advertising (GTDA) as a class of media vehicles that include webpage banner ads, video games, electronic outdoor billboards, and the next generation of digital TV, and formulate the GTDA planning problem as a transportation problem with quadratic objective. By modeling audience uncertainty, forecast errors, and the ad server's execution of the plan, we derive sufficient conditions that state when our quadratic objective is a good surrogate for several ad delivery performance metrics. Moreover, our quadratic objective allows us to construct duality-based bounds for evaluating aggregations of the audience space, leading to two efficient algorithms for solving large problems: the first intelligently refines the audience space into successively smaller blocks, and the second uses scaling to find a feasible solution given a fixed audience space partition. Near-optimal schedules can often be produced despite significant aggregation. © 2012 INFORMS.


Zhitomirsky M.E.,CNRS Statistical Physics, Magnetism and Superconductivity | Chernyshev A.L.,University of California at Irvine
Reviews of Modern Physics | Year: 2013

A theoretical overview of the phenomenon of spontaneous magnon decays in quantum antiferromagnets is presented. The intrinsic zero-temperature damping of magnons in quantum spin systems is a fascinating many-body effect, which has recently attracted significant attention in view of its possible observation in neutron-scattering experiments. An introduction to the theory of magnon interactions and a discussion of necessary symmetry and kinematic conditions for spontaneous decays are provided. Various parallels with the decays of anharmonic phonons and excitations in superfluid He4 are extensively used. Three principal cases of spontaneous magnon decays are considered: field-induced decays in Heisenberg antiferromagnets, zero-field decays in spiral antiferromagnets, and triplon decays in quantum-disordered magnets. Analytical results are compared with available numerical data and prospective materials for experimental observation of the decay-related effects are briefly discussed. © 2013 American Physical Society.


Lott I.T.,University of California at Irvine
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Individuals with Down syndrome (DS) have high levels of oxidative stress throughout the lifespan. Mouse models of DS share some structural and functional abnormalities that parallel findings seen in the human phenotype. Several of the mouse models show evidence of cellular oxidative stress and have provided a platform for antioxidant intervention. Genes that are overexpressed on chromosome 21 are associated with oxidative stress and neuronal apoptosis. The lack of balance in the metabolism of free radicals generated during processes related to oxidative stress may have a direct role in producing the neuropathology of DS including the tendency to Alzheimer disease (AD). Mitochondria are often a target for oxidative stress and are considered to be a trigger for the onset of the AD process in DS. Biomarkers for oxidative stress have been described in DS and in AD in the general population. However, intervention trials using standard antioxidant supplements or diets have failed to produce uniform therapeutic effect. This chapter will examine the biological role of oxidative stress in DS and its relationship to abnormalities in both development and aging within the disorder. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. © 2011 Elsevier B.V.


Mukamel S.,University of California at Irvine
Journal of Chemical Physics | Year: 2010

Excitons represent collective optical excitations in which the motions of electrons belonging to different chromophores are correlated. We discuss the utility of the notion of entanglement commonly used in quantum information processing, in the description of these excitations. A distinction is made between some apparent entanglement effects associated with the linear response that may be removed by a transformation of coordinates and can be handled classically, and genuine entanglement that is fundamentally quantum in nature and shows up only in the nonlinear optical response. © 2010 American Institute of Physics.


Stamos M.J.,University of California at Irvine
Journal of the American College of Surgeons | Year: 2015

Background There are limited data comparing the outcomes of preoperative oral antibiotic bowel preparation (OBP) and mechanical bowel preparation (MBP) in colorectal surgery. We sought to identify the relationship between preoperative bowel preparations (BP) and postoperative complications in colon cancer surgery. Study Design The NSQIP database was used to examine the clinical data of colon cancer patients undergoing scheduled colon resection during 2012 to 2013. Multivariate regression analysis was performed to identify correlations between BP and postoperative complications. Results We evaluated a total of 5,021 patients who underwent elective colon resection. Of these, 44.8% had only MBP, 2.3% had only OBP, 27.6% had both MBP and OBP, and 25.3% of patients did not have any type of BP. In multivariate analysis of data, MBP and OBP were not associated with decreased risk of postoperative complications in right side (adjusted odds ratio [AOR] 0.80, 0.30, p = 0.08, 0.10, respectively) or left side colon resections (AOR 1.02, 0.68, p = 0.81, 0.24, respectively). However, the combination of MBP and OBP before left side colon resections resulted in a significantly decreased risk of overall morbidity (AOR 0.63, p < 0.01), superficial surgical site infection (AOR 0.31, p < 0.01), anastomosis leakage (AOR 0.44, p < 0.01), and intra-abdominal infections (AOR 0.44, p < 0.01). Conclusions Our analysis revealed that solitary mechanical bowel preparation and solitary oral bowel preparation had no significant effects on major postoperative complications after colon cancer resection. However, a combination of mechanical and oral antibiotic preparations showed a significant decrease in postoperative morbidity. © 2015 American College of Surgeons.


Dietze M.C.,Boston University | Sala A.,University of Montana | Carbone M.S.,University of New Hampshire | Czimczik C.I.,University of California at Irvine | And 3 more authors.
Annual Review of Plant Biology | Year: 2014

Nonstructural carbon (NSC) provides the carbon and energy for plant growth and survival. In woody plants, fundamental questions about NSC remain unresolved: Is NSC storage an active or passive process? Do older NSC reserves remain accessible to the plant? How is NSC depletion related to mortality risk? Herein we review conceptual and mathematical models of NSC dynamics, recent observations and experiments at the organismal scale, and advances in plant physiology that have provided a better understanding of the dynamics of woody plant NSC. Plants preferentially use new carbon but can access decade-old carbon when the plant is stressed or physically damaged. In addition to serving as a carbon and energy source, NSC plays important roles in phloem transport, osmoregulation, and cold tolerance, but how plants regulate these competing roles and NSC depletion remains elusive. Moving forward requires greater synthesis of models and data and integration across scales from -omics to ecology. Copyright © 2014 by Annual Reviews.


Rose M.R.,University of California at Irvine
Genetics | Year: 2011

There used to be a broad split within the experimental genetics research community between those who did mechanistic research using homozygous laboratory strains and those who studied patterns of genetic variation in wild populations. The former benefited from the advantage of reproducible experiments, but faced difficulties of interpretation given possible genomic and evolutionary complexities. The latter research approach featured readily interpreted evolutionary and genomic contexts, particularly phylogeny, but was poor at determining functional significance. Such burgeoning experimental strategies as genome-wide analysis of quantitative trait loci, genotype-phenotype associations, and the products of experimental evolution are now fostering a unification of experimental genetic research that strengthens its scientific power.


Choudhary V.,University of California at Irvine
Information Systems Research | Year: 2010

Information goods vendors offer different pricing schemes such as per user pricing and site licensing. Why do competing sellers adopt different pricing schemes for the same information good? Pricing schemes affect buyers' usage levels and thus the revenue generated from different segments of buyers. This can allow competing firms in a duopoly to differentiate themselves by offering different pricing schemes. Such strategic use of pricing schemes can allow undifferentiated sellers to earn substantial profits in a friction-free market for a commoditized information good. These conditions would otherwise lead to the Bertrand equilibrium and zero profits. We show that adopting asymmetric pricing schemes can be a Nash equilibrium for information goods with negligible marginal cost of production. We extend our model to the case of information goods that are horizontally differentiated and show that sellers will offer a single-pricing scheme that is different from competitors when the sellers are weakly differentiated. When the sellers are strongly differentiated, each seller will offer multiple pricing schemes. We show that it can be optimal for a seller to offer multiple pricing schemes-metered and flat fee pricing schemes, even in the absence of transactions costs. © 2010 INFORMS.


Abe M.,Nihon University | Kalantar-Zadeh K.,University of California at Irvine
Nature Reviews Nephrology | Year: 2015

In patients with diabetes receiving chronic haemodialysis, both very high and low glucose levels are associated with poor outcomes, including mortality. Conditions that are associated with an increased risk of hypoglycaemia in these patients include decreased gluconeogenesis in the remnant kidneys, deranged metabolic pathways, inadequate nutrition, decreased insulin clearance, glucose loss to the dialysate and diffusion of glucose into erythrocytes during haemodialysis. Haemodialysis-induced hypoglycaemia is common during treatments with glucose-free dialysate, which engenders a catabolic status similar to fasting; this state can also occur with 5.55 mmol/l glucose-containing dialysate. Haemodialysis-induced hypoglycaemia occurs more frequently in patients with diabetes than in those without. Insulin therapy and oral hypoglycaemic agents should, therefore, be used with caution in patients on dialysis. Several hours after completion of haemodialysis treatment a paradoxical rebound hyperglycaemia may occur via a similar mechanism as the Somogyi effect, together with insulin resistance. Appropriate glycaemic control tailored for patients on haemodialysis is needed to avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays. In this Review we summarize the pathophysiology and current management of glycaemic disarrays in patients on haemodialysis. © 2015 Macmillan Publishers Limited. All rights reserved.


Garcia J.O.,University of California at San Diego | Srinivasan R.,University of California at Irvine | Serences J.T.,University of California at San Diego
Current Biology | Year: 2013

For neural activity to be linked with cognitive function, information is needed about both the temporal dynamics and the content of neural codes. Traditionally, recording of single neurons in animals has been the primary means of obtaining high temporal resolution and precise information about neural tuning properties such as selectivity for different sensory features. Recent functional magnetic resonance imaging (fMRI) studies in humans have been able to measure feature selectivity within specific subregions of sensory cortex (e.g., orientation selectivity in primary visual cortex, or V1) [1, 2]. However, investigating the neural mechanisms that support cognitive processing - which often occurs rapidly on a subsecond scale - with a temporally insensitive method such as fMRI severely limits the types of inferences that can be drawn. Here, we describe a new method for tracking the rapid temporal evolution of feature-selective information processing with scalp recordings of electroencephalography (EEG). We generate orientation-selective response profiles based on the spatially distributed pattern of steady-state visual evoked potential (SSVEP) responses to flickering visual stimuli. Using this approach, we report a multiplicative attentional modulation of these feature-selective response profiles with a temporal resolution of 24-120 ms, which is far faster than that achieved with fMRI. Finally, we show that behavioral performance on a discrimination task can be predicted based on the amplitude of these temporally precise feature-selective response profiles. This method thus provides a high-temporal-resolution metric that can be used to track the influence of cognitive manipulations on feature-selective information processing in human cortex. © 2013 Elsevier Ltd.


Almquist Z.W.,University of California at Irvine
Journal of Statistical Software | Year: 2010

The US Decennial Census is arguably the most important data set for social science research in the United States. The UScensus2000 suite of packages allows for convenient handling of the 2000 US Census spatial and demographic data. The goal of this article is to showcase the UScensus2000 suite of packages for R, to describe the data contained within these packages, and to demonstrate the helper functions provided for handling this data. The UScensus2000 suite is comprised of spatial and demographic data for the 50 states and Washington DC at four different geographic levels (block, block group, tract, and census designated place). The UScensus2000 suite also contains a number of functions for selecting and aggregating specific geographies or demographic information such as metropolitan statistical areas, counties, etc. These packages rely heavily on the spatial tools developed by Bivand, Pebesma, and G ́omez-Rubio (2008), i.e., the sp and maptools packages. This article will provide the necessary background for working with this data set, helper functions, and finish with an applied spatial statistics example.


Gamero-Castano M.,University of California at Irvine
Journal of Fluid Mechanics | Year: 2010

The characterization of electrosprayed droplets by means of retarding potential and time-of-flight techniques yields relevant information on the physics of the cone-jet itself. The experimental data reveal that a significant fraction of the electric power injected in the cone-jet is degraded by ohmic and viscous dissipations, as well as converted into surface energy. The degradation of energy can be cast in the form of a measurable voltage deficit that depends on the fluid's viscosity, electrical conductivity and dielectric constant, but is independent of its flow rate. These experimental facts require an identical scaling rt for both the characteristic radial and axial lengths of the cone-to-jet transition, the region where conduction current is transformed into convected surface charge. This fundamental scale is the geometric mean of the electrical relaxation length and the distance from the Taylor cone apex where the dynamic and capillary pressures become comparable. These two lengths are of the same order in a wide range of operational conditions, which further confirms the importance of the role played by electrical relaxation phenomena in the physics of cone-jets. The validity of rt is further supported by the numerical results of Higuera (J. Fluid Mech., vol. 484, 2003, pp. 303-327), whose profiles of the transition region non-dimensionalized with rt remain unchanged when the flow rate is varied. Finally, the dissipation of energy significantly increases the temperature of fluids with high conductivities, and future models for the cone-jets of these liquids will need to account for thermal effects. © 2010 Cambridge University Press.


Thornton K.R.,University of California at Irvine
Genetics | Year: 2014

fwdpp is a C++ library of routines intended to facilitate the development of forward-time simulations under arbitrary mutation and fitness models. The library design provides a combination of speed, low memory overhead, and modeling flexibility not currently available from other forward simulation tools. The library is particularly useful when the simulation of large populations is required, as programs implemented using the library are much more efficient than other available forward simulation programs. © 2014 by the Genetics Society of America.


Eweda E.,Ajman University for Science and Technology | Bershad N.J.,University of California at Irvine
IEEE Transactions on Signal Processing | Year: 2012

The least mean fourth (LMF) algorithm has several stability problems. Its stability depends on the variance and distribution type of the adaptive filter input, the noise variance, and the initialization of the filter weights. A global solution to these stability problems was presented recently for a normalized LMF (NLMF) algorithm. Here, a stochastic analysis of the mean-square deviation (MSD) of the globally stable NLMF algorithm is provided. The analysis is done in the context of adaptive noise canceling with a white Gaussian reference input and Gaussian, binary, and uniform desired signals. The analytical model is shown to accurately predict the results of Monte Carlo simulations. Comparisons of the NLMF and NLMS algorithms are then made for various parameter selections. It is then shown under what conditions the NLMF algorithm is superior to NLMS algorithm for adaptive noise canceling. © 1991-2012 IEEE.


Whooley M.A.,University of California at San Francisco | Wong J.M.,University of California at Irvine
Annual Review of Clinical Psychology | Year: 2013

During the past two decades, research in the field of depression and cardiovascular disorders has exploded. Multiple studies have demonstrated that depression is more prevalent in populations with cardiovascular disease, is a robust risk factor for the development of cardiovascular disease in healthy populations, and is predictive of adverse outcomes (such as myocardial infarction and death) among populations with preexisting cardiovascular disease. Mechanistic studies have shown that poor health behaviors, such as physical inactivity, medication nonadherence, and smoking, strongly contribute to this association. Small randomized trials have found that antidepressant therapies may improve cardiac outcomes. Based on this accumulating evidence, the American Heart Association has recommended routine screening for depression in all patients with coronary heart disease. This review examines the key epidemiological literature on depression and cardiovascular disorders and discusses our current understanding of the mechanisms responsible for this association. We also examine current recommendations for screening, diagnosis, and management of depression. We conclude by highlighting new research areas and discussing therapeutic management of depression in patients with cardiovascular disorders. Copyright © 2013 by Annual Reviews.


Jafar S.A.,University of California at Irvine
IEEE Journal on Selected Topics in Signal Processing | Year: 2012

The main contribution of this paper is the insight that the transmitters' knowledge of channel coherence intervals alone (without any knowledge of the values of channel coefficients) can be surprisingly useful in a multiuser setting, illustrated by the idea of blind interference alignment that is introduced in this work. Specifically, we explore five network communication problems where the possibility of interference alignment, and consequently the total number of degrees of freedom (DoF) with channel uncertainty at the transmitters, are unknown. These problems share the common property that in each case the best known outer bounds are essentially robust to channel uncertainty and represent the outcome with interference alignment, but the best inner boundsin some cases conjectured to be optimalpredict a total collapse of DoF, thus indicating the infeasibility of interference alignment under channel uncertainty at transmitters. For each of these settings we show that even with no knowledge of channel coefficient values at the transmitters, under certain heterogeneous block fading models, i.e., when certain users experience smaller coherence time/bandwidth than others, blind interference alignment can be achieved. In each case we also establish the DoF optimality of the blind interference alignment scheme. © 2012 IEEE.


Hawkins B.A.,University of California at Irvine
Journal of Biogeography | Year: 2010

Aim: To examine butterfly species richness gradients in seven regions/countries and to quantify geographic mean root distance (MRD) patterns. My primary goal is to determine the extent to which an explanation for butterfly richness patterns based on tropical niche conservatism and the evolution of cold tolerance, proposed for the fauna of Canada and the USA, applies to other parts of the world. Location: USA/Canada, Mexico, Europe/NW Africa, Transbaikal Siberia, Chile, South Africa and Australia. Methods: Digitized range maps for butterfly species in each region were used to map richness patterns in summer (for all areas) and winter (for USA/Canada, Europe/NW Africa and Australia). A phylogeny resolved to subfamily was used to map the geographic MRD patterns. Regression trees and general linear models examined climatic and vegetation correlates of species richness and MRD within and among regions. Results: Various combinations of climate and vegetation were strong predictors of species richness gradients within regions, but unresolved 'regional' factors contributed to the multiregional pattern. Regionally based differences in phylogenetic structure also exist, but MRD is negatively correlated with temperature both within and across areas. MRD patterns consistent with tropical niche conservatism occur in most areas. With a possible partial exception of Mexico, faunas in cold climates and in mountains are more derived than faunas in lowlands and tropical/subtropical climates. In USA/Canada, Europe and Australia, winter faunas are more derived than summer faunas. Main conclusions: The phylogenetic pattern previously found in the USA and Canada is widespread in both the Northern and Southern Hemispheres, and niche conservatism and the evolution of cold tolerance is the likely explanation for the development of the global butterfly species richness gradient over evolutionary time. Contemporary climate also influences species richness patterns but is unlikely to be a complete explanation globally. The importance of climate is also manifested in the seasonal loss of more basal butterfly elements outside the tropics in winter. © 2009 Blackwell Publishing Ltd.


Detwiler R.L.,University of California at Irvine
Journal of Geophysical Research: Solid Earth | Year: 2010

During reactive fluid flow in saturated fractures, the relative rates of dissolved mineral transport and local reactions strongly influence local aperture alterations and the resulting changes in fracture permeability (or transmissivity). In the presence of an entrapped residual nonaqueous phase (e.g., CO2 or oil), the spatial distribution of the entrapped phase will influence flow and transport and thus, local aperture alterations. These aperture alterations will in turn alter the balance of forces acting on immobile regions of the trapped phase. The resulting mobilization of the entrapped phase may subsequently alter flow pathways and fracture transmissivity in a manner that defies quantification with currently used constitutive relationships. I present results from quantitative visualization experiments in which fracture aperture and entrapped phase distribution were directly measured at high spatial resolution (75 × 75 μm) during reactive fluid flow. The experiments differed only in the orientation of the fracture with respect to gravity, which influenced both the initial entrapped phase geometry and the evolution of the entrapped phase as dissolution altered fracture apertures. The presence of the entrapped phase leads to a much earlier formation of distinct dissolution channels than has been observed in saturated fractures. Compared to a similar experiment in a fully saturated fracture, dissolution in the partially saturated fractures leads to as much as a 6-fold increase in transmissivity after an equal amount of dissolution from the fracture surface (doubling of the mean fracture aperture). Furthermore, the relative influence of gravity determines whether trapped bubbles mobilize because of capillary forces (against prevailing viscous forces) or gravitational forces, which is in the direction of prevailing viscous forces for the experiments presented here. Copyright 2010 by the American Geophysical Union.


Jafar S.A.,University of California at Irvine
IEEE Transactions on Information Theory | Year: 2011

We identify the role of equal strength interference links as bottlenecks on the ergodic sum capacity of a K user phase-fading interference network, i.e., an interference network where the fading process is restricted primarily to independent and uniform phase variations while the channel magnitudes are held fixed across time. It is shown that even though there are K(K-1) cross-links, only about K/2 disjoint and equal strength interference links suffice to determine the capacity of the network regardless of the strengths of the rest of the cross channels. This scenario is called a minimal bottleneck state. It is shown that ergodic interference alignment is capacity optimal for a network in a minimal bottleneck state. The results are applied to large networks. It is shown that large networks are close to bottleneck states with a high probability, so that ergodic interference alignment is close to optimal for large networks. Limitations of the notion of bottleneck states are also highlighted for channels where both the phase and the magnitudes vary with time. It is shown through an example that for these channels, joint coding across different bottleneck states makes it possible to circumvent the capacity bottlenecks. © 2006 IEEE.


Allison S.D.,University of California at Irvine | Wallenstein M.D.,Colorado State University | Bradford M.A.,Yale University
Nature Geoscience | Year: 2010

Most ecosystem models predict that climate warming will stimulate microbial decomposition of soil carbon, producing a positive feedback to rising global temperatures. Although field experiments document an initial increase in the loss of CO 2 from soils in response to warming, in line with these predictions, the carbon dioxide loss from soils tends to decline to control levels within a few years. This attenuation response could result from changes in microbial physiological properties with increasing temperature, such as a decline in the fraction of assimilated carbon that is allocated to growth, termed carbon-use efficiency. Here we explore these mechanisms using a microbial-enzyme model to simulate the responses of soil carbon to warming by 5 C. We find that declines in microbial biomass and degradative enzymes can explain the observed attenuation of soil-carbon emissions in response to warming. Specifically, reduced carbon-use efficiency limits the biomass of microbial decomposers and mitigates the loss of soil carbon. However, microbial adaptation or a change in microbial communities could lead to an upward adjustment of the efficiency of carbon use, counteracting the decline in microbial biomass and accelerating soil-carbon loss. We conclude that the soil-carbon response to climate warming depends on the efficiency of soil microbes in using carbon. © 2010 Macmillan Publishers Limited.


Turney K.,University of California at Irvine
Journal of Health and Social Behavior | Year: 2011

An increasing body of literature documents considerable inequalities in the health of young children in the United States, though maternal depression is one important, yet often overlooked, determinant of children's health. In this article, the author uses data from the Fragile Families and Child Wellbeing Study (N = 4,048) and finds that maternal depression, particularly recurrent or chronic depression, puts children at risk of having unfavorable health when they are five years old. This finding persists despite adjusting for a host of demographic characteristics of the mothers and children (including children's prior health) and is consistent across multiple health outcomes. Family instability, maternal health, and socioeconomic status account for the association between maternal depression and children's health. Given that poor childhood health may lead to poor health and low socioeconomic status in adulthood, maternal depression may contribute to the intergenerational transmission of inequality. © American Sociological Association 2011.


Masoomi H.,University of California at Irvine
Surgical technology international | Year: 2012

Roux-en-Y Gastric Bypass is the gold standard procedure for weight loss surgery and is the most commonly performed bariatric operation in the United States. Laparoscopic gastric bypass (LGBP) has become the predominantly used technique for weight loss surgery since 2004. The aim of this study was to compare surgical outcomes of LGBP versus open gastric bypass (OGBP) for the treatment of morbid obesity. Using the Nationwide Inpatient Sample database, clinical data of morbidly obese patients who underwent LGBP or OGBP from 2006 to 2008 were analyzed. Outcome measures included patient characteristics, comorbidities, postoperative complications, length of hospital stay (LOS), hospital charges, and in-hospital mortality. A total of 226,043 morbidly obese patients underwent gastric bypass during the three-year period (LGBP: 183,452 [81.16%], OGBP: 42,591[18.84%]). The majority of patients in both groups were female (LGBP: 81.0% vs. OGBP: 78.5%, p < 0.01) and Caucasian (LGBP: 73.9% vs. OGBP: 72.6%, p < 0.01). Most comorbidities were significantly higher in the OGBP group. All specific postoperative complications were significantly higher in the OGBP group (urinary tract infection [UTI], pneumonia, acute renal failure, respiratory failure, myocardial infarction, venous thromboembolism, ileus, gastrointestinal leak, wound infection, and bowel obstruction). LGBP was associated with lower overall postoperative complications (3.5% vs. 10.8%; p < 0.01), shorter LOS (2.4 days vs. 4.2 days; p < 0.01), lower mortality (0.06 vs. 0.52; p < 0.01), and lower hospital costs ($39,570 vs. $45,629; p < 0.01) compared with the OGBP. LGBP was associated with shorter LOS, lower morbidity, lower mortality, and lower hospital costs compared with those of OGBP. The laparoscopic approach to gastric bypass should be considered the gold standard approach for the treatment of morbid obesity.


Kalantar-Zadeh K.,University of California at Irvine
Clinical Journal of the American Society of Nephrology | Year: 2012

Background and objectives Mineral and bone disorders (MBDs) are common in long-term dialysis patients and are risk factors for unfavorable outcomes. The associations between pretransplant levels of MBD surrogates and outcomes after kidney transplantation are not clear. Design, setting, participants, & measurements Data from the Scientific Registry of Transplant Recipients up to June 2007 were linked to the 5-year (July 2001-June 2006) cohort of a large dialysis organization in the United States. All dialysis patients who received a kidney transplant during this period were identified and divided into groups according to increments of pretransplant MBD markers. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined. Results The 11,776 patients were aged 47±14 years and 39% were women. Compared with recipients with pretransplant time-averaged serum alkaline phosphatase of 80-120 U/L, recipients with pretransplant serum alkaline phosphatase of 120-160 and ≥160 U/L had 49% and 64% higher graft failure censored all-cause mortality in multivariable adjusted models. There was no significant association between time-averaged serum alkaline phosphatase categories and risk of death censored graft failure, delayed graft function (DGF), or acute rejection (AR). Compared with recipients with pretransplant time-averaged serum parathyroid hormone (PTH) levels of 150-300 pg/ml, there was no significant association with graft censored death among recipients with pretransplant serum PTH ≥800 pg/ml. In addition, the risk of graft failure, DGF, and AR did not show any association with time-averaged serum intact PTH level. There was no significant association between time-averaged serum calcium categories and risk of graft failure censored death, DGF, and AR. Conclusions In this cohort, hemodialysis patients with pretransplant serum alkaline phosphatase >120 U/L have unfavorable post-transplant mortality, whereas there was no association between serum PTH and serum calcium levels and post-transplant outcomes. © 2012 by the American Society of Nephrology.


Initial secretion of interferons by innate immune cells such as dendritic cells is crucial for protection against infections as well as for alerting and activating the downstream immune responses. The secretion of innate interferons, both type I and type III, by dendritic cells is severely impaired in aged subjects. This review focuses on the mechanisms responsible for the reduced interferon secretion by dendritic cells and the role this plays in the increased susceptibility of the elderly to infections, particularly of the respiratory mucosa. Copyright © 2013 S. Karger AG, Basel.


Kim M.-C.,Yonsei University | Sim E.,Yonsei University | Burke K.,University of California at Irvine
Physical Review Letters | Year: 2013

We decompose the energy error of any variational density functional theory calculation into a contribution due to the approximate functional and that due to the approximate density. Typically, the functional error dominates, but in many interesting situations the density-driven error dominates. Examples range from calculations of electron affinities to preferred geometries of ions and radicals in solution. In these abnormal cases, the error in density functional theory can be greatly reduced by using a more accurate density. A small orbital gap often indicates a substantial density-driven error. © 2013 American Physical Society.


Yu Z.,University of California at Irvine
Biostatistics | Year: 2012

Family-based association studies have been widely used to identify association between diseases and genetic markers. It is known that genotyping uncertainty is inherent in both directly genotyped or sequenced DNA variations and imputed data in silico. The uncertainty can lead to genotyping errors and missingness and can negatively impact the power and Type I error rates of family-based association studies even if the uncertainty is independent of disease status. Compared with studies using unrelated subjects, there are very few methods that address the issue of genotyping uncertainty for family-based designs. The limited attempts have mostly been made to correct the bias caused by genotyping errors. Without properly addressing the issue, the conventional testing strategy, i.e. family-based association tests using called genotypes, can yield invalid statistical inferences. Here, we propose a new test to address the challenges in analyzing case-parents data by using calls with high accuracy and modeling genotype-specific call rates. Our simulations show that compared with the conventional strategy and an alternative test, our new test has an improved performance in the presence of substantial uncertainty and has a similar performance when the uncertainty level is low. We also demonstrate the advantages of our new method by applying it to imputed markers from a genome-wide case-parents association study. © 2012 The Author.


Gaut B.,University of California at Irvine
Nature Genetics | Year: 2012

A new study reports SNP genotypes of over 1,300 Arabidopsis thaliana accessions from throughout Eurasia, providing a resource for genome-wide association studies and studies of local adaptation. The extensive data are also used to identify targets of natural selection and to describe genome-wide patterns of recombination. © 2012 Nature America, Inc. All rights reserved.


Alexandru D.,University of California at Irvine
The Permanente journal | Year: 2013

Angiocentric glioma is a recently described tumor recognized since 2007 by the World Health Organization Classification of Tumours of the Central Nervous System. We present the only case of angiocentric glioma at our institution in the last 15 years and review the literature in an attempt to establish prognostic parameters. Our search revealed only 27 cases of angiocentric glioma in the literature. The most common presenting symptom of angiocentric glioma was seizures. Gross total resection of the lesion was curative, without need for radiation or chemotherapy.


van Erp T.G.M.,University of California at Irvine
Molecular Psychiatry | Year: 2015

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen’s d=−0.46), amygdala (d=−0.31), thalamus (d=−0.31), accumbens (d=−0.25) and intracranial volumes (d=−0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.Molecular Psychiatry advance online publication, 2 June 2015; doi:10.1038/mp.2015.63. © 2015 Macmillan Publishers Limited


Kim J.H.,University of California at Irvine
International Journal of Geographical Information Science | Year: 2013

This study examines how land-use change simulation outcomes can vary based on the way the simulation model is applied, attempting to support informed model choices and model applications. This is accomplished through a series of experiments using a hypothetical model that represents the basic logic of various cell-based dynamic land-use change modeling environments. In the experiments, consideration is given to the sensitivity of the simulation results with respect to the following four application specifications: (1) the spatial resolution, (2) the temporal resolution, (3) the probability distribution, and (4) the degree of the influence of stochastic factors, under multiple growth scenarios. The experiments show that all four factors, particularly the spatiotemporal resolution and the degree to which stochastic factors are involved, can generate substantial variation in the simulation model outcomes. It is also found that the magnitude of the variation can be affected by changes in regional growth rates and the level of fluctuation, which determine the demand for new development to be allocated over the simulation time horizon. © 2013 Taylor and Francis Group, LLC.


Okkenhaug K.,Babraham Institute | Fruman D.A.,University of California at Irvine
Current Topics in Microbiology and Immunology | Year: 2010

Lymphocyte development and function are regulated by tyrosine kinase and G-protein coupled receptors. Each of these classes of receptors activates phosphoinositide 3-kinase (PI3K). In this chapter, we summarize current understanding of how PI3K contributes to key aspects of the adaptive immune system. © Springer-Verlag Berlin Heidelberg 2010.


Penner R.M.,University of California at Irvine
MRS Bulletin | Year: 2010

Nanowires composed of noble metals are attractive candidates for chemical sensors because they ere both ductile and chemically stable in air.The single application where electrodeposited metal nanowires have had the largest impact is that of hydrogen gas (H2) sensing. The development of sensitive, selective, power-efficient, rapid-responding, and inexpensive H2 sensors, for the purpose of detecting leaked H2 in proximity to devices such as fuel cells, Is an active area of research. In this application, a change In the dc electrical resistance of the nanowire from its background value signals the presence of H2 and provides an estimate of its concentration. Two types of nanowires have been studied for use as hydrogen sensors: Electrodeposited nanowires composed of pure palladium metal (Pd) reversibly absorb hydrogen to form a hydride according to Pd + xH2 → PdH2x. Alternatively, nanowires that transduce the presence of H2 may be prepared by decorating an inert, electrically conductive support such as a carbon nanotube or a nickel nanowire with one or more eletrodeposited palladium nanoparticles. These palladium nanoparticles impart selectivity to H2 and cause the electrical conductivity of the composite particle/support to be modulated in the presence of H2. Here we summarize recent contributions of electrodeposition to the development of nanowire-based sensors for H2.


Rosales-Rueda M.F.,University of California at Irvine
Journal of Health Economics | Year: 2014

The onset of a health condition during childhood impairs skill formation. A number of studies have investigated the long-lasting effects of poor health during childhood on later-in-life outcomes. However, this evidence ignores how parents respond to the onset of health conditions. Do their investments reinforce the health condition? Or compensate, or behave neutrally? If parents change their investments, the relationship between early health and later outcomes combines the biological effect and the investment responses. To address this question, I use within-sibling variation in the incidence of health conditions to control for selection from unobserved household heterogeneity. Parents invest, on average, 0.16 standard deviations less in children with mental conditions relative to their healthy siblings, using a measure of investment that includes time and resources. On the contrary, when children have a physical condition, parental investments do not differ across siblings. Results are robust to alternative measures of health conditions and the inclusion of child fixed effects. © 2014 Elsevier B.V.


Binder P.S.,University of California at Irvine | Trattler W.B.,Center for Excellence in Eye Care
Journal of Refractive Surgery | Year: 2010

PURPOSE: To assess a previously published risk score system for predicting postoperative LASIK ectasia in eyes with normal preoperative topography. METHODS: A retrospective review of one surgeon's LASIK database was performed for eyes with Randleman ectasia risk scores based on patient age <30 years, preoperative central corneal thickness <510 μm, residual stromal bed thickness <300 μm, and/or a preoperative manifest refraction spherical equivalent >-8.00 diopters that had a minimum follow-up of 1 year. RESULTS: Of 1702 eyes with myopic errors and normal topographies, 35 (2.0%) eyes had a combined risk score between 5 and 9 points, 92 (5.4%) eyes had a combined risk score of 4 or higher, and 208 (12.2%) eyes had a combined score of 3 or higher. None of these eyes developed ectasia, whereas 3 eyes with preoperative topographic keratoconus with no other risk factors developed ectasia. CONCLUSIONS: The current risk score system would have eliminated 5.4% of eyes with 4 or more points from LASIK surgery, and would have also required the surgeon to advise an additional 6.8% of eyes with a score of 3 that they were at "moderate risk" and should "proceed with caution." In eyes with normal preoperative topographies, the scoring system may not accurately predict whether patients are at increased risk for developing postoperative LASIK ectasia. Copyright © SLACK Incorporated.


Reeves A.,University of California at Irvine
Advances in experimental medicine and biology | Year: 2012

As our understanding and ability to direct the differentiation of stem cells grows, specific targets and strategies to incorporate them are essential to define. Any cell-based transplantation strategy is fundamentally a combination therapy as either phenotypic or trophic mechanisms may contribute to functional recovery of the injured spinal cord. Both the transplant population as well as the recipient site will guide the growth factor expression profile and the phenotype of the transplanted cells. Although the use of high purity populations derived from stem cells will result in more regulated repair mechanisms, multiple challenges to the use of stem cell based strategies for SCI remain.


Lander A.D.,University of California at Irvine
Cell | Year: 2011

Systems biology seeks not only to discover the machinery of life but to understand how such machinery is used for control, i.e., for regulation that achieves or maintains a desired, useful end. This sort of goal-directed, engineering-centered approach also has deep historical roots in developmental biology. Not surprisingly, developmental biology is currently enjoying an influx of ideas and methods from systems biology. This Review highlights current efforts to elucidate design principles underlying the engineering objectives of robustness, precision, and scaling as they relate to the developmental control of growth and pattern formation. Examples from vertebrate and invertebrate development are used to illustrate general lessons, including the value of integral feedback in achieving set-point control; the usefulness of self-organizing behavior; the importance of recognizing and appropriately handling noise; and the absence of "free lunch." By illuminating such principles, systems biology is helping to create a functional framework within which to make sense of the mechanistic complexity of organismal development. © 2011 Elsevier Inc.


Steele R.E.,University of California at Irvine
International Journal of Developmental Biology | Year: 2012

The sequencing of a Hydra genome marked the beginning of a new era in the use of Hydra as a developmental model. Analysis of the genome sequence has led to a number of interesting findings, has required revisiting of previous work, and most importantly presents new opportunities for understanding the developmental biology of Hydra. This review will describe the history of the Hydra genome project, a selection of results from it that are relevant to developmental biologists, and some future research opportunities provided by Hydra genomics. © UBC Press.


Bode H.R.,University of California at Irvine
International Journal of Developmental Biology | Year: 2012

Organizers and organizing centers play critical roles in axis formation and patterning during the early stages of embryogenesis in many bilaterians. The presence and activity of an organizer was first described in adult Hydra about 100 years ago, and in the following decades organizer regions were identified in a number of bilaterian embryos. In an adult Hydra, the cells of the body column are constantly in the mitotic cycle resulting in continuous displacement of the tissue to the extremities where it is sloughed. In this context, the head organizer located in the hypostome is continuously active sending out signals to maintain the structure and morphology of the head, body column and foot of the animal. The molecular basis of the head organizer involves the canonical Wnt pathway, which acts in a self-renewing manner to maintain itself in the context of the tissue dynamics of Hydra. During bud formation, Hydra's mode of asexual reproduction, a head organizer based on the canonical Wnt pathway is set up to initiate and control the development of a new Hydra. As this pathway plays a central role in vertebrate embryonic organizers, its presence and activity in Hydra indicate that the molecular basis of the organizer arose early in metazoan evolution. © UBC Press.


Han S.,University of California at Irvine
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2011

We perform molecular dynamics simulations to investigate dynamical properties of a supercritical Lennard-Jones fluid. We find that in the supercritical region there is a short-ranged deviation in dynamic character. We further find that this anomalous change is associated with the presence of the Widom line, the locus of specific heat maxima, of the liquid-vapor phase transition. The salient change in dynamics is consistent with a crossover in the correlation of the diffusion coefficient with the excess entropy. Our results lead to an interpretation that, even though a supercritical fluid excludes a singularity, its dynamical properties can be significantly affected by the existence of thermodynamic response maxima. © 2011 American Physical Society.


Wieder W.R.,U.S. National Center for Atmospheric Research | Bonan G.B.,U.S. National Center for Atmospheric Research | Allison S.D.,University of California at Irvine
Nature Climate Change | Year: 2013

Society relies on Earth system models (ESMs) to project future climate and carbon (C) cycle feedbacks. However, the soil C response to climate change is highly uncertain in these models and they omit key biogeochemical mechanisms. Specifically, the traditional approach in ESMs lacks direct microbial control over soil C dynamics. Thus, we tested a new model that explicitly represents microbial mechanisms of soil C cycling on the global scale. Compared with traditional models, the microbial model simulates soil C pools that more closely match contemporary observations. It also projects a much wider range of soil C responses to climate change over the twenty-first century. Global soils accumulate C if microbial growth efficiency declines with warming in the microbial model. If growth efficiency adapts to warming, the microbial model projects large soil C losses. By comparison, traditional models project modest soil C losses with global warming. Microbes also change the soil response to increased C inputs, as might occur with CO2 or nutrient fertilization. In the microbial model, microbes consume these additional inputs; whereas in traditional models, additional inputs lead to C storage. Our results indicate that ESMs should simulate microbial physiology to more accurately project climate change feedbacks. © 2013 Macmillan Publishers Limited. All rights reserved .


Ang A.H.-S.,University of California at Irvine
Structure and Infrastructure Engineering | Year: 2011

Civil structures and infrastructures, such as buildings, bridges, and other facilities, are constructed and built for long service lives; many for over 50 or 100 years. In this light, the performance of an engineered system over its useful life span is naturally of major concern. The concern must include the assurance of a minimum level of reliability of performance, which will necessarily require inspections, repair, and maybe even retrofitting or replacement. The whole-life cost associated with this life-cycle performance, therefore, is the pertinent cost that ought to be the basis for determining the cost during the design stage (in terms of present value); this must include the maintenance and potential damage costs, besides the initial cost, over the life of a system. In this regard, significant technical and economic uncertainties can be expected and are unavoidable; therefore, decisions required in the design of such systems must consider risk associated with the probability of non-performance and serious damage or failure, as well as of the financial risk. The importance of these factors in the decision process at the design stage is emphasised and a practical approach for life-cycle consideration in formulating risk-informed decisions in the planning and design of infrastructure systems is described. The approach is illustrated with specific applications in the optimal design of civil infrastructure systems.© 2011 Taylor & Francis.


Lander A.D.,University of California at Irvine
BMC Biology | Year: 2010

A culture's icons are a window onto its soul. Few would disagree that, in the culture of molecular biology that dominated much of the life sciences for the last third of the 20th century, the dominant icon was the double helix. In the present, post-modern, 'systems biology' era, however, it is, arguably, the hairball. © 2010 Lander; licensee BioMed Central Ltd.


Bondar A.-N.,Free University of Berlin | White S.H.,University of California at Irvine
Biochimica et Biophysica Acta - Biomembranes | Year: 2012

Changes in inter-helical hydrogen bonding are associated with the conformational dynamics of membrane proteins. The function of the protein depends on the surrounding lipid membrane. Here we review through specific examples how dynamical hydrogen bonds can ensure an elegant and efficient mechanism of long-distance intra-protein and protein-lipid coupling, contributing to the stability of discrete protein conformational substates and to rapid propagation of structural perturbations. © 2011 Elsevier B.V. All rights reserved.


Frank S.A.,University of California at Irvine
Current Biology | Year: 2013

Mutant lineages may cause cancer-like overgrowths in microbial populations. Theory predicts that microbial regulatory controls may be designed to limit the origin and competitive potential of rogue lineages. A new study shows how a Salmonella species protects itself against overgrowths. © 2013 Elsevier Ltd.


Wodarz D.,University of California at Irvine
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Previous studies have shown that during imatinib therapy, the decline of chronic myeloid leukaemia BCR-ABL transcript numbers involves a fast phase followed by a slow phase in averaged datasets. Drug resistance leads to regrowth. In this paper, variation of treatment responses between patients is examined. A significant positive correlation is found between slopes of the fast and the slow phase of decline. A significant negative correlation is found between slopes of the slow phase of decline and the regrowth phase. No correlation is found between slopes of the fast phase of decline and the regrowth phase. A mathematical model that is successfully fitted to diverse clinical profiles explains these correlations by invoking the immune response as a key determinant of tumour decline during treatment. Boosting immunity during drug therapy could enhance the response to treatment in patients. © 2010 The Royal Society.


Feng J.L.,University of California at Irvine | Grivaz J.-F.,Laboratoire Of Laccelerateur Lineaire | Nachtman J.,University of Iowa
Reviews of Modern Physics | Year: 2010

This review summarizes the state of the art in searches for supersymmetry at colliders on the eve of the Large Hadron Collider era. Supersymmetry is unique among extensions of the standard model in being motivated by naturalness, dark matter, and force unification, both with and without gravity. At the same time, weak-scale supersymmetry encompasses a wide range of experimental signals that are also found in many other frameworks. Motivations for supersymmetry are recalled and the various models and their distinctive features are reviewed. Searches for neutral and charged Higgs bosons and standard-model superpartners at the high energy frontier are summarized comprehensively, considering both canonical and noncanonical supersymmetric models, and including results from the LEP collider at CERN, HERA at DESY, and the Fermilab Tevatron. © 2010 The American Physical Society.


Frank S.A.,University of California at Irvine
PLoS Biology | Year: 2013

Gene expression varies widely in cells with the same genotype and environment [1,2]. Predicting the patterns of stochastic cellular fluctuations remains an unsolved challenge. I propose that the degree to which varying cellular components combine to determine robust phenotypes may predict the amount of variability. Microbes provide excellent experimental models to analyze the relations between robust phenotypes and stochastic variability. © 2013 Steven A.


Ribbe M.W.,University of California at Irvine
Angewandte Chemie - International Edition | Year: 2015

Unexpected similarities: Atomic-resolution structures of CO2- and NCO--bound nickel-containing carbon monoxide dehydrogenases (Ni-CODHs) reveal that the reaction pathway of this enzyme involves an intermediate that is generated by two-electron reduction. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Whiteson D.,University of California at Irvine
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We search for a unified instrumental explanation of the spectral features seen near Eγ=130 GeV in photons collected by Fermi-LAT from the galactic center and from the Earth's limb. We report for the first time a similar feature in photons originating from the vicinity of the Sun, and examine the instrumental characteristics of this Solar feature. To test an instrumental hypothesis, we identify the range of photon incident angles where most of the peak photons are observed in these three spectral features. An examination of the spectrum of photons from the rest of the sky in this angular region reveals a hint of a spectral feature near Eγ=130 GeV. These results cast further doubt on the dark-matter-annihilation interpretation of the galactic center peak. © 2013 American Physical Society.


The factors that control elemental ratios within phytoplankton, like carbon:nitrogen:phosphorus (C:N:P), are key to biogeochemical cycles. Previous studies have identified relationships between nutrient-limited growth and elemental ratios in large eukaryotes, but little is known about these interactions in small marine phytoplankton like the globally important Cyanobacteria. To improve our understanding of these interactions in picophytoplankton, we asked how cellular elemental stoichiometry varies as a function of steady-state, N- and P-limited growth in laboratory chemostat cultures of Synechococcus WH8102. By combining empirical data and theoretical modeling, we identified a previously unrecognized factor (growth-dependent variability in cell size) that controls the relationship between nutrient-limited growth and cellular elemental stoichiometry. To predict the cellular elemental stoichiometry of phytoplankton, previous theoretical models rely on the traditional Droop model, which purports that the acquisition of a single limiting nutrient suffices to explain the relationship between a cellular nutrient quota and growth rate. Our study, however, indicates that growth-dependent changes in cell size have an important role in regulating cell nutrient quotas. This key ingredient, along with nutrient-uptake protein regulation, enables our model to predict the cellular elemental stoichiometry of Synechococcus across a range of nutrient-limited conditions. Our analysis also adds to the growth rate hypothesis, suggesting that P-rich biomolecules other than nucleic acids are important drivers of stoichiometric variability in Synechococcus. Lastly, by comparing our data with field observations, our study has important ecological relevance as it provides a framework for understanding and predicting elemental ratios in ocean regions where small phytoplankton like Synechococcus dominates.The ISME Journal advance online publication, 8 April 2016; doi:10.1038/ismej.2016.50. © 2016 International Society for Microbial Ecology


Swanson J.,University of California at Irvine | Baler R.D.,U.S. National Institute on Drug Abuse | Volkow N.D.,U.S. National Institute on Drug Abuse
Neuropsychopharmacology | Year: 2011

The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and noncognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD. © 2011 Nature Publishing Group All rights reserved.


Luce R.D.,University of California at Irvine
Theory and Decision | Year: 2010

This article argues that there is a natural solution to carry out interpersonal comparisons of utility when the theory of gambles is supplemented with a group operation of joint receipts. If so, three types of people can exist, and the two types having multiplicative representations of joint receipt have, in contrast to most utility theories, absolute scales of utility. This makes possible, at least in principle, meaningful interpersonal comparisons of utility with desirable properties, thus resolving a long standing philosophical problem and having potentially important implications in economics. Two behavioral criteria are given for the three classes of people. At this point the relative class sizes are unknown.


Mei W.,University of California at Irvine | Pasquero C.,University of Milan Bicocca
Journal of Climate | Year: 2013

The spatial structure and temporal evolution of the sea surface temperature (SST) anomaly (SSTA) associated with the passage of tropical cyclones (TCs), as well as their sensitivity to TC characteristics (including TC intensity and translation speed) and oceanic climatological conditions (represented here by latitude), are thoroughly examined by means of composite analysis using satellite-derived SST data. The magnitude of the TC-generated SSTA is larger for more intense, slower-moving, and higher-latitude TCs, and it occurs earlier in time for faster-moving and higher-latitude storms. The location of maximum SSTA is farther off the TC track for faster-moving storms, and it moves toward the track with time after the TC passage. The spatial extension of the cold wake is greater for more intense and for slower-moving storms, but its shape is quite independent of TC characteristics. Consistent with previous studies, the calculations show that the mean SSTA over a TC-centered box nearly linearly correlates with the wind speed for TCs below category 3 intensity while for stronger TCs the SSTA levels off, both for tropical and subtropical regions. While the linear behavior is expected on the basis of the more vigorous mixing induced by stronger winds and is derived from a simple mixed-layer model, the level-off for intense TCs is discussed in terms of the dependence of the maximum amplitude of the area-mean SSTA on TC translation speed and depth of the prestorm mixed layer. Finally, the decay time scale of the TC-induced SSTA is shown to be dominated by environmental conditions and has no clear dependence on its initial magnitude and on TC characteristics. © 2013 American Meteorological Society.


Pai V.,University of California at Irvine
Journal of Air Transport Management | Year: 2010

This paper assesses the determinants of aircraft size and frequency of flights on US airline routes by considering market demographics, airport characteristics, airline characteristics and route characteristics. It shows that frequency and aircraft size increase with population, income, and runway length. An increase in the proportion of managerial workers in the labor force or the proportion of population below the age of 25 results in greater frequency with the use of small planes. Slot constrained airports and an increase in the number of nearby airports lead to lower flight frequency with the use of smaller planes. Hubs and low cost carriers are associated with larger plane sizes and higher frequency, while regional airline ownership leads to higher frequency and the use of smaller planes. An increase in distance between the endpoints leads to lower frequency with the use of larger planes. As airport delay rises, airlines reduce frequency and use smaller planes, though when airport cancellations rise, flight frequency increases with the use of larger planes. © 2009 Elsevier Ltd.


Clemens K.,University of California at Irvine
Virus research | Year: 2013

Retroviruses and retrotransposons package genomic RNA into virus-like particles (VLPs) in a poorly understood process. Expression of the budding yeast retrotransposon Ty3 results in the formation of cytoplasmic Ty3 VLP assembly foci comprised of Ty3 RNA and proteins, and cellular factors associated with RNA processing body (PB) components, which modulate translation and effect nonsense-mediated decay (NMD). A series of Ty3 RNA variants were tested to understand the effects of read-through translation via programmed frameshifting on RNA localization and packaging into VLPs, and to identify the roles of coding and non-coding sequences in those processes. These experiments showed that a low level of read-through translation of the downstream open reading frame (as opposed to no translation or translation without frameshifting) is important for localization of full-length Ty3 RNA to foci. Ty3 RNA variants associated with PB components via independent determinants in the native Ty3 untranslated regions (UTRs) and in GAG3-POL3 sequences flanked by UTRs adapted from non-Ty3 transcripts. However, despite localization, RNAs containing GAG3-POL3 but lacking Ty3 UTRs were not packaged efficiently. Surprisingly, sequences within Ty3 UTRs, which bind the initiator tRNA(Met) proposed to provide the dimerization interface, were not required for packaging of full-length Ty3 RNA into VLPs. In summary, our results demonstrate that Gag3 is sufficient and required for localization and packaging of RNAs containing Ty3 UTRs and support a role for POL3 sequences, translation of which is attenuated by programmed frameshifting, in both localization and packaging of the Ty3 full-length gRNA. Copyright © 2012 Elsevier B.V. All rights reserved.


Arias R.E.,University of Chile | Maradudin A.A.,University of California at Irvine
Optics Express | Year: 2013

On the basis of a rigorous, nonperturbative, purely numerical solution of the corresponding reduced Rayleigh equation for the scattering amplitudes we have studied the scattering of a surface plasmon polariton by a two dimensional dielectric defect on a planar metal surface. The profile of the defect is assumed to be an arbitrary single-valued function of the coordinates in the plane of the metal surface, and to be differentiable with respect to those coordinates. When the defect is circularly symmetric and the dependence of the scattering amplitudes on the azimuthal angle is expressed by a rotational expansion, the reduced Rayleigh equation is transformed into a pair of one-dimensional integral equations for each value of the rotational quantum number. This approach is applied to a defect in the form of an isotropic Gaussian function. The differential cross sections for the scattering of the incident surface plasmon polariton into volume electromagnetic waves in the vacuum above the surface and into other surface plasmon polaritons are calculated, as well as the intensity of the field near the surface. These results differ significantly from the corresponding results for a metallic defect on a metallic substrate. © 2013 Optical Society of America.


Chen L.,University of California at Irvine | Holst M.,University of California at San Diego
Computer Methods in Applied Mechanics and Engineering | Year: 2011

In this paper, several mesh optimization schemes based on Optimal Delaunay Triangulations are developed. High-quality meshes are obtained by minimizing the interpolation error in the weighted L1 norm. Our schemes are divided into classes of local and global schemes. For local schemes, several old and new schemes, known as mesh smoothing, are derived from our approach. For global schemes, a graph Laplacian is used in a modified Newton iteration to speed up the local approach. Our work provides a mathematical foundation for a number of mesh smoothing schemes often used in practice, and leads to a new global mesh optimization scheme. Numerical experiments indicate that our methods can produce well-shaped triangulations in a robust and efficient way. © 2010 Elsevier B.V.


Aluminum is one of the most common metal elements in the earth's crust. It is not an essential element for life and has commonly been thought of as a rather inert and insoluble mineral. Therefore, it has often been regarded as not posing a significant health hazard. In consequence, aluminum-containing agents been used in many food processing steps and also in removal by flocculation of particulate organic matter from water. In recent years, acid rain has tended to mobilize aluminum-containing minerals into a more soluble form, ionic Al3+, which has found their way into many reservoirs that constitute residential drinking water resources. As a result, the human body burden of aluminum has increased. Epidemiological studies suggest that aluminum may not be as innocuous as was previously thought and that aluminum may actively promote the onset and progression of Alzheimer's disease. Epidemiological data is strengthened by experimental evidence of aluminum exposure leading to excess inflammatory activity within the brain. Such apparently irrelevant immune activity unprovoked by an exogenous infectious agent characterizes the aging brain and is even more pronounced in several neurodegenerative diseases. The causation of most of these age-related neurological disorders is not understood but since they are generally not genetic, one must assume that their development is underlain by unknown environmental factors. There is an increasing and coherent body of evidence that implicates aluminum as being one such significant factor. Evidence is outlined supporting the concept of aluminum's involvement in hastening brain aging. This acceleration would then inevitably lead to increased incidence of specific age-related neurological diseases. © 2013 Elsevier Ireland Ltd.


DiPatrizio N.V.,University of California at Irvine
Physiology and Behavior | Year: 2014

Mounting evidence suggests that gustation is important for the orosensory detection of dietary fats, and might contribute to preferences that humans, rodents, and possibly other mammals exhibit for fat-rich foods. In contrast to sweet, sour, salty, bitter, and umami, fat is not widely recognized as a primary taste quality. Recent investigations, however, provide a wealth of information that is helping to elucidate the specific molecular, cellular, and neural mechanisms required for fat detection in mammals. The latest evidence supporting a fat taste will be explored in this review, with a particular focus on recent studies that suggest a surprising role for gut-brain endocannabinoid signaling in controlling intake and preference for fats based on their proposed taste properties. © 2014 Elsevier Inc.


McHenry M.J.,University of California at Irvine
Biology Letters | Year: 2011

Lever systems within a skeleton transmit force with a capacity determined by the mechanical advantage, A. A is the distance from input force to a joint, divided by the distance from the joint to the output force. A lever with a relatively high A in static equilibrium has a great capacity to generate force but moves a load over a small distance. Therefore, the geometry of a skeletal lever presents a trade-off between force and speed under quasi-static conditions. The present study considers skeletal dynamics that do not assume static equilibrium by modelling kicking by a locust leg, which is powered by stored elastic energy. This model predicts that the output force of this lever is proportional to A, but its maximum speed is independent of A. Therefore, no trade-off between force and velocity exists in a lever system with spring-mass dynamics. This demonstrates that themotion of a skeleton depends on the major forces that govern its dynamics and cannot be inferred from skeletal geometry alone. © 2010 The Royal Society.


Joudaki S.,University of California at Irvine
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

From a combination of probes including the cosmic microwave background (WMAP7+SPT), Hubble constant (HST), baryon acoustic oscillations (SDSS+2dFGRS), and supernova distances (Union2), we have explored the extent to which the constraints on the effective number of neutrinos and sum of neutrino masses are affected by our ignorance of other cosmological parameters, including the curvature of the universe, running of the spectral index, primordial helium abundance, evolving late-time dark energy, and early dark energy. In a combined analysis of the effective number of neutrinos and sum of neutrino masses, we find mild (2.2σ) preference for additional light degrees of freedom. However, the effective number of neutrinos is consistent with the canonical expectation of three massive neutrinos and no extra relativistic species to within 1σ when allowing for evolving dark energy and relaxing the strong inflation prior on the curvature and running. The agreement improves with the possibility of an early dark energy component, itself constrained to be less than 5% of the critical density (95% C.L.) in our expanded parameter space. In extensions of the standard cosmological model, the derived amplitude of linear matter fluctuations σ8 is found to closely agree with low-redshift cluster abundance measurements. The sum of neutrino masses is robust to assumptions of the effective number of neutrinos, late-time dark energy, curvature, and running at the level of 1.2 eV (95% C.L.). The upper bound degrades to 2.0 eV (95% C.L.) when further including the early dark energy density and primordial helium abundance as additional free parameters. Even in extended cosmological parameter spaces, Planck alone could determine the possible existence of extra relativistic species at 4σ confidence and constrain the sum of neutrino masses to 0.2 eV (68% C.L.). © 2013 American Physical Society.


Alicea J.,University of California at Irvine | Oreg Y.,Weizmann Institute of Science | Refael G.,California Institute of Technology | Von Oppen F.,Free University of Berlin | And 2 more authors.
Nature Physics | Year: 2011

The synthesis of a quantum computer remains an ongoing challenge in modern physics. Whereas decoherence stymies most approaches, topological quantum computation schemes evade decoherence at the hardware level by storing quantum information non-locally. Here we establish that a key operation-braiding of non-Abelian anyons-can be implemented using one-dimensional semiconducting wires. Such wires can be driven into a topological phase supporting long-sought particles known as Majorana fermions that can encode topological qubits. We show that in wire networks, Majorana fermions can be meaningfully braided by simply adjusting gate voltages, and that they exhibit non-Abelian statistics like vortices in a p+ip superconductor. We propose experimental set-ups that enable probing of the Majorana fusion rules and the efficient exchange of arbitrary numbers of Majorana fermions. This work should open a new direction in topological quantum computation that benefits from physical transparency and experimental feasibility.


Mooney K.A.,University of California at Irvine | Halitschke R.,Cornell University | Kessler A.,Cornell University | Agrawal A.A.,Cornell University
Science | Year: 2010

Predators determine herbivore and plant biomass via so-called trophic cascades, and the strength of such effects is influenced by ecosystem productivity. To determine whether evolutionary trade-offs among plant traits influence patterns of trophic control, we manipulated predators and soil fertility and measured impacts of a major herbivore (the aphid Aphis nerii) on 16 milkweed species (Asclepias spp.) in a phylogenetic field experiment. Herbivore density was determined by variation in predation and trade-offs between herbivore resistance and plant growth strategy. Neither herbivore density nor predator effects on herbivores predicted the cascading effects of predators on plant biomass. Instead, cascade strength was strongly and positively associated with milkweed response to soil fertility. Accordingly, contemporary patterns of trophic control are driven by evolutionary convergent trade-offs faced by plants.


Goodrich M.T.,University of California at Irvine
Annual ACM Symposium on Parallelism in Algorithms and Architectures | Year: 2011

We present data-oblivious algorithms in the external-memory model for compaction, selection, and sorting. Motivation for such problems comes from clients who use outsourced data storage services and wish to mask their data access patterns. We show that compaction and selection can be done data-obliviously using O(N/B) I/Os, and sorting can be done, with a high probability of success, using O(N/B) log M/B(N/B)) I/Os. © 2011 ACM.


Allison S.D.,University of California at Irvine
Ecology Letters | Year: 2012

Trait-based models are an emerging tool in ecology with the potential to link community dynamics, environmental responses and ecosystem processes. These models represent complex communities by defining taxa with trait combinations derived from prior distributions that may be constrained by trade-offs. Herein I develop a model that links microbial community composition with physiological and enzymatic traits to predict litter decomposition rates. This approach allows for trade-offs among traits that represent alternative microbial strategies for resource acquisition. The model predicts that optimal strategies depend on the level of enzyme production in the whole community, which determines resource availability and decomposition rates. There is also evidence for facilitation and competition among microbial taxa that co-occur on decomposing litter. These interactions vary with community investment in extracellular enzyme production and the magnitude of trade-offs affecting enzyme biochemical traits. The model accounted for 69% of the variation in decomposition rates of 15 Hawaiian litter types and up to 26% of the variation in enzyme activities. By explicitly representing diversity, trait-based models can predict ecosystem processes based on functional trait distributions in a community. The model developed herein illustrates that traits influencing microbial enzyme production are some of the key controls on litter decomposition rates. Reviews and Syntheses Reviews and Syntheses © 2012 Blackwell Publishing Ltd/CNRS.


Frank S.A.,University of California at Irvine
Journal of Evolutionary Biology | Year: 2014

Mathematical models play an increasingly important role in the interpretation of biological experiments. Studies often present a model that generates the observations, connecting hypothesized process to an observed pattern. Such generative models confirm the plausibility of an explanation and make testable hypotheses for further experiments. However, studies rarely consider the broad family of alternative models that match the same observed pattern. The symmetries that define the broad class of matching models are in fact the only aspects of information truly revealed by observed pattern. Commonly observed patterns derive from simple underlying symmetries. This article illustrates the problem by showing the symmetry associated with the observed rate of increase in fitness in a constant environment. That underlying symmetry reveals how each particular generative model defines a single example within the broad class of matching models. Further progress on the relation between pattern and process requires deeper consideration of the underlying symmetries. © 2014 European Society For Evolutionary Biology.


Hirshberg B.,Hebrew University of Jerusalem | Gerber R.B.,Hebrew University of Jerusalem | Gerber R.B.,University of California at Irvine | Krylov A.I.,University of Southern California
Nature Chemistry | Year: 2014

Nitrogen, one of the most abundant elements in nature, forms the highly stable N 2 molecule in its elemental state. In contrast, polynitrogen compounds comprising only nitrogen atoms are rare, and no molecular crystal made of these compounds has been prepared. Here, we predict the existence of such a molecular solid, consisting of N 8 molecules, that is metastable even at ambient pressure. In the solid state, the N 8 monomers retain the same structure and bonding pattern as those they adopt in the gas phase. The interactions that bind N 8 molecules together are weak van der Waals and electrostatic forces. The solid is, according to calculations, more stable than a previously reported polymeric nitrogen solid, including at low pressure (below 20 GPa). The structure and properties of the N 8 molecular crystal are discussed and a possible preparation strategy is suggested. © 2014 Macmillan Publishers Limited. All rights reserved.


Levin E.R.,University of California at Irvine
Annual Review of Medicine | Year: 2015

Steroid hormones are produced throughout the phylogenetic tree, from plants to mammals. In the past 40 years, steroid receptors localized to the nucleus have been recognized as being important to mediating steroid action in many organs. This action mainly arises from the regulation of key genes that are important for organ development and function. These include but are not limited to genes influencing the reproductive tract, mammary glands, bone, brain, fat differentiation, pituitary hormone regulation, and metabolic effects in many organs. Unfortunately, steroids also promote the development of hormone-responsive cancers, including breast, uterus, and prostate cancer. It has also been shown that steroid receptors exist outside the nucleus in many organs and cells, with unclear impact for normal development, health, and disease. This review describes the evidence from many laboratories that these receptors exist and function with nuclear receptors to provide the full impact of all steroid hormones. © 2015 by Annual Reviews.


Burton J.C.,James Franck Institute | Taborek P.,University of California at Irvine
Physical Review Letters | Year: 2011

We present boundary-integral simulations of the evolution of critically charged droplets. For such droplets, small perturbations are unstable and eventually lead to the formation of a lemon-shaped drop with very sharp tips. For perfectly conducting drops, the tip forms a self-similar cone shape with a subtended angle identical to that of a Taylor cone, and quantities such as pressure and velocity diverge in time with power-law scaling. In contrast, when charge transport is described by a finite conductivity, we find that small progeny drops are formed at the tips, whose size decreases as the conductivity is increased. These small progeny drops are of nearly critical charge, and are precursors to the emission of a sustained flow of liquid from the tips as observed in experiments of isolated charged drops. © 2011 American Physical Society.


Frank S.A.,University of California at Irvine
Journal of Evolutionary Biology | Year: 2012

George Williams defined an evolutionary unit as hereditary information for which the selection bias between competing units dominates the informational decay caused by imperfect transmission. In this article, I extend Williams' approach to show that the ratio of selection bias to transmission bias provides a unifying framework for diverse biological problems. Specific examples include Haldane and Lande's mutation-selection balance, Eigen's error threshold and quasispecies, Van Valen's clade selection, Price's multilevel formulation of group selection, Szathmáry and Demeter's evolutionary origin of primitive cells, Levin and Bull's short-sighted evolution of HIV virulence, Frank's timescale analysis of microbial metabolism and Maynard Smith and Szathmáry's major transitions in evolution. The insights from these diverse applications lead to a deeper understanding of kin selection, group selection, multilevel evolutionary analysis and the philosophical problems of evolutionary units and individuality. © 2011 The Author. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.


Dewan S.,University of California at Irvine | Ramaprasad J.,McGill University
Information Systems Research | Year: 2012

Online social media such as blogs are transforming how consumers make consumption decisions, and the music industry is at the forefront of this revolution. Based on data from a leading music blog aggregator, we analyze the relationship between music blogging and full-track sampling, drawing on theories of online social interaction. Our results suggest that intensity of music sampling is positively associated with the popularity of a blog among previous consumers and that this association is stronger in the tail than in the body of music sales distribution. At the same time, the incremental effect of music popularity on sampling is also stronger in the tail relative to the body. In the last part of the paper, we discuss the implications of our results for music sales and potential long-tailing of music sampling and sales. Put together, our analysis sheds new light on how social media are reshaping music sharing and consumption. © 2012 INFORMS.


Komarova N.L.,University of California at Irvine
PLoS ONE | Year: 2013

Identifying the exact regulatory circuits that can stably maintain tissue homeostasis is critical for our basic understanding of multicellular organisms, and equally critical for identifying how tumors circumvent this regulation, thus providing targets for treatment. Despite great strides in the understanding of the molecular components of stem-cell regulation, the overall mechanisms orchestrating tissue homeostasis are still far from being understood. Typically, tissue contains the stem cells, transit amplifying cells, and terminally differentiated cells. Each of these cell types can potentially secrete regulatory factors and/or respond to factors secreted by other types. The feedback can be positive or negative in nature. This gives rise to a bewildering array of possible mechanisms that drive tissue regulation. In this paper, we propose a novel method of studying stem cell lineage regulation, and identify possible numbers, types, and directions of control loops that are compatible with stability, keep the variance low, and possess a certain degree of robustness. For example, there are exactly two minimal (two-loop) control networks that can regulate two-compartment (stem and differentiated cell) tissues, and 20 such networks in three-compartment tissues. If division and differentiation decisions are coupled, then there must be a negative control loop regulating divisions of stem cells (e.g. by means of contact inhibition). While this mechanism is associated with the highest robustness, there could be systems that maintain stability by means of positive divisions control, coupled with specific types of differentiation control. Some of the control mechanisms that we find have been proposed before, but most of them are new, and we describe evidence for their existence in data that have been previously published. By specifying the types of feedback interactions that can maintain homeostasis, our mathematical analysis can be used as a guide to experimentally zero in on the exact molecular mechanisms in specific tissues. © 2013 Natalia L.


Rupert T.J.,University of California at Irvine
Journal of Applied Physics | Year: 2013

Molecular dynamics simulations are used to investigate strain localization in a model nanocrystalline metal. The atomic mechanisms of such catastrophic failure are first studied for two grain sizes of interest. Detailed analysis shows that the formation of a strain path across the sample width is crucial and can be achieved entirely through grain boundary deformation or through a combination of grain boundary sliding and grain boundary dislocation emission. Pronounced mechanically induced grain growth is also found within the strain localization region. The effects of testing conditions on strain localization are also highlighted, to understand the conditions that promote shear banding and compare these observations to metallic glass behavior. We observed that, while strain localization occurs at low temperatures and slow strain rates, a shift to more uniform plastic flow is observed when either strain rate or temperature is increased. We also explore how external sample dimensions influence strain localization, but find no size effect for the grain sizes and samples sizes studied here. © 2013 AIP Publishing LLC.


Frank S.A.,University of California at Irvine
Current Biology | Year: 2014

The large number of cell divisions required to make a human body inevitably leads to the accumulation of somatic mutations. Such mutations cause individuals to be somatic mosaics. Recent advances in genomic technology now allow measurement of somatic diversity. Initial studies confirmed the expected high levels of somatic mutations within individuals. Going forward, the big questions concern the degree to which those somatic mutations influence disease. Theory predicts that the frequency of mutant cells should vary greatly between individuals. Such somatic mutational variability between individuals could explain much of the diversity in the risk of disease. But how variable is mosaicism between individuals in reality? What is the relation between the fraction of cells carrying a predisposing mutation and the risk of disease? What kinds of heritable somatic change lead to disease besides classical DNA mutations? What molecular processes connect a predisposing somatic change to disease? We know that predisposing somatic mutations strongly influence the onset of cancer. Likewise, neurodegenerative diseases may often begin from somatically mutated cells. If so, both neurodegeneration and cancer may be diseases of later life for which much of the risk may be set by early life somatic mutations. © 2014 Elsevier Ltd.


Duncan G.J.,University of California at Irvine | Ziol-Guest K.M.,Institute for Children and Poverty | Kalil A.,University of Chicago
Child Development | Year: 2010

This article assesses the consequences of poverty between a child's prenatal year and 5th birthday for several adult achievement, health, and behavior outcomes, measured as late as age 37. Using data from the Panel Study of Income Dynamics (1,589) and controlling for economic conditions in middle childhood and adolescence, as well as demographic conditions at the time of the birth, findings indicate statistically significant and, in some cases, quantitatively large detrimental effects of early poverty on a number of attainment-related outcomes (adult earnings and work hours). Early-childhood poverty was not associated with such behavioral measures as out-of-wedlock childbearing and arrests. Most of the adult earnings effects appear to operate through early poverty's association with adult work hours. © 2010, Copyright the Author(s). Journal Compilation © 2010, Society for Research in Child Development, Inc.


Entringer S.,University of California at Irvine
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2013

PURPOSE OF REVIEW: To summarize recent conceptual frameworks and empirical findings addressing the role of prenatal stress and stress biology in the context of fetal programming of metabolic function and obesity risk. RECENT FINDINGS: The link between stress exposure and adverse health outcomes is well established. Growing evidence from animal and human studies now suggests that the experience of severe stress or perturbations in stress-related immune and endocrine processes during pregnancy may also impact the developing fetus to produce increased susceptibility for childhood and adult obesity, and dysregulated glycemic control. SUMMARY: Because endocrine and immune ligands commonly associated with stress play an essential role during intrauterine development in cellular growth and differentiation perturbations in these systems during pregnancy are likely to produce alterations of structure and function of the brain and peripheral physiological systems in the offspring. To systematically study the effects of intrauterine stress exposure on child metabolic function and obesity risk, a multilevel approach is required that includes molecular and cellular studies, the use of animal models, and human observational and interventional studies. Such studies will set the stage for translational research to inform the subsequent development of diagnostic and primary or secondary intervention strategies in at-risk individuals. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Goodrich M.T.,University of California at Irvine
Journal of the ACM | Year: 2011

In this article, we describe a randomized Shellsort algorithm. This algorithm is a simple, randomized, dataoblivious version of the Shellsort algorithm that always runs in O(nlog n) time and succeeds in sorting any given input permutation with very high probability. Taken together, these properties imply applications in the design of new efficient privacy-preserving computations based on the secure multiparty computation (SMC) paradigm. In addition, by a trivial conversion of this Monte Carlo algorithm to its Las Vegas equivalent, one gets the first version of Shellsort with a running time that is provably O(nlog n) with very high probability. © 2011.


Said H.M.,University of California at Irvine | Said H.M.,Medical Center
Biochemical Journal | Year: 2011

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of themechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society.


Saari D.G.,University of California at Irvine
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2016

To analyse paired comparison outcomes, such as with non-standard probabilities, a basis is created for the space of all binary interactions, whether from probabilities, correlations, etc. In this manner, the source of all transitive and non-Transitive behaviours (e.g. path dependencies) can be identified. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Novaco R.W.,University of California at Irvine
Journal of Forensic Psychiatry and Psychology | Year: 2011

Anger has had insufficient priority in the forensic field. From classical scholarship to contemporary neuroscience, anger has been known for its dynamic bearing on violence risk and for its involvement in psychiatric disorders. Anger is intrinsically and reciprocally related to threat perception, and it impels violent behavior in the absence of self-regulatory controls. Focus is given to what has been learned in forensic domains about anger as an impetus for the violent behavior of offenders. Issues bearing on anger assessment in forensic settings are discussed. Topics for further engagement in forensic research on anger are presented, including offender readiness, transdiagnostic processes, and female offender specificity. While anger treatment is not covered, interfacing discussion is provided throughout. © 2011 Copyright Taylor and Francis Group, LLC.


Lopez G.,University of California at Irvine
Instructional course lectures | Year: 2014

The landscape of orthopaedic surgical education is changing because of many factors, including advances in surgical procedures and musculoskeletal basic science along with an increased focus on ethics and patient education. Over the course of 5 years, a training program must navigate resident physicians through many rotations and effectively teach trainees to become competent orthopaedic surgeons. Each rotation must best balance service requirements and educational experiences to optimize resident education and patient outcomes. Factors such as the 80-hour work week and the current medicolegal climate limit the ability of residents to learn basic surgical skills in the operating room. The benefits of performing simulator-based surgical procedures in cadavers and using simulation for other procedures are becoming increasingly important to teach basic psychomotor skills to residents. Allowing a technically incompetent resident to graduate is a disservice to the medical profession, society, patients, and (ultimately) to the resident. Dealing with such a resident is challenging but necessary to ensure that residency programs continue to graduate competent medical professionals.


Bernard H.-U.,University of California at Irvine
Infection, Genetics and Evolution | Year: 2013

For more than 30 years, papillomaviruses are standing in the center of medical and molecular interest as they cause several important cancers in humans. Research of the sheer unlimited number of different papillomavirus genomes, their host specificity and slow mutation rate is an important a branch of these efforts and has led to fascinating insight into the phylogeny of a virus family that can be traced back for several 100 million years. © 2013.


Cramer S.C.,University of California at Irvine
Head and Neck | Year: 2011

Stroke remains a leading cause of disability. Most patients show some degree of spontaneous recovery, but this is generally incomplete. Studies on the neurobiology of this recovery are providing clues to therapeutic interventions that aim to improve patient outcomes. A number of potential such restorative therapies are reviewed. Numerous treatment strategies are under study. Most have a time window measured in days or weeks and so have the potential to help a large fraction of patients. This review considers these therapies, as well as points to consider in translating their application to human trials. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 Copyright © 2011 Wiley Periodicals, Inc.


Chernyshev A.L.,University of California at Irvine | Zhitomirsky M.E.,CNRS Statistical Physics, Magnetism and Superconductivity
Physical Review Letters | Year: 2014

Selection of the ground state of the kagome-lattice XXZ antiferromagnet by quantum fluctuations is investigated by combining nonlinear spin-wave and real-space perturbation theories. The two methods unanimously favor q=0 over 3×3 magnetic order in a wide range of the anisotropy parameter 0≤Δ 0.72. Both approaches are also in accord on the magnitude of the quantum order-by-disorder effect generated by topologically nontrivial, looplike spin-flip processes. A tentative S-Δ phase diagram of the model is proposed. © 2014 American Physical Society.


In this work, a transparent assembly was self-designed and manufactured to perform ex situ experimental study on the liquid water removal characteristics in PEM fuel cell parallel flow channels. It was found that the dominant frequency of the pressure drop across the flow channels may be utilized as an effective diagnostic tool for water removal. Peaks higher than 1 Hz in dominant frequency profile indicated water droplet removals at the outlet, whereas relatively lower peaks (between 0.3 and 0.8 Hz) corresponded to water stream removals. The pressure drop signal, although correlated with the water removal at the outlet, was readily influenced by the two phase flow transport in channel, particularly at high air flow rates. The real-time visualization images were presented to show a typical water droplet removal process. The findings suggest that dominant frequency of pressure drop signal may substitute pressure drop as a more effective and reliable diagnostic tool for water removal in PEM fuel cell flow channels. © 2009 Elsevier B.V. All rights reserved.


Chen J.,University of California at Irvine
Journal of Power Sources | Year: 2010

In this study, the air-water two phase flow behavior in PEM fuel cell parallel channels with porous media inserts was experimentally investigated using a self-designed and manufactured transparent assembly. The visualization images of the two phase flow in channels with porous media inserts were presented and three patterns were summarized. Compared with the traditional hollow channel design, the novel configuration featured less severe two phase flow mal-distribution and self-adjustment to water amount in channels, although a higher pressure drop was introduced due to the porous media inserts. The dominant frequency of pressure drop signal was found to be a diagnostic tool for water behavior in channels. The novel flow channel design with porous media inserts may become a solution to the water management problem in PEM fuel cells. © 2009 Elsevier B.V. All rights reserved.


Barbour A.G.,University of California at Irvine
Infection, Genetics and Evolution | Year: 2014

The discovery of Borrelia species that were related to the agents of relapsing fever but were transmitted by hard ticks rather than soft ticks challenged previous taxonomies based largely on microbe-host specificities and geographic considerations. One of these newly-identified organisms is the Borrelia miyamotoi sensu lato strain LB-2001 from North America and transmitted by Ixodes scapularis. This or related strains have been identified as the cause of human disease, but comparatively little is known about their biology or genetics. Using recently acquired chromosome sequence of LB-2001 together with database sequences and additional sequences determined here, I carried out comparisons of the several species of Borrelia, including those in the two major clades: the relapsing fever group of species and the Lyme disease group of species. Phylogenetic inference at the species level was based on four data sets: whole chromosomes of ∼1 Mb each, and concatenated sequences of 19 ribosomal protein genes, 3 conserved nucleic acid enzymes (rpoC, recC, and dnaE), and 4 contiguous genes for nucleotide salvage on a large plasmid. Analyses using neighbor-joining, maximum likelihood, and Bayesian methods were largely concordant for each of the trees. They showed that LB-2001 and related hard tick-associated organisms, like Borrelia lonestari, are deeply positioned within the RF group of species and that these organisms did not, as some earlier estimations had suggested, constitute a paraphyletic group. The analyses also provided further evidence that major changes in host ranges and life cycles, such as hard to soft ticks or vice versa, may not correlate well with overall sequence differences. The genetic differences between LB-2001 and B. miyamotoi sensu stricto justify provisional use of the "sensu lato" designation for LB-2001. © 2014 Elsevier B.V. All rights reserved.


Lund D.C.,100 North University Ave | Mix A.C.,Oregon State University | Southon J.,University of California at Irvine
Nature Geoscience | Year: 2011

The rise in atmospheric carbon dioxide during the last deglaciation may have been driven by the release of carbon from the abyssal ocean 1,2. This mechanism would require a poorly ventilated deep Pacific Ocean during the Last Glacial Maximum and enhanced exchange with the atmosphere during deglaciation. Here we use radiocarbon measurements of planktonic and benthic foraminiferal shells from a core collected at 2.7 km water depth in the northeast Pacific to estimate the ventilation age of deep waters using the projection age method. In contrast to the above scenario, we show that ventilation ages during the Last Glacial Maximum were similar to today. This suggests that this part of the Pacific was not an important reservoir of carbon during glacial times. During deglaciation, ventilation ages increased by ∼1,000 years, indicating a decrease in the ventilation rate, an increase in the surface water reservoir age in the Southern Ocean, or an influx of old carbon from another source. Despite the increased ventilation age during deglaciation, the deep northeast Pacific still had a higher 14C/C ratio than intermediate waters near Baja California 3. We therefore conclude that the deep northeast Pacific was apparently not old enough to be the source of deglacial radiocarbon anomalies found shallower in the water column. © 2011 Macmillan Publishers Limited. All rights reserved.


Li X.,University of California at Irvine | Li D.,Tsinghua University | Li D.,Tsinghua National Laboratory for Information Sciences and Technology
Physical Review Letters | Year: 2012

We solve the entanglement classification under stochastic local operations and classical communication (SLOCC) for general n-qubit states. For two arbitrary pure n-qubit states connected via local operations, we establish an equation between the two coefficient matrices associated with the states. The rank of the coefficient matrix is preserved under SLOCC and gives rise to a simple way of partitioning all the pure states of n qubits into different families of entanglement classes, as exemplified here. When applied to the symmetric states, this approach reveals that all the Dicke states |n with =1,[n/2] are inequivalent under SLOCC. © 2012 American Physical Society.


Papamoschou D.,University of California at Irvine
Journal of Sound and Vibration | Year: 2011

This study relates to the acoustic imaging of noise sources that are distributed and strongly directional, such as in turbulent jets. The goal is to generate high-resolution noise source maps with self-consistency, i.e., their integration over the extent of the noise source region gives the far-field pressure auto-spectrum for a particular emission direction. Self-consistency is possible by including a directivity factor in the formulation of the source cross-spectral density. The resulting source distribution is based on the complex coherence, rather than the cross-spectrum, of the measured acoustic field. For jet noise, whose spectral nature changes with emission angle, it is necessary to conduct the measurements with a narrow-aperture array. Three coherence-based imaging methods were applied to a Mach 0.9 turbulent jet: delay-and-sum beamforming; deconvolution of the beamformer output; and direct spectral estimation that relies on minimizing the difference between the measured and modeled coherences of the acoustic field. The delay-and-sum beamforming generates noise source maps with strong spatial distortions and sidelobes. Deconvolution leads to a five-fold improvement in spatial resolution and significantly reduces the intensity of the sidelobes. The direct spectral estimation produces maps very similar to those obtained by deconvolution. The coherence-based noise source maps, obtained by deconvolution or direct spectral estimation, are similar at small and large observation angles relative to the jet axis. © 2010 Elsevier Ltd All rights reserved.


McGaugh S.S.,University of Maryland University College | Olf J.,University of California at Irvine
Astrophysical Journal | Year: 2010

Local Group dwarf spheroidal satellite galaxies are the faintest extragalactic stellar systems known. We examine recent data for these objects in the plane of the Baryonic Tully-Fisher Relation (BTFR). While some dwarf spheroidals adhere to the BTFR, others deviate substantially. We examine the residuals from the BTFR and find that they are not random. The residuals correlate with luminosity, size, metallicity, ellipticity, and susceptibility of the dwarfs to tidal disruption in the sense that fainter, more elliptical, and tidally more susceptible dwarfs deviate farther from the BTFR. These correlations disfavor stochastic processes and suggest a role for tidal effects. We identify a test to distinguish between ΔCDM and MOND based on the orbits of the dwarf satellites of the Milky Way and how stars are lost from them. © 2010. The American Astronomical Society. All rights reserved.


Fisher M.,University of California at Irvine
Annals of the New York Academy of Sciences | Year: 2010

Stroke in general, and ischemic stroke in particular, are routinely defined using clinical criteria. Incorporating brain imaging and neuropathological findings into an expanded conceptual definition of stroke will result in a vastly increased prevalence of the disease. The resultant category of mixed cerebrovascular disease thus may include subclinical infarct, cerebral whitematter disease, and cerebral microbleeds. Subclinical brain infarcts occur five times more frequently than does clinical ischemic stroke. Abnormalities of cerebral white matter are present in more than 95% of the population over the age of 65 years, and magnetic resonance imaging evidence of cerebral microbleeds is found in at least 18% of the population, beginning at the age of 60 years. Pathologic evidence supports at least a partial microvascular origin for cerebral whitematter disease and cerebralmicrobleeds. Emphasizing mixed cerebrovascular disease as a conceptual framework allows for a focus on common underlying mechanisms and new therapeutic strategies. © 2010 New York Academy of Sciences.


Feig S.,University of California at Irvine
Obstetrics and Gynecology Clinics of North America | Year: 2011

Screening mammography performed annually on all women beginning at age 40 years has reduced breast cancer deaths by 30% to 50%. The cost per year of life saved is well within the range for other commonly accepted medical interventions. Various studies have estimated that reduction in treatment costs through early screening detection may be 30% to 100% or more of the cost of screening. Magnetic resonance imaging (MRI) screening is also cost-effective for very high-risk women, such as BRCA carriers, and others at 20% or greater lifetime risk. Further studies are needed to determine whether MRI is cost-effective for those at moderately high (15%-20%) lifetime risk. Future technical advances could make MRI more cost-effective than it is today. Automated whole-breast ultrasonography will probably prove cost-effective as a supplement to mammography for women with dense breasts. © 2011 Elsevier Inc.


Shi Y.,University of California at Irvine
RNA | Year: 2012

Recent studies have revealed widespread mRNA alternative polyadenylation (APA) in eukaryotes and its dynamic spatial and temporal regulation. APA not only generates proteomic and functional diversity, but also plays important roles in regulating gene expression. Global deregulation of APA has been demonstrated in a variety of human diseases. Recent exciting advances in the field have been made possible in a large part by high throughput analyses using newly developed experimental tools. Here I review the recent progress in global studies of APA and the insights that have emerged from these and other studies that use more conventional methods. Copyright © 2012 RNA Society.


Franklin S.S.,University of California at Irvine
Journal of Clinical Hypertension | Year: 2012

Once considered an inconsequential part of the aging process, the development of isolated systolic hypertension represents a late manifestation of increased elastic artery stiffness and is the predominant hypertensive subtype in the middle-aged and elderly populations. Its inherent increased risk for vascular events, such as coronary heart disease, stroke, heart failure, peripheral artery disease, chronic kidney disease, and dementia, highlights the importance of its control. The purpose of this short review is to summarize how hypertension is different in the elderly when compared with "essential hypertension" in younger adults. The emphasis will be on the multiple ways that increased artery stiffness affects the natural history and clinical manifestations of hypertension in the elderly. © 2012 Wiley Periodicals, Inc.


Guan Z.,University of California at Irvine
Chemistry - An Asian Journal | Year: 2010

Catalysis continues to spark new imagination and excitement of synthetic chemists. Discovery of new catalytic processes often makes seemingly impossible transformations proceed magically at high efficiency. In modern polymer synthesis, an exciting direction in recent years is the development of transition-metal-catalyzed polymerizations for controlling polymer topology. In this Focus Review, we highlight a few recent examples for catalytic syntheses of polyolefins having cyclic, block, and dendritic topologies, respectively. These examples showcase the power and efficiency of transition-metal catalysis for accessing various polymer topologies ranging from simple cyclic to complex globular dendritic polymers. © 2010 Wiley-VCH Verlag GmbH © Co. KGaA, Weinheim.


Daniel R.K.,University of California at Irvine
Facial Plastic Surgery | Year: 2011

Based on a 25-year experience, the author considers open tip suture techniques to be the best method of achieving consistent and reproducible tip changes that can please patients with a wide variety of tip deformities. The described technique consists of selecting the ideal combination of the following six sutures: (1) columellar strut and suture, (2) domal creation, (3) interdomal, (4) domal equalization, (5) tip position, and (6) lateral crural convexity. If additional definition is required, then tip refinement grafts can be added to accommodate thicker skin or lateral crura abnormalities. Copyright © 2011 by Thieme Medical Publishers, Inc.


DeVries T.,University of California at Los Angeles | Primeau F.,University of California at Irvine
Journal of Physical Oceanography | Year: 2011

A data-constrained ocean circulation model is used to characterize the distribution of water masses and their ages in the global ocean. The model is constrained by the time-averaged temperature, salinity, and radiocarbon distributions in the ocean, as well as independent estimates of the mean sea surface height and sea surface heat and freshwater fluxes. The data-constrained model suggests that the interior ocean is ventilated primarily by water masses forming in the Southern Ocean. Southern Ocean waters, including those waters forming in the Antarctic and subantarctic regions, make up about 55% of the interior ocean volume and an even larger percentage of the deep-ocean volume. In the deep North Pacific, the ratio of Southern Ocean to North Atlantic waters is almost 3:1. Approximately 65% of interior ocean waters make first contact with the atmosphere in the Southern Ocean, further emphasizing the central role played by the Southern Ocean in the regulation of the earth's climate. Results of the age analysis suggest that the mean ventilation age of deep waters is greater than 1000 yr throughout most of the Indian and Pacific Oceans, reaching a maximum of about 1400-1500 yr in the middepth North Pacific. The mean time for deep waters to be reexposed at the surface also reaches a maximum of about 1400-1500 yr in the deep North Pacific. Together these findings suggest that the deep North Pacific can be characterized as a "holding pen" of stagnant and recirculating waters. © 2011 American Meteorological Society.


Momtaz A.,Broadcom Corporation | Green M.M.,University of California at Irvine
IEEE Journal of Solid-State Circuits | Year: 2010

A 7-tap 40 Gb/s FFE using a 65 nm standard CMOS process is described. A number of broadbanding and calibration techniques are used, which allow high-speed operation while consuming 80 mW from a 1 V supply. ESD protection is added to 40 Gb/s IOs and an inexpensive plastic package is used to make the chip closer to a commercial product. The measured tap delay frequency response variation is less than 1 dB up to 20 GHz and tap-to-tap delay variation is less than 0.3 ps. More than 50% vertical and 70% horizontal eye opening from a closed input eye are observed. The use of a CMOS process enables further integration of this core into a DFE equalizer or a CDR/Demux based receiver. © 2006 IEEE.


Finlayson-Pitts B.J.,University of California at Irvine
Analytical Chemistry | Year: 2010

Although inorganic halogen gases are believed to play key roles in the chemistry of the lower atmosphere, many of them have not yet been detected or measured in ambient air. This article describes some of the current techniques and future needs for inorganic halogens in air. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.) © 2010 American Chemical Society.


Burke K.,University of California at Irvine
Journal of Chemical Physics | Year: 2012

Density functional theory (DFT) is an incredible success story. The low computational cost, combined with useful (but not yet chemical) accuracy, has made DFT a standard technique in most branches of chemistry and materials science. Electronic structure problems in a dazzling variety of fields are currently being tackled. However, DFT has many limitations in its present form: too many approximations, failures for strongly correlated systems, too slow for liquids, etc. This perspective reviews some recent progress and ongoing challenges. © 2012 American Institute of Physics.


Hamber H.W.,University of California at Irvine
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

In this work nonperturbative aspects of quantum gravity are investigated using the lattice formulation, and some new results are presented for critical exponents, amplitudes, and invariant correlation functions. Values for the universal scaling dimensions are compared with other nonperturbative approaches to gravity in four dimensions, and specifically to the conjectured value for the universal critical exponent ν=1/3. The lattice results are generally consistent with gravitational antiscreening, which would imply a slow increase in the strength of the gravitational coupling with distance, and presented herein are detailed estimates for exponents and amplitudes characterizing this slow rise. Furthermore, it is shown that in the lattice approach (as for gauge theories) the quantum theory is highly constrained, and eventually, by virtue of scaling, depends on a rather small set of physical parameters. Arguments are given in support of the statement that the fundamental reference scale for the growth of the gravitational coupling G with distance is represented by the observed scaled cosmological constant λ, which in gravity acts as an effective nonperturbative infrared cutoff. In this nonperturbative vacuum condensate picture a fundamental relationship emerges among the scale characterizing the running of G at large distances, the macroscopic scale for the curvature as described by the observed cosmological constant, and the behavior of invariant gravitational correlation functions at large distances. Overall, the lattice results suggest that the slow infrared growth of G with distance should become observable only on very large distance scales, comparable to λ. One may hope that future high precision satellite experiments could possibly come within reach of this small quantum correction, as suggested by the vacuum condensate picture of quantum gravity. © 2015 American Physical Society.


Nesamani K.S.,University of California at Irvine
Science of the Total Environment | Year: 2010

Rapid, but unplanned urban development and the consequent urban sprawl coupled with economic growth have aggravated auto dependency in India over the last two decades. This has resulted in congestion and pollution in cities. The central and state governments have taken many ameliorative measures to reduce vehicular emissions. However, evolution of scientific methods for emission inventory is crucial. Therefore, an attempt has been made to estimate the emissions (running and start) from on-road vehicles in Chennai using IVE model in this paper. GPS was used to collect driving patterns. The estimated emissions from motor vehicles in Chennai in 2005 were 431, 119, 46, 7, 4575, 29, and 0.41 tons/days respectively for CO, VOC, NOx, PM, CO2, CH4 and N2O. It is observed from the results that air quality in Chennai has degraded. The estimation revealed that two and three-wheelers emitted about 64% of the total CO emissions and heavy-duty vehicles accounted for more than 60% and 36% of the NOx and PM emissions respectively. About 19% of total emissions were that of start emissions. It is also estimated that on-road transport contributes about 6637 tons/day CO2 equivalent in Chennai. This paper has further examined various mitigation options to reduce vehicular emissions. The study has concluded that advanced vehicular technology and augmentation of public transit would have significant impact on reducing vehicular emissions. © 2010 Elsevier B.V. All rights reserved.


Velicogna I.,University of California at Irvine | Velicogna I.,Jet Propulsion Laboratory | Wahr J.,University of Colorado at Boulder
Geophysical Research Letters | Year: 2013

Time-variable gravity data from the Gravity Recovery and Climate Experiment (GRACE) mission have been available since 2002 to estimate the mass balance of the Greenland and Antarctic Ice Sheets. We analyze current progress and uncertainties in GRACE estimates of ice sheet mass balance. We discuss the impacts of errors associated with spherical harmonic truncation, spatial averaging, temporal sampling, and leakage from other time-dependent signals (e.g., glacial isostatic adjustment (GIA)). The largest sources of error for Antarctica are the GIA correction, the omission of l=1 terms, nontidal changes in ocean mass, and measurement errors. For Greenland, the errors come mostly from the uncertainty in the scaling factor. Using Release 5.0 (RL05) GRACE fields for January 2003 through November 2012, we find a mass change of -258 - 41 Gt/yr for Greenland, with an acceleration of -31 - 6 Gt/yr2, and a loss that migrated clockwise around the ice sheet margin to progressively affect the entire periphery. For Antarctica, we report changes of -83 - 49 and -147 - 80 Gt/yr for two GIA models, with an acceleration of -12 - 9 Gt/yr 2 and a dominance from the southeast pacific sector of West Antarctica and the Antarctic Peninsula. Key Points Comprehensive review of error sources, their impact and how to deal with them Estimates ice sheet mass balance for latest, extended GRACE releases Rapid publication for input to IPCC AR5 ©2013. American Geophysical Union. All Rights Reserved.


Coppari R.,University of Texas Southwestern Medical Center | Coppari R.,University of Geneva | Coppari R.,University of California at Irvine | Bjorbaek C.,Beth Israel Deaconess Medical Center
Nature Reviews Drug Discovery | Year: 2012

Since the discovery of leptin in 1994, we now have a better understanding of the cellular and molecular mechanisms underlying its biological effects. In addition to its established anti-obesity effects, leptin exerts antidiabetic actions that are independent of its regulation of body weight and food intake. In particular, leptin can correct diabetes in animal models of type 1 and type 2 diabetes. In addition, long-term leptin replacement therapy improves glycaemic control, insulin sensitivity and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. These results have spurred enthusiasm for the use of leptin therapy to treat diabetes. Here, we review the current understanding of the glucoregulatory functions of leptin, emphasizing its central mechanisms of action and lessons learned from clinical studies, and discuss possible therapeutic applications of leptin in the treatment of type 1 and type 2 diabetes. © 2012 Macmillan Publishers Limited. All rights reserved.


Nomura M.,University of California at Irvine
Annual Review of Biochemistry | Year: 2011

My journey into a research career began in fermentation biochemistry in an applied science department during the difficult post-World War II time in Japan. Subsequently, my desire to do research in basic science developed. I was fortunate to be a postdoctoral fellow in the United States during the early days of molecular biology. From 1957 to 1960, I worked with three pioneers of molecular biology, Sol Spiegelman, James Watson, and Seymour Benzer. These experiences helped me develop into a basic research scientist. My initial research projects at Osaka University, and subsequently at the University of Wisconsin, Madison, were on the mode of action of colicins as well as on mRNA and ribosomes. Following success in the reconstitution of ribosomal subunits, my efforts focused more on ribosomes, initially on the aspects of structure, function, and in vitro assembly, such as the construction of the 30S subunit assembly map. After this, my laboratory studied the regulation of the synthesis of ribosomes and ribosomal components in Escherichia coli. Our achievements included the discovery of translational feedback regulation of ribosomal protein synthesis and the identification of several repressor ribosomal proteins used in this regulation. In 1984, I moved to the University of California, Irvine, and initiated research on rRNA transcription by RNA polymerase I in the yeast Saccharomyces cerevisiae. The use of yeast genetics combined with biochemistry allowed us to identify genes uniquely involved in rRNA synthesis and to elucidate the mechanism of initiation of transcription. This essay is a reflection on my life as a research scientist. © 2011 by Annual Reviews. All rights reserved.


Frank S.A.,University of California at Irvine
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Somatic mutations must happen often during development because of the large number of cell divisions to expand from a single-cell zygote to a full organism. A mutation in development carries forward to all descendant cells, causing genetic mosaicism. Widespread genetic mosaicism may influence diseases that derive from a few genetically altered cells, such as cancer. I show how to predict the expected amount of mosaicism and the variation in mosaicism between individuals. I then calculate the predicted risk of cancer derived from developmental mutations. The calculations show that a significant fraction of cancer in later life likely arises from developmental mutations in early life. In addition, much of the variation in the risk of cancer between individuals may arise from variation in the degree of genetic mosaicism set in early life. I also suggest that certain types of neurodegeneration, such as amyotrophic lateral sclerosis (ALS), may derive from a small focus of genetically altered cells. If so, then the risk of ALS would be influenced by developmental mutations and the consequent variation in genetic mosaicism. New technologies promise the ability to measure genetic mosaicism by sampling a large number of cellular genomes within an individual. The sampling of many genomes within an individual will eventually allow one to reconstruct the cell lineage history of genetic change in a single body. Somatic evolutionary genomics will follow from this technology, providing new insight into the origin and progression of disease with increasing age.


Epidermal growth factor receptor (EGFR) tyrosine inhibitors were first approved for the treatment of non-small cell lung cancer (NSCLC) in 2003 in the US. Activating EGFR mutations were subsequently discovered in 2004, and heralded the era of molecular targeted therapy in NSCLC. The discovery of anaplastic lymphoma kinase (ALK) rearrangement in NSCLC in 2007 by two independent groups not only represents the first time ALK rearrangement has been discovered in common solid tumors but also represents another important milestone in the era of molecular targeted therapy in NSCLC. Crizotinib, a mesenchymal-epithelial transition (MET)/ALK multi-targeted receptor tyrosine kinase inhibitor went into early Phase I clinical development in 2007. Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites. It cumulated in the conditional approval of crizotinib by the US Food and Drug Administration on August 26, 2011 for the treatment of ALK-rearranged NSCLC. The conditional approval was based on response rates of 50% and 61% from 255 ALK-rearranged NSCLC patients enrolled in two single-arm trials. Common adverse events of crizotinib include mild transient visual disorders, mild gastrointestinal toxicities, fatigue, rare alanine transaminase elevations, and even rarer pneumonitis (1.6%). Confirmatory trials comparing crizotinib with standard chemotherapy are ongoing. It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALKrearranged NSCLC. © 2011 Ou, publisher and licensee Dove Medical Press Ltd.


Hu T.T.,Princeton University | Eisen M.B.,Howard Hughes Medical Institute | Thornton K.R.,University of California at Irvine | Andolfatto P.,Princeton University
Genome Research | Year: 2013

We create a new assembly of the Drosophila simulans genome using 142 million paired short-read sequences and previously published data for strain w501. Our assembly represents a higher-quality genomic sequence with greater coverage, fewer misassemblies, and, by several indexes, fewer sequence errors. Evolutionary analysis of this genome reference sequence reveals interesting patterns of lineage-specific divergence that are different from those previously reported. Specifically, we find that Drosophila melanogaster evolves faster than D. simulans at all annotated classes of sites, including putatively neutrally evolving sites found in minimal introns. While this may be partly explained by a higher mutation rate in D. melanogaster, we also find significant heterogeneity in rates of evolution across classes of sites, consistent with historical differences in the effective population size for the two species. Also contrary to previous findings, we find that the X chromosome is evolving significantly faster than autosomes for nonsynonymous and most noncoding DNA sites and significantly slower for synonymous sites. The absence of a X/A difference for putatively neutral sites and the robustness of the pattern to Gene Ontology and sex-biased expression suggest that partly recessive beneficial mutations may comprise a substantial fraction of noncoding DNA divergence observed between species. Our results have more general implications for the interpretation of evolutionary analyses of genomes of different quality.


Underhill D.M.,Cedars Sinai Medical Center | Pearlman E.,University of California at Irvine
Immunity | Year: 2015

We are exposed to a wide spectrum of fungi including innocuous environmental organisms, opportunistic pathogens, commensal organisms, and fungi that can actively and explicitly cause disease. Much less is understood about effective host immunity to fungi than is generally known about immunity to bacterial and viral pathogens. Innate and adaptive arms of the immune system are required for effective host defense against Candida, Aspergillus, Cryptococcus, and others, with specific elements of the host response regulating specific types of fungal infections (e.g., mucocutaneous versus systemic). Here we will review themes and controversies that are currently shaping investigation of antifungal immunity (primarily to Candida and Aspergillus) and will also examine the emerging field of the role of fungi in the gut microbiome. © 2015 Elsevier Inc.


Bai Y.,University of Wisconsin - Madison | Bai Y.,SLAC | Tait T.M.P.,University of California at Irvine
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

We explore the implications of the mono-lepton plus missing transverse energy signature at the LHC, and point out its significance on understanding how dark matter interacts with quarks, where the signature arises from dark matter pair production together with a leptonically decaying W boson radiated from the initial state quarks. We derive limits using the existing W' searches at the LHC, and find an interesting interference between the contributions from dark matter couplings to up-type and down-type quarks. Mono-leptons can actually furnish the strongest current bound on dark matter interactions for axial-vector (spin-dependent) interactions and iso-spin violating couplings. Should a signal of dark matter production be observed, this process can also help disentangle the dark matter couplings to up- and down-type quarks. © 2013 Elsevier B.V.


Huang T.,University of California at Irvine
Current Protocols in Human Genetics | Year: 2011

This protocol describes the methodology to characterize mitochondrial DNA (mtDNA) heteroplasmy by parallel sequencing. Mitochondria play an important role in essential cellular functions. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondria genomes. Mutant and wild-type mtDNA may co-exist as heteroplasmy, and cause human disease. The purpose of this protocol is to simultaneously determine mtDNA sequence and quantify the heteroplasmic level. This protocol includes a twofragment mitochondrial genome DNA PCR amplification. The PCR product is then mixed at an equimolar ratio. The samples are then barcoded and sequenced with highthroughput, next-generation sequencing technology. This technology is highly sensitive, specific, and accurate in determining mtDNA mutations and the level of heteroplasmy. © 2011 by John Wiley & Sons, Inc.


Bederman S.S.,University of California at Irvine
The Journal of bone and joint surgery. American volume | Year: 2012

Randomized controlled trials continue to be at the pinnacle of the evidence hierarchy. With this unique vantage point, they inform medical practice, clinical guidelines, health policy, and reimbursement. Prior to an emphasis on randomized controlled trials, traditional clinical research consisted primarily of uncontrolled case series and expert opinions. Randomized controlled trials are a true experiment in clinical practice and provide the most valid answers to clinical questions by reducing bias originating from patients, providers, and investigators. Riding on the coattails of other medical subspecialties, orthopaedic surgeons have recognized the importance of evidence-based medicine. From 1975 to 2005, the number of Level-I studies increased over fivefold and comprised >20% of studies published in The Journal of Bone and Joint Surgery (American Volume) (JBJS). With the emergence of comparative effectiveness research, the definition and methods of best evidence may continue to evolve. In conclusion, substantial improvements in both the quantity and the quality of randomized controlled trials in orthopaedic surgery have occurred, although unique considerations still limit their widespread use.


Cohen D.J.,University of North Carolina at Wilmington | Sarnecka B.W.,University of California at Irvine
Developmental Psychology | Year: 2014

Children's understanding of numbers is often assessed using a number-line task, where the child is shown a line labeled with 0 at one end and a higher number (e.g., 100) at the other end. The child is then asked where on the line some intermediate number (e.g., 70) should go. Performance on this task changes predictably during childhood, and this has often been interpreted as evidence of a change in the child's psychological representation of integer quantities. The present article presents theoretical and empirical evidence that the change in number-line performance actually reflects the development of measurement skills used in the task. We compare 2 versions of the number-line task: the bounded version used in the literature and a new, unbounded version. Results indicate that it is only children's performance on the bounded task (which requires subtraction or division) that changes markedly with age. In contrast, children's performance on the unbounded task (which requires only addition) remains fairly constant as they get older. Thus, developmental changes in performance on the traditional bounded number-line task likely reflect the growth of task-specific measurement skills rather than changes in the child's understanding of numerical quantities.


Alexandru D.,University of California at Irvine
The Permanente journal | Year: 2012

Compression fractures affect many individuals worldwide. An estimated 1.5 million vertebral compression fractures occur every year in the US. They are common in elderly populations, and 25% of postmenopausal women are affected by a compression fracture during their lifetime. Although these fractures rarely require hospital admission, they have the potential to cause significant disability and morbidity, often causing incapacitating back pain for many months. This review provides information on the pathogenesis and pathophysiology of compression fractures, as well as clinical manifestations and treatment options. Among the available treatment options, kyphoplasty and percutaneous vertebroplasty are two minimally invasive techniques to alleviate pain and correct the sagittal imbalance of the spine.


Wing D.A.,University of California at Irvine
Obstetrics and gynecology | Year: 2013

To compare the efficacy and safety of a 200-microgram misoprostol vaginal insert with a 10-mg dinoprostone vaginal insert for reducing the time to vaginal delivery. In a phase III, double-blind, multicenter study, women being induced with a modified Bishop score of 4 or less were randomly assigned to receive either a 200-microgram misoprostol vaginal insert or a 10-mg dinoprostone vaginal insert. Coprimary end points were time to vaginal delivery and rate of cesarean delivery. Secondary end points included time to any delivery mode, time to onset of active labor, and oxytocin use. A total of 1,358 women were randomized to receive the 200-microgram misoprostol vaginal insert (n=678) or dinoprostone vaginal insert (n=680). Women receiving the misoprostol vaginal insert had a significantly shorter median time to vaginal delivery compared with patients receiving the dinoprostone vaginal insert (21.5 hours compared with 32.8 hours, P<.001). Cesarean delivery occurred in 26.0% and 27.1% of women receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively. A significant reduction in time to any delivery (18.3 hours compared with 27.3 hours), time to onset of active labor (12.1 hours compared with 18.6 hours), and proportion of women requiring predelivery oxytocin (48.1% compared with 74.1%) was observed with the misoprostol vaginal insert compared with dinoprostone vaginal insert (P<.001 for each). Uterine tachysystole requiring intervention occurred in 13.3% and 4.0% of participants receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively (P<.001). Use of a 200-microgram misoprostol vaginal inset significantly reduced times to vaginal delivery and active labor with reduced need for oxytocin compared with the dinoprostone vaginal insert. Cesarean delivery rates were similar with both treatments. Tachysystole was more common in women receiving the 200-microgram misoprostol vaginal insert. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01127581. I.


Ou S.-H.I.,University of California at Irvine
Expert Review of Anticancer Therapy | Year: 2012

Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs. Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay. This conditional approval was based on response rates of 50-61% from 255 ALK-rearranged NSCLC patients enrolled in two ongoing single-arm crizotinib trials. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue, grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis (1.6%). Confirmatory trials comparing crizotinib to standard chemotherapy in upfront (ClinicalTrials.gov identifier: NCT01154140) and salvage (ClinicalTrials.gov identifier: NCT00932451) treatment settings of ALK-rearranged NSCLC are ongoing. It took an unprecedented rapid 4 years from the publication of the discovery of ALK-rearranged NSCLC in August 2007 to the conditional approval of crizotinib in August 2011. © 2012 Expert Reviews Ltd.


Ward G.,University of California at Irvine
Theoretical Criminology | Year: 2015

The politicization of crime challenges theoretical and empirical criminology, while drawing the discipline into politics of criminal social control. This complication and complicity is considered in the case of state organized race crime, and especially its “slow violence”, where victimization is attritional, dispersed, and hidden. Criminology is not merely compromised here—or limited in theoretical and empirical reach—but complicit, contributing to under-regulated racial violence rationalized in large part by the criminalization of race. The discipline might contribute to increased understanding of state organized race crime, and lessen its role therein, with greater commitments to critical race research and teaching. © 2014, © The Author(s) 2014.


Avise J.C.,University of California at Irvine
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Intelligent design (ID) - the latest incarnation of religious creationism - posits that complex biological features did not accrue gradually via natural evolutionary forces but, instead, were crafted ex nihilo by a cognitive agent. Yet, many complex biological traits are gratuitously complicated, function poorly, and debilitate their bearers. Furthermore, such dysfunctional traits abound not only in the phenotypes but inside the genomes of eukaryotic species. Here, I highlight several outlandish features of the human genome that defy notions of ID by a caring cognitive agent. These range from de novo mutational glitches that collectively kill or maim countless individuals (including embryos and fetuses) to pervasive architectural flaws (including pseudogenes, parasitic mobile elements, and needlessly baroque regulatory pathways) that are endogenous in every human genome. Gross imperfection at the molecular level presents a conundrum for the traditional paradigms of natural theology as well as for recent assertions of ID, but it is consistent with the notion of nonsentient contrivance by evolutionary forces. In this important philosophical sense, the science of evolutionary genetics should rightly be viewed as an ally (not an adversary) of mainstream religions because it helps the latter to escape the profound theological enigmas posed by notions of ID.


Ayala F.J.,University of California at Irvine
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

In The Descent of Man, and Selection in Relation to Sex, published in 1871, Charles Darwin wrote: "I fully . . . subscribe to the judgment of those writers who maintain that of all the differences between man and the lower animals the moral sense or conscience is by far the most important." I raise the question of whether morality is biologically or culturally determined. The question of whether the moral sense is biologically determined may refer either to the capacity for ethics (i.e., the proclivity to judge human actions as either right or wrong), or to the moral norms accepted by human beings for guiding their actions. I propose that the capacity for ethics is a necessary attribute of human nature, whereas moral codes are products of cultural evolution. Humans have a moral sense because their biological makeup determines the presence of three necessary conditions for ethical behavior: (i) the ability to anticipate the consequences of one's own actions; (ii) the ability to make value judgments; and (iii) the ability to choose between alternative courses of action. Ethical behavior came about in evolution not because it is adaptive in itself but as a necessary consequence of man's eminent intellectual abilities, which are an attribute directly promoted by natural selection. That is, morality evolved as an exaptation, not as an adaptation. Moral codes, however, are outcomes of cultural evolution, which accounts for the diversity of cultural norms among populations and for their evolution through time.


Bornkessel-Schlesewsky I.,University of South Australia | Bornkessel-Schlesewsky I.,University of Marburg | Schlesewsky M.,Johannes Gutenberg University Mainz | Small S.L.,University of California at Irvine | And 2 more authors.
Trends in Cognitive Sciences | Year: 2015

Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. © 2014 Elsevier Ltd.


Balibar E.,University of California at Irvine
Environment and Planning D: Society and Space | Year: 2012

In the wake of previous reflections on the antinomies of citizenship-which derive both from the tension between an 'insurrectional' logic of equal liberty and a 'constitutional' project of building a community of citizens, and more recently from the conflict between (national) social citizenship and neoliberal forms of global governance-this paper focuses on problems of 'representa- tion' and 'agency' linked to the idea of democratizing democracy itself. It will try in this sense to propose a more specific determination to the idea of an unfinished, although contingent, history of citizenship in the modern world. © 2012 Pion Ltd and its Licensors.


Salvesen G.S.,Sanford Burnham Institute for Medical Research | Walsh C.M.,University of California at Irvine
Seminars in Immunology | Year: 2014

Initially discovered as an initiator protease in apoptosis mediated by death receptors, caspase-8 is now known to have an apparently confounding opposing effect in securing cell survival. It is required to allow mouse embryo survival, and the survival of hematopoietic cells during their development and activation. Classic models in which caspase-8 is depleted or inhibited frequently result in inhibition of apoptosis, and conversion to death through a necrotic pathway. This bewildering switch is now known to be driven by activation of a pathway dependent on protein kinases of the RIP family, which engage a pathway known as necroptosis. If caspase-8 does not control this pathway, necrotic death results. The pro-apoptotic and pro-survival functions of caspase-8 are regulated by a specific interaction with the pseudo-caspase cFLIP, and it is thought that the heterocomplex between these two partners alters the substrate specificity of caspase-8 in favor of inactivating components of the RIP kinase pathway. The description of how caspase-8 and cFLIP coordinate the switch between apoptosis and survival is just beginning. The mechanism is not known, the differential targets are not known, and the reason of why an apoptotic initiator has been co-opted as a critical survival factor is only guessed at. Elucidating these unknowns will be important in understanding mechanisms and possible therapeutic targets in autoimmune, inflammatory, and metastatic diseases. © 2014 Elsevier Ltd.


Lee T.Q.,University of California at Irvine
Clinics in Orthopedic Surgery | Year: 2014

The capacity to perform certain activities is frequently compromised after total knee arthroplasty (TKA) due to a functional decline resulting from decreased range of motion and a diminished ability to kneel. In this manuscript, the current biomechanical understanding of hyperflexion and kneeling before and after TKA will be discussed. Patellofemoral and tibiofemoral joint contact area, contact pressure, and kinematics were evaluated in cadaveric studies using a Tekscan pressure measuring system and Microscribe. Testing was performed on intact knees and following cruciate retaining and posterior stabilized TKA at knee flexion angles of 90°, 105°, 120°, and 135°. Three loading conditions were used to simulate squatting, double stance kneeling, and single stance kneeling. Following TKA with double stance kneeling, patellofemoral contact areas did not increase significantly at high knee flexion angle (135°). Kneeling resulted in tibial posterior translation and external rotation at all flexion angles. Moving from double to single stance kneeling tended to increase pressures in the cruciate retaining group, but decreased pressures in the posterior stabilized group. The cruciate retaining group had significantly larger contact areas than the posterior stabilized group, although no significant differences in pressures were observed comparing the two TKA designs (p < 0.05). If greater than 120° of postoperative knee range of motion can be achieved following TKA, then kneeling may be performed with less risk in the patellofemoral joint than was previously believed to be the case. However, kneeling may increase the likelihood of damage to cartilage and menisci in intact knees and after TKA increases in tibiofemoral contact area and pressures may lead to polyethyelene wear if performed on a chronic, repetitive basis. © 2014 by The Korean Orthopaedic Association.


Dewan S.,University of California at Irvine | Ren F.,Peking University
Information Systems Research | Year: 2011

In this paper, we empirically investigate the impact of information technology (IT) investment on firm return and risk financial performance, emphasizing the moderating role of the firm boundary strategies of diversification and vertical integration. Our results indicate a sharp contrast between the direct and interactive effects of IT on both the return (profitability) and risk (variability of returns) dimensions. Although the direct effect of IT capital is to increase firm risk for a given level of return, we find that suitable boundary strategies can moderate the impact of IT on firm performance in a way that increases return and decreases risk, at the margin. This interaction effect is strongest in service firms, in firms with high levels of IT investment intensity, and in more recent time periods. Our results are robust to alternative proxies for firm risk, including an ex ante risk measure (variability of analysts' earnings estimates), and alternative risk-return specifications. Put together, our results provide new insights into how IT and firm boundary strategies interact to affect the risk and return performance of firms. © 2011 INFORMS.


Adams G.R.,University of California at Irvine
Medicine and Science in Sports and Exercise | Year: 2010

Recent research has demonstrated that intracellular signaling components associated with several proinflammatory cytokines have the potential to interact with signaling pathways that regulate anabolic processes in skeletal muscle. This presentation and the ensuing brief review are intended to present a selection of the potential interactions between these two critical processes. Copyright © 2009 by the American College of Sports Medicine.


The efficacy of offender rehabilitation has been a topic of much debate over the past few decades. While much of the corrections literature has focused on program effectiveness, less attention has been placed on the expansion and delivery of services to incarcerated offenders, and whether the advances that have been made with regard to rehabilitation have changed the nature of treatment delivery to inmates. Using data from three time points collected as part of the Bureau of Justice Statistics (BJS) survey of state inmates, this paper examines the criminogenic needs of offenders and how those needs have changed over time, the role inmate needs play in driving participation in institutional programs, and whether inmates with unmet treatment needs commit a disproportionate number of institutional infractions. The results suggest that inmate needs have changed substantially over the past decade, with the most extensive needs concentrated in a small proportion of inmates. Consequently, correctional institutions are not always been able to match offenders to the appropriate services, which may have a direct impact on institutional safety. © 2012 Copyright Academy of Criminal Justice Sciences.


Lee E.Y.,University of California at Irvine
Cold Spring Harbor perspectives in biology | Year: 2010

Breast cancer progression involves multiple genetic events, which can activate dominant-acting oncogenes and disrupt the function of specific tumor suppressor genes. This article describes several key oncogene and tumor suppressor signaling networks that have been implicated in breast cancer progression. Among the tumor suppressors, the article emphasizes BRCA1/2 and p53 tumor suppressors. In addition to these well characterized tumor suppressors, the article highlights the importance of PTEN tumor suppressor in counteracting PI3K signaling from activated oncogenes such as ErbB2. This article discusses the use of mouse models of human breast that recapitulate the key genetic events involved in the initiation and progression of breast cancer. Finally, the therapeutic potential of targeting these key tumor suppressor and oncogene signaling networks is discussed.


Goddard T.,University of California at Irvine
Theoretical Criminology | Year: 2012

Numerous scholars have observed that neo-liberal rationalities have resulted in the replacement of interventionist State-run welfare initiatives with community-based risk managing schemes in a process called responsibilization. These risk management policies have become influential in the domain of crime prevention and in the shaping of the future conduct of the 'at-risk' youth. This article details, ethnographically, the goals and activities of 10 responsibilized community-based organizations and the conceptualization of 'risk' by practitioners from these organizations. The findings suggest that social abandonment and surveillance-centered risk management schemes co-exist with welfarist notions. The findings have implications about whether crime prevention is as post-welfarist as some theorists maintain. © The Author(s) 2012.


Bera R.B.,University of California at Irvine
Journal of Clinical Psychiatry | Year: 2014

Compliance is a critical issue across all chronic conditions, including schizophrenia. Compliance is not an all-or-nothing phenomenon, with a continuum from taking all medications as prescribed to partial compliance to complete noncompliance. Partial compliance is a serious problem that may result in abrupt dose changes leading to unanticipated adverse effects and can demoralize the patient. Further, there is a nearly 5-fold increase in the risk of relapse in first-episode patients when antipsychotic drug treatment is discontinued. Taken together, these data indicate that it is critical to ensure continuous delivery of antipsychotic treatment. Atypical antipsychotic medications were expected to result in better adherence, primarily because of the anticipated improved efficacy and safety profile. However, atypical agents have poor adherence, irrespective of the type of atypical medication, making it difficult to predict which patients are taking their oral medications. Long-acting injectable (LAI) agents may minimize the fluctuations in peak and overall plasma levels compared with oral agents, indicating they may allow more consistent and predictable administration. Based on clinical experience in my practice, several important observations regarding LAI use in patients with schizophrenia have been identified. First, there are potential advantages to using LAIs, including assistance in understanding reasons for poor response, the possibility of eliminating daily pill ingestion, and the elimination of the abrupt loss of medication coverage. There are also several potential obstacles to the use of LAIs, including a lack of infrastructure for the delivery and disposal of syringes and the ease of use with the oral agents. Several strategies can be used to increase patient willingness to initiate and continue LAI therapy. Strategies to improve acceptance involve presenting the option with enthusiasm, ensuring proper goal setting, educating the patient that this treatment is not equivalent to emergency injections, and repeatedly recommending LAI therapy. Adherence can be improved by ensuring samples are available in the clinical setting at all times. © Copyright 2014 Physicians Postgraduate Press, Inc.


Lynch M.,University of California at Irvine
Theoretical Criminology | Year: 2012

Numerous scholars have described how the 'war on drugs' has played a central role in US penal change, especially its racialized impact. Yet there remain aspects of this 'war' that are under-explored in punishment and society scholarship. This article delineates five distinct modes by which the contemporary regulation of drugs in the USA speaks to penal change, and in so doing suggests that its reach is much more diffuse, insidious, and variegated than suggested by prevailing conceptualizations of the drug war-punishment relationship. © The Author(s) 2012.


Fortin J.-F.,University of California at San Diego | Tait T.M.P.,University of California at Irvine
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

Dark matter which interacts through a magnetic or electric dipole moment is an interesting possibility which may help resolve the discrepancy between the DAMA annual modulation signal and the null results of other searches. In this article we examine relic density and collider constraints on such dark matter, and find that for couplings needed to explain DAMA, the thermal relic density is generically in the right ballpark to account for cosmological measurements. Collider constraints are relevant for light WIMPs, but less constraining that direct searches for masses above about 10 GeV. © 2012 American Physical Society.


Rupert T.J.,University of California at Irvine
Scripta Materialia | Year: 2014

Solid solution effects on the strength of the finest nanocrystalline grain sizes are studied with molecular dynamics simulations of different Cu-based alloys. We find evidence of both solid solution strengthening and softening, with trends in strength controlled by how alloying affects the elastic modulus of the material. This behavior is consistent with a shift to collective grain boundary deformation physics, and provides a link between the mechanical behavior of very fine-grained nanocrystalline metals and metallic glasses. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Hayes G.R.,University of California at Irvine
ACM Transactions on Computer-Human Interaction | Year: 2011

Alongside the growing interest within HCI, and arguably computing more generally, in conducting research that has substantial societal benefits, there is a need for new ways to think about and to articulate the challenges of these engaged research projects as well as their results. Action Research (AR) is a class of methods and approaches for conducting democratic and collaborative research with community partners. AR has evolved over the last several decades and offers HCI researchers theoretical lenses, methodological approaches, and pragmatic guidance for conducting socially relevant, collaborative, and engaged research. In this article, I describe the historical context and origins of AR, the scientifically rigorous practice of conducting and evaluating AR projects, and the ways in which AR might meaningfully be applied to HCI research. © 2011 ACM.


The hermaphroditic Mangrove Killifish, Kryptolebias marmoratus, is the world's only vertebrate that routinely self-fertilizes. As such, highly inbred and presumably isogenic "clonal" lineages of this androdioecious species have long been maintained in several laboratories and used in a wide variety of experiments that require genetically uniform vertebrate specimens. Here we conduct a genetic inventory of essentially all laboratory stocks of the Mangrove Killifish held worldwide. At 32 microsatellite loci, these stocks proved to show extensive interline differentiation as well as some intraline variation, much of which can be attributed to post-origin de novo mutations and/or to the segregation of polymorphisms from wild progenitors. Our genetic findings also document that many of the surveyed laboratory strains are not what they have been labeled, apparently due to the rather frequent mishandling or unintended mixing of various laboratory stocks over the years. Our genetic inventory should help to clarify much of this confusion about the clonal identities and genetic relationships of laboratory lines, and thereby help to rejuvenate interest in K. marmoratus as a reliable vertebrate model for experimental research that requires or can capitalize upon "clonal" replicate specimens.


Steenbeek W.,Netherlands Institute for the Study of Crime and Law Enforcement NSCR | Hipp J.R.,University of California at Irvine
Criminology | Year: 2011

Social disorganization theory holds that neighborhoods with greater residential stability, higher socioeconomic status, and more ethnic homogeneity experience less disorder because these neighborhoods have higher social cohesion and exercise more social control. Recent extensions of the theory argue that disorder in turn affects these structural characteristics and mechanisms. Using a data set on 74 neighborhoods in the city of Utrecht in the Netherlands spanning 10 years, we tested the extended theory, which to date only a few studies have been able to do because of the unavailability of neighborhood-level longitudinal data. We also improve on previous studies by distinguishing between the potential for social control (feelings of responsibility) and the actual social control behavior. Cross-sectional analyses replicate earlier findings, but the results of longitudinal cross-lagged models suggest that disorder has large consequences for subsequent levels of social control and residential instability, thus leading to more disorder. This is in contrast to most previous studies, which assume disorder to be more a consequence than a cause. This study underlines the importance of longitudinal data, allowing for simultaneously testing the causes and consequences of disorder, as well as the importance of breaking down social control into the two dimensions of the potential for social control and the actual social control behavior. © 2011 American Society of Criminology.


Ramanan D.,University of California at Irvine | Baker S.,Microsoft
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2011

We present a taxonomy for local distance functions where most existing algorithms can be regarded as approximations of the geodesic distance defined by a metric tensor. We categorize existing algorithms by how, where, and when they estimate the metric tensor. We also extend the taxonomy along each axis. How: We introduce hybrid algorithms that use a combination of techniques to ameliorate overfitting. Where: We present an exact polynomial-time algorithm to integrate the metric tensor along the lines between the test and training points under the assumption that the metric tensor is piecewise constant. When: We propose an interpolation algorithm where the metric tensor is sampled at a number of references points during the offline phase. The reference points are then interpolated during the online classification phase. We also present a comprehensive evaluation on tasks in face recognition, object recognition, and digit recognition. © 2006 IEEE.


Arbelaez P.,University of California at Berkeley | Maire M.,California Institute of Technology | Fowlkes C.,University of California at Irvine | Malik J.,University of California at Berkeley
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2011

This paper investigates two fundamental problems in computer vision: contour detection and image segmentation. We present state-of-the-art algorithms for both of these tasks. Our contour detector combines multiple local cues into a globalization framework based on spectral clustering. Our segmentation algorithm consists of generic machinery for transforming the output of any contour detector into a hierarchical region tree. In this manner, we reduce the problem of image segmentation to that of contour detection. Extensive experimental evaluation demonstrates that both our contour detection and segmentation methods significantly outperform competing algorithms. The automatically generated hierarchical segmentations can be interactively refined by user-specified annotations. Computation at multiple image resolutions provides a means of coupling our system to recognition applications. © 2006 IEEE.


Fong A.,University of California at Irvine
American journal of obstetrics and gynecology | Year: 2014

OBJECTIVE: The purpose of this study was to assess an early hemoglobin A1c (HgbA1c) value from 5.7-6.4% as an early predictor of progression to gestational diabetes (GDM).STUDY DESIGN: A retrospective cohort study was performed on all women who delivered at a single institution over 2 years who had an early screening HgbA1c test performed at ≤20 weeks of gestation. Women with known preexisting diabetes mellitus or HgbA1c values ≥6.5% were excluded. The primary outcome was GDM development. Secondary outcomes included delivery route, maternal weight gain, birthweight, and neonatal morbidities. Women with an HgbA1c value of 5.7-6.4% were compared with those with an HgbA1c level of <5.7%.RESULTS: Nearly one-third of those patients in the HgbA1c 5.7-6.4% group (27.3%) experience the development of GDM compared with only 8.7% in the HgbA1c <5.7% group (odds ratio, 3.9; 95% confidence level, 2.0-7.7). This 3-fold increase remained significant (adjusted odds ratio, 2.4) after adjustment for age, prepregnancy body mass index, gestational age at HgbA1c collection, gestational age at screening, ethnicity, and method of screening. There were no significant differences in the need for medical treatment, weight gain, delivery route, birthweight, macrosomia, or neonatal morbidities.CONCLUSION: More than 10% of patients in our cohort had an early screening HgbA1c value of 5.7-6.4%. Women in this group have a significantly higher risk of progression to GDM compared with women with normal HgbA1c values and should be considered for closer GDM surveillance and possible intervention. Copyright © 2014 Elsevier Inc. All rights reserved.


Potter A.C.,University of California at Berkeley | Vasseur R.,University of California at Berkeley | Vasseur R.,Lawrence Berkeley National Laboratory | Parameswaran S.A.,University of California at Irvine | Parameswaran S.A.,University of California at Santa Barbara
Physical Review X | Year: 2015

We study the dynamical melting of "hot" one-dimensional many-body localized systems. As disorder is weakened below a critical value, these nonthermal quantum glasses melt via a continuous dynamical phase transition into classical thermal liquids. By accounting for collective resonant tunneling processes, we derive and numerically solve an effective model for such quantum-to-classical transitions and compute their universal critical properties. Notably, the classical thermal liquid exhibits a broad regime of anomalously slow subdiffusive equilibration dynamics and energy transport. The subdiffusive regime is characterized by a continuously evolving dynamical critical exponent that diverges with a universal power at the transition. Our approach elucidates the universal long-distance, low-energy scaling structure of many-body delocalization transitions in one dimension, in a way that is transparently connected to the underlying microscopic physics. We discuss experimentally testable signatures of the predicted scaling properties.


Rajaraman A.,University of California at Irvine
International Journal of Modern Physics A | Year: 2015

In this paper, we examine the behavior of correlation functions for a massless scalar field in de Sitter space with a quartic interaction. We find that two-loop corrections are relevant, and the resummation of these corrections generates a complicated structure whereby high momentum modes stay massless while low momentum modes develop a dynamical mass. © 2015 World Scientific Publishing Company.


Dourish P.,University of California at Irvine
DIS 2010 - Proceedings of the 8th ACM Conference on Designing Interactive Systems | Year: 2010

Many HCI researchers have recently begun to examine the opportunities to use ICTs to promote environmental sustainability and ecological consciousness on the part of technology users. This paper examines the way that traditional HCI discourse obscures political and cultural contexts of environmental practice that must be part of an effective solution. Research on ecological politics and the political economy of environmentalism highlight some missing elements in contemporary HCI analysis, and suggest some new directions for the relationship between sustainability and HCI. In particular, I propose that questions of scale - the scales of action and the scales of effects - might provide a useful new entry point for design practice. © 2010 ACM.


Kortman G.A.M.,Radboud University Nijmegen | Raffatellu M.,University of California at Irvine | Swinkels D.W.,Radboud University Nijmegen | Tjalsma H.,Radboud University Nijmegen
FEMS Microbiology Reviews | Year: 2014

Iron is abundantly present on earth, essential for most microorganisms and crucial for human health. Human iron deficiency that is nevertheless highly prevalent in developing regions of the world can be effectively treated by oral iron administration. Accumulating evidence indicates that excess of unabsorbed iron that enters the colonic lumen causes unwanted side effects at the intestinal host-microbiota interface. The chemical properties of iron, the luminal environment and host iron withdrawal mechanisms, especially during inflammation, can turn the intestine in a rather stressful milieu. Certain pathogenic enteric bacteria can, however, deal with this stress at the expense of other members of the gut microbiota, while their virulence also seems to be stimulated in an iron-rich intestinal environment. This review covers the multifaceted aspects of nutritional iron stress with respect to growth, composition, metabolism and pathogenicity of the gut microbiota in relation to human health. We aim to present an unpreceded view on the dynamic effects and impact of oral iron administration on intestinal host-microbiota interactions to provide leads for future research and other applications. © 2014 Federation of European Microbiological Societies.


This study tests the effect of the composition and distribution of economic resources and race/ethnicity in cities, as well as how they are geographically distributed within these cities, on crime rates during a 30-year period. Using data on 352 cities from 1970 to 2000 in metropolitan areas that experienced a large growth in population after World War II, this study theorizes that the effect of racial/ethnic or economic segregation on crime is stronger in cities in which race/ethnicity or income are more salient (because of greater heterogeneity or inequality). We test and find that higher levels of segregation in cities with high levels of racial/ethnic heterogeneity lead to particularly high overall levels of the types of crime studied here (aggravated assaults, robberies, burglaries, and motor vehicle thefts). Similarly, higher levels of economic segregation lead to much higher levels of crime in cities with higher levels of inequality. © 2011 American Society of Criminology.


Chentoufi A.A.,University of California at Irvine
Clinical & developmental immunology | Year: 2012

The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally "protected" exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4(+) and CD8(+) T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation "asymptomatic" clinical herpes vaccines, and discuss future mucosal "asymptomatic" prime-boost vaccines that could optimize local protective immunity.


Zlotnik A.,University of California at Irvine | Yoshie O.,Kinki University
Immunity | Year: 2012

The chemokine superfamily consists of a large number of ligands and receptors. At first glance, this family appears redundant and their ligand-receptor relationships promiscuous, making its study challenging. However, analyzing this family from the evolutionary perspective greatly simplifies understanding both the organization and function of this apparently complex system. In particular, the functions of a subgroup of chemokines (designated homeostatic chemokines) have played pivotal roles in advancing our understanding of the organization and function of the cellular networks that shape the immune system. Here, we update the full scope of the human and mouse chemokine superfamilies and their relationships and summarize several important roles that homeostatic chemokines play in the immune system. © 2012 Elsevier Inc.


Phillips S.J.,University of California at Irvine
The Nurse practitioner | Year: 2015

As the tides of healthcare in the United States continue to change, advanced practice registered nurses (APRNs) are at the forefront of legislative history. This overview provides a snapshot of legislative and regulatory activity in 2014 as reported by state Boards of Nursing and nursing organizations representing APRNs.


Widgerow A.D.,University of California at Irvine
Annals of Plastic Surgery | Year: 2014

Diabetes constitutes a global emergency with case numbers increasing exponentially every year. Diabetic foot ulcers are the leading cause of nontraumatic lower limb amputations. A complex background of pathophysiologic events has been identified with advances in molecular biology such that newer interventions are possible. Bioengineered skin substitutes currently play an important role in the diabetic foot ulcer, particularly in the "stalled" wounds that fail to show progress in their healing trajectory. However, newer designs and scaffold incorporation may herald a new generation of products with more focused targeting of these pathophysiologic events. The major background impairment is that of vasculogenesis brought about as a direct result of hyperglycemia, advanced glycation end product/ methylglyoxal generation, and its direct effect on endothelial progenitor cell production and attraction to the wound site. At the same time, glycation end products affect immunity and inflammation, increasing the susceptibility to infection. Thus, reactive oxygen species scavengers, methylglyoxal scavengers, vascular endothelial growth factor stimulators as well as various lipids and neuropeptides are all potential agents that could be incorporated into such templates. The logical sequence of events and possible interventions is detailed. In this manner, intrinsic healing is encouraged in preference to our current attempts at adding unknown quantities of specialized cellular and growth factor components which seem to provide very temporary advantages.Copyright © 2013 by Lippincott Williams & Wilkins.


Treas J.,University of California at Irvine
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2014

Objectives. To encourage research on immigrants and aging by analyzing theoretical commonalities in the two fields and identifying potential contributions of aging theories, specifically to the understanding of neglected age differences in the pace of immigrant incorporation. Methods. Survey of the historical development of assimilation theory and its successors and systematic comparison of key concepts in aging and immigrant incorporation theories. Results. Studies of immigrants, as well as of the life course, trace their origins to the Chicago School at the turn of the 20th century. Today, both theoretical perspectives emphasize adaptation as a time-dependent, multidimensional, nonlinear, and multidirectional process. Immigrant incorporation theories have not fully engaged with a key concern of aging theory - why there are age differences. Insights from cognitive aging and developmental biology, life-span developmental psychology, and age stratification and the life course suggest explanations for age differences in the speed of immigrant incorporation. Discussion. Theories of adaptation to aging and theories of immigrant incorporation developed so independently that they neglected the subject they have in common, namely, older immigrants. Because they address similar conceptual problems and share key assumptions, a productive dialogue between two vibrant fields is long overdue. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.


Frank S.A.,University of California at Irvine
Current Biology | Year: 2012

In many animal species, males suffer more from age-related disease than females. Is there a common cause for this burden on male health? Recent work supports the theory that the female transmission of mitochondria disproportionately increases the mutation load in males. © 2012 Elsevier Ltd. All rights reserved.


Said H.M.,University of California at Irvine
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2013

This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamin (WSV) transport in the large intestine and pancreas, two important organs of the digestive system that have only recently received their fair share of attention. WSV, a group of structurally unrelated compounds, are essential for normal cell function and development and, thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenously; rather, WSV are obtained from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source and a bacterial source (i.e., WSV generated by the large intestinal microbiota). Contribution of the latter source to human nutrition/health has been a subject of debate and doubt, mostly based on the absence of specialized systems for efficient uptake of WSV in the large intestine. However, recent studies utilizing a variety of human and animal colon preparations clearly demonstrate that such systems do exist in the large intestine. This has provided strong support for the idea that the microbiota-generated WSV are of nutritional value to the host, and especially to the nutritional needs of the local colonocytes and their health. In the pancreas, WSV are essential for normal metabolic activities of all its cell types and for its exocrine and endocrine functions. Significant progress has also been made in understanding the mechanisms involved in the uptake of WSV and the effect of chronic alcohol exposure on the uptake processes. © 2013 the American Physiological Society.


Di Giammartino D.C.,Columbia University | Shi Y.,Columbia University | Shi Y.,University of California at Irvine | Manley J.L.,Columbia University
Molecular Cell | Year: 2013

The 3' ends of most eukaryotic mRNAs are produced by an endonucleolytic cleavage followed by synthesis of a poly(A) tail. Poly(A) polymerase (PAP), the enzyme that catalyzes the formation of the tail, is subject to tight regulation involving several posttranslational modifications. Here we show that the enzyme poly(ADP-ribose) polymerase 1 (PARP1) modifies PAP and regulates its activity both in vitro and in vivo. PARP1 binds to and modifies PAP by poly(ADP-ribosyl)ation (PARylation) in vitro, which inhibits PAP activity. In vivo we show that PAP is PARylated during heat shock, leading to inhibition of polyadenylation in a PARP1-dependent manner. The observed inhibition reflects reduced RNA binding affinity of PARylated PAP in vitro and decreased PAP association with non-heat shock protein-encoding genes in vivo. Our results provide direct evidence that PARylation can control processing of mRNA precursors, and also identify PARP1 as a regulator of polyadenylation during thermal stress. © 2013 Elsevier Inc.


Paul M.D.,University of California at Irvine
Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery | Year: 2013

The evolution of barbed suture technologies and their application in the field of plastic surgery is now in its third decade. Much has been learned along the way. Initial excitement was often followed by disappointment as we learned more about the limited longevity of minimally invasive procedures and complications arising from various suture designs of the past. Some of the early designs, developed primarily for use in aesthetic facial procedures, included free-floating, bidirectionally barbed, nonabsorbable sutures; unidirectional barbed, nonabsorbable sutures; anchored, bidirectional, nonabsorbable double-threaded sutures; and a technology combining a nonabsorbable knotted thread and absorbable cones. More recently, a new, absorbable, unidirectional barbed suture design has become available. However, it should be noted that very limited data are available for any of the modified suture designs used in this field, and much of what has been published is based on the experience of a single user. The author has used the bidirectionally barbed Quill Knotless Tissue-Closure Device (Angiotech Pharmaceuticals, Inc, Vancouver, British Columbia, Canada), the most common barbed suture in both facial and other aesthetic plastic surgery procedures, with considerable success in various open aesthetic facial procedures, including suspension of the brow and midface, platysmaplasty, and lateral neck suspension. It is the author's experience that completion of 1 to 2 cases with this technology is sufficient to achieve competency in the closure techniques discussed in this article and that time savings can be realized using this device in various breast and body contouring procedures, including mastopexy, reduction mammoplasty, abdominoplasty, bodylift, and brachioplasty.


The discovery of activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) in 2004 heralded the era of molecular targeted therapy in NSCLC. First-generation small molecule, reversible tyrosine kinase inhibitors (TKIs) of EGFR, gefitinib and erlotinib, had been approved for second- or third-line treatment of NSCLC prior to the knowledge of these mutations. However, resistance to gefitinib and erlotinib invariably develops after prolonged clinical use. Two second-generation irreversible EGFR TKIs, afatinib (BIBW 2992) and dacomitinib (PF-00299804), that can potentially overcome the majority of these resistances are in late stage clinical development. Here I will review the clinical data of EGFR TKIs and discuss the appropriate future role of afatinib and dacomitinib in NSCLC: whether as replacement of erlotinib or gefitinib or only after erlotinib or gefitinib failure and whether different subgroups would benefit from different approaches. © 2011 Elsevier Ireland Ltd.


Sharma A.,University of California at Irvine
Current gastroenterology reports | Year: 2013

The treatment of cancer-associated pain as well as chronic non-cancer-related pain (CNCP) is an increasingly relevant topic in medicine. However, it has long been recognized that opiates can adversely affect many organ systems, most notably the gastrointestinal system. These are referred to as the spectrum of "opioid-induced bowel dysfunction" (OBD) or what we will refer to as "opioid-induced bowel disease" (OIBD) which include constipation, nausea, vomiting, delayed gastric emptying, and gastro-esophageal reflux disease (GERD), and a newer entity known as narcotic bowel syndrome (NBS). Opioid analgesics are increasingly being used for the treatment of cancer pain, non-cancer-associated pain, and postoperative pain. As we achieve our goals towards pain control, we need to be cognizant of and competent in how to prevent and treat OIBD. The basis is due in part to μ-receptor activation, decreasing the peristaltic contraction and leading to sequelae of OIBD. Treatment beyond lifestyle interventional strategy will employ laxatives and stool softeners. However, studies performed while patients were already using laxativies and stool softeners have elicited the necessity of peripherally acting agents such as methylnaltrexone (MNTX) and alvimopan. Patients responded dramatically to both medications, but these studies were limited to patients that were deemed to have advanced illness. Lubiprostone, while different in its mechanism of action from MNTX and alvimopan, has proven effective and should be considered for use in OIBD. Further investigational research will promulgate more information and allow for better and more efficient treatment options for OIBD.


Sun L.,University of California at Irvine
The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2012

Over 40 missense mutations in the human SCN1A sodium channel gene are linked to an epilepsy syndrome termed genetic epilepsy with febrile seizures plus (GEFS+). Inheritance of GEFS+ is dominant, but the underlying cellular mechanisms remain poorly understood. Here we report that knock-in of a GEFS+ SCN1A mutation (K1270T) into the Drosophila sodium channel gene, para, causes a semidominant temperature-induced seizure phenotype. Electrophysiological studies of GABAergic interneurons in the brains of adult GEFS+ flies reveal a novel cellular mechanism underlying heat-induced seizures: the deactivation threshold for persistent sodium currents reversibly shifts to a more negative voltage when the temperature is elevated. This leads to sustained depolarizations in GABAergic neurons and reduced inhibitory activity in the central nervous system. Furthermore, our data indicate a natural temperature-dependent shift in sodium current deactivation (exacerbated by mutation) may contribute to febrile seizures in GEFS+ and perhaps normal individuals.


Wong J.M.,University of California at Irvine
Journal of the American Heart Association | Year: 2013

Hostility is a significant predictor of mortality and cardiovascular events in patients with coronary heart disease (CHD), but the mechanisms that explain this association are not well understood. The purpose of this study was to evaluate potential mechanisms of association between hostility and adverse cardiovascular outcomes. We prospectively examined the association between self-reported hostility and secondary events (myocardial infarction, heart failure, stroke, transient ischemic attack, and death) in 1022 outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was assessed using the 8-item Cynical Distrust scale. Cox proportional hazard models were used to determine the extent to which candidate biological and behavioral mediators changed the strength of association between hostility and secondary events. During an average follow-up time of 7.4 ± 2.7 years, the age-adjusted annual rate of secondary events was 9.5% among subjects in the highest quartile of hostility and 5.7% among subjects in the lowest quartile (age-adjusted hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.30 to 2.17; P < 0.0001). After adjustment for cardiovascular risk factors, participants with hostility scores in the highest quartile had a 58% greater risk of secondary events than those in the lowest quartile (HR: 1.58, 95% CI: 1.19 to 2.09; P = 0.001). This association was mildly attenuated after adjustment for C-reactive protein (HR: 1.41, 95% CI, 1.06 to 1.87; P = 0.02) and no longer significant after further adjustment for smoking and physical inactivity (HR: 1.25, 95% CI: 0.94 to 1.67; P = 0.13). Hostility was a significant predictor of secondary events in this sample of outpatients with baseline stable CHD. Much of this association was moderated by poor health behaviors, specifically physical inactivity and smoking.


Mjolsness E.,University of California at Irvine
Physical Biology | Year: 2013

The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie's stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems. © 2013 IOP Publishing Ltd.


Brenig W.,TU Braunschweig | Chernyshev A.L.,University of California at Irvine
Physical Review Letters | Year: 2013

We demonstrate that pointlike defects in noncollinear magnets give rise to a highly dispersive structure in the magnon scattering, violating a standard paradigm of its momentum independence. For a single impurity spin coupled to a prototypical noncollinear antiferromagnet, we find that the resolvent is dominated by a distinct dispersive structure with its momentum dependence set by the magnon dispersion and shifted by the ordering vector. This feature is a consequence of umklapp scattering off the impurity-induced spin texture, which arises due to the noncollinear ground state of the host system. Detailed results for the staggered and uniform magnetization of this texture as well as the T matrix from numerical linear spin-wave theory are presented. © 2013 American Physical Society.


Garner C.,University of California at Irvine
Genetic Epidemiology | Year: 2010

Studying the role of rare alleles in common disease has been prevented by the impractical task of determining the DNA sequence of large numbers of individuals. Next-generation DNA sequencing technologies are being developed that will make it possible for genetic studies of common disease to study the full frequency spectrum of genetic variation, including rare alleles. This report describes a method for scanning the genome for disease susceptibility regions that show an increased number of rare alleles among a sample of disease cases versus an ethnically matched sample of controls. The method was based on a hidden Markov model and the statistical support for a disease susceptibility region characterized by rare alleles was measured by a likelihood ratio statistic. Due to the lack of empirical data, the method was evaluated through simulation. The performance of the method was tested under the null and alternative hypotheses under a range of sequence generating and hidden Markov models parameters. The results showed that the statistical method performs well at identifying true disease susceptibility regions and that performance was primarily affected by the amount of variation in the neutral sequence and the number of rare disease alleles found in the disease susceptibility region. © 2010 Wiley-Liss, Inc.


Fang Z.,University of California at Irvine
G3 (Bethesda, Md.) | Year: 2014

Genetic differentiation in natural populations is driven by geographic distance and by ecological or physical features within and between natural habitats that reduce migration. The primary population structure in wild barley differentiates populations east and west of the Zagros Mountains. Genetic differentiation between eastern and western populations is uneven across the genome and is greatest on linkage groups 2H and 5H. Genetic markers in these two regions demonstrate the largest difference in frequency between the primary populations and have the highest informativeness for assignment to each population. Previous cytological and genetic studies suggest there are chromosomal structural rearrangements (inversions or translocations) in these genomic regions. Environmental association analyses identified an association with both temperature and precipitation variables on 2H and with precipitation variables on 5H. Copyright © 2014 Fang et al.


Siwy Z.S.,University of California at Irvine | Howorka S.,University College London
Chemical Society Reviews | Year: 2010

The creation of synthetic devices that mimic functionality of biological systems is a task of fundamental importance for the future development of bio- and nanotechnology and also an ultimate test of our understanding of the biological systems. Among a plethora of bio-inspired devices, designed nanopores and nanochannels with an embedded functionality are of particular interest because of their potential applications in nanofluidic electronics, biosensing, separation, synthetic biology, and single-molecule manipulation. In this respect, nanopores with built-in stimulus-responsive properties are of special benefit. A transmembrane potential is a particularly useful stimulus as it is non-invasive, tunable, and can act over a short time scale. This critical review considers engineered solid-state and protein nanopores with voltage-responsive properties. The engineered systems show nonlinear current-voltage curves, and/or voltage-dependent switching between discrete conductance states (141 references). © 2010 The Royal Society of Chemistry.


Wallace D.C.,University of California at Irvine
Environmental and Molecular Mutagenesis | Year: 2010

The human mitochondrial genome involves over 1,000 genes, dispersed across the maternally inherited mitochondrial DNA (mtDNA) and the biparentally inherited nuclear DNA (nDNA). The mtDNA encodes 13 core proteins that determine the efficiency of the mitochondrial energy-generating system, oxidative phosphorylation (OXPHOS), plus the RNA genes for their translation within the mitochondrion. The mtDNA has a very high mutation rate, which results in three classes of clinically relevant mtDNA mutations: recently deleterious germline line mutations resulting in mitochondrial disease; ancient regional variants, a subset of which permitted humans to adapt to differences in their energetic environments; and somatic mutations that accumulate with age eroding mitochondrial energy production and providing the aging clock. Mutations in nDNA-encoded OXPHOS structural genes can also cause mitochondrial disease, and alterations in nDNA mitochondrial biogenesis genes can destabilize the mtDNA and lead to clinical phenotypes. Finally, when combined, nonpathogenic nDNA and mtDNA protein variants can be functionally incompatible and cause disease. The essential functions of the conserved mtDNA proteins and their high mutation rate raise the question as to why the cumulative mtDNA genetic load does not result in species extinction. Studies of mice harboring deleterious mtDNA mutations have shown that the mammalian ovary selectively eliminates the most deleterious mtDNA mutations. However, milder mtDNA mutations are transmitted through the ovary and the female germline and introduced into the general population. This unique genetic system provides a flexible method for generating genetic variation in cellular and organismal energetics that permits species to adapt to alterations in their regional energetic environment. © 2010 Wiley-Liss, Inc.


Shi Y.,University of California at Irvine | Manley J.L.,Columbia University
Genes and Development | Year: 2015

The key RNA sequence elements and protein factors necessary for 3′ processing of polyadenylated mRNA precursors are well known. Recent studies, however, have significantly reshaped current models for the protein– RNA interactions involved in poly(A) site recognition, painting a picture more complex than previously envisioned and also providing new insights into regulation of this important step in gene expression. Here we review the recent advances in this area and provide a perspective for future studies. © 2015 Shi and Manley


Murphy R.T.,University of California at Irvine | Pennock A.T.,Rady Childrens Hospital | Bugbee W.D.,Scripps Research Institute
American Journal of Sports Medicine | Year: 2014

Background: Multiple studies in adults have shown that osteochondral allograft transplantation is an effective treatment option for large chondral and osteochondral defects of the knee. Limited outcome data are available on osteochondral allografts in the pediatric and adolescent patient populations. Purpose: To describe a 28-year experience with osteochondral allograft transplantation in patients younger than 18 years with a focus on subjective outcome measures, return to activities, and allograft survivorship. Study Design: Case series; Level of evidence, 4. Methods: A total of 39 patients (43 knees) underwent fresh osteochondral allograft transplantation for treatment of chondral and osteochondral lesions. Twenty-six male and 17 female knees with a mean age of 16.4 years (range, 11.0-17.9 years) at index surgery were followed-up at a mean of 8.4 years (range, 1.7-27.1 years). Thirty-four knees (79%) had at least 1 previous surgery. The most common underlying causes of the lesions were osteochondritis dissecans (61%), avascular necrosis (16%), and traumatic chondral injury (14%). Mean allograft size was 8.4 cm2. The most common allograft location was the medial femoral condyle (41.9%), followed by the lateral femoral condyle (35%). Each patient was evaluated with the International Knee Documentation Committee pain, function, and total scores; a modified Merle d'Aubigné -Postel (18-point) scale; and Knee Society function score. Failure was defined as revision osteochondral allograft or conversion to arthroplasty. Results: Five knees experienced clinical failure at a median of 2.7 years (range, 1.0-14.7 years). Four failures were salvaged successfully with another osteochondral allograft transplant. One patient underwent prosthetic arthroplasty 8.6 years after revision allograft. Graft survivorship was 90% at 10 years. Of the knees whose grafts were in situ at latest follow-up, 88% were rated good/excellent (18-point scale). The mean International Knee Documentation Committee scores improved from 42 preoperatively to 75 postoperatively, and the Knee Society function score improved from 69 to 89 (both P<.05). Eighty-nine percent of patients reported "extremely satisfied" or "satisfied." Conclusion: With 88% good/excellent results and 80% salvage rate of clinical failures with an additional allograft, osteochondral allograft transplantation is a useful treatment option in pediatric and adolescent patients. © 2013 The Author(s).


Lin J.J.,University of California at Irvine | Mula M.,University of Piemonte Orientale | Hermann B.P.,University of Wisconsin - Madison
The Lancet | Year: 2012

Epilepsy is a common neurological disorder that is complicated by psychiatric, cognitive, and social comorbidities that have become a major target of concern and investigation in view of their adverse effect on the course and quality of life. In this report we define the specific psychiatric, cognitive, and social comorbidities of paediatric and adult epilepsy, their epidemiology, and real life effects; examine the relation between epilepsy syndromes and the risk of neurobehavioural comorbidities; address the lifespan effect of epilepsy on brain neurodevelopment and brain ageing and the risk of neurobehavioural comorbidities; consider the overarching effect of broader brain disorders on both epilepsy and neurobehavioural comorbidities; examine directions of causality and the contribution of selected epilepsy-related characteristics; and outline clinic-friendly screening approaches for these problems and recommended pharmacological, behavioural, and educational interventions.


Mann M.W.,University of California at Irvine
Clinics in Plastic Surgery | Year: 2011

With the recent US Food and Drug Administration (FDA) approval of polidocanol in the United States, there has been a resurgence of interest in sclerotherapy. Despite the popularity of laser therapy, sclerotherapy remains the gold standard for treating spider and reticular veins. Although this traditional method of treatment has been around for more than 100 years, better sclerosing agents and newer techniques have made sclerotherapy safer and more efficacious than ever before. This article is a primer for physicians interested in updating their skills in sclerotherapy. It reviews common sclerosants, sclerotherapy techniques, patient evaluation, complications, and recent advancements in sclerotherapy. © 2011 Elsevier Inc.


Liu W.F.,University of California at Irvine
Cardiovascular Research | Year: 2012

Cells sense a myriad of cues from their surrounding microenvironment to regulate their function. In recent years, it has become clear that physical and mechanical cues are as critical as biochemical factors in regulating cellular function. The geometry of the extracellular matrix (ECM), degree of cell spreading, and ECM rigidity all influence the physical connection between cells and their microenvironment and play a major role in regulating proliferation, differentiation, and migration. Leveraging these findings to promote specific cell behaviours will be paramount to realize the full potential of cellular therapies. In this review, I examine our current understanding of how mechanical cuesspecifically, geometric control of cell shape and matrix rigidityare transduced by stem cells to control their stemness, proliferation, and differentiation. The implications of these findings for vascular smooth muscle cell differentiation and cardiovascular tissue engineering will be highlighted. © 2012 The Author.


Carpenter L.M.,University of California at Irvine
Journal of High Energy Physics | Year: 2012

In an attempt to maximize General Gauge Mediated parameter space, I propose simple models in which gauginos and scalars are generated from disconnected mechanisms. In my models Dirac gauginos are generated through the supersoft mechanism, while independent R-symmetric scalar masses are generated through operators involving non-zero messenger supertrace. I propose several new methods for generating negative messenger supertraces which result in viable positive mass squareds for MSSM scalars. The resultant spectra are novel, compressed and may contain light fermionic SM adjoint fields. © SISSA 2012.


Amin A.,University of California at Irvine
Clinical Interventions in Aging | Year: 2013

Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety. © 2013 Amin, publisher and licensee Dove Medical Press Ltd.


Watson A.B.,NASA | Yellott J.I.,University of California at Irvine
Journal of Vision | Year: 2012

The size of the pupil has a large effect on visual function, and pupil size depends mainly on the adapting luminance, modulated by other factors. Over the last century, a number of formulas have been proposed to describe this dependence. Here we review seven published formulas and develop a new unified formula that incorporates the effects of luminance, size of the adapting field, age of the observer, and whether one or both eyes are adapted. We provide interactive demonstrations and software implementations of the unified formula.


Wallace D.C.,University of California at Irvine
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Complex structures are generated and maintained through energy flux. Structures embody information, and biological information is stored in nucleic acids. The progressive increase in biological complexity over geologic timeis thus the consequence of the information-generating power of energy flow plus the information-accumulating capacity of DNA, winnowed by natural selection. Consequently, the most important component of the biological environment is energy flow: the availability of calories and their use for growth, survival, and reproduction. Animals can exploit and adapt to available energy resources at three levels. They can evolve different anatomical forms through nuclear DNA (nDNA) mutations permitting exploitation of alternative energy reservoirs, resulting in new species. They can evolvemodified bioenergetic physiologies within a species, primarily through the high mutation rate of mitochondrial DNA (mtDNA)-encoded bioenergetic genes, permitting adjustment to regional energetic environments. They can alter the epigenomic regulation of the thousands of dispersed bioenergetic genes via mitochondrially generated high-energy intermediates permitting individual accommodation to short-term environmental energetic fluctuations. Because medicinepertains toa single species, Homosapiens, functional human variation often involves sequence changes in bioenergetic genes, most commonly mtDNA mutations, plus changes in the expression of bioenergetic genes mediated by the epigenome. Consequently, common nDNA polymorphisms in anatomical genes may represent only a fraction of the genetic variation associated with the common "complex" diseases, and the ascent ofmanhas been the product of 3.5 billion years of information generation by energy flow, accumulated and preserved in DNA and edited by natural selection.


Vaziri N.D.,University of California at Irvine
Current Opinion in Nephrology and Hypertension | Year: 2012

Purpose of Review: Chronic kidney disease (CKD) is associated with oxidative stress and inflammation which contribute to progression of kidney disease and its numerous complications. Until recently, little attention had been paid to the role of the intestine and its microbial flora in the pathogenesis of CKD-associated inflammation. This article is intended to provide an over view of the impact of uremia on the structure and function of the gut and its microbial flora and their potential link to the associated systemic inflammation. Recent Findings: Recent studies conducted in the author's laboratories have demonstrated marked disintegration of the colonic epithelial barrier structure and significant alteration of the colonic bacterial flora in humans and animals with advanced CKD. The observed disruption of the intestinal epithelial barrier complex can play an important part in the development of systemic inflammation by enabling influx of endotoxin and other noxious luminal contents into the systemic circulation. Similarly via disruption of the normal symbiotic relationship and production, absorption and retention of noxious products, alteration of the microbial flora can contribute to systemic inflammation and uremic toxicity. In fact recent studies have documented the role of colonic bacteria as the primary source of several well known pro-inflammatory/pro-oxidant uremic toxins as well as many as-yet unidentified retained compounds. Summary: CKD results in disruption of the intestinal barrier structure and marked alteration of its microbial flora-events that play a major role in the pathogenesis of inflammation and uremic toxicity. © 2012 Wolters Kluwer Health | Lippincott Williams and Wilkins.


Zhang J.A.,California Institute of Technology | Mortazavi A.,California Institute of Technology | Mortazavi A.,University of California at Irvine | Williams B.A.,California Institute of Technology | And 2 more authors.
Cell | Year: 2012

T cell development comprises a stepwise process of commitment from a multipotent precursor. To define molecular mechanisms controlling this progression, we probed five stages spanning the commitment process using RNA-seq and ChIP-seq to track genome-wide shifts in transcription, cohorts of active transcription factor genes, histone modifications at diverse classes of cis-regulatory elements, and binding repertoire of GATA-3 and PU.1, transcription factors with complementary roles in T cell development. The results highlight potential promoter-distal cis-regulatory elements in play and reveal both activation sites and diverse mechanisms of repression that silence genes used in alternative lineages. Histone marking is dynamic and reversible, and though permissive marks anticipate, repressive marks often lag behind changes in transcription. In vivo binding of PU.1 and GATA-3 relative to epigenetic marking reveals distinctive factor-specific rules for recruitment of these crucial transcription factors to different subsets of their potential sites, dependent on dose and developmental context. © 2012 Elsevier Inc.


Crinella F.M.,University of California at Irvine
Expert Review of Neurotherapeutics | Year: 2012

An earlier article hypothesized a relationship between soy-based infant formulas, manganese (Mn) neurotoxicity and symptoms of ADHD. In this update, more recent literature on ADHD, Mn and Mn neurotoxicity is reviewed, as well as the risks of Mn toxicity that may accompany ingestion of soy-based infant formula. The results of several critical studies are described, including rodent and primate models that demonstrate an association between ingestion of relatively high levels of Mn and: overactivity, disinhibition and inattention; stereotypes and disturbances of social relatedness; and alterations of dopamine D1 and D2 receptors and dopamine transporter in critical brain regions. Similar deficits have been shown in children with ADHD. In addition, ADHD-like symptoms of behavioral disinhibition were found to be correlated with Mn content in tooth enamel, apparently deposited at or before the fifth gestational month. The results are discussed in terms of their weight as a risk factor in ADHD, vis-à-vis compelling evidence of genetic, epigenetic and other environmental risk factors associated with the disorder, as well as the appropriateness of additional public policy decisions regarding the safety of soy formula. © 2012 Expert Reviews Ltd.


Steffan J.S.,University of California at Irvine
eLife | Year: 2016

Genetic studies uncover a mutation in a widely conserved protein as the cause of a neurological disorder in two brothers. © 2016, eLife Sciences Publications Ltd. All rights reserved.


Volkow N.D.,U.S. National Institute on Drug Abuse | Swanson J.M.,University of California at Irvine
New England Journal of Medicine | Year: 2013

A 31-year-old middle-school teacher sought medical help because she was having trouble keeping up with her job assignments and responsibilities. Her primary symptoms were an inability to stay focused and being easily distracted. She reported day-dreaming with multiple thoughts at the same time, an inability to complete tasks on time, frequently forgetting to do things at work, and being unable to remain still during solitary activities (e.g., watching a movie and reading a book). Her friends described her as excessively talkative, disorganized, impatient, and careless. From childhood, her teachers noted that she was inattentive and messy and often did not turn in homework. She was able to do reasonably well in school despite her symptoms, but more recently, her job demands have overwhelmed her, and she is considering quitting. What would you advise? Copyright © 2013 Massachusetts Medical Society.


Krakowski A.C.,University of California at San Diego | Ghasri P.,University of California at Irvine
Pediatrics | Year: 2015

Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by generalized skin fragility, severe blistering, and wounding that heals with mutilating scarring. Patients are in constant need of effective wound therapies as they often succumb to aggressive metastatic squamous cell carcinomas or to sepsis that may develop from their chronic wounds. Herein, we demonstrate accelerated wound healing with use of a fractionated CO2 laser protocol in a 22-year-old man with RDEB. His 9-month-old, non-healing wound decreased from 7 cm in diameter to 2 cm in diameter (a 92% reduction in wound surface area) within 4 weeks of a single laser treatment, and he had near-complete re-epithelialization within 4 weeks of his second laser treatment without blistering or other adverse effects. This novel intervention of using fractionated CO2 for photo-microdebridement could help revolutionize wound care for patients who have RDEB and whose chronic wounds serve as one of their greatest sources of morbidity and mortality. Dissemination to a pediatric audience is critical so that laser protocols might be more thoroughly investigated and incorporated into wound management strategies for this uniquely vulnerable population.


Chodera J.D.,Sloan Kettering Cancer Center | Mobley D.L.,University of California at Irvine
Annual Review of Biophysics | Year: 2013

Recent calorimetric studies of interactions between small molecules and biomolecular targets have generated renewed interest in the phenomenon of entropy-enthalpy compensation. In these studies, entropic and enthalpic contributions to binding are observed to vary substantially and in an opposing manner as the ligand or protein is modified, whereas the binding free energy varies little. In severe examples, engineered enthalpic gains can lead to completely compensating entropic penalties, frustrating ligand design. Here, we examine the evidence for compensation, as well as its potential origins, prevalence, severity, and ramifications for ligand engineering. We find the evidence for severe compensation to be weak in light of the large magnitude of and correlation between errors in experimental measurements of entropic and enthalpic contributions to binding, though a limited form of compensation may be common. Given the difficulty of predicting or measuring entropic and enthalpic changes to useful precision, or using this ormation in design, we recommend ligand engineering efforts instead focus on computational and experimental methodologies to directly assess changes in binding free energy. Copyright © 2013 by Annual Reviews.


Kern M.J.,University of California at Irvine | Samady H.,Emory University
Journal of the American College of Cardiology | Year: 2010

Over the last 15 years, the use of invasive coronary physiology in the catheterization laboratory has demonstrated favorable outcomes for decision making in patients with intermediate single-vessel stenoses, complex bifurcation and ostial branch stenoses, multivessel coronary artery disease, and left main stenoses. A recent large multicenter study (FAME [FFR versus Angiography for Multivessel Evaluation]) found that a physiologically-guided approach was superior to the standard angiographically-guided approach for percutaneous revascularization in patients with multivessel coronary artery disease. This review addresses selected pertinent concepts and studies supporting the integration of coronary physiology in the catheterization laboratory for optimal patient outcomes. © 2010 American College of Cardiology Foundation.


We prove a unique continuation principle for spectral projections of Schrödinger operators. We consider a Schrödinger operator H = -Δ + V on L2(ℝd),and let H Λ denote its restriction to a finite box Λ with either Dirichlet or periodic boundary condition. We prove unique continuation estimates of the type χ I (H Λ) W χ I (H Λ) ≥ κ χ I (H Λ) with κ > 0 for appropriate potentials W ≥ 0 and intervals I. As an application, we obtain optimal Wegner estimates at all energies for a class of non-ergodic random Schrödinger operators with alloy-type random potentials ('crooked' Anderson Hamiltonians). We also prove optimal Wegner estimates at the bottom of the spectrum with the expected dependence on the disorder (the Wegner estimate improves as the disorder increases), a new result even for the usual (ergodic) Anderson Hamiltonian. These estimates are applied to prove localization at high disorder for Anderson Hamiltonians in a fixed interval at the bottom of the spectrum. © 2013 Springer-Verlag Berlin Heidelberg.


Allen R.J.,University of California at Irvine | Sherwood S.C.,University of New South Wales
Climate Dynamics | Year: 2011

The equilibrium response of atmospheric circulation to the direct radiative effects of natural or anthropogenic aerosols is investigated using the Community Atmosphere Model (CAM3) coupled to two different ocean boundary conditions: prescribed climatological sea surface temperatures (SSTs) and a slab ocean model. Anthropogenic and natural aerosols significantly affect the circulation but in nearly opposite ways, because anthropogenic aerosols tend to have a net local warming effect and natural aerosols a net cooling. Aerosol forcings shift the Intertropical Convergence Zone and alter the strength of the Hadley circulation as found in previous studies, but also affect the Hadley cell width. These effects are due to meridional gradients in warming caused by heterogeneous net heating, and are stronger with interactive SST. Aerosols also drive model responses at high latitudes, including polar near-surface warming by anthropogenic aerosols in summer and an Arctic Oscillation (AO)-type responses in winter: anthropogenic aerosols strengthen wintertime zonal wind near 60°N, weaken it near 30°N, warm the troposphere, cool the stratosphere, and reduce Arctic surface pressure, while natural aerosols produce nearly opposite changes. These responses are shown to be due to modulation of stratospheric wave-driving consistent with meridional forcing gradients in midlatitudes. They are more pronounced when SST is fixed, apparently because the contrast in land-ocean heating drives a predominantly wavenumber-2 response in the northern hemisphere which is more efficient in reaching the stratosphere, showing that zonal heating variations also affect this particular response. The results suggest that recent shifts from reflecting to absorbing aerosol types probably contributed to the observed decadal variations in tropical width and AO, although studies with more realistic temporal variations in forcing would be needed to quantify this contribution. © 2010 The Author(s).


Jenkins J.M.,University of California at Irvine | Foster E.M.,University of Alabama at Birmingham
American Journal of Public Health | Year: 2014

Objectives. We examined the relationship between breastfeeding exclusivity and duration and children's health and cognitive outcomes at ages 2 and 4 years. Methods. We used the Early Childhood Longitudinal Study-Birth Cohort, a nationally representative sample of 10 700 children born in the United States in 2001. Parent interviews and child assessments were conducted in measurement waves at 9 months, 2 years, 4 years, and in kindergarten, with the focus on ages 2 and 4 years. We employed propensity scores as a means of adjusting for confounding involving observed characteristics. Results. Outcome analyses using propensity scores showed some small effects of breastfeeding on key outcomes at age 4 years but not at age 2 years. Effects appeared to be concentrated in reading and cognitive outcomes. Overall, we found no consistent evidence for dosage effects of breastfeeding exclusivity. Our sensitivity analyses revealed that a small amount of unobserved confounding could be responsible for the resulting benefits. Conclusions. Our study revealed little or no effect of breastfeeding exclusivity and duration on key child outcomes.


Conventional radiocarbon calculations correct for isotopic fractionation using an assumed value of 2.0 for the fractionation of 14C relative to 13C. In other words, isotopic discrimination in physical and chemical processes is assumed to cause relative shifts in 14C 12C ratios that are exactly double those of 13C 12C. This paper analyzes a 1984 experiment that produced a value for the fractionation ratio in photosynthesis of 2.3, which is used to this day by some researchers in the fields of hydrology and speleothem geochemistry. While the value of 2.3 is almost certainly incorrect, theoretical work suggests that the true value may indeed deviate from 2.0, which would have significant implications for 14C calculations. © 2011 by the Arizona Board of Regents on behalf of the University of Arizona.


Bartell S.M.,University of California at Irvine
Journal of Exposure Science and Environmental Epidemiology | Year: 2012

Regression of log serum concentrations or log urine concentrations on time elapsed after primary exposure ceases is a common method for estimating the elimination rates and corresponding half-lives for environmental contaminants. However, this method produces bias in the presence of ongoing background exposures. A general formula for the amount of bias introduced by background exposures under any single compartment pharmacokinetic model is derived here, and simpler expressions and graphical results are presented for the special case of regularly spaced biomarker measurements. The formulas are also applied to evaluate the potential bias from background exposures in recently published half-life estimates for perfluorooctanoate. These published half-lives are likely to be overestimated because of bias from background exposures, by about 1-26%. Background exposures can contribute substantial bias to half-life estimates based on longer follow-up times, even when the background contribution constitutes a small fraction of total exposure at baseline .© 2012 Macmillan Publishers Limited All rights reserved.


Bitler M.P.,University of California at Irvine
Journal of Policy Analysis and Management | Year: 2015