Showing papers by "Dartmouth College published in 2011"
TL;DR: The ease, low cost and flexibility of the microtiter plate assay has made it a critical tool for the study of biofilm formation, and this protocol will focus on the use of this assay to studyBiofilm formation by the model organism Pseudomonas aeruginosa.
Abstract: Biofilms are communities of microbes attached to surfaces, which can be found in medical, industrial and natural settings. In fact, life in a biofilm probably represents the predominate mode of growth for microbes in most environments. Mature biofilms have a few distinct characteristics. Biofilm microbes are typically surrounded by an extracellular matrix that provides structure and protection to the community. Microbes growing in a biofilm also have a characteristic architecture generally comprised of macrocolonies (containing thousands of cells) surrounded by fluid-filled channels. Biofilm-grown microbes are also notorious for their resistance to a range of antimicrobial agents including clinically relevant antibiotics. The microtiter dish assay is an important tool for the study of the early stages in biofilm formation, and has been applied primarily for the study of bacterial biofilms, although this assay has also been used to study fungal biofilm formation. Because this assay uses static, batch-growth conditions, it does not allow for the formation of the mature biofilms typically associated with flow cell systems. However, the assay has been effective at identifying many factors required for initiation of biofilm formation (i.e, flagella, pili, adhesins, enzymes involved in cyclic-di-GMP binding and metabolism) and well as genes involved in extracellular polysaccharide production. Furthermore, published work indicates that biofilms grown in microtiter dishes do develop some properties of mature biofilms, such a antibiotic tolerance and resistance to immune system effectors. This simple microtiter dish assay allows for the formation of a biofilm on the wall and/or bottom of a microtiter dish. The high throughput nature of the assay makes it useful for genetic screens, as well as testing biofilm formation by multiple strains under various growth conditions. Variants of this assay have been used to assess early biofilm formation for a wide variety of microbes, including but not limited to, pseudomonads, Vibrio cholerae, Escherichia coli, staphylococci, enterococci, mycobacteria and fungi. In the protocol described here, we will focus on the use of this assay to study biofilm formation by the model organism Pseudomonas aeruginosa. In this assay, the extent of biofilm formation is measured using the dye crystal violet (CV). However, a number of other colorimetric and metabolic stains have been reported for the quantification of biofilm formation using the microtiter plate assay. The ease, low cost and flexibility of the microtiter plate assay has made it a critical tool for the study of biofilms.
1,631 citations
TL;DR: In this article, the authors evaluated the importance of financial literacy by studying its relation to the stock market: are more financially knowledgeable individuals more likely to hold stocks? To assess the direction of causality, they make use of questions measuring financial knowledge before investing in the stock markets.
1,591 citations
TL;DR: Nipype solves issues by providing Interfaces to existing neuroimaging software with uniform usage semantics and by facilitating interaction between these packages using Workflows, and provides an environment that encourages interactive exploration of algorithms, eases the design of Workflows within and between packages, and reduces the learning Curve.
Abstract: Current neuroimaging software offer users an incredible opportunity to analyze their data in different ways, with different underlying assumptions. Several sophisticated software packages (e.g., AFNI, BrainVoyager, FSL, FreeSurfer, Nipy, R, SPM) are used to process and analyze large and often diverse (highly multi-dimensional) data. However, this heterogeneous collection of specialized applications creates several issues that hinder replicable, efficient and optimal use of neuroimaging analysis approaches: 1) No uniform access to neuroimaging analysis software and usage information; 2) No framework for comparative algorithm development and dissemination; 3) Personnel turnover in laboratories often limits methodological continuity and training new personnel takes time; 4) Neuroimaging software packages do not address computational efficiency; and 5) Methods sections in journal articles are inadequate for reproducing results. To address these issues, we present Nipype (Neuroimaging in Python: Pipelines and Interfaces; http://nipy.org/nipype), an open-source, community-developed, software package and scriptable library. Nipype solves the issues by providing Interfaces to existing neuroimaging software with uniform usage semantics and by facilitating interaction between these packages using Workflows. Nipype provides an environment that encourages interactive exploration of algorithms, eases the design of Workflows within and between packages, allows rapid comparative development of algorithms and reduces the learning curve necessary to use different packages. Nipype supports both local and remote execution on multi-core machines and clusters, without additional scripting. Nipype is BSD licensed, allowing anyone unrestricted usage. An open, community-driven development philosophy allows the software to quickly adapt and address the varied needs of the evolving neuroimaging community, especially in the context of increasing demand for reproducible research.
1,343 citations
University of Kentucky1, Dartmouth College2, Washington University in St. Louis3, Wake Forest University4, Anschutz Medical Campus5, Oregon Health & Science University6, Society of Thoracic Surgeons7, Yeshiva University8, Stanford University9, University of Toronto10, Englewood Hospital and Medical Center11, Duke University12, University of Pittsburgh13, Flinders University14, Harvard University15
TL;DR: Much has changed since the previously published 2007 STS blood management guidelines and this document contains new and revised recommendations.
1,090 citations
Constantine A. Gatsonis1, Denise R. Aberle2, Christine D. Berg, William C. Black3 +1333 more•Institutions (31)
TL;DR: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer.
Abstract: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5% It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest The NLST is such a trial The rationale for and design of the NLST are presented
1,036 citations
TL;DR: A compilation of the patterns of fossil and molecular diversification, comparative developmental data, and information on ecological feeding strategies indicate that the major animal clades diverged many tens of millions of years before their first appearance in the fossil record.
Abstract: Diverse bilaterian clades emerged apparently within a few million years during the early Cambrian, and various environmental, developmental, and ecological causes have been proposed to explain this abrupt appearance. A compilation of the patterns of fossil and molecular diversification, comparative developmental data, and information on ecological feeding strategies indicate that the major animal clades diverged many tens of millions of years before their first appearance in the fossil record, demonstrating a macroevolutionary lag between the establishment of their developmental toolkits during the Cryogenian [(850 to 635 million years ago (Ma)], and the later ecological success of metazoans during the Ediacaran (635 to 541 Ma) and Cambrian (541 to 488 Ma) periods. We argue that this diversification involved new forms of developmental regulation, as well as innovations in networks of ecological interaction within the context of permissive environmental circumstances.
1,029 citations
TL;DR: In this article, an ultra-high-density array that tiles the promoters of 56 cell-cycle genes was used to interrogate 108 samples representing diverse perturbations, identifying 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle.
Abstract: Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.
969 citations
01 Jun 2011
TL;DR: This work uses an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations and identifies 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle.
Abstract: Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.
933 citations
TL;DR: Why the line between dynamic and operational capabilities is unavoidably blurry is explained, implications for capabilities that promote economically important but seemingly gradual change are drawn, and recommendations for future research are provided.
Abstract: We explain why the line between dynamic and operational (or ordinary) capabilities is unavoidably blurry, draw implications for capabilities that promote economically important but seemingly gradual change, and provide recommendations for future research that takes these issues into account. Copyright © 2011 John Wiley & Sons, Ltd.
932 citations
TL;DR: In this article, the early stages of biofilm formation are examined using static biofilm assays, which are suitable for either small or relatively large-scale studies and can be used individually or in combination for the study of biofilms.
Abstract: Many bacteria can exist as surface-attached aggregations known as biofilms. Presented in this unit are several approaches for the study of these communities. The focus here is on static biofilm systems, which are particularly useful for examination of the early stages of biofilm formation, including initial adherence to the surface and microcolony formation. Furthermore, most of the techniques presented are easily adapted to the study of biofilms under a variety of conditions and are suitable for either small- or relatively large-scale studies. Unlike assays involving continuous-flow systems, the static biofilm assays described here require very little specialized equipment and are relatively simple to execute. In addition, these static biofilm systems allow analysis of biofilm formation with a variety of readouts, including microscopy of live cells, macroscopic visualization of stained bacteria, and viability counts. Used individually or in combination, these assays provide useful means for the study of biofilms.
923 citations
University of Edinburgh1, Public Health Foundation of India2, International Centre for Diarrhoeal Disease Research, Bangladesh3, Centers for Disease Control and Prevention4, University of Barcelona5, University of Oxford6, University of the Witwatersrand7, National Institutes of Health8, University of California, Berkeley9, Fukushima Medical University10, Medical Research Council11, All India Institute of Medical Sciences12, University of Colorado Denver13, Research Institute for Tropical Medicine14, Kenya Medical Research Institute15, Johns Hopkins University16, Pasteur Institute17, Delta State University18, University of Pretoria19, Columbia University20, World Health Organization21, Emory University22, Dartmouth College23, University of Split24
TL;DR: The role of influenza in childhood mortality from ALRI is estimated by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality.
TL;DR: Recent neuroimaging research on self-regulatory failure is highlighted, which support a balance model of self-regulation whereby self-Regulatory failure occurs whenever the balance is tipped in favor of subcortical areas, either due to particularly strong impulses or when prefrontal function itself is impaired.
01 Jan 2011
TL;DR: The authors summarizes the recent literature on peer effects in student outcomes at the elementary, secondary, and post-secondary levels at the university and high school levels. But the linear-in-means model masks considerable heterogeneity in the effects experienced by different types of students.
Abstract: This chapter summarizes the recent literature on peer effects in student outcomes at the elementary, secondary, and post-secondary levels. Linear-in-means models find modest sized and statistically significant peer effects in test scores. But the linear-in-means model masks considerable heterogeneity in the effects experienced by different types of students. Using nonlinear models, one prevalent finding is larger peer effects in which high ability students benefit from the presence of other high ability students. Studies that stratify students by race and ability often find that students are affected both by the racial composition of their peers and by the achievement of their same-race peers. At the university level, several studies find modest sized effects from dormmate and roommate background on own academic performance. For both university and high school students, the measured peer effects on “social” outcomes such as drinking are larger than the effects on academic outcomes. Many authors find substantial peer effects in drinking, drug use, and criminal behavior. This chapter suggest areas for future investigation and data collection.
California Institute of Technology1, Johns Hopkins University2, University of Arizona3, University of California, Los Angeles4, Monterey Institute for Research in Astronomy5, University of Hawaii6, Harvard University7, Dartmouth College8, Notre Dame High School9, Embry–Riddle Aeronautical University10, Goddard Space Flight Center11, University of Maryland, College Park12
TL;DR: The Wide-field Infrared Survey Explorer (WISE) has surveyed the entire sky at four infrared wavelengths with greatly improved sensitivity and spatial resolution compared to its predecessors, the Infrared Astronomical Satellite and the Cosmic Background Explorer.
Abstract: The Wide-field Infrared Survey Explorer (WISE) has surveyed the entire sky at four infrared wavelengths with greatly improved sensitivity and spatial resolution compared to its predecessors, the Infrared Astronomical Satellite and the Cosmic Background Explorer. NASA's Planetary Science Division has funded an enhancement to the WISE data processing system called "NEOWISE" that allows detection and archiving of moving objects found in the WISE data. NEOWISE has mined the WISE images for a wide array of small bodies in our solar system, including near-Earth objects (NEOs), Main Belt asteroids, comets, Trojans, and Centaurs. By the end of survey operations in 2011 February, NEOWISE identified over 157,000 asteroids, including more than 500 NEOs and ~120 comets. The NEOWISE data set will enable a panoply of new scientific investigations.
TL;DR: Tether-pulling force measurements in cells and in plasma membrane spheres demonstrate that caveola flattening and disassembly is the primary actin- and ATP-independent cell response that buffers membrane tension surges during mechanical stress.
North Carolina State University1, Commonwealth Scientific and Industrial Research Organisation2, Dartmouth College3, University of Copenhagen4, Canadian Food Inspection Agency5, Natural History Museum6, Wayne State University7, National University of Singapore8, University of Chicago9, University of Illinois at Urbana–Champaign10, Smithsonian Institution11, American Museum of Natural History12, Simon Fraser University13, Iowa State University14
TL;DR: It is demonstrated that flies experienced three episodes of rapid radiation—lower Diptera (220 Ma), lower Brachycera (180 Ma), and Schizophora (65 Ma)—and a number of life history transitions to hematophagy, phytophagy and parasitism in the history of fly evolution over 260 million y.
Abstract: Flies are one of four superradiations of insects (along with beetles, wasps, and moths) that account for the majority of animal life on Earth. Diptera includes species known for their ubiquity (Musca domestica house fly), their role as pests (Anopheles gambiae malaria mosquito), and their value as model organisms across the biological sciences (Drosophila melanogaster). A resolved phylogeny for flies provides a framework for genomic, developmental, and evolutionary studies by facilitating comparisons across model organisms, yet recent research has suggested that fly relationships have been obscured by multiple episodes of rapid diversification. We provide a phylogenomic estimate of fly relationships based on molecules and morphology from 149 of 157 families, including 30 kb from 14 nuclear loci and complete mitochondrial genomes combined with 371 morphological characters. Multiple analyses show support for traditional groups (Brachycera, Cyclorrhapha, and Schizophora) and corroborate contentious findings, such as the anomalous Deuterophlebiidae as the sister group to all remaining Diptera. Our findings reveal that the closest relatives of the Drosophilidae are highly modified parasites (including the wingless Braulidae) of bees and other insects. Furthermore, we use micro-RNAs to resolve a node with implications for the evolution of embryonic development in Diptera. We demonstrate that flies experienced three episodes of rapid radiation—lower Diptera (220 Ma), lower Brachycera (180 Ma), and Schizophora (65 Ma)—and a number of life history transitions to hematophagy, phytophagy, and parasitism in the history of fly evolution over 260 million y.
TL;DR: The capacity for efficient crosstalk between the amygdala and the mPFC, which is represented as the strength of the amygdala-mPFC circuitry, is crucial to beneficial outcomes in terms of reported anxiety.
Henry Ford Health System1, University of Kentucky2, Virginia Mason Medical Center3, Mayo Clinic4, University of Arizona5, University of California, San Diego6, Henry Ford Hospital7, Cornell University8, Dartmouth College9, Duke University10, Washington University in St. Louis11, City University of New York12
TL;DR: This guideline provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with sudden sensorineural hearing loss in adult patients (aged 18 and older), with particular emphasis on managing SSNHL.
Abstract: Objective. Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence-based recommendations for the diagnosis...
TL;DR: A new and exciting vista has opened for seaweed extracts in both plant and animal applications as improved analytical techniques and instrumentation coupled with the use of molecular genetic tools are establishing that seaweeds extracts can modify plant andAnimal responses at a fundamental level.
Abstract: Both micro- and macroalgae have long been used to augment plant productivity and food production in various regions of the world through their beneficial effects when applied to soils. Interactions of algae with the soil community undoubtedly are complex and benefits are dependent on the crop and the local environmental conditions. This has resulted in much speculation as to mechanisms involved as well as the validity of the results reported. It is now 60 years since the first commercial seaweed extract was manufactured for agricultural use. These aqueous extracts allowed for the first time the direct application of soluble seaweed constituents to specific plant organs such as leaves and roots. The earlier concept that benefits of seaweeds and their extracts were due mainly to their manurial value or to their micronutrient suites is no longer tenable. Seaweeds likewise have been used for millennia as fodder supplements to improve animal nutrition and productivity. Recent research is focusing on their mode of action, specific health benefits, and the mechanisms of action in animals. Improved analytical techniques and instrumentation coupled with the use of molecular genetic tools are establishing that seaweed extracts can modify plant and animal responses at a fundamental level. It therefore seems appropriate to review key developments over the years and to remark on novel findings. A new and exciting vista has opened for seaweed extracts in both plant and animal applications.
TL;DR: These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date, and the clinical benefits continue to outweigh the risks of adverse effects.
Abstract: Purpose Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis. Results At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event...
TL;DR: This paper developed a general equilibrium model of international trade that features selection across multiple products, products and countries, where firms' export decisions depend on a combination of product productivity and country consumer tastes.
Abstract: This paper develops a general equilibrium model of international trade that features selection across …rms, products and countries. Firms’export decisions depend on a combination of …rm “productivity”and …rm-product-country “consumer tastes”, both of which are stochastic and unknown prior to the payment of a sunk cost of entry. Higher-productivity …rms export a wider range of products to a larger set of countries than lower-productivity …rms. Trade liberalization induces endogenous reallocations of resources that foster productivity growth both within and across …rms. Empirically, we …nd key implications of the model to be consistent with U.S. trade
TL;DR: A high-dimensional model of the representational space in human ventral temporal (VT) cortex in which dimensions are response-tuning functions that are common across individuals and patterns of response are modeled as weighted sums of basis patterns associated with these response tunings is presented.
TL;DR: A new set of diagnostic criteria is proposed for DSM‐5 that attempts to sharpen the A1 criterion, eliminates the A2 criterion, proposes four rather than three symptom clusters, and expands the scope of the B–E criteria beyond a fear‐based context.
Abstract: This is a review of the relevant empirical literature concerning the DSM-IV-TR diagnostic criteria for PTSD. Most of this work has focused on Criteria A1 and A2, the two components of the A (Stressor) Criterion. With regard to A1, the review considers: (a) whether A1 is etiologically or temporally related to the PTSD symptoms; (b) whether it is possible to distinguish "traumatic" from "non-traumatic" stressors; and (c) whether A1 should be eliminated from DSM-5. Empirical literature regarding the utility of the A2 criterion indicates that there is little support for keeping the A2 criterion in DSM-5. The B (reexperiencing), C (avoidance/numbing) and D (hyperarousal) criteria are also reviewed. Confirmatory factor analyses suggest that the latent structure of PTSD appears to consist of four distinct symptom clusters rather than the three-cluster structure found in DSM-IV. It has also been shown that in addition to the fear-based symptoms emphasized in DSM-IV, traumatic exposure is also followed by dysphoric, anhedonic symptoms, aggressive/externalizing symptoms, guilt/shame symptoms, dissociative symptoms, and negative appraisals about oneself and the world. A new set of diagnostic criteria is proposed for DSM-5 that: (a) attempts to sharpen the A1 criterion; (b) eliminates the A2 criterion; (c) proposes four rather than three symptom clusters; and (d) expands the scope of the B-E criteria beyond a fear-based context. The final sections of this review consider: (a) partial/subsyndromal PTSD; (b) disorders of extreme stress not otherwise specified (DESNOS)/complex PTSD; (c) cross- cultural factors; (d) developmental factors; and (e) subtypes of PTSD.
01 Aug 2011
TL;DR: Neuroimaging in Python: Pipelines and interfaces as discussed by the authors is an open-source, community-developed, software package and scriptable library for neuroimaging analysis using Python.
Abstract: Current neuroimaging software offer users an incredible opportunity to analyze their data in different ways, with different underlying assumptions. Several sophisticated software packages (e.g., AFNI, BrainVoyager, FSL, FreeSurfer, Nipy, R, SPM) are used to process and analyze large and often diverse (highly multi-dimensional) data. However, this heterogeneous collection of specialized applications creates several issues that hinder replicable, efficient and optimal use of neuroimaging analysis approaches: 1) No uniform access to neuroimaging analysis software and usage information; 2) No framework for comparative algorithm development and dissemination; 3) Personnel turnover in laboratories often limits methodological continuity and training new personnel takes time; 4) Neuroimaging software packages do not address computational efficiency; and 5) Methods sections in journal articles are inadequate for reproducing results. To address these issues, we present Nipype (Neuroimaging in Python: Pipelines and Interfaces; http://nipy.org/nipype), an open-source, community-developed, software package and scriptable library. Nipype solves the issues by providing Interfaces to existing neuroimaging software with uniform usage semantics and by facilitating interaction between these packages using Workflows. Nipype provides an environment that encourages interactive exploration of algorithms, eases the design of Workflows within and between packages, allows rapid comparative development of algorithms and reduces the learning curve necessary to use different packages. Nipype supports both local and remote execution on multi-core machines and clusters, without additional scripting. Nipype is BSD licensed, allowing anyone unrestricted usage. An open, community-driven development philosophy allows the software to quickly adapt and address the varied needs of the evolving neuroimaging community, especially in the context of increasing demand for reproducible research.
TL;DR: VISTA suppresses T cell proliferation and cytokine production and can influence autoimmunity and antitumor responses in mice.
Abstract: The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. Furthermore, anti-VISTA treatment exacerbates the development of the T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis in mice. Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. These findings show that VISTA, a novel immunoregulatory molecule, has functional activities that are nonredundant with other Ig superfamily members and may play a role in the development of autoimmunity and immune surveillance in cancer.
Lawrence Berkeley National Laboratory1, University of California, Berkeley2, University of Oxford3, University of California, Santa Barbara4, Las Cumbres Observatory Global Telescope Network5, Liverpool John Moores University6, California Institute of Technology7, Dartmouth College8, University of Toronto9, University of Tokyo10, Scuola Normale Superiore di Pisa11, Max Planck Society12, Weizmann Institute of Science13, Tel Aviv University14
TL;DR: Early observations of type Ia supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs find that the exploding star was probably a carbon–oxygen white dwarf, and from the lack of an early shock it is concluded that the companion was likely a main-sequence star.
Abstract: Type Ia supernovae have been used empirically as ‘standard candles’ to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon–oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor.
TL;DR: Aflatoxin biomarkers of internal and biologically effective doses have been integral to the establishment of the etiologic role of this toxin in human disease through better estimates of exposure, expanded knowledge of the mechanisms of disease pathogenesis, and as tools for implementing and evaluating preventive interventions.
TL;DR: A systematic review of the literature from 1960 to August 2008 found effective treatments for PDN are available, but many have side effects that limit their usefulness, and few studies have sufficient information on treatment effects on function and QOL.
Abstract: Objective: To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). Methods: We performed a systematic review of the literature from 1960 to August 2008 and classified the studies according to the American Academy of Neurology classification of evidence scheme for a therapeutic article, and recommendations were linked to the strength of the evidence. The basic question asked was: “What is the efficacy of a given treatment (pharmacologic: anticonvulsants, antidepressants, opioids, others; and nonpharmacologic: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?” Results and Recommendations: Pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness, and few studies have sufficient information on treatment effects on function and QOL. Neurology ® 2011;76:1–1
TL;DR: The concept of reverse innovation as mentioned in this paper refers to the case where an innovation is adopted first in poor (emerging) economies before "trickling up" to rich countries, and it raises interesting theoretical questions, such as what kinds of innovation emerging economies are likely to spawn, why such innovations might diffuse to richer countries, what competitive advantages local and foreign firms enjoy in this process, and how it affects the global strategy and organization of established MNEs.
Abstract: ‘Reverse innovation’ refers to the case where an innovation is adopted first in poor (emerging) economies before ‘trickling up’ to rich countries. Although examples of reverse innovation are still rare, it raises interesting theoretical questions, such as what kinds of innovation emerging economies are likely to spawn, why such innovations might diffuse to rich countries, what competitive advantages local and foreign firms enjoy in this process, and how it affects the global strategy and organization of established MNEs. Research on reverse innovation can enrich and extend mainstream theories of innovation, internationalization, MNE management, and FDI spillovers.