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New York University is a private, nonsectarian American research university based in New York City. NYU's main campus is located at Greenwich Village in Lower Manhattan. Founded in 1831, NYU is one of the largest private nonprofit institutions of American higher education.NYU was elected to the Association of American Universities in 1950. NYU counts 35 Nobel Prize winners, three Abel Prize winners, 10 National Medal of Science recipients, 16 Pulitzer Prize winners, over 30 Academy Award winners, four Putnam Competition winners, Russ Prize, Gordon Prize, and Draper Prize winners, Turing Award winners, and Emmy, Grammy, and Tony Award winners among its faculty and alumni. NYU also has MacArthur and Guggenheim Fellowship holders as well as National Academy of science and National Academy of Engineering members among its past and present graduates and faculty.NYU is organized into more than 20 schools, colleges, and institutes, located in six centers throughout Manhattan and Downtown Brooklyn, as well as more than a dozen other sites across the world, with plans for further expansion. According to the Institute of International Education, NYU sends more students to study abroad than any other US college or university, and the College Board reports more online searches by international students for "NYU" than for any other university. Wikipedia.

This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (. p<0.01) in Malawi and by 0.03 (. p<0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior. © 2014 The Author.

Vandersickel N.,Ghent University | Zwanziger D.,New York University
Physics Reports | Year: 2012

In 1967, Faddeev and Popov were able to quantize the Yang-Mills theory by introducing new particles called ghost through the introduction of a gauge. Ever since, this quantization has become a standard textbook item. Some years later, Gribov discovered that the gauge fixing was not complete, gauge copies called Gribov copies were still present and could affect the infrared region of quantities like the gauge dependent gluon and ghost propagator. This feature was often in the literature related to confinement. Some years later, the semi-classical approach of Gribov was generalized to all orders and the GZ action was born. Ever since, many related articles were published. This review tends to give a pedagogic review of the ideas of Gribov and the subsequent construction of the GZ action, including many other topics related to the Gribov region. It is shown how the GZ action can be viewed as a non-perturbative tool which has relations with other approaches toward confinement. Many different features related to the GZ action shall be discussed in detail, such as BRST breaking, the KO criterion, the propagators, etc. We shall also compare with the lattice data and other non-perturbative approaches, including stochastic quantization. © 2012 Elsevier B.V.

Madias J.E.,New York University
International Journal of Cardiology | Year: 2013

Takotsubo syndrome (TTS) is characterized by electrocardiogram (ECG) diffuse ST-segment elevations (+ ST), and T-wave inversions with prolongation of the QTc interval. Thus ECG-wise, TTS is not different from acute coronary syndromes (ACSs). However unlike acute ST-elevation myocardial infarction, one type of ACS, a rapid conversion of + ST to T-wave inversion with prolongation of the QTc interval is seen in TTS. The author hypothesizes that this conversion is paralleled by a change of segmental myocardial dyskinesis to akinesis, development of myocardial edema, and reversion of the cardioinhibitory ß-2 adrenergic receptor function, to its cardiostimulatory normal status. This hypothesis does not negate the plausibility that the ECG changes in TTS are due to myocardial ischemia/injury as traditionally perceived in ACSs. The reasons of the counterintuitive concurrence of the cardiac contractility to normal, or previous baseline status, while myocardial edema and T-wave inversions persist for several weeks in patients with TTS, are still elusive. © 2013 Elsevier Ireland Ltd.

Teran J.,University of California at Los Angeles | Fauci L.,Tulane University | Shelley M.,New York University
Physical Review Letters | Year: 2010

Microorganisms navigate through complex environments such as biofilms and mucosal tissues and tracts. To understand the effect of a complex medium upon their locomotion, we investigate numerically the effect of fluid viscoelasticity on the dynamics of an undulating swimming sheet. First, we recover recent small-amplitude results for infinite sheets that suggest that viscoelasticity impedes locomotion. We find the opposite result when simulating free swimmers with large tail undulations, with both velocity and mechanical efficiency peaking for Deborah numbers near one. We associate this with regions of highly stressed fluid aft of the undulating tail. © 2010 The American Physical Society.

Wyart M.,Princeton University | Wyart M.,New York University
Physical Review Letters | Year: 2010

An approximate relation between the vibrational entropy and the mean square displacement of the particles is derived. Using observations of the short-time dynamics in liquids of various fragility, it is argued that (i) if the crystal entropy is significantly smaller than the liquid entropy at Tg, the extrapolation of the vibrational entropy leads to the correlation TK T0, where TK is the Kauzmann temperature and T0 is the temperature extracted from the Vogel-Fulcher fit of the viscosity, and (ii) the jump in specific heat associated with vibrational entropy is very small for strong liquids, and increases with fragility. The analysis suggests that these correlations stem from the stiffening of the Boson peak under cooling, underlying the importance of this phenomenon on the dynamical arrest. © 2010 The American Physical Society.

Ofri D.,New York University
Academic Medicine | Year: 2015

Medical caregivers are always telling stories because stories provide meaning to much of their working lives. Although there is surely an element of shock value in the stories that medical professionals choose to share, the compulsion to tell a story is largely motivated by the profound emotions kindled by the clinical experience. This impulse needs to be recognized by the profession, even nurtured. However, as Wells and colleagues highlight in this issue, social media adds a new twist to storytelling. Exponential amplification combined with lack of space for nuance is a toxic brew. This needs to be explicitly emphasized with medical trainees. Although privacy rules already exist, the meaning of professionalism is to cleave to the spirit of the law, not just the letter of the law. Caregivers' primary duty is toward patients, not to writing careers or to online following. Consent should be obtained wherever possible. Identifying characteristics must be changed. Any story that might be damaging, hurtful, or embarrassing to a patient does not belong in the public sphere. Nevertheless, those in medicine need to recognize that the impulse to tell a story is innate in the human race, especially so in the caregiving professions. Experienced caregivers need to help students understand that stories provide depth and meaning to medicine but, when broadcast inappropriately, can cause harm. Copyright © by the Association of American Medical Colleges. Unauthorized reproduction of this article is prohibited.

Lebovitz H.E.,New York University
Reviews in Endocrine and Metabolic Disorders | Year: 2016

Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure. © 2016, The Author(s).

Johnson-Laird P.N.,Princeton University | Johnson-Laird P.N.,New York University | Khemlani S.S.,U.S. Navy | Goodwin G.P.,University of Pennsylvania
Trends in Cognitive Sciences | Year: 2015

This review addresses the long-standing puzzle of how logic and probability fit together in human reasoning. Many cognitive scientists argue that conventional logic cannot underlie deductions, because it never requires valid conclusions to be withdrawn - not even if they are false; it treats conditional assertions implausibly; and it yields many vapid, although valid, conclusions. A new paradigm of probability logic allows conclusions to be withdrawn and treats conditionals more plausibly, although it does not address the problem of vapidity. The theory of mental models solves all of these problems. It explains how people reason about probabilities and postulates that the machinery for reasoning is itself probabilistic. Recent investigations accordingly suggest a way to integrate probability and deduction. © 2015 Elsevier Ltd.

Yan R.,New York University
Astronomical Journal | Year: 2011

Accurate relative spectrophotometry is critical for many science applications. Small wavelength-scale residuals in the flux calibration can significantly impact the measurements of weak emission and absorption features in the spectra. Using Sloan Digital Sky Survey data, we demonstrate that the average spectra of carefully selected red-sequence galaxies can be used as a spectroscopic standard to improve the relative spectrophotometry precision to 0.1% on small wavelength scales (from a few to hundreds of Angstroms). We achieve this precision by comparing stacked spectra across tiny redshift intervals. The redshift intervals must be small enough that any systematic stellar population evolution is minimized and is less than the spectrophotometric uncertainty. This purely empirical technique does not require any theoretical knowledge of true galaxy spectra. It can be applied to all large spectroscopic galaxy redshift surveys that sample a large number of galaxies in a uniform population. © 2011. The American Astronomical Society. All rights reserved.

Rosenfeld R.M.,New York University
Otolaryngology - Head and Neck Surgery | Year: 2010

Reviewing manuscripts is central to editorial peer review, which arose in the early 1900s in response to the editor's need for expert advice to help select quality articles from numerous submissions. Most reviewers learn by trial and error, often giving up along the way because the process is far from intuitive. This primer will help minimize errors and maximize enjoyment in reviewing. Topics covered include responding to a review invitation, crafting comments to editors and authors, offering a recommended disposition, dealing with revised manuscripts, and understanding roles and responsibilities. The target audience is primarily novice reviewers, but seasoned reviewers should also find useful pearls to assist their efforts. © 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Palamar J.J.,New York University
Prevention Science | Year: 2014

Attitudes toward drug use strongly determine whether an individual initiates use. Personal disapproval toward the use of a particular drug is strongly protective against use; however, little is known regarding how the use of one drug affects attitudes toward the use of other drugs. Since marijuana use is on the rise in the US and disapproval toward use is decreasing, research is needed to determine whether the use of marijuana or other licit or illicit drugs reduces disapproval toward the use of “harder,” more potentially dangerous drugs. The Monitoring the Future study assesses a national representative sample of high school seniors in the US each year. This study investigated predictors of disapproval toward the use of powder cocaine, crack, lysergic acid diethylamide (LSD), heroin, amphetamine, and ecstasy (“Molly”) in a weighted sample of 29,054 students from five cohorts (2007–2011). Results suggest that lifetime use of cigarettes and use of more than one hard drug consistently lowered odds of disapproval. In multivariable models, lifetime alcohol use did not affect odds of disapproval and lifetime marijuana use (without the use of any “harder” drugs) lowered odds of disapproval of LSD, amphetamine, and ecstasy, but not cocaine, crack, or heroin. In conclusion, marijuana use within itself is not a consistent risk factor for lower disapproval toward the use of harder drugs. Cigarette and hard drug use, however, are more consistent risk factors. As marijuana prevalence increases and policy becomes more lenient toward recreational and medicinal use, public health and policy experts need to ensure that attitudinal-related risk does not increase for the use of other drugs. © 2013, Society for Prevention Research.

Gilmartin M.J.,New York University
Medical Care Research and Review | Year: 2013

Despite the substantial amount of useful prior work on turnover among nurses, our understanding of the causal mechanisms explaining why nurses voluntarily leave their jobs is limited. The purpose of this article is to promote the development of stronger conceptual models of the causes of voluntary turnover among nurses. The author compares the nursing-specific literature to research on voluntary turnover from the general management field over the past 30 years and examines the evolution of key theories used in the nursing literature. Results of this review comparing nursing research with that in the broader field suggest that, over time, nursing research has not kept pace with conceptualizations from general management explaining why people either remain at or quit their jobs. The author argues that conceptual models of turnover among nurses can benefit significantly from drawing more effectively on particular models and concepts available in general management studies of turnover. © The Author(s) 2013.

Yazici H.,Istanbul University | Yazici Y.,New York University
Journal of Autoimmunity | Year: 2014

With no specific histologic, laboratory or imaging features the diagnosis/classification of Behçet's Disease (BD) remains clinical. As such, disease criteria are needed. The International Study Group Criteria set is the most widely used. It has some limitations, especially in telling BD from Crohn's disease. On the other hand the main issue, as it also applies to many of the other criteria sets in rheumatology, is our lack of appreciation of a list of misconceptions - some examples of which are unluckily also found in the 2010 ACR/EULAR RA Criteria set- about diagnostic/classification criteria making and their implementation. 1. The view that classification and diagnostic criteria should be different is ill advised in that the cerebral/arithmetic basis of both are the same. 2. The default promise of diagnostic criteria to come once we formulate a classification criteria set is an extension of the previous misconception. 3.Taking pains to avoid circularity in criteria making is unwarranted since the essence of criteria making is circular. In addition we fail to exploit the utility of the disease criteria in ruling out, rather than ruling in, the diseases we seek. Finally we also fail to appreciate the paramount importance of the Bayesian prior (the pretest) probability in formulating and implementing these disease criteria. To formulate criteria tailored to subspecialties, as well as giving the often forgotten family history more importance in our criteria sets are some ways to improve the prior probability on which our diagnostic/classification decisions will be based. We first have to reconcile with ourselves that probabilities are very important in our practice and research. Moreover that reconciliation must also be shared with the public, which includes our patients. © 2014 Elsevier Ltd.

Zhou M.,New York University
Pathology | Year: 2013

Intraductal carcinoma of the prostate (IDC-P) is characterised by proliferation of malignant secretory cells that markedly expand prostatic ducts and acini. Its morphological features and diagnostic criteria have been refined in recent studies. Its molecular characteristics have also been increasingly elucidated. IDC-P is strongly associated with high grade and high volume invasive prostate cancer and unfavourable clinical outcomes. Therefore, it is critical to recognise and report IDC-P, especially in prostate biopsies where the clinical implications of the diagnosis are greatest. IDC-P has to be distinguished from several other prostate lesions with similar histological appearance. The distinction between IDC-P and high grade prostatic intraepithelial neoplasia is most important as they have drastically different implications for patient management. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy. This article will review the historical aspect, diagnostic criteria, molecular genetics, and clinical significance of IDC-P. © 2013 Royal College of Pathologists of Australasia.

Squires A.,New York University
Health Policy and Planning | Year: 2011

In the context of nurse migration, experts view trade agreements as either vehicles for facilitating migration or as contributing to brain-drain phenomena. Using a case study design, this study explored the effects of the North American Free Trade Agreement (NAFTA) on the development of Mexican nursing. Drawing results from a general thematic analysis of 48 interviews with Mexican nurses and 410 primary and secondary sources, findings show that NAFTA changed the relationship between the State and Mexican nursing. The changed relationship improved the infrastructure capable of producing and monitoring nursing human resources in Mexico. It did not lead to the mass migration of Mexican nurses to the United States and Canada. At the same time, the economic instability provoked by the peso crisis of 1995 slowed the implementation of planned advances. Subsequent neoliberal reforms decreased nurses' security as workers by minimizing access to full-time positions with benefits, and decreased wages. This article discusses the linkages of these events and the effects on Mexican nurses and the development of the profession. The findings have implications for nursing human resources policy-making and trade in services. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2010; all rights reserved.

Wichterle H.,Columbia University | Gifford D.,Massachusetts Institute of Technology | Mazzoni E.,New York University
Science | Year: 2013

A universal method for classifying neuronal subtypes will increase our understanding of the human brain.

Schwartz M.D.,New York University
Journal of General Internal Medicine | Year: 2012

To establish and sustain the high-performing health care system envisioned in the Affordable Care Act (ACA), current provisions in the law to strengthen the primary care workforcemust be funded, implemented, and tested. However, the United States is heading towards a severe primary care workforce bottleneck due to ballooning demand and vanishing supply. Demand will be fueled by the silver tsunami of 80 million Americans retiring over the next 20 years and the expanded insurance coverage for 32 million Americans in the ACA. The primary care workforce is declining because of decreased production and accelerated attrition. To mitigate the looming primary care bottleneck, even bolder policies will be needed to attract, train, and sustain a sufficient number of primary care professionals. General internistsmust continue their vital leadership in this effort. © Society of General Internal Medicine 2011.

Objective. To determine whether there is an association between the toll-like receptor 4 (TLR4) +896A>G single nucleotide polymorphism and asthma by conducting a systematic review and meta-analysis. Methods. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search for relevant studies was performed using PubMed (MEDLINE), Scopus, and HuGE Literature Finder databases with additional consultation of the reference lists of included studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for the allelic comparison (G vs. A) and the genotypic comparison assuming a dominant genetic model (AG + GG vs. AA). I2 statistics were calculated to assess the presence of between-study heterogeneity and funnel plots were inspected for indication of publication bias. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates. Results. Meta-analysis of nine studies consisting of 1838 asthma cases and 1764 controls did not find a significant association between TLR4 +896A>G and asthma (genotypic OR = 1.12, 95% CI: 0.91-1.39, p = .27). Between-study heterogeneity was not detected (I2 = 0%) and publication bias was not evident. Sensitivity analysis demonstrated the stability of the null association. Conclusions. The meta-analysis findings suggest a lack of direct association between the TLR4 +896A>G polymorphism and asthma, but gene-environment and gene-gene interaction effects and other considerations involving this polymorphism may exist. Therefore, further study is necessary to fully elucidate the role of TLR4 +896A>G in asthma. Copyright © 2012 Informa Healthcare USA, Inc.

Rangan S.,New York University | Madan R.,Qualcomm
IEEE Journal on Selected Areas in Communications | Year: 2012

Interference coordination is a fundamental challenge in emerging femtocellular deployments. This paper considers a broad class of interference coordination and resource allocation problems for wireless links based on utility maximization with a general linear mixing interference model suitable for complex femtocellular systems. The resulting optimization problems are typically hard to solve optimally even using centralized algorithms but are an essential computational step in implementing rate-fair and queue stabilizing scheduling policies in wireless networks. We consider a belief propagation framework to solve such problems approximately. In particular, we construct approximations to the belief propagation iterations to obtain computationally simple and distributed algorithms with low communication overhead. Notably, our methods are very general and apply to, semi-static and dynamic interference coordination problems including the optimization of transmit powers, transmit beamforming vectors, fractional frequency reuse (FFR) and sub-band allocations to maximize the above objective. Numerical results for femtocell deployments demonstrate that such algorithms compute a very good operating point in typically just a couple of iterations. © 2006 IEEE.

Valid diagnostic criteria support generalizations about treatment effectiveness, allowing progress in developing empirically supported treatments. The DSM-5 revision provides an opportunity to consider whether diagnostic changes are increasing validity. In this paper, I first offer broad suggestions for conceptually advancing diagnostic validity while awaiting greater etiological understanding. These include, for example, improving "conceptual validity" (disorder/nondisorder differentiation); extending diagnosis beyond disorders to include mismatches between normal variation and social demands ("psychological justice"); placing disorder etiology in evolutionary context as harmful failure of biologically designed functioning ("harmful dysfunction"); and taking an integrative theoretical approach to human meaning systems. The paper then examines the DSM-5's controversial decision to eliminate the major depression bereavement exclusion (BE), detailing the evidence and attendant debate. Elimination was defended by citing several hypotheses (e.g., excluded cases are similar to other MDD; exclusions risk missing suicidal cases; medication works with excluded cases), all of which were either empirically falsified or based on faulty arguments. Most dramatically, excluded cases were empirically demonstrated to have no more depression on follow-up than those who never had MDD. I conclude that BE elimination undermined rather than increased conceptual validity and usefulness for treatment research. Finally, I draw some general lessons from the DSM-5 BE debacle. © 2013 Elsevier Ltd.

Perl A.,New York University
Nature Reviews Rheumatology | Year: 2016

Mechanistic target of rapamycin (mTOR, also known as mammalian target of rapamycin) is a ubiquitous serine/threonine kinase that regulates cell growth, proliferation and survival. These effects are cell-type-specific, and are elicited in response to stimulation by growth factors, hormones and cytokines, as well as to internal and external metabolic cues. Rapamycin was initially developed as an inhibitor of T-cell proliferation and allograft rejection in the organ transplant setting. Subsequently, its molecular target (mTOR) was identified as a component of two interacting complexes, mTORC1 and mTORC2, that regulate T-cell lineage specification and macrophage differentiation. mTORC1 drives the proinflammatory expansion of T helper (T H) type 1, T H 17, and CD4 - CD8 - (double-negative, DN) T cells. Both mTORC1 and mTORC2 inhibit the development of CD4 + CD25 + FoxP3 + T regulatory (T REG) cells and, indirectly, mTORC2 favours the expansion of T follicular helper (T FH) cells which, similarly to DN T cells, promote B-cell activation and autoantibody production. In contrast to this proinflammatory effect of mTORC2, mTORC1 favours, to some extent, an anti-inflammatory macrophage polarization that is protective against infections and tissue inflammation. Outside the immune system, mTORC1 controls fibroblast proliferation and chondrocyte survival, with implications for tissue fibrosis and osteoarthritis, respectively. Rapamycin (which primarily inhibits mTORC1), ATP-competitive, dual mTORC1/mTORC2 inhibitors and upstream regulators of the mTOR pathway are being developed to treat autoimmune, hyperproliferative and degenerative diseases. In this regard, mTOR blockade promises to increase life expectancy through treatment and prevention of rheumatic diseases. © 2016 Macmillan Publishers Limited.

Zarate J.M.,New York University
Frontiers in Human Neuroscience | Year: 2013

Singing provides a unique opportunity to examine music performance-the musical instrument is contained wholly within the body, thus eliminating the need for creating artificial instruments or tasks in neuroimaging experiments. Here, more than two decades of voice and singing research will be reviewed to give an overview of the sensory-motor control of the singing voice, starting from the vocal tract and leading up to the brain regions involved in singing. Additionally, to demonstrate how sensory feedback is integrated with vocal motor control, recent functional magnetic resonance imaging (fMRI) research on somatosensory and auditory feedback processing during singing will be presented. The relationship between the brain and singing behavior will be explored also by examining: (1) neuroplasticity as a function of various lengths and types of training, (2) vocal amusia due to a compromised singing network, and (3) singing performance in individuals with congenital amusia. Finally, the auditory-motor control network for singing will be considered alongside dual-stream models of auditory processing in music and speech to refine both these theoretical models and the singing network itself. © 2013 Zarate.

Gentry C.,IBM | Wichs D.,New York University
Proceedings of the Annual ACM Symposium on Theory of Computing | Year: 2011

An argument system for NP is succinct, if its communication complexity is polylogarithmic the instance and witness sizes. The seminal works of Kilian '92 and Micali '94 show that such arguments can be constructed under standard cryptographic hardness assumptions with four rounds of interaction, and that they be made non-interactive in the random-oracle model. However, we currently do not have any construction of succinct non-interactive arguments (SNARGs) in the standard model with a proof of security under any simple cryptographic assumption. In this work, we give a broad black-box separation result, showing that black-box reductions cannot be used to prove the security of any SNARG construction based on any falsifiable cryptographic assumption. This includes essentially all common assumptions used in cryptography (one-way functions, trapdoor permutations, DDH, RSA, LWE etc.). More generally, we say that an assumption is falsifiable if it can be modeled as an interactive game between an adversary and an efficient challenger that can efficiently decide if the adversary won the game. This is similar, in spirit, to the notion of falsifiability of Naor '03, and captures the fact that we can efficiently check if an adversarial strategy breaks the assumption. Our separation result also extends to designated verifier SNARGs, where the verifier needs a trapdoor associated with the CRS to verify arguments, and slightly succinct SNARGs, whose size is only required to be sublinear in the statement and witness size. © 2011 ACM.

If a prime goal of energy policy is to achieve energy security, why is there a controversy over the proposed Keystone XL pipeline, designed to deliver new supplies of oil from within North America? This Viewpoint seeks answers in the debate over the underlying purposes of energy policy: how does one answers the question "what do we want from energy policy?" Perceptions of feasible answers and policy options change over time, as witnessed in the 1970s. Analogous shifts in opinion are changing today's policy debates and widening the contradictions in policy purposes. Attention to the existence of these contradictions, without illusions, is necessary to meet the policy challenges of the future effectively. © 2013 Elsevier Ltd.

Lobel I.,New York University | Ozdaglar A.,Massachusetts Institute of Technology
IEEE Transactions on Automatic Control | Year: 2011

We consider the problem of cooperatively minimizing the sum of convex functions, where the functions represent local objective functions of the agents. We assume that each agent has information about his local function, and communicate with the other agents over a time-varying network topology. For this problem, we propose a distributed subgradient method that uses averaging algorithms for locally sharing information among the agents. In contrast to previous works on multi-agent optimization that make worst-case assumptions about the connectivity of the agents (such as bounded communication intervals between nodes), we assume that links fail according to a given stochastic process. Under the assumption that the link failures are independent and identically distributed over time (possibly correlated across links), we provide almost sure convergence results for our subgradient algorithm. © 2006 IEEE.

Seeman N.C.,New York University
Nano Letters | Year: 2010

During the past decade, the field of structural DNA nanotechnology has grown enormously, not only in the number of its participants but also qualitatively in its capabilities. A number of goals evident in 2001 have been achieved: These include the extension of self-assembled crystalline systems from 2D to 3D and the achievement of 2D algorithmic assembly. A variety of nanoscale walking devices have been developed. A key unanticipated development was the advent of DNA origami, which has vastly expanded the scale of addressable DNA structures. Nanomechanical devices have been incorporated into 2D arrays, and into 2D origami structures, as well, leading to capture systems and to a nanomechanical assembly line. DNA has been used to scaffold non-DNA species, so that one of its key goals has been achieved. Biological replication of DNA nanostructures with simple topologies has also been accomplished. The increase in the number of participants in the enterprise holds great promise for the coming decade. © 2010 American Chemical Society.

Miller S.T.,New York University
Blood | Year: 2011

Acute chest syndrome describes new respiratory symptoms and findings, often severe and progressive, in a child with sickle cell disease and a new pulmonary infiltrate. It may be community-acquired or arise in children hospitalized for pain or other complications. Recognized etiologies include infection, most commonly with atypical bacteria, and pulmonary fat embolism (PFE); the cause is often obscure and may be multifactorial. Initiation of therapy should be based on clinical findings. Management includes macrolide antibiotics, supplemental oxygen, modest hydration and often simple transfusion. Partial exchange transfusion should be reserved for children with only mild anemia (Hb > 9 g/dL) but deteriorating respiratory status. Therapy with corticosteroids may be of value; safety, efficacy and optimal dosing strategy need prospective appraisal in a clinical trial. On recovery, treatment with hydroxyurea should be discussed to reduce the likelihood of recurrent episodes. © 2011 by The American Society of Hematology.

Egan P.J.,New York University | Mullin M.,Duke University
Nature | Year: 2016

As climate change unfolds, weather systems in the United States have been shifting in patterns that vary across regions and seasons. Climate science research typically assesses these changes by examining individual weather indicators, such as temperature or precipitation, in isolation, and averaging their values across the spatial surface. As a result, little is known about population exposure to changes in weather and how people experience and evaluate these changes considered together. Here we show that in the United States from 1974 to 2013, the weather conditions experienced by the vast majority of the population improved. Using previous research on how weather affects local population growth to develop an index of people's weather preferences, we find that 80% of Americans live in counties that are experiencing more pleasant weather than they did four decades ago. Virtually all Americans are now experiencing the much milder winters that they typically prefer, and these mild winters have not been offset by markedly more uncomfortable summers or other negative changes. Climate change models predict that this trend is temporary, however, because US summers will eventually warm more than winters. Under a scenario in which greenhouse gas emissions proceed at an unabated rate (Representative Concentration Pathway 8.5), we estimate that 88% of the US public will experience weather at the end of the century that is less preferable than weather in the recent past. Our results have implications for the public's understanding of the climate change problem, which is shaped in part by experiences with local weather. Whereas weather patterns in recent decades have served as a poor source of motivation for Americans to demand a policy response to climate change, public concern may rise once people's everyday experiences of climate change effects start to become less pleasant. © 2016 Macmillan Publishers Limited. All rights reserved.

Bangalore S.,New York University | Pursnani S.,California Pacific Medical Center | Kumar S.,University of Nebraska at Omaha | Bagos P.G.,University of Central Greece
Circulation | Year: 2013

Background-Contemporary studies have shown that spontaneous but not procedural myocardial infarction (MI) is related to subsequent mortality. Whether percutaneous coronary intervention (PCI) reduces spontaneous (nonprocedural) MI is unknown. Methods and Results-PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials until October 2012 comparing PCI with optimal medical therapy (OMT) for stable ischemic heart disease and reporting MI outcomes: spontaneous nonprocedural MI, procedural MI, and all MI, including procedure-related MI. Given the varying length of follow-up between trials, a mixed-effect Poisson regression meta-analysis was used. From 12 randomized clinical trials with 37 548 patient-years of follow-up, PCI compared with OMT alone was associated with a significantly lower incident rate ratio (IRR) for spontaneous nonprocedural MI (IRR=0.76; 95% confidence interval [CI], 0.58-0.99) at the risk of a higher rate of procedural MI (IRR=4.11; 95% CI, 2.53-6.88) without any difference in the risk of all MI (IRR=0.96; 95% CI, 0.74-1.21). The point estimate for PCI versus OMT for all-cause mortality (IRR=0.88; 95% CI, 0.75-1.03) and cardiovascular mortality (IRR=0.70; 95% CI, 0.44-1.09) paralleled that for spontaneous nonprocedural MI (but not procedural or all nonfatal MI), although these were not statistically significant. Conclusions-PCI compared with OMT reduced spontaneous MI at the risk of procedural MI without any difference in all MI. Consistent with prior studies showing that spontaneous MI but not procedural MI is related to subsequent mortality, in the present report the point estimate for reduced mortality with PCI compared with OMT paralleled the prevention of spontaneous MI with PCI. Further studies are needed to determine whether these associations are causal. © 2012 American Heart Association, Inc.

Cronstein B.N.,New York University
Journal of Hepatology | Year: 2010

COMMENTARY ON: Increased caffeine consumption is associated with reduced hepatic fibrosis. Apurva A. Modi, Jordan J. Feld, Yoon Park, David E. Kleiner, James E. Everhart, T. Jake Liang, Jay H. Hoofnagle. Hepatology, 2010 Jan;51(1):201-9. Copyright© 2009 by the American Association for the Study of Liver Diseases. © 2010 European Association for the Study of the Liver.

Cronstein B.N.,New York University
F1000 Biology Reports | Year: 2011

Adenosine - a purine nucleoside generated extracellularly from adenine nucleotides released by cells as a result of direct stimulation, hypoxia, trauma, or metabolic stress - is a well-known physiologic and pharmacologic agent. Recent studies demonstrate that adenosine, acting at its receptors, promotes wound healing by stimulating both angiogenesis and matrix production. Subsequently, adenosine and its receptors have also been found to promote fibrosis (excess matrix production) in the skin, lungs, and liver, but to diminish cardiac fibrosis. A commonly ingested adenosine receptor antagonist, caffeine, blocks the development of hepatic fibrosis, an effect that likely explains the epidemiologic finding that coffee drinking, in a dose-dependent fashion, reduces the likelihood of death from liver disease. Accordingly, adenosine may be a good target for therapies that prevent fibrosis of the lungs, liver, and skin. © 2011 Faculty of 1000 Ltd.

Littman D.R.,New York University | Littman D.R.,Howard Hughes Medical Institute | Pamer E.G.,Sloan Kettering Cancer Center
Cell Host and Microbe | Year: 2011

The commensal microbiota that inhabit different parts of the gastrointestinal (GI) tract have been shaped by coevolution with the host species. The symbiotic relationship of the hundreds of microbial species with the host requires a tuned response that prevents host damage, e.g., inflammation, while tolerating the presence of the potentially beneficial microbes. Recent studies have begun to shed light on immunological processes that participate in maintenance of homeostasis with the microbiota and on how disturbance of host immunity or the microbial ecosystem can result in disease-provoking dysbiosis. Our growing appreciation of this delicate host-microbe relationship promises to influence our understanding of inflammatory diseases and infection by microbial pathogens and to provide new therapeutic opportunities. © 2011 Elsevier Inc.

Fenyo D.,New York University | Beavis R.C.,University of Manitoba
Bioinformatics | Year: 2015

Summary: The Global Proteome Machine and Database (GPMDB) representational state transfer (REST) service was designed to provide simplified access to the proteomics information in GPMDB using a stable set of methods and parameters. Version 1 of this interface gives access to 25 methods for retrieving experimental information about protein post-translational modifications, amino acid variants, alternate splicing variants and protein cleavage patterns. © The Author 2015. Published by Oxford University Press.

Higham J.P.,New York University
Behavioral Ecology | Year: 2014

The honesty of animal communication has long been disputed and continues to be largely associated with the "handicap principle," in which strategic costs are paid by signalers in order to maintain signal honesty. Recently, several manuscripts have forcefully made the point that costly signaling models do not require handicaps (realized signal costs) to be paid by signalers. The aim of the present manuscript is to reiterate, clarify, and develop some of those ideas. Although the message that handicaps are not necessary for honest signaling seems to have been readily accepted, the point that handicaps are also not sufficient for honest signaling has been less well understood by the communication community. I argue that the central separation should not be between "handicaps" and "other" mechanisms such as "indices" and "punishment of cheaters." Indices, for example, are in fact a trivial exemplar of costly signaling, in which the cost functions associated with exhibiting a greater level of signal of signal expression are simply infinite. I advocate that the essential distinction is between circumstances where there is alignment of interest between signaler and receiver and those where there is not. I reenforce the view that the current focus on measuring the realized costs of signals ("handicaps") is misplaced, as without further constraints the costly signaling paradigm makes no predictions about whether honest signalers pay strategic costs for giving their own signals. Rather, it only predicts potential costs for individuals giving dishonest signals - costs that are often not paid in an honest system. © The Author 2013.

Han W.-J.,New York University
Child Development | Year: 2012

Using the Early Childhood Longitudinal Study, Kindergarten Cohort, this study examines the role that bilingualism plays in children's academic developmental trajectories during their early school years, with particular attention on the school environment (N=16,380). Growth-curve results showed that despite starting with lower math scores in kindergarten, Mixed Bilingual children fully closed the math gap with their White English Monolingual peers by fifth grade. However, because non-English-Dominant Bilinguals and non-English Monolinguals started kindergarten with significantly lower reading and math scores compared to their English Monolingual peers, by fifth grade the former groups still had significantly lower scores. School-level factors explained about one third of the reductions in the differences in children's academic performance. © 2011 The Author. Child Development © 2011 Society for Research in Child Development, Inc.

Yates-Doerr E.,New York University
Medical Anthropology Quarterly | Year: 2012

The Public Health Nutrition (PHN) community categorizes dietary-related chronic illnesses as "noncommunicable," fixing these afflictions within individual bodies where they are best managed by individual choices. Yet within clinical encounters in Guatemala, nutritionists and patients treat eating and dieting as relational, transmissible practices. Patients actively seek nutritionists' care, asserting their self-care attempts have failed and they need support from others; nutritionists meanwhile develop treatment plans that situate "personal choice" as lying outside the control of a solitary individual. This article moves between international policy-pedagogy and patient-nutritionist interactions to examine forms of personhood, responsibility, and rationalities of choice present in body weight-management practices in Guatemala. Although nutrition discourses might appear to exemplify how institutional (bio)power manifests through internalized self-monitoring and preoccupation for one's own self, I argue that within the lived experiences of "nutrition-in-action," the self-body of the patient becomes broadly conceived to include the nutritionist, the family, and the broader community. © 2012 by the American Anthropological Association.

Goldfarb D.S.,New York University
Clinical Journal of the American Society of Nephrology | Year: 2011

Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to "salt out" (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of L-cystine methyl ester and L-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, L-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria. © 2011 by the American Society of Nephrology.

Rhodes M.,New York University
Child Development | Year: 2012

Four studies examined children's (ages 3-10, Total N=235) naïve theories of social groups, in particular, their expectations about how group memberships constrain social interactions. After introduction to novel groups of people, preschoolers (ages 3-5) reliably expected agents from one group to harm members of the other group (rather than members of their own) but expected agents to help members of both groups equally often. Preschoolers expected between-group harm across multiple ways of defining social groups. Older children (ages 6-10) reliably expected agents to harm members of the other group and to help members of their own. Implications for the development of social cognition are discussed. © 2012 The Author. Child Development © 2012 Society for Research in Child Development, Inc.

Espinosa G.,New York University
Current Opinion in Urology | Year: 2013

PURPOSE OF REVIEW: Nutrition seems to modify the pathogenesis of benign prostatic hyperplasia (BPH) effect symptomology in men suffering from lower urinary tract symptoms (LUTS). Although there are numerous pharmaceuticals and procedures for these conditions, nutrition may improve outcomes as a primary approach or in tandem with BPH medications or procedures. The purpose of this review is to highlight the benefits of nutrition and dietary supplements in men with BPH and LUTS. RECENT FINDINGS: Dietary factors have an impact on metabolic disorders that lead to diabetes and obesity - both of which inversely effect BPH and LUTS. Dietary patterns associated with increased risks include starches and red meats, whereas moderate alcohol intake and polyunsaturated fat and vegetable consumption decrease risks. Dietary supplements of zinc, saw palmetto, and beta-sitosterol in relieving BPH symptoms have had mixed results. Randomized clinical trials of nutritional practices and other lifestyle alterations such as exercise for the prevention or treatment of BPH and LUTS have yet to be performed. SUMMARY: Nutritional practices may provide for the prevention and treatment of BPH and LUTS while positively affecting other systemic parameters. Whereas there are a few clinical randomized trials for the prevention and treatment of BPH and LUTS, nutritional modifications may have a healthy lifestyle alternative with minimal to no adverse effects. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.

Mukhopadhyay S.,New York University
Current Opinion in Pulmonary Medicine | Year: 2011

PURPOSE OF REVIEW: Histologic examination and microbiologic cultures are the gold standards for the diagnosis of infectious granulomatous lung diseases. Although biopsies require invasive procedures, they often yield information that cannot be obtained by other methods. The aims of this article are to outline the major infections that cause granulomatous inflammation in the lung and to familiarize clinicians with the utility of histologic examination in their diagnosis. RECENT FINDINGS: The histopathologic features of acute pulmonary histoplasmosis and granulomatous Pneumocystis pneumonia have been described in detail, the relative contributions of histology and microbiologic cultures in the diagnosis of blastomycosis have been delineated, and Cryptococcus gattii has emerged as a significant cause of granulomatous pulmonary nodules. SUMMARY: The major infectious causes of granulomatous lung disease are mycobacteria and fungi. Histologic examination is particularly important in the diagnosis of pulmonary granulomatous infections when clinical, radiologic and serologic findings are nonspecific. Histology and microbiology play complementary but distinct roles in diagnosis. For organisms that grow slowly in cultures, histology has the additional advantage of being able to provide a rapid diagnosis. © 2011 Lippincott Williams & Wilkins, Inc.

Pedersen J.T.,Lundbeck | Sigurdsson E.M.,New York University
Trends in Molecular Medicine | Year: 2015

Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future. © 2015 Elsevier Ltd.

Ohno M.,Nathan Kline Institute | Ohno M.,New York University
Frontiers in Molecular Neuroscience | Year: 2014

Cell signaling in response to an array of diverse stress stimuli converges on the phosphorylation of eukaryotic initiation factor-2α (eIF2α). Evidence is accumulating that persistent eIF2α phosphorylation at Ser51 through prolonged overactivation of regulatory kinases occurs in neurodegenerative diseases such as Alzheimer's disease (AD), leading to shutdown of general translation and translational activation of a subset of mRNAs. Recent advances in the development of gene-based strategies and bioavailable inhibitors, which specifically target one of the eIF2α kinases, have enabled us to investigate pathogenic roles of dysregulated eIF2α phosphorylation pathways. This review provides an overview of animal model studies in this field, focusing particularly on molecular mechanisms by which the dysregulation of eIF2α kinases may account for synaptic and memory deficits associated with AD. A growing body of evidence suggests that correcting aberrant eIF2α kinase activities may serve as disease-modifying therapeutic interventions to treat AD and related cognitive disorders. © 2014 Ohno.

Vouloumanos A.,New York University | Waxman S.R.,Northwestern University
Trends in Cognitive Sciences | Year: 2014

Infants' exposure to human speech within the first year promotes more than speech processing and language acquisition: new developmental evidence suggests that listening to speech shapes infants' fundamental cognitive and social capacities. Speech streamlines infants' learning, promotes the formation of object categories, signals communicative partners, highlights information in social interactions, and offers insight into the minds of others. These results, which challenge the claim that for infants, speech offers no special cognitive advantages, suggest a new synthesis. Far earlier than researchers had imagined, an intimate and powerful connection between human speech and cognition guides infant development, advancing infants' acquisition of fundamental psychological processes. © 2014 Elsevier Ltd.

Sirlin A.,New York University | Ferroglia A.,New York City College of Technology
Reviews of Modern Physics | Year: 2013

The aim of this article is to review the important role played by radiative corrections in precision electroweak physics, in the framework of both the Fermi theory of weak interactions and the standard theory of particle physics. Important theoretical developments, closely connected with the study and applications of the radiative corrections, are also reviewed. The role of radiative corrections in the analysis of some important signals of new physics is also discussed. © 2013 American Physical Society.

Abramsky S.,University of Oxford | Brandenburger A.,New York University
New Journal of Physics | Year: 2011

We use the mathematical language of sheaf theory to give a unified treatment of non-locality and contextuality, in a setting that generalizes the familiar probability tables used in non-locality theory to arbitrary measurement covers; this includes Kochen-Specker configurations and more. We show that contextuality, and non-locality as a special case, correspond exactly to obstructions to the existence of global sections. We describe a linear algebraic approach to computing these obstructions, which allows a systematic treatment of arguments for non-locality and contextuality. We distinguish a proper hierarchy of strengths of no-go theorems, and show that three leading examples-due to Bell, Hardy and Greenberger, Horne and Zeilinger, respectively-occupy successively higher levels of this hierarchy. A general correspondence is shown between the existence of local hidden-variable realizations using negative probabilities, and no-signalling; this is based on a result showing that the linear subspaces generated by the non-contextual and no-signalling models, over an arbitrary measurement cover, coincide. Maximal non-locality is generalized to maximal contextuality, and characterized in purely qualitative terms, as the non-existence of global sections in the support. A general setting is developed for the Kochen-Specker-type results, as generic, modelindependent proofs of maximal contextuality, and a new combinatorial condition is given, which generalizes the 'parity proofs' commonly found in the literature. We also show how our abstract setting can be represented in quantum mechanics. This leads to a strengthening of the usual no-signalling theorem, which shows that quantum mechanics obeys no-signalling for arbitrary families of commuting observables, not just those represented on different factors of a tensor product. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

Wyart M.,New York University
Physical Review Letters | Year: 2012

The requirement that packings of frictionless hard spheres, arguably the simplest structural glass, cannot be compressed by rearranging their network of contacts is shown to yield a new constraint on their microscopic structure. This constraint takes the form a bound between the distribution of contact forces P(f) and the pair distribution function g(r): if P(f)∼fθ and g(r)∼(r-σ 0) -γ, where σ 0 is the particle diameter, one finds that γ≥1/(2+θ). This bound plays a role similar to those found in some glassy materials with long-range interactions, such as the Coulomb gap in Anderson insulators or the distribution of local fields in mean-field spin glasses. There are grounds to believe that this bound is saturated, yielding a mechanism to explain the avalanches of rearrangements with power-law statistics that govern plastic flow in packings. © 2012 American Physical Society.

The forces driving the evolutionary loss or simplification of traits such as vision and pigmentation in cave animals are still debated. Three alternative hypotheses are direct selection against the trait, genetic drift, and indirect selection due to antagonistic pleiotropy. Recent work establishes that Astyanax cavefish exhibit vibration attraction behavior (VAB), a presumed behavioral adaptation to finding food in the dark not exhibited by surface fish. Genetic analysis revealed two regions in the genome with quantitative trait loci (QTL) for both VAB and eye size. These observations were interpreted as genetic evidence that selection for VAB indirectly drove eye regression through antagonistic pleiotropy and, further, that this is a general mechanism to account for regressive evolution. These conclusions are unsupported by the data; the analysis fails to establish pleiotropy and ignores the numerous other QTL that map to, and potentially interact, in the same regions. It is likely that all three forces drive evolutionary change. We will be able to distinguish among them in individual cases only when we have identified the causative alleles and characterized their effects. © 2013 Borowsky; licensee BioMed Central Ltd.

A renormalization group approach is used to show that a one-dimensional system of bosons subject to a lattice quench exhibits a finite-time dynamical phase transition where an order parameter within a light cone increases as a nonanalytic function of time after a critical time. Such a transition is also found for a simultaneous lattice and interaction quench where the effective scaling dimension of the lattice becomes time dependent, crucially affecting the time evolution of the system. Explicit results are presented for the time evolution of the boson interaction parameter and the order parameter for the dynamical transition as well as for more general quenches. © 2012 American Physical Society.

Chen X.J.,New York University
Microbiology and Molecular Biology Reviews | Year: 2013

Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of doublestrand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a singlestrand annealing mechanism independent of the canonical RecA/ Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.

Bergman M.,New York University
Endocrine | Year: 2013

In view of the global shift from communicable to chronic, non-communicable diseases including obesity, prediabetes, and type 2 diabetes mellitus, the increasing prevalence of the latter creates a considerable challenge to the clinician and public health infrastructure. Despite the substantial research efforts in the last 10-15 years highlighting the considerable benefit of lifestyle modification in thwarting the insidious progression to diabetes and its complications, many individuals will ineluctably progress even when initially responsive. Furthermore, the vast majority of individuals with prediabetes remain undiagnosed and untreated. Therefore, the responsibilities of the medical and public health communities involve identifying new methods for screening and identifying those at risk as well as refining therapeutic approaches availing as many high-risk individuals as possible to novel treatment modalities. © 2013 Springer Science+Business Media New York.

Fisch G.S.,New York University
American Journal of Medical Genetics, Part C: Seminars in Medical Genetics | Year: 2012

Since its initial description by Kanner in 1943, the criteria by which a diagnosis of autism or autism-like disorders was made-and their alleged etiologies portrayed-have undergone manifold changes, from a psychiatric disorder engendered by "refridgerator" parents to a neurodevelopmental disability produced in the main by genetic abnormalities. In addition, the behavioral characterization of autism has also entered the public consciousness and professional domains increasingly in the past 30 years, the effects of which we are continually coming to terms. A diagnosis of autism that once seemed quite unusual is now considered almost epidemic. Increasing numbers of individuals diagnosed with autism and related pervasive developmental disabilities will, in turn, affect the calculated prevalence of the disorder. In this essay, I attempt to account for the increasing prevalence of autism and autism-related disorders by examining its changing criteria, the individuals and instruments used to make the diagnosis, the reliability and validity of same, and the sample sizes and other aspects of the methodology needed to make an accurate estimate of its prevalence. © 2012 Wiley Periodicals, Inc.

Klein H.L.,New York University | Symington L.S.,Columbia University
Cell | Year: 2012

The Sgs1 DNA helicase and its mammalian homolog BLM control crossover formation in mitotic cells. Zakharyevich et al. and De Muyt et al. now uncover a key role for Sgs1 in meiotic crossover regulation, which in turn reveals a joint molecule resolution pathway that produces the majority of crossovers in budding yeast. © 2012 Elsevier Inc.

Tuchman E.,New York University
Journal of Addictive Diseases | Year: 2010

Substance use was considered to be primarily a male problem, and many substance abuse studies are conducted with a predominance of male participants. However, recent substance abuse research indicates significant gender differences in the substance-related epidemiology, social factors and characteristics, biological responses, progressions to dependence, medical consequences, co-occurring psychiatric disorders, and barriers to treatment entry, retention, and completion. The epidemiology of women's drug use presents challenges separate from those raised by men's drug use. A convergence of evidence suggests that women with substance use disorders are more likely than men to face multiple barriers affecting access and entry to substance abuse treatment. Gender-specific medical problems as a result of the interplay of gender-specific drug use patterns and sex-related risk behaviors create an environment in which women are more vulnerable than men to human immunodeficiency virus. Individual characteristics and treatment approaches can differentially affect outcomes by gender. All of these differences have important clinical, treatment, and research implications. Copyright © Taylor & Francis Group.

Greenberg D.F.,New York University
Justice Quarterly | Year: 2014

Methodological issues that must be considered in doing research on the New York City crime drop include the choice of a spatial unit of analysis, the choice of a mathematical representation of the processes responsible for the drop, and the choice of estimators. This paper considers the strengths and weaknesses of a time series analysis of data for New York alone, a panel analysis for the city's precincts, and a panel analysis for a sample of cities, for studying the drop. The possibilities and limitations of precinct-level data are illustrated with annual precinct data for New York between 1988 and 2001. The paper considers static and dynamic fixed effects panel models estimated in various ways, including difference and systems generalized method of moments. These analyses find no evidence that misdemeanor arrests reduced levels of homicide, robbery, or aggravated assaults. Felony arrests reduced robberies, but only to a modest degree. Most of the decline in these three felonies had other causes. © 2013 Academy of Criminal Justice Sciences.

Rehder B.,New York University
Journal of Experimental Psychology: Learning Memory and Cognition | Year: 2015

Two experiments tested how the functional form of the causal relations that link features of categories affects category-based inferences. Whereas independent causes can each bring about an effect by themselves, conjunctive causes all need to be present for an effect to occur. The causal model view of category representations is extended to include a representation of conjunctive causes and then predictions are derived for 3 category-based judgments: classification, conditional feature predictions, and feature likelihoods. Experiment 1 revealed that subjects' judgments on all 3 tasks were not only sensitive to whether causes were independent or conjunctive but also conformed to the causal model predictions, albeit with an important exception. Experiment 2 revealed that inferences with independent and conjunctive causes were affected quite differently by a manipulation of the strengths of the causal relations (and in the manner predicted by the model). This is the 1st study to show how a single representation of a category's causal knowledge can account for 3 category-based judgments with the same model parameters. Other models of causal-based categories are unable to account for the observed effects. © 2014 American Psychological Association.

Citrome L.,New York University
International Journal of Clinical Practice | Year: 2011

Objective: To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. Data sources: The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as and for the search term 'lurasidone'. Product labelling provided additional information. Study selection: All available clinical reports of studies were identified. Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis: Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥ 350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥ 20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥ 30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were somnolence (broadly defined), akathisia, nausea, parkinsonism and agitation. As estimated from product labelling, NNH vs. placebo was dose dependent for somnolence, with a NNH of 6 for lurasidone 120 mg/day, compared with NNHs of 8, 11 and 20, for 80, 40 and 20 mg/day, respectively. For akathisia NNH was 6 for lurasidone 120 mg/day, compared to NNHs of 9, 13 and 34 for 80, 40 and 20 mg/day, respectively. Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, prolactin or the ECG QT interval. Conclusions: Lurasidone 40 and 80 mg/day appear efficacious and tolerable in the treatment of schizophrenia. Doses above 80 mg/day do not appear to confer added benefit and may be associated with a dose-related increase in certain adverse reactions. Principal advantages over some other second-generation antipsychotics are lurasidone's highly favourable metabolic profile and once-daily dosing regimen. Additional data regarding long-term efficacy and effectiveness will help characterise this new agent when used in maintenance treatment. © 2010 Blackwell Publishing Ltd.

Springer T.A.,Harvard University | Dustin M.L.,New York University
Current Opinion in Cell Biology | Year: 2012

Integrins dynamically equilibrate between three conformational states on cell surfaces. A bent conformation has a closed headpiece. Two extended conformations contain either a closed or an open headpiece. Headpiece opening involves hybrid domain swing-out and a 70 å separation at the integrin knees, which is conveyed by allostery from the hybrid-proximal end of the βI domain to a 3 å rearrangement of the ligand-binding site at the opposite end of the βI domain. Both bent-closed and extended-closed integrins have low affinity, whereas extended-open integrin affinity is 10 3 to 10 4 higher. Integrin-mediated adhesion requires the extended-open conformation, which in physiological contexts is stabilized by post-ligand binding events. Integrins thus discriminate between substrate-bound and soluble ligands. Analysis of LFA-1-ICAM-1 interactions in the immunological synapse suggests that bond lifetimes are on the order of seconds, which is consistent with high affinity interactions subjected to cytoskeletal forces that increase the dissociation rate. LFA-1 βI domain antagonists abrogate function in the immunological synapse, further supporting a critical role for high affinity LFA-1. © 2011 Elsevier Ltd.

Philips M.R.,New York University
Nature Cell Biology | Year: 2012

Ras GTPases are tethered to cellular membranes by a farnesyl lipid that modifies a carboxy-terminal cysteine. One of the ways Ras traffics between membranes is via fluid-phase diffusion, suggesting that a cytosolic chaperone might be needed to shield the farnesyl lipid during transport. PDE6δ is now revealed to be a farnesyl-binding chaperone that facilitates the trafficking and signalling of Ras. © 2012 Macmillan Publishers Limited. All rights reserved.

Yan X.,New York University
High Altitude Medicine and Biology | Year: 2014

High altitude hypoxia has been shown to have significant impact on cognitive performance. This article reviews the aspects in which, and the conditions under which, decreased cognitive performance has been observed at high altitudes. Neural changes related to high altitude hypoxia are also reviewed with respect to their possible contributions to cognitive impairments. In addition, potential adaptation mechanisms are reviewed among indigenous high altitude residents and long-term immigrant residents, with discussions about methodological concerns related to these studies. © 2014 Mary Ann Liebert, Inc.

Trasande L.,New York University
Health Affairs | Year: 2014

There is mounting evidence that bisphenol A (BPA), a chemical used in the production of polycarbonate plastics and the linings of aluminum cans, may have adverse health consequences. The Food and Drug Administration has banned BPA from baby bottles and sippy cups but has deferred further action on other food uses-that is, uses in metalbased food and beverage containers. This article quantifies the potential social costs of childhood obesity and adult coronary heart disease attributable to BPA exposure in the United States in 2008 and models the potential health and economic benefits associated with replacing BPA in all food uses. BPA exposure was estimated to be associated with 12,404 cases of childhood obesity and 33,863 cases of newly incident coronary heart disease, with estimated social costs of $2.98 billion in 2008. Removing BPA from food uses might prevent 6,236 cases of childhood obesity and 22,350 cases of newly incident coronary heart disease per year, with potential annual economic benefits of $1.74 billion (sensitivity analysis: $889 million-$13.8 billion per year). Although more data are needed, these potentially large health and economic benefits could outweigh the costs of using a safer substitute for BPA. © 2014 Project HOPE- The People-to-People Health Foundation, Inc.

Abu-Khzam F.N.,New York University
Journal of Computer and System Sciences | Year: 2010

For a given parameterized problem, π, a kernelization algorithm is a polynomial-time pre-processing procedure that transforms an arbitrary instance of π into an equivalent one whose size depends only on the input parameter(s). The resulting instance is called a problem kernel. In this paper, a kernelization algorithm for the 3-Hitting Set problem is presented along with a general kernelization for d-Hitting Set. For 3-Hitting Set, an arbitrary instance is reduced into an equivalent one that contains at most 5k 2+k elements. This kernelization is an improvement over previously known methods that guarantee cubic-order kernels. Our method is used also to obtain quadratic kernels for several other problems. For a constant d≥3, a kernelization of d-Hitting Set is achieved by a non-trivial generalization of the 3-Hitting Set method, and guarantees a kernel whose order does not exceed (2d-1)kd-1+k. © 2009 Elsevier Inc. All rights reserved.

Palamar J.J.,New York University
Journal of psychoactive drugs | Year: 2014

Support for marijuana (cannabis) legalization is increasing in the US, and state-level marijuana policies are rapidly changing. Research is needed to examine correlates of opinions toward legalization among adolescents approaching adulthood as they are at high risk for use. Data were examined from a national representative sample of high school seniors in the Monitoring the Future study (years 2007-2011; N = 11,594) to delineate correlates of opinions toward legalization. A third of students felt marijuana should be entirely legal and 28.5% felt it should be treated as a minor violation; 48.0% felt that if legal to sell it should be sold to adults only, and 10.4% felt it should be sold to anyone. Females, conservatives, religious students, and those with friends who disapprove of marijuana use tended to be at lower odds for supporting legalization, and Black, liberal, and urban students were at higher odds for supporting more liberal policies. Recent and frequent marijuana use strongly increased odds for support for legalization; however, 16.7% of non-lifetime marijuana users also reported support for legalization. Findings should be interpreted with caution as state-level data were not available, but results suggest that support for marijuana legalization is common among specific subgroups of adolescents.

Rushlow C.A.,New York University | Shvartsman S.Y.,Princeton University
Current Opinion in Genetics and Development | Year: 2012

Dorsoventral pattern of . Drosophila embryo is specified by the nuclear localization gradient of the transcription factor Dorsal. Genetic and genomic studies of this morphogen gradient provided important insights into spatial control of gene expression in development. Recent live imaging experiments revealed hitherto unappreciated dynamics of the Dorsal gradient and posed new questions about the mechanisms of its transcriptional interpretation. Some of these questions can be answered by models in which the morphogenetic capacity of the Dorsal gradient is potentiated by spatially uniform factors, such as Zelda, a transcription factor that plays a key role in the activation of zygotic transcription. Combinatorial effects of uniform and graded factors play an important role in the transcriptional and signaling cascades initiated by Dorsal and may explain differential positioning of gene expression borders by other morphogen gradients. © 2012 Elsevier Ltd.

Tee W.-W.,Howard Hughes Medical Institute | Shen S.S.,Howard Hughes Medical Institute | Shen S.S.,New York University | Oksuz O.,Howard Hughes Medical Institute | And 2 more authors.
Cell | Year: 2014

Erk1/2 activation contributes to mouse ES cell pluripotency. We found a direct role of Erk1/2 in modulating chromatin features required for regulated developmental gene expression. Erk2 binds to specific DNA sequence motifs typically accessed by Jarid2 and PRC2. Negating Erk1/2 activation leads to increased nucleosome occupancy and decreased occupancy of PRC2 and poised RNAPII at Erk2-PRC2-targeted developmental genes. Surprisingly, Erk2-PRC2-targeted genes are specifically devoid of TFIIH, known to phosphorylate RNA polymerase II (RNAPII) at serine-5, giving rise to its initiated form. Erk2 interacts with and phosphorylates RNAPII at its serine 5 residue, which is consistent with the presence of poised RNAPII as a function of Erk1/2 activation. These findings underscore a key role for Erk1/2 activation in promoting the primed status of developmental genes in mouse ES cells and suggest that the transcription complex at developmental genes is different than the complexes formed at other genes, offering alternative pathways of regulation. © 2014 Elsevier Inc.

Palmer A.N.,New York University
Geomorphology | Year: 2011

Certain caves formed by dissolution of bedrock have maze patterns composed of closed loops in which many intersecting fractures or pores have enlarged simultaneously. Their origin can be epigenic (by shallow circulation of meteoric groundwater) or hypogenic (by rising groundwater or production of deep-seated solutional aggressiveness). Epigenic mazes form by diffuse infiltration through a permeable insoluble caprock or by floodwater supplied by sinking streams. Most hypogenic caves involve deep sources of aggressiveness. Transverse hypogenic cave origin is a recently proposed concept in which groundwater of mainly meteoric origin rises across strata in the distal portions of large flow systems, to form mazes in soluble rock sandwiched between permeable but insoluble strata. The distinction between maze types is debated and is usually based on examination of diagnostic cave features and relation of caves to their regional setting. In this paper, the principles of mass transfer are applied to clarify the limits of each model, to show how cave origin is related to groundwater discharge, dissolution rate, and time. The results show that diffuse infiltration and floodwater can each form maze caves at geologically feasible rates (typically within 500ka). Transverse hypogenic mazes in limestone, to enlarge significantly within 1Ma, require an unusually high permeability of the non-carbonate beds (generally ≧10-4cm/s), large discharge, and calcite saturation no greater than 90%, which is rare in deep diffuse flow in sedimentary rocks. Deep sources of aggressiveness are usually required. The origin of caves by transverse hypogenic flow is much more favorable in evaporite rocks than in carbonate rocks. © 2011 Elsevier B.V.

Radcliffe N.M.,New York University
Clinical Ophthalmology | Year: 2014

Glaucomatous optic atrophy is the second most common cause of blindness worldwide, and lowering intraocular pressure (IOP) is the only proven method to slow or stop the progression of the disease. Approximately 40% of patients with elevated IOP will require more than one medication to obtain a modest 20% reduction in IOP, and as a result, some patients may require two medications, provided in either two separate bottles or in one bottle with the use of fixed-combination therapies. Each therapy has its own unique safety and efficacy profile. Topical beta-blockers have a particularly favorable ocular-tolerability profile, and several studies of fixed-combination medications containing the beta-blocker timolol maleate have shown a lower prevalence of some ocular adverse events for the fixed-combination therapy compared to the non-beta-blocker individual component. In this review, we examined clinical data pertaining to the ocular surface tolerability of fixed-combination medications containing timolol maleate in comparison to the individual components. In particular, preference was given to prospective, randomized, multicenter trials of 3 months in duration or longer that compared a fixed-combination therapy to monotherapy with the individual components. A review of the literature revealed that some fixed-combination therapies can provide a reduced risk of common side effects compared to their individual components, with conjunctival hyperemia and ocular allergy being less frequent in some timolol-containing fixed-combination therapies. This effect appears to be most significant for latanoprost 0.005%, bimatoprost 0.03%, and brimonidine 0.2%. © 2014 Radcliffe.

Rao R.S.,New York University
Obesity Surgery | Year: 2012

Bariatric procedures are now known to have an effect on hunger as well as on metabolism. The role of central nervous pathways in causing these effects after bariatric surgery is now being elucidated. A brief overview of these pathways has been presented for the sake of bariatric surgeons. A PubMed search was made using various search phrases to retrieve all original articles concerning the effect of bariatric surgery on the neural pathways. The mechanisms regulating the food intake and energy expenditure can be broadly divided into homeostatic and hedonic systems. The effect of bariatric surgery on the homeostatic system in animal models is not clear. A decrease in preference for sweet taste and high calorie foods has been demonstrated in animal models. The effect of bariatric surgery on the hedonic system in humans has been consistent with decreased activation of the hedonic system being demonstrated by functional MRI and decreased preference for intake of high energy foods also being observed post-surgery. The effect of bariatric surgery on dopamine signaling, which is involved in the hedonic system, is however not clear. Functional MRI studies have also demonstrated increased activation of the hypothalamus after surgery. Various studies utilizing questionnaires have demonstrated increased satiety and decreased hunger after bariatric surgery. © 2012 Springer Science + Business Media, LLC.

Yazici Y.,New York University
Clinical and Experimental Rheumatology | Year: 2010

Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so. The safety profile of MTX has been studied over 25 years with very few clinically important adverse events in the weekly low-doses used for RA treatment. The importance of MTX in earlier and more aggressive management of RA patients cannot be overstated. MTX courses show some of the longest continuation rates reported in clinical medicine, due to both effectiveness and safety. The safety profile of MTX indicates that it is among the safest of any mediation used for the treatment of any arthritis. Better information on the effectiveness and safety of weekly-low dose MTX should be communicated to all health professionals involved in the management of RA patients. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2010.

Hostinar C.E.,University of Minnesota | Sullivan R.M.,New York University | Gunnar M.R.,University of Minnesota
Psychological Bulletin | Year: 2014

Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary- adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social. © 2014 American Psychological Association.

Introduction and Aims. Illicit drug use is a stigmatised behaviour; therefore, users tend to experience rejection and remain secretive about use. However, stigma-related rejection and secrecy can adversely affect those who reject abstinence. This study aimed to modify measures to assess these concepts with regard to illicit drug use and examine how they relate to use of various drugs and associated perception of public stigma. Design and Methods. An Internet-based convenience sample (n=700) was surveyed to pilot items modified from previous scales in order to assess these concepts with regard to drug use. As perceived rejection and secrecy are related and potentially overlapping constructs, exploratory factor analysis was conducted to examine the underlying structure of items previously used to assess these concepts. These variables were examined in relation to sociodemographic characteristics, perceived public stigma and use of various drugs (marijuana, powder cocaine, ecstasy and nonmedical use of opioids and prescription stimulants). Results. After factor reduction, perceived rejection and secrecy loaded as two distinct, but related concepts. These modified measures had moderate to high internal consistency and both concepts were positively related to perceived public stigma and use of various drugs. Discussion and Conclusions. This pilot study demonstrated validity evidence for these measures and results suggest that illicit drug use and associated stigma are related to increased feelings of rejection and secrecy in users. Research is needed to examine whether stigma towards users serves as a deterrent to use because rejection and secrecy are associated with adverse psychosocial outcomes. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Michael Belmont H.,New York University
Bulletin of the Hospital for Joint Diseases | Year: 2013

This 2013 update on the treatment of systemic lupus erythrematosus provides rationale for universal use of antimalarials even absent skin or joint manifestations, but chiefly focuses on the management options for refractory cutaneous, articular, and renal disease and current status of biologics; both FDA approved belimumab and off-label infliximab, rituximab, abatacept, and tociluzimab. A discussion of antiphospholipid syndrome secondary to lupus, specifically use of aspirin for asymptomatic patients, suggestions for catastrophic antibody syndrome, and potential roles for rituximab and eculizumab are provided. This review is a companion to an article published in this journal last year and in combination provides recommendations for standard care in routine cases of lupus as well as for the problematic, intractable patient. © 2013, Bull Hosp Jt Dis. All rights reserved.

Gardner L.B.,New York University
Molecular Cancer Research | Year: 2010

Nonsense-mediated RNA decay (NMD) has long been viewed as an important constitutive mechanism to rapidly eliminate mutated mRNAs. More recently, it has been appreciated that NMD also degrades multiple nonmutated transcripts and that NMD can be regulated by wide variety of cellular stresses. Many of the stresses that inhibit NMD, including cellular hypoxia and amino acid deprivation, are experienced in cells exposed to hostile microenvironments, and several NMD-targeted transcripts promote cellular adaptation in response to these environmental stresses. Because adaptation to the microenvironment is crucial in tumorigenesis, and because NMD targets many mutated tumor suppressor gene transcripts, the regulation of NMD may have particularly important implications in cancer. This review briefly outlines the mechanisms by which transcripts are identified and targeted by NMD and reviews the evidence showing that NMD is a regulated process that can dynamically alter gene expression. Although much of the focus in NMD research has been in identifying the proteins that play a role in NMD and identifying NMD-targeted transcripts, recent data about the potential functional significance of NMD regulation, including the stabilization of alternatively spliced mRNA isoforms, the validation of mRNAs as bona fide NMD targets, and the role of NMD in tumorigenesis, are explored. ©2010 AACR.

Rayner K.J.,University of Ottawa | Moore K.J.,New York University
Circulation Research | Year: 2014

Recent discoveries of microRNAs (miRNAs) that control high-density lipoprotein abundance and function have expanded our knowledge of the mechanisms regulating this important lipoprotein subclass. miRNAs have been shown to regulate gene networks that control high-density lipoprotein biogenesis and uptake, as well as discrete steps in the reverse cholesterol transport pathway. Furthermore, high-density lipoprotein itself has been shown to transport miRNAs selectively in health and disease, offering new possibilities of how this lipoprotein may alter gene expression in distal target cells and tissues. Collectively, these discoveries offer new insights into the mechanisms governing high-density lipoprotein metabolism and function and open new avenues for the development of therapeutics for the treatment of cardiovascular disease. © 2013 American Heart Association, Inc.

Serganov A.,New York University | Patel D.J.,Sloan Kettering Cancer Center
Annual Review of Biophysics | Year: 2012

Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits. © 2012 by Annual Reviews. All rights reserved.

Goff D.C.,New York University
Current Opinion in Psychiatry | Year: 2015

Purpose of review The ketamine model has dominated drug discovery in schizophrenia over the past decade, supported by genetic and postmortem evidence implicating glutamatergic transmission. This review assesses recent successes and disappointments of glutamatergic agents and identifies promising new directions.Recent findings Strategies focused on enhancing activity of the N-methyl D-aspartate (NMDA) receptor via direct agonists at the glycine site or by inhibition of glycine reuptake have produced modest and often inconsistent evidence of efficacy, as have approaches to reduce excessive glutamate release by lamotrigine or by mGluR2/3 agonists. Strategies targeting a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors have also met with only limited success. Newer approaches include selective allosteric modulation of NMDA receptor subunits and of mGluR5 receptors. In addition, intracellular pathways downstream of NMDA receptors may also provide new treatment targets, as exemplified by phosphodiesterase (PDE) inhibitors.Summary Targeting glutamatergic transmission remains one of the most promising strategies in schizophrenia, particularly early in the course of illness, but therapeutic approaches may require greater specificity for receptor subtype type, illness phase, and individual biology in order to enhance efficacy and overcome problems with reproducibility of clinical results. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Erlebacher A.,New York University
Trends in Endocrinology and Metabolism | Year: 2010

How the fetal 'allograft' avoids rejection during pregnancy remains a major unresolved immunological paradox. Recent work has suggested that fetomaternal tolerance is in fact maintained by a number of redundant mechanisms, but their relative importance has remained poorly defined. In this paper, I discuss an emerging controversy regarding the ability of maternal T cells to mediate fetal rejection at a time when they appear to be ignorant of fetal and placental antigens. This paradox within a paradox highlights two major research directions in the field of reproductive immunology that, when ultimately reconciled, promise to give significant insight into mechanisms of impaired fertility and compromised fetal and maternal health. © 2010 Elsevier Ltd.

Barcellos-Hoff M.H.,New York University
Journal of Mammary Gland Biology and Neoplasia | Year: 2010

Ionizing radiation is a well-established carcinogen in human breast and rodent mammary gland. This review addresses evidence that radiation elicits the critical stromal context for cancer, affecting not only frequency but the type of cancer. Recent data from the breast tumors of women treated with radiation therapy and the cellular mechanisms evident in experimental models suggest that radiation effects on stromal-epithelial interactions and tissue composition are a major determinant of cancer development. © Springer Science+Business Media, LLC 2010.

Citrome L.,New York University
Expert Opinion on Drug Safety | Year: 2011

Introduction: Ziprasidone is a second-generation antipsychotic approved for the treatment of schizophrenia and bipolar disorder. The purpose of this review is to assess the overall safety profile of ziprasidone, including its risk for prolonging the electrocardiogram (ECG) QT interval. Areas covered: This paper is a review of product labeling and English language reports located through PubMed and information available on regulatory agency websites, with a focus on the safety and tolerability of ziprasidone. Expert opinion: Although ziprasidone can prolong the ECG QT interval, this has not resulted in increases in sudden death or cardiac sudden death as noted in a large, simple trial and supported by almost a decade of real-world use in the US. Ziprasidone's principal advantage over some other second-generation antipsychotics has been its overall favorable weight and metabolic profile. Similar to most second-generation antipsychotics, ziprasidone has a lower propensity for extrapyramidal side effects and hyperprolactinemia compared to first-generation antipsychotics. © 2011 Informa UK, Ltd.

Citrome L.,New York University
Postgraduate Medicine | Year: 2011

Three new second-generation antipsychotics were approved by the US Food and Drug Administration in 2009 and 2010: iloperidone, asenapine, and lurasidone. All 3 agents are approved for the treatment of acute schizophrenia in adults, and asenapine is also approved for the maintenance treatment of schizophrenia and as a monotherapy or as an adjunct to lithium or valproate for the treatment of bipolar manic or mixed episodes. The expectation is that these new agents will be less problematic regarding treatment-emergent weight gain and metabolic disturbances, which unfortunately can occur with several other second-generation antipsychotics. Asenapine is a sublingual preparation, in contrast to iloperidone and lurasidone, which are swallowed. Iloperidone and asenapine are dosed twice daily, in contrast to lurasidone, which is dosed once daily with food. Both asenapine and lurasidone can be initiated at a dose that is possibly therapeutic, but iloperidone requires 4 days of titration to reach its recommended target dose range. Although both asenapine and lurasidone can be associated with dose-related treatment-emergent akathisia, iloperidone is essentially free of extrapyramidal adverse effects or akathisia throughout its recommended dose range. Sedation and/or somnolence have been reported with each medication. They are the most common adverse events associated with asenapine treatment, and are clearly dose-related for lurasidone. In contrast, no therapeutic dose response for iloperidone, asenapine, or lurasidone is clearly evident from short-term clinical trials. Longer-term and naturalistic studies will be helpful in evaluating these agents and their role in the psychiatric armamentarium. © Postgraduate Medicine.

Lake B.M.,New York University | Salakhutdinov R.,Kings College | Tenenbaum J.B.,Massachusetts Institute of Technology
Science | Year: 2015

People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms-for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world's alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches.We also present several "visual Turing tests" probing the model's creative generalization abilities, which in many cases are indistinguishable from human behavior.

Lu Y.,Northwestern University | Liang F.-X.,New York University | Wang X.,Northwestern University
Molecular Cell | Year: 2014

Signaling in the ancestral branch of the unfolded protein response (UPR) is initiated by unconventional splicing of HAC1/. XBP1 mRNA during endoplasmic reticulum (ER) stress. In mammals, IRE1α has been known to cleave the XBP1 intron. However, the enzyme responsible for ligation of two XBP1 exons remains unknown. Using an XBP1 splicing-based synthetic circuit, we identify RtcB as the primary UPR RNA ligase. In RtcB knockout cells, XBP1 mRNA splicing is defective during ER stress. Genetic rescue and invitro splicing show that the RNA ligase activity of RtcB is directly required for the splicing of XBP1 mRNA. Taken together, these data demonstrate that RtcB is the long-sought RNA ligase that catalyzes unconventional RNA splicing during the mammalian UPR. © 2014 Elsevier Inc.

Poeppel D.,New York University | Poeppel D.,Max Planck Institute for Empirical Aesthetics
Current Opinion in Neurobiology | Year: 2014

New tools and new ideas have changed how we think about the neurobiological foundations of speech and language processing. This perspective focuses on two areas of progress. First, focusing on spatial organization in the human brain, the revised functional anatomy for speech and language is discussed. The complexity of the network organization undermines the well-regarded classical model and suggests looking for more granular computational primitives, motivated both by linguistic theory and neural circuitry. Second, focusing on recent work on temporal organization, a potential role of cortical oscillations for speech processing is outlined. Such an implementational-level mechanism suggests one way to deal with the computational challenge of segmenting natural speech. © 2014 Elsevier Ltd.

Seeman N.C.,New York University
Annual Review of Biochemistry | Year: 2010

The combination of synthetic stable branched DNA and sticky-ended cohesion has led to the development of structural DNA nanotechnology over the past 30 years. The basis of this enterprise is that it is possible to construct novel DNA-based materials by combining these features in a self-assembly protocol. Thus, simple branched molecules lead directly to the construction of polyhedrons, whose edges consist of double helical DNA and whose vertices correspond to the branch points. Stiffer branched motifs can be used to produce self-assembled two-dimensional and three-dimensional periodic lattices of DNA (crystals). DNA has also been used to make a variety of nanomechanical devices, including molecules that change their shapes and molecules that can walk along a DNA sidewalk. Devices have been incorporated into two-dimensional DNA arrangements; sequence-dependent devices are driven by increases in nucleotide pairing at each step in their machine cycles. © 2010 by Annual Reviews. All rights reserved.

Hymes K.B.,New York University
Clinical Lymphoma, Myeloma and Leukemia | Year: 2010

The term epigenetics refers to modifications in gene activity that occur without directly affecting the DNA sequence, and irregularities in cellular epigenetics have been implicated in the development of a number of malignancies. As such, there is considerable interest in the anticancer effects of agents that can modify cellular epigenetics. Histone deacetylase (HDAC) inhibitors represent a class of anticancer agents that have shown promise in the treatment of both solid and hematologic malignancies. Although there are a number of HDAC inhibitors in advanced stages of clinical development, vorinostat, and more recently, romidepsin, are currently the only HDAC inhibitors approved for use. Vorinostat was approved in the United States in 2006 for the treatment of cutaneous manifestations of T-Cell lymphoma in patients with progressive, persistent, or recurrent disease on or following 2 systemic therapies. Romidepsin was approved in the United States in 2009 for the treatment of cutaneous T-Cell lymphoma (CTCL) in patients who have received ≥1 prior systemic therapy. This review aims to assess the clinical progress that vorinostat and other HDAC inhibitors have made in symptom relief and treatment of patients with CTCL and to provide practical advice for the management of associated toxicities.

Murthy A.S.,New York University
Seminars in Reproductive Medicine | Year: 2010

Obesity is increasing in prevalence worldwide. Obese women are at similar risk of unintended pregnancy as normal weight women, although limited data are available on the effects of obesity on the efficacy of contraception. Conflicting data exist regarding efficacy of oral contraceptives in obese women, although trends of oral contraceptive failure are no higher than compared with those of normal weight women. The risk of venous thromboembolism is increased with obesity, and this risk may be additive when using a combined hormonal method. Bariatric surgery can lead to increased fertility; postoperative recommendations include avoiding pregnancy in the first year. Contraceptive use patterns in these women are largely unknown. Surgeons need greater awareness of the need for use of effective long-acting methods, and consensus guidelines need to be established. © 2010 by Thieme Medical Publishers, Inc.

Parekh N.,New York University | Chandran U.,University of New Brunswick | Bandera E.V.,University of New Brunswick
Annual Review of Nutrition | Year: 2012

Although obesity is a well-known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colo-rectal cancer. We note that the evidence overrepresents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors. Copyright © 2012 by Annual Reviews. All rights reserved.

Stern D.B.,New York University
Psychoanalytic Quarterly | Year: 2012

We are used to the idea that trauma in the past interrupts our capacity to grasp the present. But present or recent trauma can have a similar dissociative effect on our capacity to experience the more distant past. Contemporary trauma can rob the past of its goodness, leaving one feeling as if the past is gone, dead, separated from the present. The vitalization of the present by the past or the past by the present requires that experiences be linked across time. These links are created, in both directions, via categories of experience characterized by shared affect (Modell 1990, 2006). Such categories are created, in turn, by metaphor; and the construction of these metaphors across time requires that one be able to occupy self states in both the past and the present that can then bear witness to one another. Trauma can result in the dissociation of these self-states from one another, leading to a disconnection of present and past. © The Psychoanalytic Quarterly, 2012.

Ganzel B.L.,Cornell University | Morris P.A.,New York University
Development and Psychopathology | Year: 2011

We previously used the theory of allostasis as the foundation for a model of the current stress process. This work highlighted the core emotional systems of the brain as the central mediator of the relationship between stress and health. In this paper, we extend this theoretical approach to consider the role of developmental timing. In doing so, we note that there are strong implicit models that underlie current developmental stress research in the social and life sciences. We endeavor to illustrate these models explicitly as we review the evidence behind each one and discuss their implications. We then extend these models to reflect recent findings from research in life span human neuroscience. The result is a new set of developmental allostatic models that provide fodder for future empirical research, as well as novel perspectives on intervention. © Cambridge University Press 2011.

Understanding exotic-native plant relationships within the context of landscape-scale environmental factors such as rainfall, topography, disturbance and forest structure, is important for distinguishing the role of invasions in native plant community change. In this study, the relationship between Lantana camara invasion and native forest understorey vegetation was described after accounting for environmental influences. Rainfall, terrain slope, altitude and fire frequency were measured from GIS layers, and tree density, dry above-ground L. camara biomass, and native plant abundance and species richness were measured in nested plots (four 1 × 1-m plots for grass, tree seedlings and L. camara within one 5-m-radius plot for tree saplings and herbs and shrubs within one 10-m-radius plot for trees) at 80 locations distributed across Bandipur Tiger Reserve, a tropical deciduous forest in southern India. Relationships between environmental factors and L. camara abundance were described using a multiple regression. Further, the role of L. camara abundance in explaining residual variation in native vegetation, after accounting for environmental influences, was described using linear models. Lantana camara abundance decreased with increasing tree density, supporting the notion that it thrives in disturbed forest with fewer trees. Whereas native tree seedling and herb and shrub density showed no relationship to L. camara abundance, both tree sapling density and grass volume decreased under L. camara biomass exceeding 2 kg m -2. These data suggest that, by association with grass decline and decreased recruitment of tree saplings, L. camara may be linked to the gradual transition of these tropical deciduous forests into exotic-dominated shrubland, and overall native biodiversity loss. © Copyright Cambridge University Press 2011.

Citrome L.,New York University
Clinical Schizophrenia and Related Psychoses | Year: 2011

Lurasidone is a second-generation antipsychotic newly approved by the U.S. Food and Drug Administration for the treatment of schizophrenia. Similar to most other second-generation antipsychotics, lurasidone is a full antagonist at dopamine D2 and serotonin 5HT2A receptors. Efficacy within the dose range of 40-120 mg/d was established in four 6-week, randomized, controlled trials. The recommended starting dose is 40 mg/d and the maximum recommended dose is 80 mg/d. Doses above 80 mg/d do not appear to confer added benefit and may be associated with a dose-related increase in certain adverse reactions such as somnolence and akathisia. Lurasidone is administered once daily with at least 350 calories of food in order to optimize bioavailability. Lurasidone is primarily metabolized in the liver through the CYP3A4 enzyme system, and coadministration with drugs that are strong inhibitors of CYP3A4 (such as ketoconazole) or strong inducers (such as rifampin) are contraindicated. Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or the ECG QT interval.

Devi L.,Nathan Kline Institute | Ohno M.,Nathan Kline Institute | Ohno M.,New York University
Neuropsychopharmacology | Year: 2012

Increasing evidence suggests that reductions in brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) may have a role in the pathogenesis of Alzheimer's disease (AD). However, the efficacy and safety profile of BDNF therapy (eg, gene delivery) remains to be established toward clinical trials. Here, we evaluated the effects of 7,8-dihydroxyflavone (7,8-DHF), a recently identified small-molecule TrkB agonist that can pass the blood-brain barrier, in the 5XFAD transgenic mouse model of AD. 5XFAD mice at 12-15 months of age and non-transgenic littermate controls received systemic administration of 7,8-DHF (5 mg/kg, i.p.) once daily for 10 consecutive days. We found that 7,8-DHF rescued memory deficits of 5XFAD mice in the spontaneous alternation Y-maze task. 5XFAD mice showed impairments in the hippocampal BDNF-TrkB pathway, as evidenced by significant reductions in BDNF, TrkB receptors, and phosphorylated TrkB. 7,8-DHF restored deficient TrkB signaling in 5XFAD mice without affecting endogenous BDNF levels. Meanwhile, 5XFAD mice exhibited elevations in the Β-secretase enzyme (BACE1) that initiates amyloid-Β (AΒ) generation, as observed in sporadic AD. Interestingly, 7,8-DHF blocked BACE1 elevations and lowered levels of the Β-secretase- cleaved C-terminal fragment of amyloid precursor protein (C99), AΒ40, and AΒ42 in 5XFAD mouse brains. Furthermore, BACE1 expression was decreased by 7,8-DHF in wild-type mice, suggesting that BDNF-TrkB signaling is also important for downregulating baseline levels of BACE1. Together, our findings indicate that TrkB activation with systemic 7,8-DHF can ameliorate AD-associated memory deficits, which may be, at least in part, attributable to reductions in BACE1 expression and Β-amyloidogenesis. © 2012 American College of Neuropsychopharmacology. All rights reserved.

Wolff E.N.,New York University
Oxford Review of Economic Policy | Year: 2014

This study investigates wealth trends from 1983 to 2010. The most telling finding is that median wealth plummeted over the years 2007-10 by 47 per cent. The inequality of net worth, after almost two decades of little movement, was up sharply between 2007 and 2010.Relative indebtedness continued to expand during the late 2000s for the middle class, though the proximate causes were declining net worth and income, rather than an increase in absolute indebtedness. The sharp fall in median net worth and the rise in its inequality from 2007 to 2010 are traceable to the high leverage of middle-class families and the high share of homes in their portfolio. The racial and ethnic disparity in wealth holdings, after remaining more or less stable from 1983 to 2007, widened considerably between 2007 and 2010. Hispanics, in particular, got hammered by the Great Recession in terms of net worth and net equity in their homes. Households under age 45 also got pummelled by the Great Recession, as their relative and absolute wealth declined sharply from 2007 to 2010. © The Author 2014. Published by Oxford University Press.

Lewis S.Z.,The American College | Diekemper R.,The American College | Addrizzo-Harris D.J.,New York University
Chest | Year: 2013

Background: The objective was to develop high-quality and comprehensive evidence-based guidelines on the diagnosis and management of lung cancer. Methods: A carefully crafted panel of lung cancer experts, methodologists, and other specialists was assembled and reviewed for relevant conflicts of interest. The American College of Chest Physicians guideline methodology was used. Population, intervention, comparator, outcome (PICO)-based key questions and defined criteria for eligible studies were developed to inform the search strategies, subsequent evidence summaries, and recommendations. Research studies, systematic reviews, and meta-analyses, where they existed, were assessed for quality and summarized to inform the recommendations. Results: Each recommendation was developed with supporting evidence and the consensus of the writing committees. Controversial recommendations were identified for further consultation by the entire panel, with anonymous voting to achieve consensus. Conclusions: The final recommendations can be trusted by health-care providers, patients, and other stakeholders since they are based on the current evidence in these areas and were developed with trustworthy processes for guideline development. Copyright © by the American College of Chest Physicians 2013.

Wyman K.M.,New York University
Harvard Environmental Law Review | Year: 2013

In recent years there have been suggestions that climate change might generate 200 million or more migrants by 2050. In response to these suggestions, and concerns that existing law and policy will be inadequate to deal with the expected displacement, there recently have been several proposals for new legally binding multilateral instruments specifically addressing climate migration. This Article makes three contributions to the nascent literature on the legal and policy responses to migration induced by climate change. First, it identifies the two principal gaps in existing law and policy that underpin to a significant extent the recent proposals for a new binding multilateral instrument, describing these gaps as the "rights" gap and the "funding" gap. Second, this Article analyzes three of the leading proposals for a new binding multilateral instrument. It identifies the ways that these proposals would respond to the rights and funding gaps and emphasizes the proposals' limitations Third, this Article emphasizes that addressing climate migration ultimately requires increasing the resilience of communities especially vulnerable to climate change. It then identifies ways to mitigate the effects of the rights and funding gaps by reducing existing vulnerabilities to climate change, without a new binding multilateral instrument. While a series of measures relying largely on existing legal and policy tools may seem less satisfying than proposals for a new binding multilateral instrument, these measures are more likely to address the concerns about human vulnerability to climate change that the proposals for new binding multilateral instruments have admirably highlighted.

This paper proves a long-standing conjecture regarding the optimal design of the M/M/s queue. The classical Erlang delay formula is shown to be a convex function of the number of servers when the server utilization is held constant. This means that when the server utilization is held constant, the marginal decrease in the probability that all servers are busy in the M/M/s queue brought about by the addition of two extra servers is always less than twice the decrease brought about by the addition of one extra server. As a consequence, a method of marginal analysis yields the optimal number of servers that minimize the waiting and service costs when the server utilization is held constant. In addition, it is shown that the expected number of customers in the queue and in the system, as well as the expected waiting time and sojourn in the M/M/s queue, are convex in the number of servers when the server utilization is held constant. These results are useful in design studies involving capacity planning in service operations. The classical Erlang loss formula is also shown to be a convex function of the number of servers when the server utilization is held constant. © 2011 INFORMS.

Cooper P.,New York University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We demonstrate a bijection between reparametrization invariant effective actions for relativistic p-branes in flat target space and effective actions for transverse brane perturbations with nonlinearly realized Poincaré symmetry. Starting with an action with nonlinearly realized symmetry, we construct the corresponding reparametrization invariant action by introducing Stückelberg fields. They combine with the transverse modes to form a Lorentz vector. The manifest Lorentz symmetry of the reparametrization invariant action follows directly from the nonlinearly realized Lorentz symmetry of the initial action in terms of the physical modes. © 2013 American Physical Society.

Yu T.-Q.,New York University | Tuckerman M.E.,Courant Institute of Mathematical Sciences
Physical Review Letters | Year: 2011

The ability of certain organic molecules to form multiple crystal structures, known as polymorphism, has important ramifications for pharmaceuticals and high energy materials. Here, we introduce an efficient molecular dynamics method for rapidly identifying and thermodynamically ranking polymorphs. The new method employs high temperature and adiabatic decoupling to the simulation cell parameters in order to sample the Gibbs free energy of the polymorphs. Polymorphism in solid benzene is revisited, and a resolution to a long-standing controversy concerning the benzene II structure is proposed. © 2011 American Physical Society.

Troy A.S.,Franklin And Marshall College | Shallcross A.J.,New York University | Mauss I.B.,University of California at Berkeley
Psychological Science | Year: 2013

Emotion regulation is central to psychological health. For instance, cognitive reappraisal (reframing an emotional situation) is generally an adaptive emotion-regulation strategy (i.e., it is associated with increased psychological health). However, a person-by-situation approach suggests that the adaptiveness of different emotion-regulation strategies depends on the context in which they are used. Specifically, reappraisal may be adaptive when stressors are uncontrollable (when the person can regulate only the self) but maladaptive when stressors can be controlled (when the person can change the situation). To test this prediction, we measured cognitive-reappraisal ability, the severity of recent life stressors, stressor controllability, and level of depression in 170 participants. For participants with uncontrollable stress, higher cognitive-reappraisal ability was associated with lower levels of depression. In contrast, for participants with controllable stress, higher cognitive-reappraisal ability was associated with greater levels of depression. These findings support a theoretical model in which particular emotion-regulation strategies are not adaptive or maladaptive per se; rather, their adaptiveness depends on the context. © The Author(s) 2013.

Zwanziger D.,New York University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Recent numerical studies of the gluon propagator in the minimal Landau and Coulomb gauges in space-time dimension two, three, and four pose a challenge to the Gribov confinement scenario. In these gauges all configurations are transverse, ∂·A=0, and lie inside the Gribov region Ω, where the Faddeev-Popov operator, M(A)=-∂μDμ(A), is positive, that is, (ψ,M(A)ψ)≥0 for all ψ. We prove, without approximation, that for these gauges the continuum gluon propagator D(k) in SU(N) gauge theory satisfies the bound d-1d1(2π)d∫ddkD(k)k2≤N. This holds for the Landau gauge, in which case d is the dimension of space-time, and for the Coulomb gauge, in which case d is the dimension of ordinary space and D(k) is the instantaneous spatial gluon propagator. This bound implies that lim kd-2D(k)=0, where D(k) is the gluon propagator at momentum k, and consequently D(0)=0 in the Landau gauge in space-time d=2 and in the Coulomb gauge in space dimension d=2, but D(0) may be finite in higher dimensions. These results are compatible with numerical studies of the Landau-and Coulomb-gauge propagator. In four-dimensional space-time a regularization is required, and we also prove an analogous bound on the lattice gluon propagator, 1d(2π)d∫-ππddkΣμcos-2(k μ/2)Dμμ(k)4Σλsin -2(kλ/2)≤N. Here we have taken the infinite-volume limit of lattice gauge theory at fixed lattice spacing, and the lattice momentum componant kμ is a continuous angle, -π≤kμ≤π. Unexpectedly, this implies a bound on a renormalization-group invariant that governs the overall normalization of the continuum gluon propagator in the minimum Landau and Coulomb gauges in four space-time dimensions, which, moreover, is compatible with the perturbative renormalization group when the theory is asymptotically free. © 2013 American Physical Society.

De Rham C.,University of Geneva | Gabadadze G.,New York University | Tolley A.J.,Case Western Reserve University
Physical Review Letters | Year: 2011

We construct four-dimensional covariant nonlinear theories of massive gravity which are ghost-free in the decoupling limit to all orders. These theories resum explicitly all the nonlinear terms of an effective field theory of massive gravity. We show that away from the decoupling limit the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order. We also show that the same remains true to all orders in a similar toy model. © 2011 American Physical Society.

Dhar V.,New York University
Communications of the ACM | Year: 2013

Vasant Dhar states that data science or big data is gaining increasing significance with the potential of providing automated actionable knowledge creation and predictive models for use by both humans and computers. Data science implies a focus involving data and the systematic study of the organization, properties, and analysis of data and its role in inference, including confidence in the inference. Data science is different from statistics and other existing disciplines in several important ways. The emphasis on prediction is particularly strong in the machine learning and knowledge discovery in databases, or KDD, communities. The emphasis on predictive accuracy implicitly favors 'simple' theories over more complex theories in that the accuracy of sparser models tends to be more robust on future data. The requirement on predictive accuracy on observations that will occur in the future is a key consideration in data science.

Loeb A.,Harvard University | Weiner N.,New York University | Weiner N.,Institute for Advanced Study
Physical Review Letters | Year: 2011

We show that cold dark matter particles interacting through a Yukawa potential could naturally explain the recently observed cores in dwarf galaxies without affecting the dynamics of objects with a much larger velocity dispersion, such as clusters of galaxies. The velocity dependence of the associated cross section as well as the possible exothermic nature of the interaction alleviates earlier concerns about strongly interacting dark matter. Dark matter evaporation in low-mass objects might explain the observed deficit of satellite galaxies in the Milky Way halo and have important implications for the first galaxies and reionization. © 2011 American Physical Society.

Badr H.,Mount Sinai School of Medicine | Krebs P.,New York University
Psycho-Oncology | Year: 2013

Objective Quality of life (QOL) is a multidimensional construct that includes physical, psychological, and relationship well-being. Methods We conducted a systematic review and meta-analysis of randomized controlled studies published between 1980 and 2012 of interventions conducted with both cancer patients and their partners that were aimed at improving QOL. Using bibliographic software and manual review, two independent raters reviewed 752 articles with a systematic process for reconciling disagreement, yielding 23 articles for systematic review and 20 for meta-analysis. Results Most studies were conducted in breast and prostate cancer populations. Study participants (N = 2645) were primarily middle aged (mean = 55 years old) and white (84%). For patients, the weighted average effect size (g) across studies was 0.25 (95% CI = 0.12-0.32) for psychological outcomes (17 studies), 0.31 (95% CI = 0.11-0.50) for physical outcomes (12 studies), and 0.28 (95% CI = 0.14-0.43) for relationship outcomes (10 studies). For partners, the weighted average effect size was 0.21 (95% CI = 0.08-0.34) for psychological outcomes (12 studies) and 0.24 (95% CI = 0.6-0.43) for relationship outcomes (7 studies). Conclusion Therefore, couple-based interventions had small but beneficial effects in terms of improving multiple aspects of QOL for both patients and their partners. Questions remain regarding when such interventions should be delivered and for how long. Identifying theoretically based mediators and key features that distinguish couple-based from patient-only interventions may help strengthen their effects on patient and partner QOL. Copyright © 2012 John Wiley & Sons, Ltd.

Megibow A.J.,New York University
Radiologic Clinics of North America | Year: 2012

The vast array of possible histologies for a given pancreatic mass makes the specific diagnosis of a solid pancreatic mass in an individual patient challenging. This article discusses and reviews the imaging findings of those entities that are likely to be encountered in clinical practice, specifically pancreatic endocrine tumors, solid pseudopapillary tumor, secondary pancreatic masses, and heterotopic spleen. © 2012 Elsevier Inc.

Schmidt B.L.,New York University
Pain | Year: 2015

Cancer pain sends a message. It is frightening to the patient. It heralds progression or recurrence to the oncologist. It is a biological readout of the cancer-nerve interaction for the scientist. Nerves have been considered bystanders within the cancer microenvironment. However, emerging information suggests that nerves are recruited and participate in the carcinogenic process. These newly formed fibers respond to mediators secreted by constituents of the cancer microenvironment. In this manner, these nerves serve as bellwethers and sensors embedded within the cancer. When we rigorously assess patients' cancer pain, we gain insight into the action of cancer. An enhanced understanding of cancer pain offers biological questions that if answered might not only provide relief from cancer pain but might also improve survival.

Siolas D.,New York University | Hannon G.J.,Howard Hughes Medical Institute
Cancer Research | Year: 2013

Tumor graft models (also known as patient-derived xenografts or PDX) are based on the transfer of primary tumors directly from the patient into an immunodeficient mouse. Because PDX mice are derived from human tumors, they offer a tool for developing anticancer therapies and personalizedmedicine for patients with cancer. In addition, these models can be used to study metastasis and tumor genetic evolution. This review examines the development, challenges, and broad use of these attractive preclinical models. ©2013 AACR.

Ouimet M.,New York University
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2013

The incidence of diseases characterized by a dysregulation of lipid metabolism such as obesity, diabetes and atherosclerosis is rising at alarming rates, driving research to uncover new therapies to manage dyslipidemias and resolve the metabolic syndrome conundrum. Autophagy and lipid homeostasis - both ancient cellular pathways - have seemingly co-evolved to share common regulatory elements, and autophagy has emerged as a prominent mechanism involved in the regulation of lipid metabolism. This review highlights recent findings on the role of autophagy in the regulation of cellular cholesterol homeostasis and lipoprotein metabolism, with special emphasis on macrophages. From modulation of inflammation to regulation of cellular cholesterol levels, a protective role for autophagy in atherosclerosis is emerging. The manipulation of autophagic activity represents a new possible therapeutic approach for the treatment complex metabolic disorders such as obesity and the metabolic syndrome. © 2013 Elsevier B.V.

Yoshihara H.,New York University
European Spine Journal | Year: 2012

Recently, the sacroiliac joint (SIJ) has gained increased attention as a source of persistent or new pain after lumbar/lumbosacral fusion. The underlying pathophysiology of SIJ pain may be increased mechanical load, iliac crest bone grafting, or a misdiagnosis of SIJ syndrome. Imaging studies show more frequent degeneration of the SIJ in patients with lumbar/lumbosacral fusion than in patients without such fusion. Using injection tests, it has been shown that SIJ pain is the cause of persistent symptoms in a considerable number of patients after fusion surgery. Recent articles reporting on surgical outcomes of SIJ fusion include a high percentage of patients who had lumbar/lumbosacral fusion or surgery before, although well-controlled clinical studies are necessary to assess the efficacy of surgical treatment. Taking these findings into consideration, the possibility that the SIJ is the source of pain should be considered in patients with failed back surgery syndrome after lumbar/lumbosacral fusion. © Springer-Verlag 2012.

Blaser M.J.,New York University | Blaser M.J.,New York Harbor Medical Center
Science | Year: 2016

Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.

D'Eustachio P.,New York University
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The Reactome Knowledgebase is an online, manually curated resource that provides an integrated view of the molecular details of human biological processes that range from metabolism to DNA replication and repair to signaling cascades. Its data model allows these diverse processes to be represented in a consistent way to facilitate usage as online text and as a resource for data mining, modeling, and analysis of large-scale expression data sets over the full range of human biological processes.

Alabi A.A.,Stanford Institute for Neuro Innovation and Translational Neurosciences | Tsien R.W.,New York University
Annual Review of Physiology | Year: 2013

Regulated exocytosis and endocytosis are critical to the function of many intercellular networks, particularly the complex neural circuits underlying mammalian behavior. Kiss-and-run (KR) is an unconventional fusion between secretory vesicles and a target membrane that releases intravesicular content through a transient, nanometer-sized fusion pore. The fusing vesicle retains its gross shape, precluding full integration into the planar membrane, and enough molecular components for rapid retrieval, reacidification, and reuse. KR makes judicious use of finite presynaptic resources, and mounting evidence suggests that it influences synaptic information transfer. Here we detail emerging perspectives on KR and its role in neurotransmission. We additionally formulate a restraining force hypothesis as a plausible mechanistic basis for KR and its physiological modulation in small nerve terminals. Clarification of the mechanism and function of KR has bearing on understanding the kinetic transitions underlying SNARE-mediated fusion, interactions between vesicles and their local environment, and the influence of release dynamics on neural information processing. Copyright © 2013 by Annual Reviews. All rights reserved.

Barcellos-Hoff M.H.,New York University
Journal of Mammary Gland Biology and Neoplasia | Year: 2013

Radiation exposure is a well-documented risk factor for breast cancer in women. Compelling epidemiological evidence in different exposed populations around the world demonstrate that excess breast cancer increases with radiation doses above 10 cGy. Both frequency and type of breast cancer are affected by prior radiation exposure. Many epidemiological studies suggest that radiation risk is inversely related to age at exposure; exposure during puberty poses the greatest risk while exposures past the menopause appear to carry very low risk. These observations are supported by experimental studies in mice and rats, which together provide the basis for the pubertal 'window of susceptibility' hypothesis for carcinogenic exposure. One line of experimental investigation suggests that the pubertal epithelium is more sensitive because DNA damage responses are less efficient, an other suggests that radiation affects stem cells self-renewal. A recent line of investigation suggests that the irradiated microenvironment mediates cancer risk. Studying the biological basis for radiation effects provides potential routes for protection in vulnerable populations, which include survivors of childhood cancers, as well as insights into the biology for certain types of sporadic cancer. © 2013 Springer Science+Business Media New York.

Hegde D.,New York University
Nature Biotechnology | Year: 2012

Despite recent patent law reforms, the US Patent and Trademark Office's ability to deal with inefficiencies in patent examination will continue to rely on the annual Congressional appropriations process. © 2012 Nature America, Inc. All rights reserved.

Tenner S.,New York University | Baillie J.,Carteret MedicalGroup | Dewitt J.,Indiana University | Vege S.S.,Mayo Medical School
American Journal of Gastroenterology | Year: 2013

This guideline presents recommendations for the management of patients with acute pancreatitis (AP). During the past decade, there have been new understandings and developments in the diagnosis, etiology, and early and late management of the disease. As the diagnosis of AP is most often established by clinical symptoms and laboratory testing, contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically. Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed. Patients with organ failure and/or the systemic inflammatory response syndrome (SIRS) should be admitted to an intensive care unit or intermediary care setting whenever possible. Aggressive hydration should be provided to all patients, unless cardiovascular and/or renal comorbidites preclude it. Early aggressive intravenous hydration is most beneficial within the first 12-24 h, and may have little benefit beyond. Patients with AP and concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography (ERCP) within 24 h of admission. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to lower the risk of severe post-ERCP pancreatitis in high-risk patients. Routine use of prophylactic antibiotics in patients with severe AP and/or sterile necrosis is not recommended. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis may be useful in delaying intervention, thus decreasing morbidity and mortality. In mild AP, oral feedings can be started immediately if there is no nausea and vomiting. In severe AP, enteral nutrition is recommended to prevent infectious complications, whereas parenteral nutrition should be avoided. Asymptomatic pancreatic and/or extrapancreatic necrosis and/or pseudocysts do not warrant intervention regardless of size, location, and/or extension. In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed, preferably for 4 weeks, to allow the development of a wall around the necrosis. © 2013 by the American College of Gastroenterology.

Bello J.P.,New York University
IEEE Transactions on Audio, Speech and Language Processing | Year: 2011

This paper presents a novel method for measuring the structural similarity between music recordings. It uses recurrence plot analysis to characterize patterns of repetition in the feature sequence, and the normalized compression distance, a practical approximation of the joint Kolmogorov complexity, to measure the pairwise similarity between the plots. By measuring the distance between intermediate representations of signal structure, the proposed method departs from common approaches to music structure analysis which assume a block-based model of music, and thus concentrate on segmenting and clustering sections. The approach ensures that global structure is consistently and robustly characterized in the presence of tempo, instrumentation, and key changes, while the used metric provides a simple to compute, versatile and robust alternative to common approaches in music similarity research. Finally, experimental results demonstrate success at characterizing similarity, while contributing an optimal parameterization of the proposed approach. © 2006 IEEE.

Yan D.,SUNY Upstate Medical University | Hutchison R.E.,New York University | Mohi G.,SUNY Upstate Medical University
Blood | Year: 2012

The JAK2V617F mutation has been identified in most cases of Ph-negative myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Expression of JAK2V617F results in constitutive activation of multiple signaling molecules/pathways. However, the key signaling downstream of JAK2V617F required for transformation and induction of MPNs remains elusive. Using a mouse genetic strategy, we show here that Stat5 is absolutely required for the pathogenesis of PV induced by Jak2V617F. Whereas expression of Jak2V617F in mice resulted in all the features of human PV, including an increase in red blood cells, hemoglobin, hematocrit, white blood cells, platelets, and splenomegaly, deletion of Stat5 in the Jak2V617F knockin mice normalized all the blood parameters and the spleen size. Furthermore, deletion of Stat5 completely abrogated erythropoietin (Epo)-independent erythroid colony formation evoked by Jak2V617F, a hallmark feature of PV. Re-expression of Stat5 in Stat5-deficient Jak2V617F knockin mice completely rescued the defects in transformation of hematopoietic progenitors and the PV phenotype. Together, these results indicate a critical function for Stat5 in the pathogenesis of PV. These findings also provide strong support for the development of Stat5 inhibitors as targeted therapies for the treatment of PV and other JAK2V617F-positive MPNs. © 2012 by The American Society of Hematology.

Weintraub D.,University of Pennsylvania | Nirenberg M.J.,New York University
Neurodegenerative Diseases | Year: 2013

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized complication of dopamine replacement therapy in Parkinson's disease (PD). Other impulsive-compulsive behaviors have been linked to dopaminergic medications; these include punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), particularly at higher dosages; in contrast, DDS is primarily associated with shorter-Acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Risk factors for ICDs may include male sex; younger age; younger age at PD onset; a pre-PD history of ICD(s); personal or family history of substance abuse; bipolar disorder; gambling problems; and impulsive personality traits. The primary treatment of ICDs in PD is discontinuation of DA therapy. Not all patients can tolerate this, however, due to worsening motor symptoms and/or DA withdrawal syndrome (a severe, stereotyped drug withdrawal syndrome similar to that of other psychostimulants). While psychiatric medications are frequently used to treat ICDs in the general population, there is no empirical evidence to suggest that they are effective in PD. Given the paucity of treatment options and potentially serious consequences of ICDs in PD, it is critical for patients to be monitored closely for their development. As empirically validated treatments for ICDs emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD. Copyright © 2012 S. Karger AG, Basel.

Mitra A.,New York University | Giamarchi T.,University of Geneva
Physical Review Letters | Year: 2011

An interaction quench in a Luttinger liquid can drive it into an athermal steady state. We analyze the effects on such an out of equilibrium state of a mode coupling term due to a periodic potential. Employing a perturbative renormalization group approach we show that even when the periodic potential is an irrelevant perturbation in equilibrium, it has important consequences on the athermal steady state as it generates a temperature as well as a dissipation and hence a finite lifetime for the bosonic modes. © 2011 American Physical Society.

Pothuri B.,New York University
Annals of Oncology | Year: 2013

Ovarian cancer is the deadliest among gynecologic cancers. Hereditary cancer related to BRCA1/2 gene mutations account for ~10%-12% of ovarian cancers. The BRCA1/2 proteins are important in homologous recombination (HR)repair of DNA. Patients with BRCA1/2 mutations have been reported to have improved chemosensitivity to platinum agents, longer disease-free intervals, and longer survivals than nonhereditary counterparts. Recent interest in poly(ADPribosyl) polymerase (PARP) proteins which are key components of base excision repair, has led to the development of PARP inhibitors; tumors arising in BRCA1/2 mutation carriers and/or with HR deficiency (HRD) are particularly sensitive to the action of these drugs. As 60%-80% of all advanced ovarian cancers are high-grade serous type, exhibiting HRD in at least 50% (referred as BRCAness) future antitumor strategies may depend on identifying these defects through molecular testing. Once HRD becomes amenable to routine testing, a larger group of ovarian cancer patients than are currently considered for PARP inhibitor trials, may benefit from such targeted therapy. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Lebovitz H.E.,New York University
Obesity Surgery | Year: 2013

Is bariatric surgery as primary therapy for type 2 diabetes mellitus (T2DM) with body mass index (BMI) <35 kg/m2 justified? Open-label studies have shown that bariatric surgery causes remission of diabetes in some patients with BMI <35 kg/m2. All such patients treated had substantial weight loss. Diabetes remission was less likely in patients with lower BMI than those with higher BMI, in patients with longer than shorter duration and in patients with lesser than greater insulin reserve. Relapse of diabetes increases with time after surgery and weight regain. Deficiencies of data are lack of randomized long-term studies comparing risk/benefit of bariatric surgery to contemporary intensive medical therapy. Current data do not justify bariatric surgery as primary therapy for T2DM with BMI <35 kg/m 2. © 2013 The Author(s).

Wilkens S.,New York University
F1000Prime Reports | Year: 2015

All living organisms depend on primary and secondary membrane transport for the supply of external nutrients and removal or sequestration of unwanted (toxic) compounds. Due to the chemical diversity of cellular molecules, it comes as no surprise that a significant part of the proteome is dedicated to the active transport of cargo across the plasma membrane or the membranes of subcellular organelles. Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy of the chemical gradient of another molecule (secondary transport). Primary transporters include the rotary motor ATPases (F-, A-, and V-ATPases), P-type ATPases and a large family of integral membrane proteins referred to as "ABC" (ATP-binding cassette) transporters. ABC transporters are widespread in all forms of life and are characterized by two nucleotide-binding domains (NBD) and two transmembrane domains (TMDs). ATP hydrolysis on the NBD drives conformational changes in the TMD, resulting in alternating access from inside and outside of the cell for unidirectional transport across the lipid bilayer. Common to all ABC transporters is a signature sequence or motif, LSGGQ, that is involved in nucleotide binding. Both importing and exporting ABC transporters are found in bacteria, whereas the majority of eukaryotic family members function in the direction of export. Recent progress with the X-ray crystal structure determination of a variety of bacterial and eukaryotic ABC transporters has helped to advance our understanding of the ATP hydrolysis-driven transport mechanism but has also illustrated the large structural and functional diversity within the family. © 2015 Faculty of 1000 Ltd.

Motivation: The formation of aragonite mineral in the mollusk shell or pearl nacre requires the participation of a diverse set of proteins that form the mineralized extracellular matrix. Although self-assembly processes have been identified for several nacre proteins, these proteins do not contain known globular protein-protein binding domains. Thus, we hypothesize that other sequence features are responsible for nacre matrix protein-protein assembly processes and ultimately aragonite biosynthesis.Results: Of 39 mollusk aragonite-associated protein sequences, 100% contain at least one region of intrinsic disorder or unfolding, with the highest percentages found in framework and pearl-associated proteins relative to the intracrystalline proteins. In some instances, these intrinsically disordered regions were identified as bind/fold sequences, and a limited number correlate with known biomineral-relevant sequences. Interestingly, 95% of the aragonite-associated protein sequences were found to contain at least one occurrence of amyloid-like or cross-β strand aggregation-prone supersecondary motifs, and this correlates with known aggregation and aragonite formation functions in three experimentally tested protein sequences. Collectively, our findings indicate that aragonite-associated proteins have evolved signature sequence traits of intrinsic disorder and aggregation-prone regions that are important for their role(s) in matrix assembly and mineralization. © 2012 The Author.

Sacktor T.C.,New York University
Molecular Brain | Year: 2012

Long-term memory is believed to be maintained by persistent modifications of synaptic transmission within the neural circuits that mediate behavior. Thus, long-term potentiation (LTP) is widely studied as a potential physiological basis for the persistent enhancement of synaptic strength that might sustain memory. Whereas the molecular mechanisms that initially induce LTP have been extensively characterized, the mechanisms that persistently maintain the potentiation have not. Recently, however, a candidate molecular mechanism linking the maintenance of LTP and the storage of long-term memory has been identified. The persistent activity of the autonomously active, atypical protein kinase C (aPKC) isoform, PKMζ, is both necessary and sufficient for maintaining LTP. Furthermore, blocking PKMζ activity by pharmacological or dominant negative inhibitors disrupts previously stored long-term memories in a variety of neural circuits, including spatial and trace memories in the hippocampus, aversive memories in the basolateral amygdala, appetitive memories in the nucleus accumbens, habit memory in the dorsal lateral striatum, and elementary associations, extinction, and skilled sensorimotor memories in the neocortex. During LTP and memory formation, PKMζ is synthesized de novo as a constitutively active kinase. This molecular mechanism for memory storage is evolutionarily conserved. PKMζ formation through new protein synthesis likely originated in early vertebrates ∼500 million years ago during the Cambrian period. Other mechanisms for forming persistently active PKM from aPKC are found in invertebrates, and inhibiting this atypical PKM disrupts long-term memory in the invertebrate model systems Drosophila melanogaster and Aplysia californica. Conversely, overexpressing PKMζ enhances memory in flies and rodents. PKMζ persistently enhances synaptic strength by maintaining increased numbers of AMPA receptors at postsynaptic sites, a mechanism that might have evolved from the general function of aPKC in trafficking membrane proteins to the apical compartment of polarized cells. This mechanism of memory may have had adaptive advantages because it is both stable and reversible, as demonstrated by the downregulation of experience-dependent, long-term increases in PKMζ after extinction and reconsolidation blockade that attenuate learned behavior. Thus, PKMζ, the "working end" of LTP, is a component of an evolutionarily conserved molecular mechanism for the persistent, yet flexible storage of long-term memory. © 2012 Sacktor; licensee BioMed Central Ltd.

Salzer J.L.,New York University
Journal of the peripheral nervous system : JPNS | Year: 2012

Axons in the vertebrate peripheral nervous system are intimately associated with Schwann cells. Axons regulate the Schwann cell phenotype, determining whether they myelinate individual axons or ensheathe multiple, small axons in Remak bundles. Our current understanding of the axonal signals that drive Schwann cells towards these distinct morphological and phenotypic fates is briefly reviewed here. Elucidation of these signals, and the intracellular pathways they regulate, may lead to new, rational therapies for the treatment of inherited and acquired neuropathies. © 2012 Peripheral Nerve Society.

Aggarwal S.K.,New York University
Clinical Journal of Pain | Year: 2013

This article attempts to cover pragmatic clinical considerations involved in the use of cannabinergic medicines in pain practice, including geographical and historical considerations, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, indications, and contraindications. Topics include molecular considerations such as the 10-fold greater abundance of cannabinoid type 1 receptors compared to μ-opioid receptors in the central nervous system and anatomic distributions of cannabinoid receptors in pain circuits. METHODS:: The article uses a narrative review methodology drawing from authoritative textbooks and journals of cannabinoid medicine, Food and Drug Administration-approved cannabinoid drug labels, and current and historical pain medicine literature to address core clinical considerations. To survey the current evidence base for pain management with cannabinergic medicines, a targeted PubMed search was performed to survey the percentage of positive and negative published randomized-controlled trial (RCT) results with this class of pain medicines, using appropriate search limit parameters and the keyword search string "cannabinoid OR cannabis-based AND pain." RESULTS:: Of the 56 hits generated, 38 published RCTs met the survey criteria. Of these, 71% (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain-relieving effects, whereas 29% (11) did not. DISCUSSION:: Cannabis and other cannabinergic medicines' efficacies for relieving pain have been studied in RCTs, most of which have demonstrated a beneficial effect for this indication, although most trials are short-term. Adverse effects are generally nonserious and well tolerated. Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate. © 2013 by Lippincott Williams and Wilkins.

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

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

Gonzalez M.E.,New York University
Seminars in Perinatology | Year: 2013

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin diseases characterized by increased skin fragility and variable degrees of extracutaneous involvement. The clinical spectrum ranges from localized skin disease to a life-threatening and disabling disease with extensive extracutaneous involvement. All four major types of EB, namely EB simplex, Junctional EB, Dystrophic EB and Kindler syndrome, can present with blistering and erosions at birth and cannot be distinguished clinically in the newborn period. The extensive differential diagnosis of blistering and erosions in the neonate must be considered and common etiologies ruled out. The diagnosis of EB can be confirmed via a skin biopsy for immunoflourescence mapping. This review discusses the four major subtypes of EB and their associated extracutaneous features. The evaluation of a newborn suspected of having EB, including diagnosis and management, is also reviewed. © 2013 Elsevier Inc.

Blum R.,New York University
Journal of Cellular Biochemistry | Year: 2014

The early 1980s revelation of cis-acting genomic elements, known as transcriptional enhancers, is still regarded as one of the fundamental discoveries in the genomic field. However, only with the emergence of genome-wide techniques has the genuine biological scope of enhancers begun to be fully uncovered. Massive scientific efforts of multiple laboratories rapidly advanced the overall perception that enhancers are typified by common epigenetic characteristics that distinguish their activating potential. Broadly, chromatin modifiers and transcriptional regulators lay down the essential foundations necessary for constituting enhancers in their activated form. Basing on genome-wide ChIP-sequencing of enhancer-related marks we identified myogenic enhancers before and after muscle differentiation and discovered that MyoD was bound to nearly a third of condition-specific enhancers. Experimental studies that tested the deposition patterns of enhancer-related epigenetic marks in MyoD-null myoblasts revealed the high dependency that a specific set of muscle enhancers have towards this transcriptional regulator. Re-expression of MyoD restored the deposition of enhancer-related marks at myotube-specific enhancers and partially at myoblasts-specific enhancers. Our proposed mechanistic model suggests that MyoD is involved in recruitment of methyltransferase Set7, acetyltransferase p300 and deposition of H3K4me1 and H3K27ac at myogenic enhancers. In addition, MyoD binding at enhancers is associated with PolII occupancy and with local noncoding transcription. Modulation of muscle enhancers is suggested to be coordinated via transcription factors docking, including c-Jun and Jdp2 that bind to muscle enhancers in a MyoD-dependent manner. We hypothesize that distinct transcription factors may act as placeholders and mediate the assembly of newly formed myogenic enhancers. © 2014 Wiley Periodicals, Inc.

Pola J.,New York University
Vision Research | Year: 2011

A large number of experiments show that perisaccadic flash mislocalization can vary according to the spatial location of the flash relative to the saccade, especially in the presence of background stimuli. The temporal attributes of this mislocalization suggest that, around the time of a saccade, a transient compression of visual space occurs. The present study offers a model to account for such compression. A basic aspect of the model is that the mislocalization is a consequence of flash retinal signal persistence interacting with an extraretinal signal. Of central importance, however, the model suggests that the extraretinal signal is different when a saccade occurs in the dark from when a saccade occurs with background stimuli. In the dark, the extraretinal signal begins to change with little or no time difference from one retinal locus to another, resulting in little or no compression. However, in the presence of background stimuli, the extraretinal signal begins at considerably different times across the retina, giving rise to a large amount of compression. © 2010 Elsevier Ltd.

Amodio D.M.,New York University
Nature Reviews Neuroscience | Year: 2014

Despite global increases in diversity, social prejudices continue to fuel intergroup conflict, disparities and discrimination. Moreover, as norms have become more egalitarian, prejudices seem to have 'gone underground', operating covertly and often unconsciously, such that they are difficult to detect and control. Neuroscientists have recently begun to probe the neural basis of prejudice and stereotyping in an effort to identify the processes through which these biases form, influence behaviour and are regulated. This research aims to elucidate basic mechanisms of the social brain while advancing our understanding of intergroup bias in social behaviour. © 2014 Macmillan Publishers Limited. All rights reserved.

Luo H.,CAS Institute of Biophysics | Liu Z.,CAS Institute of Biophysics | Poeppel D.,New York University
PLoS Biology | Year: 2010

Integrating information across sensory domains to construct a unified representation of multi-sensory signals is a fundamental characteristic of perception in ecological contexts. One provocative hypothesis deriving from neurophysiology suggests that there exists early and direct cross-modal phase modulation. We provide evidence, based on magnetoencephalography (MEG) recordings from participants viewing audiovisual movies, that low-frequency neuronal information lies at the basis of the synergistic coordination of information across auditory and visual streams. In particular, the phase of the 2-7 Hz delta and theta band responses carries robust (in single trials) and usable information (for parsing the temporal structure) about stimulus dynamics in both sensory modalities concurrently. These experiments are the first to show in humans that a particular cortical mechanism, delta-theta phase modulation across early sensory areas, plays an important "active" role in continuously tracking naturalistic audio-visual streams, carrying dynamic multi-sensory information, and reflecting cross-sensory interaction in real time. © 2010 Luo et al.

Type 2 diabetes and other non-communicable diseases (NCD) are a growing public health challenge globally. An estimated 285 million people, corresponding to 6.4 % of the world's adult population has diabetes. This is expected to reach 552 million by 2030, 7.8 % of the adult population, with the African region expected to experience the greatest increase. A much larger segment of the world's population, approximating 79 million individuals in the US alone, has prediabetes. Multiple factors including genetic predisposition, insulin resistance, increased insulin secretory demand, glucotoxicity, lipotoxicity, impaired incretin release/action, amylin accumulation, and decreased β-cell mass play a causative role in the progressive β-cell dysfunction characteristic of prediabetes. Interventions preventing progression to type 2 diabetes should therefore delay or prevent β-cell failure. This article will first review the principal pathophysiological mechanisms underlying prediabetes and subsequently address treatment considerations based on these in the prevention of type 2 diabetes. In view of long-standing safety data with demonstrated efficacy and cost-effectiveness in the prevention of type 2 diabetes in high-risk individuals, metformin should be considered as initial therapy for those unable to comply with or lifestyle modification or where the latter has been ineffective in decreasing progression to type 2 diabetes. © 2012 Springer Science+Business Media New York.

Jamieson D.,New York University
Climatic Change | Year: 2013

In this paper I discuss the nature of geoengineering, some of its attractions, and some reasons for concern. I claim that there is confusion in the use of the term 'geoengineering' that is related to larger concerns about the language in which responses to climate change are discussed. I conclude that despite some reasonable grounds for suspicion, research in areas that involve carbon dioxide removal and solar radiation management should go on as part of the general portfolio of climate-related research, competing with the full panoply of other possible responses to climate change. © 2013 Springer Science+Business Media Dordrecht.

Grepin K.A.,New York University
Journal of Acquired Immune Deficiency Syndromes | Year: 2011

Over the past decade, HIV programs have been successfully scaled up in many developing countries, leading some to wonder how the investments made into HIV infrastructure could be leveraged to deliver additional health services. Although the concept is appealing from many perspectives, integrating additional health services into existing vertical HIV infrastructure may not mitigate some of the challenges these programs have introduced in implementing countries. In addition, this approach to integration may countervail parallel efforts of the global health community to strengthen health systems and improve aid effectiveness. It might also undermine the HIV programs themselves. International donors and health system planners should carefully consider whether the benefits outweigh the potential costs of these well-intentioned integration efforts. © 2011 by Lippincott Williams & Wilkins.

Ma T.,New York University
Journal of Alzheimer's Disease | Year: 2014

Understanding the molecular signaling pathways that go awry in Alzheimer's disease (AD) would provide insights into developing novel therapies for this devastating neurodegenerative disease. Previous work has established that hyperactive glycogen synthase kinase-3 (GSK3) is linked to both "sporadic" and "genetic" forms of AD, suggesting a crucial role of GSK3 in AD pathogenesis. Therefore, inhibition of GSK3 activity has been intensely investigated as a potential therapeutic intervention for AD. GSK3 exists in two isoforms: GSK3α and GSK3β. Markedly, recent studies indicate specific contributions of each of the α and β isoforms of GSK3 to AD pathogenesis, suggesting a role of both isoforms in the disease. Here I review recent relevant work investigating isoform-specific roles of GSK3 in AD pathophysiology, highlighting the emerging role of GSK3α, which has been largely overlooked in favor of the more extensive studies of GSK3β. © 2014-IOS Press and the authors. All rights reserved.

Stein R.A.,New York University
International Journal of Clinical Practice | Year: 2014

A major biomedical advance from recent years was the finding that gene expression and phenotypic traits may be shaped by potentially reversible and heritable modifications that occur without altering the sequence of the nucleotides, and became known as epigenetic changes. The term 'epigenetics' dates back to the 1940s, when it was first used in context of cellular differentiation decisions that are made during development. Since then, our understanding of epigenetic modifications that govern development and disease expanded considerably. The contribution of epigenetic changes to shaping phenotypes brings at least two major clinically relevant benefits. One of these, stemming from the reversibility of epigenetic changes, involves the possibility to therapeutically revert epigenetic marks to re-establish prior gene expression patterns. The strength and the potential of this strategy are illustrated by the first four epigenetic drugs that were approved in recent years and by the additional candidates that are at various stages in preclinical studies and clinical trials. The second particularity is the finding that epigenetic changes precede the appearance of histopathological modifications. This has the potential to facilitate the emergence of epigenetic biomarkers, some of which already entered the clinical arena, catalysing a major shift in prophylactic and therapeutic strategies, and promising to fill a decades-old gap in preventive medicine. © 2014 John Wiley & Sons Ltd.

Massaad C.A.,Baylor College of Medicine | Klann E.,New York University
Antioxidants and Redox Signaling | Year: 2011

The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age- or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function. © 2011 Mary Ann Liebert, Inc.

Feske S.,New York University
Annals of the New York Academy of Sciences | Year: 2011

Mutations in genes encoding the calcium-release activated calcium (CRAC) channel abolish calcium influx in cells of the immune system and cause severe congenital immunodeficiency. Patients with autosomal recessive mutations in the CRAC channel gene ORAI1, its activator stromal interaction molecule 1 (STIM1), and mice with targeted deletion of Orai1, Stim1, and Stim2 genes reveal important roles for CRAC channels in adaptive and innate immune responses to infection and in autoimmunity. Because CRAC channels have important functions outside the immune system, deficiency of either ORAI1 or STIM1 is associated with a unique clinical phenotype. This review will give an overview of CRAC channel function in the immune system, examine the consequences of CRAC channel deficiency for immunity in human patients and mice, and discuss genetic defects in immunoreceptor-associated signaling molecules that compromise calcium influx and cause immunodeficiency. © 2011 New York Academy of Sciences.

Mitra A.,New York University | Giamarchi T.,University of Geneva
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

A perturbative renormalization group approach is employed to study the effect of a periodic potential on a system of one-dimensional bosons in a nonequilibrium steady state due to an initial interaction quench. The renormalization group flows are modified significantly from the well-known equilibrium Berezinski-Kosterlitz-Thouless form. They show several new features such as a generation of an effective temperature, generation of dissipation, as well as a change in the location of the quantum critical point separating the weak- and strong-coupling phases. Detailed results on the weak-coupling side of the phase diagram are presented, such as the renormalization of the parameters and the asymptotic behavior of the correlation functions. The physical origin of the generated temperature and friction is discussed. © 2012 American Physical Society.

Moghaddam B.,University of Pittsburgh | Javitt D.,New York University
Neuropsychopharmacology | Year: 2012

Glutamate is the primary excitatory neurotransmitter in mammalian brain. Disturbances in glutamate-mediated neurotransmission have been increasingly documented in a range of neuropsychiatric disorders including schizophrenia, substance abuse, mood disorders, Alzheimer's disease, and autism-spectrum disorders. Glutamatergic theories of schizophrenia are based on the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists to induce schizophrenia-like symptoms, as well as emergent literature documenting disturbances of NMDAR-related gene expression and metabolic pathways in schizophrenia. Research over the past two decades has highlighted promising new targets for drug development based on potential pre-and postsynaptic, and glial mechanisms leading to NMDAR dysfunction. Reduced NMDAR activity on inhibitory neurons leads to disinhibition of glutamate neurons increasing synaptic activity of glutamate, especially in the prefrontal cortex. Based on this mechanism, normalizing excess glutamate levels by metabotropic glutamate group 2/3 receptor agonists has led to potential identification of the first non-monoaminergic target with comparable efficacy as conventional antipsychotic drugs for treating positive and negative symptoms of schizophrenia. In addition, NMDAR has intrinsic modulatory sites that are active targets for drug development, several of which show promise in preclinical/early clinical trials targeting both symptoms and cognition. To date, most studies have been done with orthosteric agonists and/or antagonists at specific sites. However, allosteric modulators, both positive and negative, may offer superior efficacy with less danger of downregulation. © 2012 American College of Neuropsychopharmacology. All rights reserved.

Manel N.,French Institute of Health and Medical Research | Littman D.R.,New York University | Littman D.R.,Howard Hughes Medical Institute
Cell | Year: 2011

Two groups have identified SAMHD1, a protein encoded by an Aicardi-Goutires Syndrome susceptibility gene, as the factor that restricts infection of macrophages and dendritic cells with HIV-1. Here we discuss implications of this discovery for induction of antiviral protective immunity. © 2011 Elsevier Inc.

Systemic lupus erythematosus (SLE) is characterized by the dysfunction of T cells, B cells, and dendritic cells, the release of pro-inflammatory nuclear materials from necrotic cells, and the formation of antinuclear antibodies (ANA) and immune complexes of ANA with DNA, RNA, and nuclear proteins. Activation of the mammalian target of rapamycin (mTOR) has recently emerged as a key factor in abnormal activation of T and B cells in SLE. In T cells, increased production of nitric oxide and mitochondrial hyperpolarization (MHP) were identified as metabolic checkpoints upstream of mTOR activation. mTOR controls the expression T-cell receptor-associated signaling proteins CD4 and CD3ζ through increased expression of the endosome recycling regulator Rab5 and HRES-1/Rab4 genes, enhances Ca2 fluxing and skews the expression of tyrosine kinases both in T and B cells, and blocks the expression of Foxp3 and the generation of regulatory T cells. MHP, increased activity of mTOR, Rab GTPases, and Syk kinases, and enhanced Ca2 flux have emerged as common T and B cell biomarkers and targets for treatment in SLE. © 2010 Informa UK Ltd.

Schmidt A.M.,New York University
Vascular Pharmacology | Year: 2015

Emerging evidence links the receptor for advanced glycation endproducts (RAGE) to the pathogenesis of tissue damage in chronic metabolic and inflammatory diseases. In human subjects, multiple reports suggest that in the plasma/serum, circulating levels of distinct forms of soluble RAGEs may be biomarkers of the presence or absence, and the extent of chronic disease. These considerations prompt us to consider in this review, what are soluble RAGEs; how are they formed; what might be their natural functions; and may they serve as biomarkers of inflammatory and metabolic disease activity? In this brief review, we seek to address what is known and suggest new areas for scientific investigation to uncover the biology of soluble RAGEs. © 2015 Elsevier Inc..

Cruz F.,Hospital Sao Joao | Nitti V.,New York University
Neurourology and Urodynamics | Year: 2014

Following use of botulinum toxin in the 1980s for the treatment of detrusor sphincter dyssynergia in patients with spinal cord injury (SCI), the potential therapeutic value of this neurotoxin in urology has been the subject of much interest. The DIGNITY (Double-blind InvestiGation of purified Neurotoxin complex In neurogenic deTrusor overactivitY) clinical research program aimed to compare onabotulinumtoxinA with placebo in terms of efficacy and safety in patients with neurogenic detrusor overactivity (NDO) due to SCI or multiple sclerosis. The EMBARK clinical research program mirrored these aims in patients with overactive bladder with urinary incontinence (UI). Each program comprised two phase III, randomized, placebo-controlled studies. In all four trials, primary efficacy endpoints were met, and significant benefits of onabotulinumtoxinA versus placebo were demonstrated across a range of secondary endpoints, including measures of health-related quality of life. The most common adverse event across both programs was urinary tract infection. Interim analyses of data from ongoing long-term extensions to these phase III trials have provided promising evidence for the efficacy of repeated injections. While further investigation is recommended to enrich the dataset, the available evidence indicates that onabotulinumtoxinA provides an effective treatment option for these two populations, which were previously considered very difficult to treat. © 2014 Wiley Periodicals, Inc.

Diemont S.A.W.,New York University
Frontiers in Ecology and the Environment | Year: 2013

Swidden is an agroforestry system in which woody vegetation is regenerated after a period of annual cropping. Associated with most forested areas of the tropical world, swidden is often blamed for deforestation but it also plays a role in forest conservation. Here, we examine the contemporary milpa, a type of swidden agriculture common to Latin America and historically used by the Maya people of the lowlands of southern Mexico and northern Central America; we focus on one group in particular, the Lakandon people of Chiapas. One element of milpa agriculture that receives a considerable amount of criticism is the burning of cut vegetation after clearing. Fire can have negative effects on ecosystems but swidden cultivators are often sophisticated managers of fire. Among the benefits of fire use in this setting is its contribution to nutrient flow and to long-term soil fertility in the form of biochar, charcoal produced by low-temperature pyrolysis in agriculture. When properly managed, the milpa cycle can result in long-term carbon sequestration and an increasingly fertile anthrosol (soil that has been greatly modified by long-term human activity) and enriched woodland vegetation. © The Ecological Society of America.

Barcellos-Hoff M.H.,New York University | Lyden D.,New York Medical College | Lyden D.,Champalimaud Metastasis Center | Wang T.C.,Columbia University
Nature Reviews Cancer | Year: 2013

The concept of the tumour microenvironment recognizes that the interplay between cancer cells and stromal cells is a crucial determinant of cancer growth. In this Perspectives article, we propose the novel concept that the tumour microenvironment is built through rate-limiting steps during multistage carcinogenesis. Construction of a 'precancer niche' is a necessary and early step that is required for initiated cells to survive and evolve; subsequent niche expansion and maturation accompany tumour promotion and progression, respectively. As such, cancer niches represent an emergent property of a tumour that could be a robust target for cancer prevention and therapy. © 2013 Macmillan Publishers Limited.

Vologodskii A.,New York University | Frank-Kamenetskii M.D.,Boston University
Nucleic Acids Research | Year: 2013

During the past decade, the issue of strong bending of the double helix has attracted a lot of attention. Here, we overview the major experimental and theoretical developments in the field sorting out reliably established facts from speculations and unsubstantiated claims. Theoretical analysis shows that sharp bends or kinks have to facilitate strong bending of the double helix. It remains to be determined what is the critical curvature of DNA that prompts the appearance of the kinks. Different experimental and computational approaches to the problem are analyzed. We conclude that there is no reliable evidence that any anomalous behavior of the double helix happens when DNA fragments in the range of 100 bp are circularized without torsional stress. The anomaly starts at the fragment length of about 70 bp when sharp bends or kinks emerge in essentially every molecule. Experimental data and theoretical analysis suggest that kinks may represent openings of isolated base pairs, which had been experimentally detected in linear DNA molecules. The calculation suggests that although the probability of these openings in unstressed DNA is close to 10 -5, it increases sharply in small DNA circles reaching 1 open bp per circle of 70 bp. © The Author(s) 2013. Published by Oxford University Press.

Mercado C.L.,New York University
Radiologic Clinics of North America | Year: 2014

The updated American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) has been newly released. This article summarizes the changes and updates that have been made to BI-RADS. The goal of the revised edition continues to be the same: to improve clarification in image interpretation, maintain reporting standardization, and simplify the monitoring of outcomes. The new BI-RADS also introduces new terminology to provide a more universal lexicon across all 3 imaging modalities. © 2014 Elsevier Inc.

Blum R.,New York University | Kloog Y.,Tel Aviv University
Cell Death and Disease | Year: 2014

Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease. © 2014 Macmillan Publishers Limited.

Alter A.L.,New York University | Hershfield H.E.,University of California at Los Angeles
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Although humans measure time using a continuous scale, certain numerical ages inspire greater self-reflection than others. Six studies show that adults undertake a search for existential meaning when they approach a new decade in age (e.g., at ages 29, 39, 49, etc.) or imagine entering a new epoch, which leads them to behave in ways that suggest an ongoing or failed search for meaning (e.g., by exercising more vigorously, seeking extramarital affairs, or choosing to end their lives).

Tambe P.,New York University | Hitt L.M.,University of Pennsylvania
Information Systems Research | Year: 2012

This paper uses newly collected panel data that allow for significant improvements in the measurement and modeling of information technology (IT) productivity to address some longstanding empirical limitations in the IT business value literature. First, we show that using generalized method of moments-based estimators to account for the endogeneity of IT spending produces coefficient estimates that are only about 10% lower than unadjusted estimates, suggesting that the effects of endogeneity on IT productivity estimates may be relatively small. Second, analysis of the expanded panel suggests that (a) IT returns are substantially lower in midsize firms than in Fortune 500 firms; (b) they materialize more slowly in large firms-in midsize firms, unlike in larger firms, the short-run contribution of IT to output is similar to the long-run output contribution; and (c) the measured marginal product of IT spending is higher from 2000 to 2006 than in any previous period, suggesting that firms, and especially large firms, have been continuing to develop new, valuable IT-enabled business process innovations. Furthermore, we show that the productivity of IT investments is higher in manufacturing sectors and that our productivity results are robust to controls for IT labor quality and outsourcing levels. © 2012 INFORMS.

Determining how riparian zone hydrological conditions may change in response to precipitation in various geomorphic settings is critical to determine the occurrence of hot moments of biogeochemical transformations for phosphorus, nitrogen, sulfate, mercury and greenhouse gases in these systems. The author investigate water table response to precipitation at a high temporal resolution (15min) in a riparian zone located in a deeply incised glacial till valley (20m) with approximately 2m of alluvium over a confining layer, in Indiana, USA. During storms, larger water table fluctuations (approximately 100cm) occurred near the stream than near the toe slope (10-25cm). A quick rise in water table near the stream occurred for all storms, with partial flow reversals occurring for three of seven storms. The quick rise of the water table near the stream was associated with a decrease in hillslope water contributions to the stream during storms and the development of a water table down valley gradient for most storms. Water table fluctuations, groundwater flow velocities and electrical conductivity data indicated that riparian zone water table response to precipitation was primarily regulated by pressure wave processes. Regardless of the storm, high water tables persisted for at least 2days after the cessation of precipitation. Although this suggests that high-resolution precipitation data may be useful to quantify hot moments of biogeochemical transformation associated with high water tables in riparian zones, precipitation data alone are not sufficient to correctly estimate the magnitude of riparian water table level changes during storms. © 2011 John Wiley & Sons, Ltd.

Boyd D.,New York University
Communications of the ACM | Year: 2012

FACEBOOK'S TERMS OF service explicitly require its users to provide their "real names and information." Indeed, the norm among many Facebook users is to provide a first and last name that appears to be genuine. Thus, when Google+ launched in the summer of 2011, it tried to emulate Facebook by requiring that new users provide similar credentials. Many early adopters responded by providing commonly used nicknames, pseudonyms, and stage names. Google, determined to ensure compliance, began expelling people who did not abide by the "real names" requirements. They ejected high-profile geeks, including Limor Fried and Blake Ross for failing to use their real names; they threatened to eject Violet Blue, a well-known sex educator and columnist. © 2012 ACM.

In the laboratory, food restriction has been shown to induce neuroadaptations in brain reward circuitry which are likely to be among those that facilitate survival during periods of food scarcity in the wild. However, the upregulation of mechanisms that promote foraging and reward-related learning may pose a hazard when food restriction is self-imposed in an ecology of abundant appetitive rewards. For example, episodes of loss of control during weight-loss dieting, use of drugs with addictive potential as diet aids, and alternating fasting with alcohol consumption in order to avoid weight gain, may induce synaptic plasticity that increases the risk of enduring maladaptive reward-directed behavior. In the present mini-review, representative basic research findings are outlined which indicate that food restriction alters the function of mesoaccumbens dopamine neurons, potentiates cellular and behavioral responses to D-1 and D-2 dopamine receptor stimulation, and increases stimulus-induced synaptic insertion of AMPA receptors in nucleus accumbens. Possible mechanistic underpinnings of increased drug reward magnitude, drug-seeking, and binge intake of sucrose in food-restricted animal subjects are discussed and possible implications for human weight-loss dieting are considered. © 2011 Elsevier Inc.

Ghose A.,New York University | Yao Y.,Lehigh University
Information Systems Research | Year: 2011

Price dispersion is an important indicator of market efficiency. Internet-based electronic markets have the potential to reduce transaction and search costs, thereby creating more efficient, "frictionless" markets, as predicted by theories in information economics. However, earlier work has reported significant levels of price dispersion on the Internet, which is in contrast to theoretical predictions. A key feature of the existing stream of work has been its use of posted prices to estimate price dispersion. In theory, this can lead to an overestimation of price dispersion because a sale may not have occurred at the posted price. In this research, we use a unique data set of actual transaction prices collected from both the electronic and offline markets of buyers in a businessto-business market to evaluate the extent of price dispersion. We find that price dispersion in the electronic market is as low as 0.22%, which is substantially less than that reported in the existing literature. This near-zero price dispersion suggests that in some electronic markets the "law of one price" can prevail when we consider transaction prices, instead of posted prices. We further develop a theoretical framework that identifies several new drivers of price dispersion using transaction data. In particular, we focus on four product-level and market-level attributes-product cost, order cycle time, own price elasticity, and transaction quantity, and we estimate their impact on price dispersion. We also examine the electronic market's moderating role in the relationship between these drivers and price dispersion. Finally, we estimate the efficiency gains that accrue from transactions in the relatively friction-free market and find that the electronic market can enhance consumer surplus by as much as $97.92 million per year. © 2011 INFORMS.

Ghose A.,New York University | Goldfarb A.,University of Toronto | Han S.P.,City University of Hong Kong
Information Systems Research | Year: 2013

We explore how Internet browsing behavior varies between mobile phones and personal computers. Smaller screen sizes on mobile phones increase the cost to the user of browsing for information. In addition, a wider range of offline locations for mobile Internet usage suggests that local activities are particularly important. Using data on user behavior at a (Twitter-like) microblogging service, we exploit exogenous variation in the ranking mechanism of posts to identify the ranking effects. We show that (1) ranking effects are higher on mobile phones suggesting higher search costs: links that appear at the top of the screen are especially likely to be clicked on mobile phones and (2) the benefit of browsing for geographically close matches is higher on mobile phones: stores located in close proximity to a user's home are much more likely to be clicked on mobile phones. Thus, the mobile Internet is somewhat less "Internet-like": search costs are higher and distance matters more. We speculate on how these changes may affect the future direction of Internet commerce. © 2013 Informs.

Burtch G.,University of Minnesota | Ghose A.,New York University | Wattal S.,Temple University
Information Systems Research | Year: 2013

Crowd-funded markets have recently emerged as a novel source of capital for entrepreneurs. As the economic potential of these markets is now being realized, they are beginning to go mainstream, a trend reflected by the explicit attention crowdfunding has received in the American Jobs Act as a potential avenue for economic growth, as well as the recent focus that regulators such as the U.S. Securities and Exchange Commission have placed upon it. Although the formulation of regulation and policy surrounding crowd-funded markets is becoming increasingly important, the behavior of crowdfunders, an important aspect that must be considered in this formulation effort, is not yet well understood. A key factor that can influence the behavior of crowd funders is information on prior contribution behavior, including the amount and timing of others' contributions, which is published for general consumption. With that in mind, in this study, we empirically examine social influence in a crowd-funded marketplace for online journalism projects, employing a unique data set that incorporates contribution events and Web traffic statistics for approximately 100 story pitches. This data set allows us to examine both the antecedents and consequences of the contribution process. First, noting that digital journalism is a form of public good, we evaluate the applicability of two competing classes of economic models that explain private contribution toward public goods in the presence of social information: substitution models and reinforcement models. We also propose a new measure that captures both the amount and the timing of others' contribution behavior: contribution frequency (dollars per unit time). We find evidence in support of a substitution model, which suggests a partial crowding-out effect, where contributors may experience a decrease in their marginal utility from making a contribution as it becomes less important to the recipient. Further, we find that the duration of funding and, more importantly, the degree of exposure that a pitch receives over the course of the funding process, are positively associated with readership upon the story's publication. This appears to validate the widely held belief that a key benefit of the crowdfunding model is the potential it offers for awareness and attention-building around causes and ventures. This last aspect is a major contribution of the study, as it demonstrates a clear linkage between marketing effort and the success of crowd-funded projects. © 2013 Informs.

Thomas S.J.,U.S. Army | Endy T.P.,New York University
Current Opinion in Infectious Diseases | Year: 2013

Purpose of Review: Dengue is a global health problem and of concern to travelers and deploying military personnel, with development and licensure of an effective tetravalent dengue vaccine a public health priority. The recent performance of the lead dengue vaccine in a phase 2b efficacy trial underscores dengue vaccine development challenges. This review focuses on current issues in dengue vaccination. Recent Findings: The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. Recent estimates on the burden of DENV infection determined that there are 390 million dengue infections per year, three times the current estimate by the WHO. There are no licensed antivirals or vaccines to treat or prevent dengue though many are in preclinical or clinical development. DENV illness results from a complex interaction of viral properties and host immune responses. Immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays are challenging dengue vaccine development efforts. Summary: Dengue vaccine development efforts have numerous complex challenges to overcome before a well tolerated and effective vaccine is licensed and available. In this review, the authors discuss the current issues in dengue vaccination. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Vanderberg J.P.,New York University
Parasitology International | Year: 2014

The malaria infection is initiated in mammals by injection of the sporozoite stage of the parasite through the bite of Plasmodium-infected, female Anopheles mosquitoes. Sporozoites are injected into extravascular portions of the skin while the mosquito is probing for a blood source. Sporozoite gliding motility allows them to locate and penetrate blood vessels of the dermis or subcutaneous tissues; once in the blood, they reach the liver, within which they continue their development. Some of the injected parasites invade dermal lymph vessels and travel to the proximal draining lymphatic node, where they interact with host immunocytes. The host responds to viable or attenuated sporozoites with antibodies directed against the immunodominant circumsporozoite protein (CSP), as well as against other sporozoite proteins. These CSP antibodies can inhibit the numbers of sporozoites injected by mosquitoes and the motility of those injected into the skin. This first phase of the immune response is followed by cell-mediated immunity involving CD8 T-cells directed against the developing liver stage of the parasite. This review discusses the early history of imaging studies, and focuses on the role that imaging has played in enabling a better understanding of both the induction and effector functions of the immune responses against sporozoites. © 2013 Elsevier Ireland Ltd.

Evidence is emerging that during the development of Alzheimer's disease (AD), changes in the synthesis and metabolism of cholesterol and progesterone are occurring that may or may not affect the progression of the disease. The concept arose from the recognition that dehydrocholesterol 24-reductase (DHCR24/Seladin-1), one of the nine enzymes in the endoplasmic reticulum that determines the transformation of lanosterol to cholesterol, is selectively reduced in late AD. As a consequence, the tissue level of desmosterol increases, affecting the expression of ABC transporters and the structure of lipid rafts, both determinants of amyloid-β processing. However, the former effect is considered beneficial and the latter detrimental to processing. Other determinants of desmosterol tissue levels are 24,25 epoxycholesterol and the ABCG1 and ABCG4 transporters. Progesterone and its metabolites are determinants of tissue levels of desmosterol and several other sterol intermediates in cholesterol synthesis. Animal models indicate marked elevations in the tissue levels of these sterols at early time frames in the progression of neurodegenerative diseases. The low level of neuroprogesterone and metabolites in AD are consonant with the low level of desmosterol and may have a role in amyloid-β processing. The sparse data that has accumulated appears to be a sufficient basis for proposing a systematic evaluation of the biologic roles of sterol intermediates in the slowly progressive neurodegeneration characteristic of AD. © 2013 - IOS Press and the authors. All rights reserved.

Low-density lipoprotein cholesterol (LDL-C) is currently the primary target in the management of dyslipidemia, and statins are first-line pharmacologic interventions. Adjunct therapy such as niacins, fibrates, bile acid sequestrants, or cholesterol absorption inhibitors may be considered to help reduce cardiovascular risk. This review discusses the need for alternative adjunct treatment options and the potential place for omega-3 fatty acids as such. The cardiovascular benefits of fish consumption are attributed to the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and a variety of omega-3 fatty acid products are available with varied amounts of EPA and DHA. The product types include prescription drugs, food supplements, and medical foods sourced from fish, krill, algal and plant oils or purified from these oils. Two prescription omega-3 fatty acids are currently available, omega-3 fatty acid ethyl esters (contains both EPA and DHA ethyl esters), and icosapent ethyl (IPE; contains high-purity EPA ethyl ester). A pharmaceutical containing free fatty acid forms of omega-3 is currently in development. Omega-3 fatty acid formulations containing EPA and DHA have been shown to increase LDL-C levels while IPE has been shown to lower triglyceride levels without raising LDL-C levels, alone or in combination with statin therapy. In addition, recent studies have not been able to demonstrate reduced cardiovascular risk following treatment with fibrates, niacins, cholesterol absorption inhibitors, or omega-3 fatty acid formulations containing both EPA and DHA in statin-treated patients; thus, there remains a need for further cardiovascular outcomes studies for adjunct therapy. © 2013 The Author.

Deshaies E.M.,New York University
Journal of Clinical Neuroscience | Year: 2013

The Solitaire-FR (eV3/Covidien, Irvine, CA, USA) retrievable stent (SFR), designed for mechanical thrombectomy in acute ischemic stroke, recently received Food and Drug Administration approval in the USA. Clot retrieval is performed by deploying the SFR through a microcatheter directly into the thrombus, to capture the clot and restore perfusion. In order to perform this maneuver, a balloon guide catheter must be used to apply negative suction and reverse flow within the cervical arteries, thus minimizing the chance of antegrade blood flow dislodging the thrombus from the stent. This technique requires at least an 8-French system that can increase the risk of arterial injury at the access site particularly in older patients with smaller or highly atherosclerotic peripheral arteries, and may provide inadequate aspiration in the vertebrobasilar system where only one vertebral artery is accessed and aspirated. The author describes a technique whereby a 6-French tri-axial system is used to deliver the SFR through a Penumbra Aspiration Microcatheter (Penumbra, Inc., Alameda, CA, USA) to provide intracranial aspiration in close proximity to the stent. © 2013 Elsevier Ltd. All rights reserved.

Lecun Y.,Facebook | Lecun Y.,New York University | Bengio Y.,University of Montreal | Hinton G.,Google | Hinton G.,Kings College
Nature | Year: 2015

Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech. © 2015 Macmillan Publishers Limited. All rights reserved.

Cadwell K.,New York University
Immunity | Year: 2015

The mammalian virome includes diverse commensal and pathogenic viruses that evoke a broad range of immune responses from the host. Sustained viral immunomodulation is implicated in a variety of inflammatory diseases, but also confers unexpected benefits to the host. These outcomes of viral infections are often dependent on host genotype. Moreover, it is becoming clear that the virome is part of a dynamic network of microorganisms that inhabit the body. Therefore, viruses can be viewed as a component of the microbiome, and interactions with commensal bacteria and other microbial agents influence their behavior. This piece is a review of our current understanding of how the virome, together with other components of the microbiome, affects the function of the host immune system to regulate health and disease. The virome includes diverse viruses that interact with commensal microorganisms and evoke multifaceted immune responses. Cadwell examines the interplay between the virome, host immune system, and other members of the microbiome and discuss implications for human health and disease. © 2015 Elsevier Inc..

Mirbabayi M.,New York University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We identify different helicity degrees of freedom of Fierz-Paulian massive gravity around generic backgrounds. We show that the two-parameter family proposed by de Rham, Gabadadze, and Tolley always propagates five degrees of freedom and therefore is free from the Boulware-Deser ghost. The analysis has a number of by-products, among which (a) it shows how the original decoupling limit construction ensures ghost freedom of the full theory, (b)it reveals an enhanced symmetry of the theory around linearized backgrounds, and (c) it allows us to give an algorithm for finding dispersion relations. The proof naturally extends to generalizations of the theory with a reference metric different from Minkowski. © 2012 American Physical Society.

Suzuki W.A.,New York University | Naya Y.,Peking University
Annual Review of Neuroscience | Year: 2014

Anatomically, the perirhinal cortex sits at the boundary between the medial temporal lobe and the ventral visual pathway. It has prominent interconnections not only with both these systems, but also with a wide range of unimodal and polymodal association areas. Consistent with these diverse projections, neurophysiological studies reveal a multidimensional set of mnemonic signals that include stimulus familiarity, within- and between-domain associations, associative recall, and delay-based persistence. This wide range of perirhinal memory signals not only includes signals that are largely unique to the perirhinal cortex (i.e., object familiarity), consistent with dual-process theories, but also includes a range of signals (i.e., associative flexibility and recall) that are strongly associated with the hippocampus, consistent with single-process theories. These neurophysiological findings have important implications for bridging the gap between single-process and dual-process models of medial temporal lobe function. © Copyright ©2014 by Annual Reviews. All rights reserved.

Block N.,New York University
Trends in Cognitive Sciences | Year: 2014

Can we consciously see more items at once than can be held in visual working memory? This question has eluded resolution because the ultimate evidence is subjects' reports in which phenomenal consciousness is filtered through working memory. However, a new technique makes use of the fact that unattended 'ensemble properties' can be detected 'for free' without decreasing working memory capacity. © 2014.

Fazel M.,University of Oxford | Hoagwood K.,New York University | Stephan S.,University of Maryland Baltimore County | Ford T.,University of Exeter
The Lancet Psychiatry | Year: 2014

Mental health services embedded within school systems can create a continuum of integrative care that improves both mental health and educational attainment for children. To strengthen this continuum, and for optimum child development, a reconfiguration of education and mental health systems to aid implementation of evidence-based practice might be needed. Integrative strategies that combine classroom-level and student-level interventions have much potential. A robust research agenda is needed that focuses on system-level implementation and maintenance of interventions over time. Both ethical and scientific justifications exist for integration of mental health and education: integration democratises access to services and, if coupled with use of evidence-based practices, can promote the healthy development of children. © 2014 Elsevier Ltd.

D'Amico G.,New York University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We study perturbations around some cosmological backgrounds in the de Rham-Gabadadze-Tolley theory of massive gravity. We develop a general formalism to calculate the perturbations around any background. We derive the Lagrangian for fluctuations in the small-scale limit, and for the open Friedman-Robertson- Walker solution we repeat the analysis around the full background. We find that the perturbations display similar properties: the longitudinal modes of the massive graviton are instantaneous at quadratic level, but they acquire a kinetic term at cubic order. © 2012 American Physical Society.

Thurman D.J.,Emory University | Hesdorffer D.C.,Columbia University | French J.A.,New York University
Epilepsia | Year: 2014

Summary Objective There is not yet a clear consensus on the incidence of sudden unexpected death in epilepsy (SUDEP) or the extent of its burden on public health. In this systematic review, we seek to summarize the incidence of SUDEP and its age distribution, as well as the years of potential life lost and cumulative risks of SUDEP for persons with epilepsy.Methods We conducted a systematic search for epidemiologic studies of sudden death in epilepsy and rated their quality of evidence. We pooled data from comparable higher quality population-based studies of SUDEP incidence across all age groups, calculating the overall incidence of SUDEP per 100,000 population, and per 1,000 people with epilepsy. Using standard formulas, we also calculated the years of potential life lost and cumulative risks associated with SUDEP.Results SUDEP has an estimated overall crude annual incidence rate of 0.81 cases per 100,000 population, or 1.16 cases per 1,000 patients with epilepsy. Comparing years of potential life lost from SUDEP with selected other neurologic diseases, SUDEP ranks second only to stroke.Significance Despite limitations to the data on which our analysis is based, we conclude that the public health burden of SUDEP, which has previously been underappreciated, is substantial and deserves much more attention from clinicians, researchers, and the public health community. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © 2014 International League Against Epilepsy.

Ma W.J.,New York University | Jazayeri M.,Massachusetts Institute of Technology
Annual Review of Neuroscience | Year: 2014

Organisms must act in the face of sensory, motor, and reward uncertainty stemming from a pandemonium of stochasticity and missing information. In many tasks, organisms can make better decisions if they have at their disposal a representation of the uncertainty associated with task-relevant variables. We formalize this problem using Bayesian decision theory and review recent behavioral and neural evidence that the brain may use knowledge of uncertainty, confidence, and probability. © Copyright ©2014 by Annual Reviews. All rights reserved.

Ckless K.,New York University
Advances in Experimental Medicine and Biology | Year: 2014

In general protein posttranslation modifications (PTMs) involve the covalent addition of functional groups or molecules to specific amino acid residues in proteins. These modifications include phosphorylation, glycosylation, S-nitrosylation, acetylation, lipidation, among others (Angew Chem Int Ed Engl 44(45):7342–7372, 2005). Although other amino acids can undergo different kinds of oxidative posttranslational modifications (oxPTMs) (Exp Gerontol 36(9):1495– 1502, 2001), in this chapter oxPTM will be considered specifically related to Cysteine oxidation, and redox proteomics here is translated as a comprehensive investigation of oxPTMs, in biological systems, using diverse technical approaches. Protein Cysteine residues are not the only amino acid that can be target for oxidative modifications in proteins (Exp Gerontol 36(9):1495–1502, 2001; Biochim Biophys Acta 1814(12):1785–1795, 2011), but certainly it is among the most reactive amino acid (Nature 468(7325):790–795, 2010). Interestingly, it is one of the least abundant amino acid, but it often occurs in the functional sites of proteins (J Mol Biol 404(5):902–916, 2010). In addition, the majority of the Cysteine oxidations are reversible, indicating potential regulatory mechanism of proteins. The global analysis of oxPTMs has been increasingly recognized as an important area of proteomics, because not only maps protein caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS), but also explores protein modulation involving ROS/RNS. Furthermore, the tools and strategies to study this type oxidation are also very abundant and developed, offering high degree of accuracy on the results. As a consequence, the redox proteomics field focuses very much on analyzing Cysteine oxidation in proteins under several experimental conditions and diseases states. Therefore, the identification and localization of oxPTMs within cellular milieu became critical to understand redox regulation of proteins in physiological and pathological conditions, and consequently an important information to develop better strategies for treatment and prevention of diseases associated with oxidative stress. There is a wide range of techniques available to investigate oxPTMs, including gel-based and non-gel-based separation approaches to be combined with sophisticated methods of detection, identification, and quantification of these modifications. The strategies and approaches to study oxPTMs and the respective applications related to physiological and pathological conditions will be discussed in more detail in this chapter. © 2014, Springer International Publishing Switzerland.

Hollingsworth A.D.,New York University
Current Opinion in Colloid and Interface Science | Year: 2013

Electrode impedance is a significant artifact in low frequency dielectric measurements involving conducting media. In their recent review article regarding the dielectric dispersion of aqueous colloidal systems, Grosse and Delgado [1] presented an electrode polarization model that provides a physical explanation of the effect of electrolyte concentration and mobility, electrode spacing, and frequency. Although the model properly predicts the undesired phenomenon, the low frequency scaling, often used to identify electrode polarization effects, is incorrect. The apparent dielectric constant actually follows an ω-2 frequency dependence for ω/κ2D≪1, where κ-1 is the Debye length and D is an average ion diffusion coefficient. Strictly speaking, the predicted scaling with exponent -1.5 is applicable only for sufficiently high frequencies, where electrode polarization is insignificant. This letter is intended to help clarify matters: the asymptotic behavior of the polarization model is examined, and the approximate expressions representing the real part of the complex dielectric constant of a parallel plate cell containing electrolyte solutions or colloidal suspensions are discussed. © 2013 Elsevier Ltd.

Selesnick I.W.,New York University
Signal Processing | Year: 2011

Numerous signals arising from physiological and physical processes, in addition to being non-stationary, are moreover a mixture of sustained oscillations and non-oscillatory transients that are difficult to disentangle by linear methods. Examples of such signals include speech, biomedical, and geophysical signals. Therefore, this paper describes a new nonlinear signal analysis method based on signal resonance, rather than on frequency or scale, as provided by the Fourier and wavelet transforms. This method expresses a signal as the sum of a 'high-resonance' and a 'low-resonance' component - a high-resonance component being a signal consisting of multiple simultaneous sustained oscillations; a low-resonance component being a signal consisting of non-oscillatory transients of unspecified shape and duration. The resonance-based signal decomposition algorithm presented in this paper utilizes sparse signal representations, morphological component analysis, and constant-Q (wavelet) transforms with adjustable Q-factor. © 2010 Elsevier B.V. All rights reserved.

Loh S.N.,New York University
Metallomics | Year: 2010

The p53 tumor suppressor is a transcription factor that contains a single zinc ion near its DNA binding interface. Zn2+ is required for site-specific DNA binding and proper transcriptional activation. In addition to its functional significance, zinc plays a dominant role in determining whether p53 folds productively or misfolds. Insufficient zinc and excess zinc cause p53 to misfold by distinct mechanisms which both result in functional loss. The zinc-binding status of p53 in the cell is impacted significantly by the presence of tumorigenic mutations and by metal ion homeostasis. This review discusses mechanisms by which zinc modulates folding and misfolding of p53, how improper metal binding and release leads to loss of function and cancer, and how misfolding can be rescued by metallochaperones. © 2010 The Royal Society of Chemistry.

Walsh M.G.,New York University
International Journal for Parasitology | Year: 2011

The relevance of parasitic infection for the increasing incidence of asthma is a topic of considerable debate. Large population-based studies examining the association between helminth infection and specific measures of lung function in humans are lacking. This report sought to examine this association by exploring the differences in forced expiratory volume in 1s (FEV 1) among participants with and without infection with Toxocara spp. using data from the Third National Health and Nutrition Examination Survey, undertaken by the United States Department of Health and Human Services, during 1988-1994. The results showed a significant association between diminished lung function and previous infection with Toxocara spp. Those with antibody evidence of Toxocara infection displayed FEV 1 that was 105.3mL less than those without previous infection. This relationship persisted while controlling for age, sex, education level, BMI, smoking status, ethnicity, immigration, rural residence and dog ownership (fully-adjusted difference=73mL). These findings suggest diminished lung function in the presence of Toxocara infection and illustrate the urgent need for longitudinal data to more clearly define the immunological relationship with helminth infection and its potential influence on lung function. © 2010 Australian Society for Parasitology Inc.

Daskalakis D.,New York University
Topics in Antiviral Medicine | Year: 2011

Detection of acute HIV infection is important to public health because this stage is one of high infectiousness and appears to account for a disproportionate amount of HIV transmission. Newer technologies in HIV testing, including third-generation enzyme immunoassays (EIAs) that detect anti-HIV IgM and IgG antibodies, fourth-generation combination EIAs that detect both anti-HIV antibodies and HIV p24 antigen, and nucleic acid- based testing for HIV RNA, have markedly reduced the interval between infection and detection of infection. Rapid diagnostic tests including assays for IgG and IgM anti-HIV antibodies have high sensitivity and specificity. The availability and wide use of these newer technologies have motivated review of recommended HIV testing algorithms. Individuals' knowledge of their HIV serostatus contributes to reducing transmission risk behaviors. Thus, widespread testing, facilitated by newer technology, allows more individuals to know their serostatus and is the first step in any successful effort to curb the incidence of HIV infection. © 2011, IAS-USA.

Aral S.,New York University | Dellarocas C.,Boston University | Godes D.,University of Maryland University College
Information Systems Research | Year: 2013

Social media are fundamentally changing the way we communicate, collaborate, consume, and create. They represent one of the most transformative impacts of information technology on business, both within and outside firm boundaries. This special issue was designed to stimulate innovative investigations of the relationship between social media and business transformation. In this paper we outline a broad research agenda for understanding the relationships among social media, business, and society. We place the papers comprising the special issue within this research framework and identify areas where further research is needed. We hope that the flexible framework we outline will help guide future research and develop a cumulative research tradition in this area. © 2013 INFORMS.

Sturman E.D.,New York University
Psychological Assessment | Year: 2011

According to social rank theory, involuntary subordination may be adaptive in species that compete for resources as a mechanism to switch off fighting behaviors when loss is imminent (thus saving an organism from injury). In humans, major depression is thought to occur when involuntary subordination becomes prolonged. The present study sought to operationalize involuntary subordination. Study 1 involved a reanalysis of a Gilbert and Allan (1998) study, with the hypothesis that social comparison (i.e., perceived status), submissive behavior, feelings of defeat, and entrapment would load on a common factor (interpreted as involuntary subordination). Exploratory and confirmatory factor analysis supported this model. In Study 2 measures of these same variables were administered to a group of undergraduate students. Eight items were selected from each measure (on the basis of item-total correlations) to form the Involuntary Subordination Questionnaire (ISQ). In Study 3 scores on the ISQ showed high levels of internal consistency and test-retest reliability in a sample of undergraduate students. Scores on the ISQ were significantly positively correlated with various neurotic personality styles and negatively correlated with variables indicating dominance or mastery. Involuntary subordination scores also significantly predicted change in social anxiety symptoms over 9 weeks. In Study 4 scores on the ISQ were examined in relation to nonverbal behaviors. In men, the ISQ was correlated with behaviors indicating a lack of confidence and submissiveness. Involuntary subordination appears to be a relatively stable trait with implications for personality, mood, and real-world behavior. © 2011 American Psychological Association.

Fileviez Perez P.,New York University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

The predictions for the mass of the light CP-even Higgs are investigated in the context of a simple extension of the Minimal Supersymmetric Standard Model where the baryon and lepton numbers are local gauge symmetries. This theory predicts the existence of light charged and neutral leptons which give extra contributions to the Higgs mass at the one-loop level. We show the possibility to satisfy the LEP2 bound and achieve a Higgs mass around 125 GeV in a supersymmetric spectrum with light sfermions and small left-right mixing in the stop sector. We make a brief discussion of the unique leptonic signals at the Large Hadron Collider. This theory predicts baryon number violation at the low scale and one could avoid the current LHC bounds on the supersymmetric mass spectrum. © 2012 Elsevier B.V.

Moore K.J.,New York University | Tabas I.,Columbia University
Cell | Year: 2011

In atherosclerosis, the accumulation of apolipoprotein B-lipoproteins in the matrix beneath the endothelial cell layer of blood vessels leads to the recruitment of monocytes, the cells of the immune system that give rise to macrophages and dendritic cells. Macrophages derived from these recruited monocytes participate in a maladaptive, nonresolving inflammatory response that expands the subendothelial layer due to the accumulation of cells, lipid, and matrix. Some lesions subsequently form a necrotic core, triggering acute thrombotic vascular disease, including myocardial infarction, stroke, and sudden cardiac death. This Review discusses the central roles of macrophages in each of these stages of disease pathogenesis. © 2011 Elsevier Inc.

This study investigated the role of morphological awareness weaknesses in the reading difficulties encountered by Spanish-speaking language minority learners and their native English-speaking peers in sixth grade. One hundred and thirty-eight students (82 language minority learners; 56 native English speakers) were assessed on English measures of reading comprehension, silent word reading fluency, and derivational morphological awareness. Students with specific reading comprehension difficulties, specific word reading difficulties, and combined difficulties were identified using categorical cut-scores. Findings indicated that morphological awareness differentiated skilled readers from students with reading difficulties. Substantial proportions of students with reading difficulties (38%-63%, depending on reading difficulty subtype) demonstrated weaknesses in morphological awareness. Language minority learners with reading difficulties were particularly likely to demonstrate weaknesses in morphological awareness (55%-64%), compared to native English speakers with similar reading difficulties (13%-50%). Findings suggest the diagnostic potential of morphological awareness for adolescent learners with reading difficulties, especially those from language minority backgrounds. © Hammill Institute on Disabilities 2013.

Wakefield J.C.,New York University
Epidemiology and Psychiatric Sciences | Year: 2015

The revision effort leading to the publication of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was flawed in process, goals and outcome. The revision process suffered from lack of an adequate public record of the rationale for changes, thus shortchanging future scholarship. The goals, such as dimensionalising diagnosis, incorporating biomarkers and separating impairment from diagnosis, were ill-considered and mostly abandoned. However, DSM-5's greatest problem, and the target of the most vigorous and sustained criticism, was its failure to take seriously the false positives problem. By expanding diagnosis beyond plausible boundaries in ways inconsistent with DSM-5's own definition of disorder, DSM-5 threatened the validity of psychiatric research, including especially psychiatric epidemiology. I present four examples: increasing the symptom options while decreasing the diagnostic threshold for substance use disorder, elimination of the bereavement exclusion from major depression, allowing verbal arguments as evidence of intermittent explosive disorder and expanding attention-deficit/hyperactivity disorder to adults before addressing its manifest false positives problems. © Cambridge University Press 2015.

Mohr I.,New York University | Sonenberg N.,McGill University
Cell Host and Microbe | Year: 2012

By controlling gene expression at the level of mRNA translation, organisms temporally and spatially respond swiftly to an ever-changing array of environmental conditions. This capacity for rapid response is ideally suited for mobilizing host defenses and coordinating innate responses to infection. Not surprisingly, a growing list of pathogenic microbes target host mRNA translation for inhibition. Infection with bacteria, protozoa, viruses, and fungi has the capacity to interfere with ongoing host protein synthesis and thereby trigger and/or suppress powerful innate responses. This review discusses how diverse pathogens manipulate the host translation machinery and the impact of these interactions on infection biology and the immune response. © 2012 Elsevier Inc.

Selesnick I.W.,New York University
IEEE Transactions on Signal Processing | Year: 2011

This paper describes a discrete-time wavelet transform for which the Q-factor is easily specified. Hence, the transform can be tuned according to the oscillatory behavior of the signal to which it is applied. The transform is based on a real-valued scaling factor (dilation-factor) and is implemented using a perfect reconstruction over-sampled filter bank with real-valued sampling factors. Two forms of the transform are presented. The first form is defined for discrete-time signals defined on all of BBZ. The second form is defined for discrete-time signals of finite-length and can be implemented efficiently with FFTs. The transform is parameterized by its Q-factor and its oversampling rate (redundancy), with modest oversampling rates (e.g., three to four times overcomplete) being sufficient for the analysis/synthesis functions to be well localized. © 2011 IEEE.

Dustin M.L.,New York University
Journal of Clinical Investigation | Year: 2012

Immunological and neural synapses share properties such as the synaptic cleft, adhesion molecules, stability, and polarity. However, the mismatch in scale has limited the utility of these comparisons. The discovery of phosphatase micro-exclusion from signaling elements in immunological synapses and innate phagocytic synapses define a common functional unit at a common sub-micron scale across synapse types. Bundling of information from multiple antigen receptor microclusters by an immunological synapse has parallels to bundling of multiple synaptic inputs into a single axonal output by neurons, allowing integration and coincidence detection. Bonafide neuroimmune synapses control the inflammatory reflex. A better understanding of the shared mechanisms between immunological and neural synapses could aid in the development of new therapeutic modalities for immunological, neurological, and neuroimmunological disorders alike.

Reynolds H.R.,New York University
Current Opinion in Cardiology | Year: 2012

PURPOSE OF REVIEW: A substantial minority of myocardial infarction (MI) patients have no obstructive coronary artery disease (CAD) at angiography. Women more commonly have this type of MI, but both sexes are affected. This is not an innocuous problem. Multiple studies have shown 2% death or reinfarction in short-term to mid-term follow-up. RECENT FINDINGS: Two large autopsy series confirmed MI without obstructive CAD as a cause of death. Intravascular ultrasound (IVUS) and cardiac MRI (CMR) were studied in patients with MI without obstructive CAD. Plaque rupture was found in nearly 40% and late gadolinium enhancement was seen in nearly 40%, with little overlap in imaging findings. Additional CMR studies in similar patients have shown variable frequencies and patterns of late enhancement, but consistently demonstrate an ability to identify nonischemic causes (myocarditis, infiltrative disease). Ischemic myocardial injury on CMR may be due to plaque rupture but also occurs in patients without plaque rupture. These cases may be caused by vasospasm, embolism, dissection, or branch occlusion. SUMMARY: MI without obstructive CAD is a heterogeneous disorder with different mechanisms in different patients. Plaque rupture is common. In the absence of clear demonstration of a nonischemic cause, treatment should include guideline-recommended secondary prevention, including antiplatelet and antiatherosclerotic medications. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.

Llinas R.R.,New York University
Journal of Physiology | Year: 2011

Theories concerning the role of the climbing fibre system in motor learning, as opposed to those addressing the olivocerebellar system in the organization of motor timing, are briefly contrasted. The electrophysiological basis for the motor timing hypothesis in relation to the olivocerebellar system is treated in detail. © 2011 The Author. Journal compilation © 2011 The Physiological Society.

Javitt D.C.,New York University
Israel Journal of Psychiatry and Related Sciences | Year: 2010

Schizophrenia is a serious mental disorder that affects up to 1% of the population worldwide. Traditional models of schizophrenia have emphasized dopaminergic dysfunction. Over the last 20 years, however, limitations of the dopamine model have become increasingly apparent, necessitating development of alternative models. Glutamatergic models are based upon the observation that the psychotomimetic agents such as phencyclidine (PCP) and ketamine induce psychotic symptoms and neurocognitive disturbances similar to those of schizophrenia by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. Because glutamate/NMDA receptors are located throughout the brain, glutamatergic models predict widespread cortical dysfunction with particular involvement of NMDA receptors throughout the brain. Further, NMDA receptors are located on brain circuits that regulate dopamine release, suggesting that dopaminergic deficits in schizophrenia may also be secondary to underlying glutamatergic dysfunction. Agents that stimulate NMDA receptor-mediated neurotransmission, including glycine-site agonists and glycine transport inhibitors, have shown encouraging results in preclinical studies and are currently undergoing clinical development. Encouraging results have been observed as well with agents such as metabotropic 2/3 agonists that decrease resting glutamate levels, reversing potential disruption in firing patterns within prefrontal cortex and possibly other brain regions. Overall, these findings suggest that glutamatergic theories may lead to new conceptualizations and treatment approaches that would not be possible based upon dopaminergic models alone.

Lippmann M.,New York University
Critical Reviews in Toxicology | Year: 2014

Airborne fibers, when sufficiently biopersistent, can cause chronic pleural diseases, as well as excess pulmonary fibrosis and lung cancers. Mesothelioma and pleural plaques are caused by biopersistent fibers thinner than ∼0.1 μm and longer than ∼5 μm. Excess lung cancer and pulmonary fibrosis are caused by biopersistent fibers that are longer than ∼20 μm. While biopersistence varies with fiber type, all amphibole and erionite fibers are sufficiently biopersistent to cause pathogenic effects, while the greater in vivo solubility of chrysotile fibers makes them somewhat less causal for the lung diseases, and much less causal for the pleural diseases. Most synthetic vitreous fibers are more soluble in vivo than chrysotile, and pose little, if any, health pulmonary or pleural health risk, but some specialty SVFs were sufficiently biopersistent to cause pathogenic effects in animal studies. My conclusions are based on the following: 1) epidemiologic studies that specified the origin of the fibers by type, and especially those that identified their fiber length and diameter distributions; 2) laboratory-based toxicologic studies involving fiber size characterization and/or dissolution rates and long-term observation of biological responses; and 3) the largely coherent findings of the epidemiology and the toxicology. The strong dependence of effects on fiber diameter, length, and biopersistence makes reliable routine quantitative exposure and risk assessment impractical in some cases, since it would require transmission electronic microscopic examination, of representative membrane filter samples, for determining statistically sufficient numbers of fibers longer than 5 and 20 μm, and those thinner than 0.1 μm, based on the fiber types. © 2014 Informa Healthcare USA, Inc.

Recent investigations on PM2.5 constituents' effects in community residents have substantially enhanced our knowledge on the impacts of specific components, especially the HEI-sponsored National Particle Toxicity Component (NPACT) studies at NYU and UW-LRRI that addressed the impact of long-term PM2.5 exposure on cardiovascular disease (CVD) effects. NYU's mouse inhalation studies at five sites showed substantial variations in aortic plaque progression by geographic region that was coherent with the regional variation in annual IHD mortality in the ACS-II cohort, with both the human and mouse responses being primarily attributable to the coal combustion source category. The UW regressions of associations of CVD events and mortality in the WHI cohort, and of CIMT and CAC progression in the MESA cohort, indicated that had stronger associations with CVD-related human responses than OC, EC, or Si. The LRRI's mice had CVD-related biomarker responses to . NYU also identified components most closely associated with daily hospital admissions (OC, EC, Cu from traffic and Ni and V from residual oil). For daily mortality, they were from coal combustion (, Se, and As). While the recent NPACT research on PM2.5 components that affect CVD has clearly filled some major knowledge gaps, and helped to define remaining uncertainties, much more knowledge is needed on the effects in other organ systems if we are to identify and characterize the most effective and efficient means for reducing the still considerable adverse health impacts of ambient air PM. More comprehensive speciation data are needed for better definition of human responses. © 2014 Informa Healthcare USA, Inc.

Hubbard E.J.A.,New York University
Methods | Year: 2014

One of the most powerful aspects of biological inquiry using model organisms is the ability to control gene expression. A holy grail is both temporal and spatial control of the expression of specific gene products - that is, the ability to express or withhold the activity of genes or their products in specific cells at specific times. Ideally such a method would also regulate the precise levels of gene activity, and alterations would be reversible. The related goal of controlled or purposefully randomized expression of visible markers is also tremendously powerful. While not all of these feats have been accomplished in Caenorhabditis elegans to date, much progress has been made, and recent technologies put these goals within closer reach. Here, I present published examples of successful two-component site-specific recombination in C. elegans. These technologies are based on the principle of controlled intra-molecular excision or inversion of DNA sequences between defined sites, as driven by FLP or Cre recombinases. I discuss several prospects for future applications of this technology. © 2014 Elsevier Inc.

de Rham C.,University of Geneva | Gabadadze G.,New York University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We calculate the cubic order terms in a covariant theory that gives a nonlinear completion of the Fierz-Pauli massive spin-2 action. The resulting terms have specially tuned coefficients guarantying the absence of a ghost at this order in the decoupling limit. We show in this limit that: (1) The quadratic theory propagates helicity-2, 1, and helicity-0 states of massive spin-2. (2) The cubic terms with six derivatives - which would give ghosts on local backgrounds - cancel out automatically. (3) There is a four-derivative cubic term for the helicity-0 field, that has been known to be ghost-free on any local background. (4) There are four-derivative cubic terms that mix two helicity-0 fields with one helicity-2, or two helicity-1 fields with one helicity-0; none of them give ghosts on local backgrounds. (5) In the absence of external sources, all the cubic mixing terms can be removed by nonlinear redefinitions of the helicity-2 and helicity-1 fields. Notably, the helicity-2 redefinition generates the quartic Galileon term. These findings hint to an underlying nonlinearly realized symmetry, that should be responsible for what appears as the accidental cancellation of the ghost. © 2010 Elsevier B.V.

Appadurai A.,New York University
Environment and Urbanization | Year: 2012

Enumerations of informal settlements undertaken by their own community organizations have become increasingly common. These help urban poor communities to mobilize knowledge about themselves - knowledge that is valuable for their own discussions, that helps develop better relations with local governments. This commentary discusses why it is important for communities to have the right to undertake their own research, and how this can become an irreversible force for stronger negotiations with those who see them as a burden, a blight or a vote bank. © 2012 International Institute for Environment and Development (IIED).

Kuo S.P.,New York University
Physics of Plasmas | Year: 2015

Featured observations in high-frequency (HF) heating experiments conducted at Arecibo, EISCAT, and high frequency active auroral research program are discussed. These phenomena appearing in the F region of the ionosphere include high-frequency heater enhanced plasma lines, airglow enhancement, energetic electron flux, artificial ionization layers, artificial spread-F, ionization enhancement, artificial cusp, wideband absorption, short-scale (meters) density irregularities, and stimulated electromagnetic emissions, which were observed when the O-mode HF heater waves with frequencies below foF2 were applied. The implication and associated physical mechanism of each observation are discussed and explained. It is shown that these phenomena caused by the HF heating are all ascribed directly or indirectly to the excitation of parametric instabilities which instigate anomalous heating. Formulation and analysis of parametric instabilities are presented. The results show that oscillating two stream instability and parametric decay instability can be excited by the O-mode HF heater waves, transmitted from all three heating facilities, in the regions near the HF reflection height and near the upper hybrid resonance layer. The excited Langmuir waves, upper hybrid waves, ion acoustic waves, lower hybrid waves, and field-aligned density irregularities set off subsequent wave-wave and wave-electron interactions, giving rise to the observed phenomena. © 2015 AIP Publishing LLC.

Treisman J.E.,New York University
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2013

Drosophila eye development has been extensively studied, due to the ease of genetic screens for mutations disrupting this process. The eye imaginal disc is specified during embryonic and larval development by the Pax6 homolog Eyeless and a network of downstream transcription factors. Expression of these factors is regulated by signaling molecules and also indirectly by growth of the eye disc. Differentiation of photoreceptor clusters initiates in the third larval instar at the posterior of the eye disc and progresses anteriorly, driven by the secreted protein Hedgehog. Within each cluster, the combined activities of Hedgehog signaling and Notch-mediated lateral inhibition induce and refine the expression of the transcription factor Atonal, which specifies the founding R8 photoreceptor of each ommatidium. Seven additional photoreceptors, followed by cone and pigment cells, are successively recruited by the signaling molecules Spitz, Delta, and Bride of sevenless. Combinations of these signals and of intrinsic transcription factors give each ommatidial cell its specific identity. During the pupal stages, rhodopsins are expressed, and the photoreceptors and accessory cells take on their final positions and morphologies to form the adult retina. Over the past few decades, the genetic analysis of this small number of cell types arranged in a repetitive structure has allowed a remarkably detailed understanding of the basic mechanisms controlling cell differentiation and morphological rearrangement. © 2012 Wiley Periodicals, Inc.

Rapp R.,New York University
Science Technology and Human Values | Year: 2011

Over the last three decades, an escalating portion of U.S. school children has been classified for special education; those with diagnoses entitled to services now number 15 percent of all public school pupils. At the same time, American scientists have focused increasingly on juvenile brains, studying what one psychiatric epidemiologist labeled "social incapacities." This article reports on the laboratory labors of two scientific groups: neuroscientists who scan children's brains in search of resting state differences according to diagnosis and psychiatric epidemiologists who look to epigenetics to distinguish differential diagnostic populations. The article focuses on the medicalization of childhood differences and the harmonies and discordances between what researchers and parents understand to be at the root of children's learning and social capacities. © The Author(s) 2011.

Kesden M.,New York University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

A star orbiting a supermassive black hole can be tidally disrupted if the black hole's gravitational tidal field exceeds the star's self gravity at pericenter. Some of this stellar tidal debris can become gravitationally bound to the black hole, leading to a bright electromagnetic flare with bolometric luminosity proportional to the rate at which material falls back to pericenter. In the Newtonian limit, this flare will have a light curve that scales as t -5 /3 if the tidal debris has a flat distribution in binding energy. We investigate the time dependence of the black-hole mass accretion rate when tidal disruption occurs close enough the black hole that relativistic effects are significant. We find that for orbits with pericenters comparable to the radius of the marginally bound circular orbit, relativistic effects can double the peak accretion rate and halve the time it takes to reach this peak accretion rate. The accretion rate depends on both the magnitude of the black-hole spin and its orientation with respect to the stellar orbit; for orbits with a given pericenter radius in Boyer-Lindquist coordinates, a maximal black-hole spin anti-aligned with the orbital angular momentum leads to the largest peak accretion rate. © 2012 American Physical Society.

Volavka J.,New York University
Psychiatric Quarterly | Year: 2014

Schizophrenia without any comorbidity confers a modest, but statistically significant elevation of the risk for violence. That risk is considerably increased by comorbid antisocial personality disorder or psychopathy as well as by comorbid substance use disorders. These comorbidities are frequent. Conduct disorder and conduct disorder symptoms elevate the risk for aggressive behavior in patients with schizophrenia. Violence among adults with schizophrenia may follow at least two distinct pathways-one associated with premorbid conditions, including antisocial conduct, and another associated with the acute psychopathology of schizophrenia. Aggressive behavior in bipolar disorder occurs mainly during manic episodes, but it remains elevated in euthymic patients in comparison with controls. The risk of violent behavior is increased by comorbidity with borderline personality disorder, antisocial personality disorder, and substance use disorders. These comorbidities are frequent. Borderline personality disorder and bipolar disorder are related in their phenomenology and response to medication. These two disorders share a tendency to impulsiveness, and impulsive behavior, including impulsive aggression, is particularly expressed when they co-occur. © 2013 Springer Science+Business Media.

Elgindi T.M.,New York University
Archive for Rational Mechanics and Analysis | Year: 2014

We investigate the (slightly) super-critical two-dimensional Euler equations. The paper consists of two parts. In the first part we prove well-posedness in Cs spaces for all s > 0. We also give growth estimates for the Cs norms of the vorticity for 0 < s ≦ 1. In the second part we prove global regularity for the vortex patch problem in the super-critical regime. This paper extends the results of Chae et al. where they prove well-posedness for the so-called LogLog-Euler equation. We also extend the classical results of Chemin and Bertozzi-Constantin on the vortex patch problem to the slightly supercritical case. Both problems we study in the setting of the whole space. © 2013 Springer-Verlag Berlin Heidelberg.

Lane-Donovan C.,University of Texas Southwestern Medical Center | Philips G.T.,University of Texas Southwestern Medical Center | Philips G.T.,New York University | Herz J.,University of Texas Southwestern Medical Center
Neuron | Year: 2014

Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adultbrain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease (AD) pathogenesis and neurodegeneration. This Review summarizes our current understanding of the role lipoprotein receptors play in CNS function and AD pathology, with a special emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. The low-density lipoprotein receptors have diverse biological functions that transcend lipid metabolism. Lane-Donovan, Philips, and Herz review current understanding of lipoprotein receptor function in the CNS and AD pathology, with an emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. © 2014 Elsevier Inc.

Kriaucionis S.,University of Oxford | Tahiliani M.,New York University
Cold Spring Harbor Perspectives in Biology | Year: 2014

Methylation of the base cytosine in DNA is critical for silencing endogenous retroviruses, regulating gene expression, and establishing cellular identity, and has long been regarded as an indelible epigenetic mark. The recent discovery that the ten eleven translocation (TET) proteins can oxidize 5-methylcyto-sine (5mC) resulting in the formation of 5-hydroxymethylcyto-sine (5hmC) and other oxidized cytosine variants in the genome has triggered a paradigm shift in our understanding of how dynamic changes in DNA methylation regulate transcription and cellular differentiation, thus influencing normal development and disease. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Hasko G.,The New School | Cronstein B.,New York University
Frontiers in Immunology | Year: 2013

Adenosine, a purine nucleoside generated by the dephosphorylation of adenine nucleotides, is a potent endogenous physiologic and pharmacologic regulator of many functions. Adenosine was first reported to inhibit the inflammatory actions of neutrophils nearly 30 years ago and since then the role of adenosine and its receptors as feedback regulators of inflammation has been well established. Here we review the effects of adenosine, acting at its receptors, on neutrophil and monocyte/macrophage function in inflammation. Moreover, we review the role of adenosine in mediating the anti-inflammatory effects of methotrexate, the anchor drug in the treatment of Rheumatoid Arthritis and other inflammatory disorders. © 2013 Haskó and Cronstein.

Teraoka I.,New York University
Optics Communications | Year: 2014

Stabilization of whispering gallery mode (WGM) resonance wavelength by the thermal mechanism, originally presented by Carmon et al. [Optics Express 12 (2004) 4742-4750], is analyzed. Analytical expressions are derived for the resonance peak broadening and roll-off ramp rate in the pump-in wavelength scan. Also obtained are simple expressions for the resonance wavelength fluctuations due to ambient temperature changes and mode power fluctuations. The thermal mechanism does not pass these perturbations onto the WGM resonance wavelength, providing a robust stabilization scheme. © 2013 Elsevier B.V. © 2013 Elsevier Ltd. All rights reserved.

Ginter E.,Institute of Preventive and Clinical Medicine IPCM | Simko V.,New York University
Advances in Experimental Medicine and Biology | Year: 2013

In the second half of the 20th century it became obvious that a relentless increase in Type 2 diabetes mellitus (T2DM), affecting the economically affluent countries, is gradually afficting also the developing world. This chapter shows the threat that the T2DM epidemic represents to mankind, with the astonishing recent discoveries on the role of obesity and of body fat in this metabolic disorder. Presently, the highest prevalence of T2DM is in Saudi Arabia. T2DM is very high in over 10% of adults in the USA, Switzerland and Austria. Prevalence is low in Norway, China and in Iceland. Predictions of epidemiologists for the first third of the 21st century claim up to 2.5 times increase in the prevalence of T2DM in the Middle East, Sub-Saharan Africa, India, rest of Asia and in the Latin America. In China the number of patients with T2DM will double in 2030. In the economically advanced countries the increase will be about 50% in 2030. Increasing urbanization, aging populations, obesity and falling levels of physical activity are all contributing to the rise of T2DM worldwide. The main cause of T2DM pandemic is growing prevalence of obes ity in Europe and USA. In the North America and European Union countries obesity is considered to be responsible for up to 70-90% of T2DM in adult population. The precise mechanism by which obesity leads to insulin resistance and to T2DM is not completely known but it may be related to several biochemical factors such as abnormalities in free fatty acids, adipokines, leptin and other substances. © 2012 Landes Bioscience and Springer Science+Business Media.

Serganov A.,New York University | Patel D.J.,Sloan Kettering Cancer Center
Current Opinion in Structural Biology | Year: 2012

Regulatory mRNAs elements termed riboswitches respond to elevated concentrations of cellular metabolites by modulating expression of associated genes. Riboswitches attain their high metabolite selectivity by capitalizing on the intrinsic tertiary structures of their sensor domains. Over the years, riboswitch structure and folding have been amongst the most researched topics in the RNA field. Most recently, novel structures of single-ligand and cooperative double-ligand sensors have broadened our knowledge of architectural and molecular recognition principles exploited by riboswitches. The structural information has been complemented by extensive folding studies, which have provided several important clues on the formation of ligand-competent conformations and mechanisms of ligand discrimination. These studies have greatly improved our understanding of molecular events in riboswitch-mediated gene expression control and provided the molecular basis for intervention into riboswitch-controlled genetic circuits. © 2012 Elsevier Ltd.

Rosen S.,New York University
Journal of vision | Year: 2014

Crowding is the inability to identify an object among flankers in the periphery. It is due to inappropriate incorporation of features from flanking objects in perception of the target. Crowding is characterized by measuring critical spacing, the minimum distance needed between a target and flankers to allow recognition. The existing Bouma law states that, at a given point and direction in the visual field, critical spacing, measured from the center of a target object to the center of a similar flanking object, is the same for all objects (Pelli & Tillman, 2008). Because flipping an object about its center preserves its center-to-center spacing to other objects, according to the Bouma law, crowding should be unaffected. However, because crowding is a result of feature combination, the location of features within an object might matter. In a series of experiments, we find that critical spacing is affected by the location of features within the flanker. For some flankers, a flip greatly reduces crowding even though it maintains target-flanker spacing and similarity. Our results suggest that the existing Bouma law applies to simple one-part objects, such as a single roman letter or a Gabor patch. Many objects consist of multiple parts; for example, a word is composed of multiple letters that crowd each other. To cope with such complex objects, we revise the Bouma law to say that critical spacing is equal across parts, rather than objects. This accounts for old and new findings. © 2014 ARVO.

Avitabile C.,New York University
Journal of Human Resources | Year: 2012

We use data from the evaluation sample of Mexico's Food Assistance Program (PAL) to study whether including the attendance at health and nutrition classes among the requirements for receiving a transfer affects the health behavior of adults living in localities targeted by the program. The experimental trial has four different treatment types, randomly assigned to four groups of localities, one of which receives the in-kind transfer without the requirement to attend any health or nutrition sessions. Adult women living in localities where the in-kind transfer is conditional on class attendance display a significantly better health behavior than those living in localities where it is not. There is no significant evidence of changes in health outcomes among men. © 2012 by the Board of Regents of the University of Wisconsin System.

Silver J.M.,New York University
Psychiatric Clinics of North America | Year: 2014

A minority of individuals will continue to experience debilitating symptoms for more than several months after sustaining a concussion. These problems may have multiple causes, including persistence of the original concussion symptoms, but they also may be due to factors such as depression and anxiety, physical problems, and psychological issues (including coping with an adverse insurance and legal system). This article reviews the differential diagnosis and treatment strategies for patients with chronic symptoms that persist after a concussion. © 2014 Elsevier Inc.

Marcus G.F.,New York University
Topics in Cognitive Science | Year: 2012

Is the human tendency toward musicality better thought of as the product of a specific, evolved instinct or an acquired skill? Developmental and evolutionary arguments are considered, along with issues of domain-specificity. The article also considers the question of why humans might be consistently and intensely drawn to music if musicality is not in fact the product of a specifically evolved instinct. © 2012 Cognitive Science Society, Inc.

Freedman J.,New York University | Iserovich P.,Columbia University
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. To ascertain the presence of additional pro-inflammatory cytokines in glaucomatous aqueous, and their relationship with IOP. METHODS. To quantify the levels of 23 pro-inflammatory cytokines, and correlate levels with IOP, aqueous humor samples were analyzed from 23 eyes with open angle glaucoma (OAG) undergoing glaucoma filtration procedures, and from 24 Molteno blebs during the hypertensive phase. Control aqueous was derived from 13 eyes without glaucoma undergoing cataract removal. RESULTS. A significant difference (P < 0.05) was noted between hypertensive bleb aqueous and controls in the amount TGF-β2, interleukins IL-6, IL-10, and chemokine (C-X-C motif) ligand 1 (CXCL1; GROα). The levels of these cytokines were higher in the glaucomatous aqueous, but not significantly so. A significant difference was noted in levels of chemokine (CC motif) ligand 2 (CCL2; MCP-1, monocyte chemotactic protein-1) in the glaucoma eye and bleb aqueous compared with controls. Of the 23 cytokines tested for, 19 were found in the bleb group, 14 in the glaucoma group, and 16 in the control group. Compared with controls, all cytokines levels were higher in the glaucoma group and highest in the bleb group. CONCLUSIONS. The study confirms the well documented presence of TGF-β2 in glaucomatous aqueous. The presence of significant levels of CCL2 in glaucomatous aqueous is a new finding. The finding of higher levels of all the cytokines in the aqueous from the encysted blebs, in which the IOP was the highest, suggests that their levels increase with an increase in IOP, as well as the possibility that encysted blebs form cytokines. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Cao P.,State University of New York at Stony Brook | Abedini A.,New York University | Raleigh D.P.,State University of New York at Stony Brook
Current Opinion in Structural Biology | Year: 2013

Amyloid formation in the pancreas by islet amyloid polypeptide (IAPP) leads to β-cell death and dysfunction, contributing to islet transplant failure and to type-2 diabetes. IAPP is stored in the β-cell insulin secretory granules and cosecreted with insulin in response to β-cell secretagogues. IAPP is believed to play a role in the control of food intake, in controlling gastric emptying and in glucose homeostasis. The polypeptide is natively unfolded in its monomeric state, but is one of the most amyloidogenic sequences known. The mechanisms of IAPP amyloid formation in vivo and in vitro are not understood; the mechanisms of IAPP induced cell death are unclear; and the nature of the toxic species is not completely defined. Recent work is shedding light on these important issues. © 2012.

Kolupaeva V.,New York University | Janssens V.,Catholic University of Leuven
FEBS Journal | Year: 2013

The retinoblastoma/pocket protein family is one of the master regulators of the eukaryotic cell cycle. It includes the retinoblastoma protein (Rb) and the related p107 and p130 proteins. The importance of the Rb pathway for homeostasis and tumour suppression is evident from the fact that inactivating mutations in Rb are frequently associated with many cancers. Rbs regulate the cell cycle by controlling the activity of the E2F family of transcription factors. The activity of Rb proteins themselves is modulated by their phosphorylation status at several Ser/Thr residues: phosphorylation by cyclin-dependent kinases inactivates Rb proteins and positively influences the transcription of genes necessary for cell cycle progression. Although the mechanisms of cyclin-dependent kinase-mediated inactivation of Rb proteins are understood in great detail, our knowledge of the process that counteracts Rb phosphorylation is still quite limited. The present review focuses on the Ser/Thr phosphatases that are responsible for the dephosphorylation and thus activation of Rb proteins. Two major scenarios are considered: (a) when pocket proteins are dephosphorylated during regular cell cycle progression and (b) when rapid dephosphorylation is dictated by external stress or growth inhibitory conditions, such as oxidative stress, UV radiation or other DNA-damaging stimuli, and cell differentiation factors. It transpires that protein phosphatase 1 and protein phosphatase 2A can efficiently modulate pocket protein activity in a highly context-dependent manner and both are tightly regulated by the presence of different regulatory subunits or interacting proteins. © 2012 The Authors Journal compilation © 2012 FEBS.

Selesnick I.W.,New York University | Bayram I.,Technical University of Istanbul
IEEE Transactions on Signal Processing | Year: 2014

This paper addresses the problem of sparsity penalized least squares for applications in sparse signal processing, e.g., sparse deconvolution. This paper aims to induce sparsity more strongly than L1 norm regularization, while avoiding non-convex optimization. For this purpose, this paper describes the design and use of non-convex penalty functions (regularizers) constrained so as to ensure the convexity of the total cost function F to be minimized. The method is based on parametric penalty functions, the parameters of which are constrained to ensure convexity of F. It is shown that optimal parameters can be obtained by semidefinite programming (SDP). This maximally sparse convex (MSC) approach yields maximally non-convex sparsity-inducing penalty functions constrained such that the total cost function F is convex. It is demonstrated that iterative MSC (IMSC) can yield solutions substantially more sparse than the standard convex sparsity-inducing approach, i.e., L1 norm minimization. © 2014 IEEE.

Mao H.,New York University | Talbot R.,University of Houston
Atmospheric Chemistry and Physics | Year: 2012

A comprehensive analysis was conducted using long-term continuous measurements of gaseous elemental mercury (Hg 0), reactive gaseous mercury (RGM), and particulate phase mercury (Hg P) at coastal (Thompson Farm, denoted as TF), marine (Appledore Island, denoted as AI), and elevated inland (Pac Monadnock, denoted as PM) sites from the AIRMAP Observatories in southern New Hampshire, USA. Decreasing trends in background Hg 0 were identified in the 7.5-and 5.5-yr records at TF and PM with decline rates of 3.3 parts per quadrillion by volume (ppqv) yr -1 and 6.3 ppqv yr -1, respectively. Common characteristics at these sites were the reproducible annual cycle of Hg 0 with its maximum in winter-spring and minimum in fall, comprised of a positive trend in the warm season (spring-early fall) and a negative one in the cool season (late fall-winter). Year-to-year variability was observed in the warm season decline in Hg 0 at TF varying from a minimum total (complete) seasonal loss of 43 ppqv in 2009 to a maximum of 92 ppqv in 2005, whereas variability remained small at AI and PM. The coastal site TF differed from the other two sites with its exceptionally low levels (as low as below 50 ppqv) in the nocturnal inversion layer possibly due to dissolution in dew water. Measurements of Hg 0 at PM exhibited the smallest diurnal to annual variability among the three environments, where peak levels rarely exceeded 250 ppqv and the minimum was typically 100 ppqv. It should be noted that summertime diurnal patterns at TF and AI were opposite in phase indicating strong sink(s) for Hg 0 during the day in the marine boundary layer, which was consistent with the hypothesis of Hg 0 oxidation by halogen radicals there. Mixing ratios of RGM in the coastal and marine boundary layers reached annual maxima in spring and minima in fall, whereas at PM levels were generally below the limit of detection (LOD) except in spring. RGM levels at AI were higher than at TF and PM indicating a stronger source strength in the marine environment. Mixing ratios of Hg P at AI and TF were close in magnitude to RGM levels and were mostly below 1 ppqv. Diurnal variation in Hg P was barely discernible at TF and AI in spring and summer. Higher levels of HgP were observed during the day, while values that were smaller, but above the LOD, occurred at night. © 2012 Author(s).

Rowan M.,New York University
Theoretical Criminology | Year: 2012

This article begins by arguing against the claim of some scholars that the opinions and attitudes of ordinary citizens about criminal justice policy are bounded either by feelings of hostility toward criminal offenders or by indifference toward their rights as human beings. The purpose of this discussion will be to demonstrate that there is sufficient cause to think that meaningful democratic engagement on criminal justice issues is possible, such that an inquiry into the democratic legitimacy of criminal justice policy is worth taking up. This discussion sets the stage for an inquiry into the conditions of democratic legitimacy. The article critiques the view that institutionalized deliberation is a sufficient condition for regarding criminal justice policies as legitimate and argues instead for a radical-democratic approach to evaluating the democratic legitimacy of criminal justice policies. © SAGE Publications 2011.

Brataas A.,Norwegian University of Science and Technology | Kent A.D.,New York University | Ohno H.,Tohoku University
Nature Materials | Year: 2012

The magnetization of a magnetic material can be reversed by using electric currents that transport spin angular momentum. In the reciprocal process a changing magnetization orientation produces currents that transport spin angular momentum. Understanding how these processes occur reveals the intricate connection between magnetization and spin transport, and can transform technologies that generate, store or process information via the magnetization direction. Here we explain how currents can generate torques that affect the magnetic orientation and the reciprocal effect in a wide variety of magnetic materials and structures. We also discuss recent state-of-the-art demonstrations of current-induced torque devices that show great promise for enhancing the functionality of semiconductor devices. © 2012 Macmillan Publishers Limited. All rights reserved.

Reiss A.B.,Winthrop University | Cronstein B.N.,New York University
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Macrophages rely on reverse cholesterol transport mechanisms to rid themselves of excess cholesterol. By reducing accumulation of cholesterol in the artery wall, reverse cholesterol transport slows or prevents development of atherosclerosis. In stable macrophages, efflux mechanisms balance influx mechanisms, and accumulating lipids do not overwhelm the cell. Under atherogenic conditions, inflow of cholesterol exceeds outflow, and the cell is ultimately transformed into a foam cell, the prototypical cell in the atherosclerotic plaque. Adenosine is an endogenous purine nucleoside released from metabolically active cells by facilitated diffusion and generated extracellularly from adenine nucleotides. Under stress conditions, such as hypoxia, a depressed cellular energy state leads to an acute increase in the extracellular concentration of adenosine. Extracellular adenosine interacts with 1 or more of a family of G protein-coupled receptors (A 1, A 2A, A 2B, and A 3) to modulate the function of nearly all cells and tissues. Modulation of adenosine signaling participates in regulation of reverse cholesterol transport. Of particular note for the development of atherosclerosis, activation of A 2A receptors dramatically inhibits inflammation and protects against tissue injury. Potent antiatherosclerotic effects of A 2A receptor stimulation include inhibition of macrophage foam cell transformation and upregulation of the reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP binding cassette transporter A1. Thus, A 2A receptor agonists may correct or prevent the adverse effects of inflammatory processes on cellular cholesterol homeostasis. This review focuses on the importance of extracellular adenosine acting at specific receptors as a regulatory mechanism to control the formation of foam cells under conditions of lipid loading. © 2012 American Heart Association, Inc.

Postmenopausal bleeding is "cancer until proven otherwise." A thin distinct endometrial echo on transvaginal ultrasound has a risk of malignancy of 1 in 917 and does not require an endometrial biopsy. If the endometrial echo is poorly visualized, then in such women, saline infusion sonohysterography is an appropriate next step. The prevalence of asymptomatic endometrial thickening (mostly due to inactive polyps) is high, approximately 10% to 17% of postmenopausal women. The risk of malignancy in such polyps is low (approximately 0.1%), and in structures that mimic polyps, it is also low (0.3%). The incidence of serious complications from an operative intervention in such postmenopausal women is not insignificant (1.3%-3.6%). Thus, automatic intervention in such women, without any high-risk status, is not warranted. © 2011 by The North American Menopause Society.

Blaser M.J.,New York University
Journal of Clinical Investigation | Year: 2014

The collection of bacteria, viruses, and fungi that live in and on the human body, collectively known as the microbiome, has recently emerged as an important factor in human physiology and disease. The gut in particular is a biological niche that is home to a diverse array of microbes that influence nearly all aspects of human biology through their interactions with their host; new technologies are beginning to reveal important aspects of host-microbe interactions. Articles in this Review series address how perturbations of the microbiota, such as through antibiotic use, influence its overall structure and function; how our microbiome influences the impact of infectious agents, such as C. difficile; how our microbiome mediates metabolism of xenobiotics; how the microbiota contribute to immunity as well as to metabolic and inflammatory diseases; and the role of commensal microbes in oncogenesis.

Babesiosis is an emerging arthropod-borne infection that has been increasing in incidence for the last decade in the northeastern United States. Babesiosis may share features of its landscape epidemiology with other arthropod-borne infections transmitted by the same tick vectors in similar geographic spaces. This study examined 11 years of surveillance data in New York State to measure the relationship between forest fragmentation and the incidence of human babesiosis. Adjusted Poisson models showed that increasing edges of contact between forested land and developed land, as measured by their shared perimeters, was associated with a higher incidence of babesiosis cases (incident rate ratio [IRR]=1.015, 95% confidence interval [CI] 1.01-1.02; p<0.001), even after controlling for the total developed land area and forest density, and temperature and precipitation. Each 10-km increase in perimeter contact between forested land and developed land per county was associated with a 1.5% increase in babesiosis risk. Higher temperature was also strongly associated with increasing babesiosis risk (IRR=1.18, 95% CI 1.10-1.27; p<0.001), wherein each degree Celsius increase was associated with an 18% increase in babesiosis risk. While direct causal conclusions cannot be drawn from these data, these findings do identify a potentially important signal in the epidemiology of babesiosis and suggest that the underlying physical landscape may play a role in shaping points of contact between humans and tick vectors and the subsequent transmission of Babesia microti. © Copyright 2013, Mary Ann Liebert, Inc. 2013.

Goff D.C.,New York University
Schizophrenia Bulletin | Year: 2012

As a partial agonist at the glycine site of the NMDA receptor, D-cycloserine (DCS) has been viewed as lacking potency to fully test the NMDA receptor hypofunction theory of schizophrenia. However, findings of full agonist activity at a subset of NMDA receptors that may have particular relevance to schizophrenia, plus a growing body of evidence demonstrating enhancement of learning and neuroplasticity in animal models, suggest novel therapeutic strategies with DCS in schizophrenia. Preliminary studies with once-weekly administration have supported this potential new role for DCS in schizophrenia by demonstrating benefit for negative symptoms, memory consolidation, and facilitation of cognitive behavioral therapy for delusions. © 2012 The Author.

Cohen D.J.,New York University
Hematology/Oncology Clinics of North America | Year: 2012

The Hedgehog (Hh) pathway is a signaling cascade that is evolutionally highly conserved and plays an important role in embryonic pattern formation and stem cell response to tissue damage. Given the pivotal role the Hh pathway plays in embryonic development in terms of proliferation and differentiation, it is not surprising that it has also been implicated in tumorigenesis and tumor growth acceleration in a vast variety of malignancies. This article summarizes the mechanism of Hh pathway signal transduction, discusses the models of pathway activation, reviews the clinical data using Hh inhibitors, and discusses challenges to the development of pathway inhibitors. © 2012 Elsevier Inc..

Zephyrin L.C.,New York University
Obstetrics and Gynecology | Year: 2016

There are more than 2 million women veterans living in the United States. Many women do not identify themselves as veterans. As women's health care providers, it is important to understand and recognize the potentially complex health and social needs of women veterans and the role of military service on their lives. The reproductive health needs of women veterans may be shaped by their military experiences and coexisting medical or mental health conditions. Military sexual trauma and combat exposure are common causes of posttraumatic stress disorder and can affect overall health and well-being. Screening for military service is important in all women, and inclusion of this as a key demographic variable in research and clinical encounters can further inform health care considerations. The following key topics are addressed: who are women veterans, health and social risk factors associated with a history of military service, reproductive health across the life course, military sexual trauma and reproductive health of women veterans, how to take a military history, and the essential role of women's health providers, including obstetrician-gynecologists, in enhancing health systems and providing high-quality care to veterans. © 2016 by The American College of Obstetricians and Gynecologists.

Chirico W.J.,New York University
BMC Cell Biology | Year: 2011

Background: Nonclassical (unconventional) protein secretion is thought to represent the primary secretion mechanism for several cytosolic proteins, such as HIV-Tat, galectin 1, interleukin-1β, and several proteins that shuttle between the nucleus and cytosol, such as fibroblast growth factor 1 (FGF1), FGF2, and nucleolin. Four nonclassical secretory pathways have been described including direct transport (presumably through transporters in the plasma membrane), secretion via exosomes, lysosomal secretion, and blebbing. The purpose of this study was to gain mechanistic insight into nonclassical protein secretion using phosphoglycerate kinase 1 (PGK1), a previously identified nonclassical secretory protein, as a reporter protein.Results: Upon shifting HeLa cells into serum-free media PGK1 was released as a free soluble protein without cell loss. Release occurred in two phases: a rapid early phase and a slow late phase. Using a repertory of inhibitors, PGK1 release was shown not to rely on the classical secretory pathway. However, components of the cytoskeleton partially contributed to its release. Significantly, the presence of serum or bovine serum albumin in the media inhibited PGK1 release.Conclusions: These results are consistent with a novel model of protein release termed oncotic release, in which a change in the colloidal osmotic pressure (oncotic pressure) upon serum withdrawal creates nonlethal oncotic pores in the plasma membrane through which PGK1 - and likely other nearby proteins - are released before the pores are rapidly resealed. These findings identify an alternative mechanism of release for FGF1, HIV-Tat, and galectin 1 whose reported nonclassical secretion is induced by serum withdrawal. Oncotic release may occur in routine cell biological experiments during which cells are washed with serum-free buffers or media and in pathophysiological conditions, such as edema, during which extracellular protein concentrations change. © 2011 Chirico; licensee BioMed Central Ltd.

Schlame M.,New York University
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2013

Cardiolipin, the specific phospholipid of mitochondria, is involved in the biogenesis, the dynamics, and the supramolecular organization of mitochondrial membranes. Cardiolipin acquires a characteristic composition of fatty acids by post-synthetic remodeling, a process that is crucial for cardiolipin homeostasis and function. The remodeling of cardiolipin depends on the activity of tafazzin, a non-specific phospholipid-lysophospholipid transacylase. This review article discusses recent findings that suggest a novel function of tafazzin in mitochondrial membranes. By shuffling fatty acids between molecular species, tafazzin transforms the lipid composition and by doing so supports changes in the membrane conformation, specifically the generation of membrane curvature. Tafazzin activity is critical for the differentiation of cardiomyocytes, in which the characteristic cristae-rich morphology of cardiac mitochondria evolves. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. © 2012 Elsevier B.V.

Homeostatic synaptic plasticity is a negative-feedback mechanism for compensating excessive excitation or inhibition of neuronal activity. When neuronal activity is chronically suppressed, neurons increase synaptic strength across all affected synapses via synaptic scaling. One mechanism for this change is alteration of synaptic AMPA receptor (AMPAR) accumulation. Although decreased intracellular Ca2+ levels caused by chronic inhibition of neuronal activity are believed to be an important trigger of synaptic scaling, the mechanism of Ca2+-mediated AMPAR-dependent synaptic scaling is not yet understood. Here, we use dissociated mouse cortical neurons and employ Ca2+ imaging, electrophysiological, cell biological, and biochemical approaches to describe a novel mechanism in which homeostasis of Ca2+ signaling modulates activity deprivation-induced synaptic scaling by three steps: (1) suppression of neuronal activity decreases somatic Ca2+ signals; (2) reduced activity of calcineurin, a Ca2+-dependent serine/threonine phosphatase, increases synaptic expression of Ca2+-permeable AMPARs (CPARs) by stabilizing GluA1 phosphorylation; and (3) Ca2+ influx via CPARs restores CREB phosphorylation as a homeostatic response by Ca2+-induced Ca2+ release from the ER. Therefore, we suggest that synaptic scaling not only maintains neuronal stability by increasing postsynaptic strength but also maintains nuclear Ca2+ signaling by synaptic expression of CPARs and ER Ca2+ propagation.

The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility complex genes. In addition, fungal-killing genes had significantly greater expression in frogs previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases. However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings, suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus. Copyright © 2014 Ellison et al.

Irvine W.T.M.,James Franck Institute | Bowick M.J.,Syracuse University | Chaikin P.M.,New York University
Nature Materials | Year: 2012

Understanding the effect of curvature and topological frustration in crystals yields insights into the fragility of the ordered state. For instance, a one-dimensional crystal of identical charged particles can accommodate an extra particle (interstitial) if all the particle positions are readjusted, yet in a planar hexagonal crystal interstitials remain trapped between lattice sites and diffuse by hopping. Using optical tweezers operated independently of three-dimensional imaging, we inserted interstitials in a lattice of similar colloidal particles sitting on flat or curved oil/glycerol interfaces, and imaged the ensuing dynamics. We find that, unlike in flat space, the curved crystals self-heal through a collective particle rearrangement that redistributes the increased density associated with the interstitial. This process can be interpreted in terms of the out-of-equilibrium interaction of topological defects with each other and with the underlying curvature. Our observations suggest the existence of particle fractionalization on curved surface crystals. © 2012 Macmillan Publishers Limited. All rights reserved.

Kanellopoulos A.J.,Laservisiongr Eye Institute | Kanellopoulos A.J.,New York University | Asimellis G.,Laservisiongr Eye Institute
American Journal of Ophthalmology | Year: 2014

Purpose To evaluate in vivo epithelial thickness in dry eye by anterior segment optical coherence tomography. Design Observational, retrospective case-control study. Methods Two age-matched groups of female subjects, 70 eyes each, age ≈ 55 years, were studied in clinical practice setting: a control (unoperated, no ocular pathology) and a dry eye group (clinically confirmed dry eye, unoperated and no other ocular pathology). Corneal epithelium over the entire cornea was topographically imaged via a novel anterior segment optical coherence tomography (AS-OCT) system. Average, central, and peripheral epithelial thickness as well as topographic epithelial thickness variability were measured. Results For the control group, central epithelial thickness was 53.0 ± 2.7 μm (45-59 μm). Average epithelium thickness was 53.3 ± 2.7 μm (46.7-59.6 μm). Topographic thickness variability was 1.9 ± 1.1 μm (0.7-6.1 μm). For the dry eye group, central epithelial thickness was 59.5 ± 4.2 μm (50-72 μm) and average thickness was 59.3 ± 3.4 μm (51.4-70.5 μm). Topographic thickness variability was 2.5 ± 1.5 μm (0.9-6.9 μm). All pair tests of respective epithelium thickness metrics between the control and dry eye group show statistically significant difference (P <.05). Conclusions This study, based on very user-friendly, novel AS-OCT imaging, indicates increased epithelial thickness in dry eyes. The ease of use and the improved predictability offered by AS-OCT epithelial imaging may be a significant clinical advantage. Augmented epithelial thickness in the suspect cases may be employed as an objective clinical indicator of dry eye. © 2014 by Elsevier Inc. All rights reserved.

Sexual boundary violations are as old as psychoanalysis itself. Yet, although this professional, intellectual, clinical, and personal dilemma is receiving more attention in the literature, it endures. Do analysts not want to think or talk about it? Is our shared shame, or even ambivalence, in the way? Is the primal crime inherently unstoppable? The author examines her own experience of a sexual boundary violation from clinical and theoretical perspectives. Locating her analyst's transgression in its 1970s cultural history, the article attempts to decipher what led up to it: What did the analyst do and not do, say and not say? How did the analyst's character combust with her author's to produce a conflagration about which the analyst never spoke and the author/patient remained silent for thirty years? And under what circumstances can the damage inflicted by such an ethical lapse be transformed? © 2011 William Alanson White Institute, New York, NY. All rights reserved.

Over the past several decades, numerous studies have attempted to define the general role that proteins play in the nucleation of biominerals in organisms. Recently, with the emergence of the non-classical nucleation scheme involving pre-nucleation cluster formation, amorphous mineral cluster assembly, and maturation/stabilization scenarios, there is a growing realization that proteins could efficiently regulate many steps in this process, resulting in precise control over the development of biogenic crystals or the indefinite stabilization of amorphous mineral phases in a wide variety of organisms. In this Highlight, we present a generic scheme where nucleation-specific biomineralization proteins containing intrinsically disordered and aggregation-prone sequences assemble to form a liquid- or fluid-like phase similar to that formed in the polymer-induced liquid phase (PILP) and in vitro liquid protein systems. This assembled protein phase is compatible with the physical-chemical properties of prenucleation clusters and amorphous mineral clusters, and can provide an environment for subsequent stabilization and/or transformation of the mineral phase under appropriate conditions and locations. We foresee some important applications arising from Nature's use of protein assemblies to create, stabilize, and transform amorphous mineral precursor phases. © 2013 The Royal Society of Chemistry.

Objective: Ephedrine is not only efficacious in the treatment of numerous ailments, but also has a long history of misuse. Research was needed to examine ephedrine policy over time in order to determine potential regulatory flaws that allowed misuse to continue. Methods: This review is based on primary literature derived from systematic searches of historical and scientific archives, as well as grey literature. Results: Ephedrine managed to pass through numerous regulatory loopholes within seventy years. Despite warnings of misuse over the latter half of the century, ephedrine, and its herbal source, ephedra, were regulated in a piecemeal fashion and remained easily available to the public. Health authorities have struggled to control ephedrine, as an amphetamine "look-alike," as a methamphetamine precursor, as a dietary supplement, and as a medication. Despite being a potentially dangerous stimulant, under-regulation was perhaps more problematic than the substance itself. Conclusions: Tighter control of all ephedrine products, drugs and dietary supplements alike, might have prevented adverse outcomes and allowed this substance to remain available in a safer manner. Stringent regulation of all ephedrine products is necessary to prevent misuse and to protect the public's health. © 2010 Elsevier Ireland Ltd.

Khurana K.K.,New York University
Diagnostic Cytopathology | Year: 2012

The advancement of telecommunication technology in the area of digital transfer of images form distant site has resulted in exploration of this technology in the area of cytopathology. Telecytology facilitates the electronic transmission of microscopic images using static, dynamic, and whole slide imaging systems. Recent articles have generated an interest in the use of this technology for immediate assessment of fine-needle aspirations. Telecytology has potential for use in second opinion, quality assurance, slide archiving, proficiency testing, and distance-based education. This review discusses the current and potential applications of telecytology in cytopathology practice and its limitation and advantages. Copyright © 2012 Wiley Periodicals, Inc.

Angelotta C.,New York University
Journal of Nervous and Mental Disease | Year: 2015

Nonsuicidal self-injury (NSSI) is a newly proposed diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Some contemporary historiography dismisses NSSI as a fiction of modern psychiatry. Although the exact definition and psychological meaning attributed to self-harm has not been static over history, there is a clear thread that connects Western asylum psychiatrists' thinking about self-harm to the current stand-alone diagnostic category of NSSI. Nineteenth-century psychiatrists identified a clinically meaningful difference between self-harm with and without the intent to die, between self-injurers who were psychotic and those who were not, and between self-injurers who made a single, serious mutilation and those who repetitively self-injured without causing permanent bodily damage. These same distinctions are apparent in the definition of NSSI. Thus, NSSI is a formalization of long-held observations about a category of people who repetitively self-injure without suicidal intent. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Demographic scholarship suggests that schooling plays an important role in transforming fertility preferences in the early stages of fertility decline. However, there is limited evidence on the relationship between schooling and fertility preferences that addresses the endogeneity of schooling. I use the implementation of Universal Primary Education (UPE) policies in Malawi, Uganda, and Ethiopia in the mid-1990s to conduct a fuzzy regression discontinuity analysis of the effect of schooling on women’s desired fertility. Findings indicate that increased schooling reduced women’s ideal family size and very high desired fertility across all three countries. Additional analyses of potential pathways through which schooling could have affected desired fertility suggest some pathways—such as increasing partner’s education—were common across contexts, whereas other pathways were country-specific. This analysis contributes to demographic understandings of the factors influencing individual-level fertility behaviors and thus aggregate-level fertility decline in sub-Saharan Africa. © 2015, Population Association of America.

Using and adopting Simon Szreter’s framework on how economic growth had a deleterious effect on children’s health during the Industrial Revolution, this article presents a parallel argument that economic growth, in modern times, also has disrupted the lives of our children expressed by increasing rates of childhood obesity. A comprehensive perspective is presented that describes how economic growth in postindustrial United States has distracted our nation’s attention away from a public health’s concern for the health of children and social justice. The new normal of childhood obesity represents a disconnection from the harmful reality of childhood obesity and displaces the value of childhood health too far behind adult’s pursuits of utility. To provide children a fair opportunity to health, and to help children secure their own future liberty and utility, children need to be able to achieve “just levels” of health that would ordinarily exist if remediable injustices that threaten health were reasonably addressed and eliminated. © 2015 Society for Public Health Education.

Wachsmuth D.,New York University
Environment and Planning D: Society and Space | Year: 2014

This paper is a theoretical reexamination of the traditional concept of the city in the context of urbanization processes that exceed it. Recent decades have seen a proliferation of new variations on the city concept, as well as calls to discard it altogether. I argue that both options are inadequate. The city has generally been understood as a category of analysis-a moment in urbanization processes-but might now be better understood as a category of practice: an ideological representation of urbanization processes. I substantiate this claim through an examination of three tropes of the traditional city which in material terms have been superseded in recent decades in the Global North but retain their force as ideological representations of contemporary urban spatial practice: the opposition between city and country, the city as a self-contained system, and the city as an ideal type. © 2014 Pion and its Licensors.

Pastores G.M.,New York University
BioDrugs | Year: 2010

Imiglucerase is a recombinant formulation of human glucocerebrosidase, which is administered to patients with Gaucher disease (GD) as enzyme replacement therapy (ERT). Imiglucerase is generated from transduced Chinese hamster ovary cells, and modified by sequential deglycosylation of its carbohydrate side chains to expose α-mannosyl residues that mediate the uptake of the intravenously infused enzyme. The majority of patients initiate therapy on a fortnightly basis, using imiglucerase doses ranging from 30 to 60Ukg bodyweight per infusion. Treatment has been shown to either stabilize or reverse several features of GD resulting from hematologic, visceral, and skeletal involvement. The treatment is well tolerated, and infusion-related adverse events such as pruritus and hives, observed primarily in patients who have developed antibodies to the exogenous enzyme, are readily managed. These findings have made ERT the standard of care for patients with GD type 1 (the non-neuronopathic form). Imiglucerase is also given to a majority of GD type 3 patients, as a means of assuaging their systemic problems. However, ERT has not been shown to eliminate the neurologic problems that these patients ultimately experience. Currently, two different enzyme formulations are in clinical trials. In addition, alternative therapeutic options are being explored as a substitute or complementary approach to ERT in the management of GD patients. The latter medications are oral agents that act to reduce substrate load either by inhibiting its synthesis or enhancing the residual activity of the endogenous mutant enzyme. Ongoing investigations are providing new insights into downstream mechanisms of disease, which may serve as further targets for adjunctive treatments. Cost of care considerations remain a topic of debate. © 2010 Adis Data Information BV.

Q fever has been associated with exposure to domesticated livestock and the agricultural industry. However large population-based studies examining the relationship are lacking. This report sought to describe the association between Coxiella burnetii infection and participation in agricultural work in the 2003-2004 National Health and Nutrition Examination Survey. Adjusted logistic regression analysis showed that agricultural workers were six times more likely to have antibody evidence of C. burnetii infection than those employed in other occupations (odds ratio 6·5, 95% confidence interval 1·7- 25·3). These findings suggest that agricultural workers may experience greater C. burnetii infection and emphasize an important need for more detailed study of people engaged in this work. © 2011 Cambridge University Press.

Salzer J.L.,New York University
Cold Spring Harbor Perspectives in Biology | Year: 2015

Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between axons and Schwann cells. Extrinsic signals from the axon, and the extracellular matrix, drive Schwann cells to adopt a myelinating fate, whereas myelination reorganizes the axon for its role in conduction and is essential for its integrity. Here, we review our current understanding of the development, molecular organization, and function ofmyelinating Schwann cells. Recent findings into the extrinsic signals that drive Schwann cell myelination, their cognate receptors, and the downstream intracellular signaling pathways they activate will be described. Together, these studies provide important new insights into how these pathways converge to activate the transcriptional cascade of myelination and remodel the actin cytoskeleton that is critical for morphogenesis of the myelin sheath. © 2015, Cold Spring Harbor Laboratory Press; all rights reserved.

IMPORTANCE: Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature. OBJECTIVES: To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature. DESIGN AND SETTING: Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. MAIN OUTCOMES AND MEASURES: For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. RESULTS: Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published. CONCLUSIONS AND RELEVANCE: When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct. Copyright 2015 American Medical Association. All rights reserved.

Taouli B.,New York University | Koh D.-M.,Royal Marsden Hospital
Radiology | Year: 2010

Magnetic resonance (MR) imaging plays an increasingly important role in the evaluation of patients with liver disease because of its high contrast resolution, lack of ionizing radiation, and the possibility of performing functional imaging sequences. With advances in hardware and coil systems, diffusion-weighted (DW) MR imaging can now be applied to liver imaging with improved image quality. DW MR imaging enables qualitative and quantitative assessment of tissue diffusivity (apparent diffusion coefficient) without the use of gadolinium chelates, which makes it a highly attractive technique, particularly in patients with severe renal dysfunction at risk for nephrogenic systemic fibrosis. In this review, acquisition parameters, postprocessing, and quantification methods applied to liver DW MR imaging will be discussed. The current clinical uses of DW MR imaging (liver lesion detection and characterization, compared and combined with conventional sequences) and the emerging applications of DW MR imaging (tumor treatment response and diagnosis of liver fibrosis and cirrhosis) will be reviewed. Also, limitations, mainly image quality and reproducibility of diffusion parameters, and future directions of liver DW MR imaging will be discussed. © RSNA, 2010.

Transcription-coupled repair (TCR) is a phenomenon that exists in a wide variety of organisms from bacteria to humans. This mechanism allows cells to repair the actively transcribed DNA strand much faster than the non-transcribed one. At the sites of bulky DNA damage RNA polymerase stalls, initiating recruitment of the repair machinery. It is a commonly accepted paradigm that bacterial cells utilize a sole coupling factor, called Mfd to initiate TCR. According to that model, Mfd removes transcription complexes stalled at the lesion site and simultaneously recruits repair machinery. However, this model was recently put in doubt by various discrepancies between the proposed universal role of Mfd in the TCR and its biochemical and phenotypical properties. Here, I present a second pathway of bacterial TCR recently discovered in my laboratory, which does not involve Mfd but implicates a common repair factor, UvrD, in a central position in the process. © 2015 WILEY Periodicals, Inc.

Delmar M.,New York University
Pediatric Cardiology | Year: 2012

Most commonly, arrhythmogenic cardiomyopathy (also known as arrhythmogenic right ventricular cardiomyopathy, or ARVC) is caused by mutations in desmosomal proteins. The question arises as to the mechanisms by which mutations in mechanical junctions, affect the rhythm of the heart. We have proposed that a component of the arrhythmogenic substrate may include changes in the function of both, gap junctions and sodium channels. Here, we review the relevant literature on this subject. © Springer Science+Business Media,