Showing papers by "Stanford University published in 2008"
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Abstract: We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.
13,008 citations
Book•
01 Jan 2008TL;DR: In this article, the authors present an up-to-date treatment of all aspects of the design and implementation of systems for gathering, indexing, and searching documents; methods for evaluating systems; and an introduction to the use of machine learning methods on text collections.
Abstract: Class-tested and coherent, this groundbreaking new textbook teaches web-era information retrieval, including web search and the related areas of text classification and text clustering from basic concepts. Written from a computer science perspective by three leading experts in the field, it gives an up-to-date treatment of all aspects of the design and implementation of systems for gathering, indexing, and searching documents; methods for evaluating systems; and an introduction to the use of machine learning methods on text collections. All the important ideas are explained using examples and figures, making it perfect for introductory courses in information retrieval for advanced undergraduates and graduate students in computer science. Based on feedback from extensive classroom experience, the book has been carefully structured in order to make teaching more natural and effective. Although originally designed as the primary text for a graduate or advanced undergraduate course in information retrieval, the book will also create a buzz for researchers and professionals alike.
11,804 citations
31 Mar 2008
TL;DR: This whitepaper proposes OpenFlow: a way for researchers to run experimental protocols in the networks they use every day, based on an Ethernet switch, with an internal flow-table, and a standardized interface to add and remove flow entries.
Abstract: This whitepaper proposes OpenFlow: a way for researchers to run experimental protocols in the networks they use every day. OpenFlow is based on an Ethernet switch, with an internal flow-table, and a standardized interface to add and remove flow entries. Our goal is to encourage networking vendors to add OpenFlow to their switch products for deployment in college campus backbones and wiring closets. We believe that OpenFlow is a pragmatic compromise: on one hand, it allows researchers to run experiments on heterogeneous switches in a uniform way at line-rate and with high port-density; while on the other hand, vendors do not need to expose the internal workings of their switches. In addition to allowing researchers to evaluate their ideas in real-world traffic settings, OpenFlow could serve as a useful campus component in proposed large-scale testbeds like GENI. Two buildings at Stanford University will soon run OpenFlow networks, using commercial Ethernet switches and routers. We will work to encourage deployment at other schools; and We encourage you to consider deploying OpenFlow in your university network too
9,138 citations
Roger E. McLendon1, Allan H. Friedman1, Darrell D. Bigner1, Erwin G. Van Meir2 +230 more•Institutions (23)
TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Abstract: Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
6,761 citations
TL;DR: The theoretical charge capacity for silicon nanowire battery electrodes is achieved and maintained a discharge capacity close to 75% of this maximum, with little fading during cycling.
Abstract: There is great interest in developing rechargeable lithium batteries with higher energy capacity and longer cycle life for applications in portable electronic devices, electric vehicles and implantable medical devices. Silicon is an attractive anode material for lithium batteries because it has a low discharge potential and the highest known theoretical charge capacity (4,200 mAh g(-1); ref. 2). Although this is more than ten times higher than existing graphite anodes and much larger than various nitride and oxide materials, silicon anodes have limited applications because silicon's volume changes by 400% upon insertion and extraction of lithium which results in pulverization and capacity fading. Here, we show that silicon nanowire battery electrodes circumvent these issues as they can accommodate large strain without pulverization, provide good electronic contact and conduction, and display short lithium insertion distances. We achieved the theoretical charge capacity for silicon anodes and maintained a discharge capacity close to 75% of this maximum, with little fading during cycling.
6,104 citations
TL;DR: Using a coordinate descent procedure for the lasso, a simple algorithm is developed that solves a 1000-node problem in at most a minute and is 30-4000 times faster than competing methods.
Abstract: We consider the problem of estimating sparse graphs by a lasso penalty applied to the inverse covariance matrix. Using a coordinate descent procedure for the lasso, we develop a simple algorithm--the graphical lasso--that is remarkably fast: It solves a 1000-node problem ( approximately 500,000 parameters) in at most a minute and is 30-4000 times faster than competing methods. It also provides a conceptual link between the exact problem and the approximation suggested by Meinshausen and Buhlmann (2006). We illustrate the method on some cell-signaling data from proteomics.
5,577 citations
State Street Corporation1, University of California, Santa Barbara2, University of Hawaii at Manoa3, Stanford University4, Wildlife Conservation Society5, Arizona State University6, University of North Carolina at Chapel Hill7, National Oceanic and Atmospheric Administration8, Environmental Defense Fund9, Ocean Conservancy10, The Nature Conservancy11, University of Maine12, University of British Columbia13
TL;DR: This article developed an ecosystem-specific, multiscale spatial model to synthesize 17 global data sets of anthropogenic drivers of ecological change for 20 marine ecosystems and found that no area is unaffected by human influence and that a large fraction (41%) is strongly affected by multiple drivers.
Abstract: The management and conservation of the world's oceans require synthesis of spatial data on the distribution and intensity of human activities and the overlap of their impacts on marine ecosystems. We developed an ecosystem-specific, multiscale spatial model to synthesize 17 global data sets of anthropogenic drivers of ecological change for 20 marine ecosystems. Our analysis indicates that no area is unaffected by human influence and that a large fraction (41%) is strongly affected by multiple drivers. However, large areas of relatively little human impact remain, particularly near the poles. The analytical process and resulting maps provide flexible tools for regional and global efforts to allocate conservation resources; to implement ecosystem-based management; and to inform marine spatial planning, education, and basic research.
5,365 citations
TL;DR: A novel method for sparse signal recovery that in many situations outperforms ℓ1 minimization in the sense that substantially fewer measurements are needed for exact recovery.
Abstract: It is now well understood that (1) it is possible to reconstruct sparse signals exactly from what appear to be highly incomplete sets of linear measurements and (2) that this can be done by constrained l1 minimization. In this paper, we study a novel method for sparse signal recovery that in many situations outperforms l1 minimization in the sense that substantially fewer measurements are needed for exact recovery. The algorithm consists of solving a sequence of weighted l1-minimization problems where the weights used for the next iteration are computed from the value of the current solution. We present a series of experiments demonstrating the remarkable performance and broad applicability of this algorithm in the areas of sparse signal recovery, statistical estimation, error correction and image processing. Interestingly, superior gains are also achieved when our method is applied to recover signals with assumed near-sparsity in overcomplete representations—not by reweighting the l1 norm of the coefficient sequence as is common, but by reweighting the l1 norm of the transformed object. An immediate consequence is the possibility of highly efficient data acquisition protocols by improving on a technique known as Compressive Sensing.
4,869 citations
TL;DR: This study provides a working guide to boosted regression trees (BRT), an ensemble method for fitting statistical models that differs fundamentally from conventional techniques that aim to fit a single parsimonious model.
Abstract: Summary 1 Ecologists use statistical models for both explanation and prediction, and need techniques that are flexible enough to express typical features of their data, such as nonlinearities and interactions 2 This study provides a working guide to boosted regression trees (BRT), an ensemble method for fitting statistical models that differs fundamentally from conventional techniques that aim to fit a single parsimonious model Boosted regression trees combine the strengths of two algorithms: regression trees (models that relate a response to their predictors by recursive binary splits) and boosting (an adaptive method for combining many simple models to give improved predictive performance) The final BRT model can be understood as an additive regression model in which individual terms are simple trees, fitted in a forward, stagewise fashion 3 Boosted regression trees incorporate important advantages of tree-based methods, handling different types of predictor variables and accommodating missing data They have no need for prior data transformation or elimination of outliers, can fit complex nonlinear relationships, and automatically handle interaction effects between predictors Fitting multiple trees in BRT overcomes the biggest drawback of single tree models: their relatively poor predictive performance Although BRT models are complex, they can be summarized in ways that give powerful ecological insight, and their predictive performance is superior to most traditional modelling methods 4 The unique features of BRT raise a number of practical issues in model fitting We demonstrate the practicalities and advantages of using BRT through a distributional analysis of the short-finned eel ( Anguilla australis Richardson), a native freshwater fish of New Zealand We use a data set of over 13 000 sites to illustrate effects of several settings, and then fit and interpret a model using a subset of the data We provide code and a tutorial to enable the wider use of BRT by ecologists
4,787 citations
TL;DR: A chemical route to produce graphene nanoribbons with width below 10 nanometers was developed, as well as single ribbons with varying widths along their lengths or containing lattice-defined graphene junctions for potential molecular electronics.
Abstract: We developed a chemical route to produce graphene nanoribbons (GNR) with width below 10 nanometers, as well as single ribbons with varying widths along their lengths or containing lattice-defined graphene junctions for potential molecular electronics. The GNRs were solution-phase-derived, stably suspended in solvents with noncovalent polymer functionalization, and exhibited ultrasmooth edges with possibly well-defined zigzag or armchair-edge structures. Electrical transport experiments showed that, unlike single-walled carbon nanotubes, all of the sub-10-nanometer GNRs produced were semiconductors and afforded graphene field effect transistors with on-off ratios of about 10(7) at room temperature.
4,579 citations
TL;DR: Next-generation DNA sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.
Abstract: DNA sequence represents a single format onto which a broad range of biological phenomena can be projected for high-throughput data collection. Over the past three years, massively parallel DNA sequencing platforms have become widely available, reducing the cost of DNA sequencing by over two orders of magnitude, and democratizing the field by putting the sequencing capacity of a major genome center in the hands of individual investigators. These new technologies are rapidly evolving, and near-term challenges include the development of robust protocols for generating sequencing libraries, building effective new approaches to data-analysis, and often a rethinking of experimental design. Next-generation DNA sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.
TL;DR: The cclib platform as discussed by the authors is a platform for the development of package-independent computational chemistry algorithms, which can automatically detect, parse, and convert the extracted information into a standard internal representation.
Abstract: There are now a wide variety of packages for electronic structure calculations, each of which differs in the algorithms implemented and the output format. Many computational chemistry algorithms are only available to users of a particular package despite being generally applicable to the results of calculations by any package. Here we present cclib, a platform for the development of package-independent computational chemistry algorithms. Files from several versions of multiple electronic structure packages are automatically detected, parsed, and the extracted information converted to a standard internal representation. A number of population analysis algorithms have been implemented as a proof of principle. In addition, cclib is currently used as an input filter for two GUI applications that analyze output files: PyMOlyze and GaussSum. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Radboud University Nijmegen1, National Institutes of Health2, Stanford University3, University of California, Los Angeles4, University of Lausanne5, University of Alabama6, University of Paris7, University of Michigan8, University of Texas Health Science Center at San Antonio9, University of Strasbourg10, University of Manchester11, University College London12, Oregon Health & Science University13, Complutense University of Madrid14, University of Aberdeen15, Duke University16, Charité17, University at Buffalo18, Wayne State University19, University of Sydney20, University of Genoa21, University of Florida22, University of Pennsylvania23
TL;DR: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Abstract: BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Mayo Clinic1, University College London2, University of California, Los Angeles3, Arizona State University4, University of California, Davis5, University of California, San Diego6, Boston University7, University of California, San Francisco8, Siemens9, General Electric10, Philips11, Johns Hopkins University12, Stanford University13, University of Virginia14
TL;DR: The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom‐based monitoring of all scanners could be used as a model for other multisite trials.
Abstract: Dementia, one of the most feared associates of increasing longevity, represents a pressing public health problem and major research priority. Alzheimer's disease (AD) is the most common form of dementia, affecting many millions around the world. There is currently no cure for AD, but large numbers of novel compounds are currently under development that have the potential to modify the course of the disease and slow its progression. There is a pressing need for imaging biomarkers to improve understanding of the disease and to assess the efficacy of these proposed treatments. Structural magnetic resonance imaging (MRI) has already been shown to be sensitive to presymptomatic disease (1-10) and has the potential to provide such a biomarker. For use in large-scale multicenter studies, however, standardized methods that produce stable results across scanners and over time are needed.
The Alzheimer's Disease Neuroimaging Initiative (ADNI) study is a longitudinal multisite observational study of elderly individuals with normal cognition, mild cognitive impairment (MCI), or AD (11,12). It is jointly funded by the National Institutes of Health (NIH) and industry via the Foundation for the NIH. The study will assess how well information (alone or in combination) obtained from MRI, (18F)-fludeoyglucose positron emission tomography (FDG PET), urine, serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical and neuropsychometric assessments, can measure disease progression in the three groups of elderly subjects mentioned above. At the 55 participating sites in North America, imaging, clinical, and biologic samples will be collected at multiple time points in 200 elderly cognitively normal, 400 MCI, and 200 AD subjects. All subjects will be scanned with 1.5 T MRI at each time point, and half of these will also be scanned with FDG PET. Subjects not assigned to the PET arm of the study will be eligible for 3 T MRI scanning. The goal is to acquire both 1.5 T and 3 T MRI studies at multiple time points in 25% of the subjects who do not undergo PET scanning [R2C1]. CSF collection at both baseline and 12 months is targeted for 50% of the subjects. Sampling varies by clinical group. Healthy elderly controls will be sampled at 0, 6, 12, 24, and 36 months. Subjects with MCI will be sampled at 0, 6, 12, 18, 24, and 36 months. AD subjects will be sampled at 0, 6, 12, and 24 months.
Major goals of the ADNI study are: to link all of these data at each time point and make this repository available to the general scientific community; to develop technical standards for imaging in longitudinal studies; to determine the optimum methods for acquiring and analyzing images; to validate imaging and biomarker data by correlating these with concurrent psychometric and clinical assessments; and to improve methods for clinical trials in MCI and AD. The ADNI study overall is divided into cores, with each core managing ADNI-related activities within its sphere of expertise: clinical, informatics, biostatistics, biomarkers, and imaging. The purpose of this report is to describe the MRI methods and decision-making process underlying the selection of the MRI protocol employed in the ADNI study.
05 Jun 2008
TL;DR: Theories of human behavior differ in their conceptions of human nature and what they regard as the basic determinants and mechanisms governing self-development, adaptation, and change as discussed by the authors, which is rooted in an agentic perspective.
Abstract: Theories of human behavior differ in their conceptions of human nature and what they regard as the basic determinants and mechanisms governing self-development, adaptation, and change. Social cognitive theory is rooted in an agentic perspective ( Bandura 1986, 2006a). To be an agent is to influence one's own functioning and events that affect one's life. In this view people are contributors to their life circumstances, not just products of them.
Keywords:
Information Processing and Cognitions;
Psychology
TL;DR: The motivation, design principles and priorities that have shaped the development of MEGA are discussed and how MEGA might evolve in the future to assist researchers in their growing need to analyze large data set using new computational methods are discussed.
Abstract: The Molecular Evolutionary Genetics Analysis (MEGA) software is a desktop application designed for comparative analysis of homologous gene sequences either from multigene families or from different species with a special emphasis on inferring evolutionary relationships and patterns of DNA and protein evolution. In addition to the tools for statistical analysis of data, MEGA provides many convenient facilities for the assembly of sequence data sets from files or web-based repositories, and it includes tools for visual presentation of the results obtained in the form of interactive phylogenetic trees and evolutionary distance matrices. Here we discuss the motivation, design principles and priorities that have shaped the development of MEGA. We also discuss how MEGA might evolve in the future to assist researchers in their growing need to analyze large data set using new computational methods.
TL;DR: The results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
Abstract: It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO−PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via π−π stacking. The resulting NGO−PEG−SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO−PEG−SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
TL;DR: These experiments demonstrate solution-processed GO films have potential as transparent electrodes and sheet resistance and optical transparency using different reduction treatments.
Abstract: Processable, single-layered graphene oxide (GO) is an intriguing nanomaterial with tremendous potential for electronic applications. We spin-coated GO thin-films on quartz and characterized their sheet resistance and optical transparency using different reduction treatments. A thermal graphitization procedure was most effective, producing films with sheet resistances as low as 102 −103 Ω/square with 80% transmittance for 550 nm light. Our experiments demonstrate solution-processed GO films have potential as transparent electrodes.
TL;DR: Graph implementations as mentioned in this paper is a generic method for representing a convex function via its epigraph, described in a disciplined convex programming framework, which allows a very wide variety of smooth and nonsmooth convex programs to be easily specified and efficiently solved.
Abstract: We describe graph implementations, a generic method for representing a convex function via its epigraph, described in a disciplined convex programming framework. This simple and natural idea allows a very wide variety of smooth and nonsmooth convex programs to be easily specified and efficiently solved, using interiorpoint methods for smooth or cone convex programs.
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TL;DR: This article offers an approach, built on the technique of statistical simulation, to extract the currently overlooked information from any statistical method and to interpret and present it in a reader-friendly manner.
Abstract: Social Scientists rarely take full advantage of the information available in their statistical results. As a consequence, they miss opportunities to present quantities that are of greatest substantive interest for their research and express the appropriate degree of certainty about these quantities. In this article, we offer an approach, built on the technique of statistical simulation, to extract the currently overlooked information from any statistical method and to interpret and present it in a reader-friendly manner. Using this technique requires some expertise, which we try to provide herein, but its application should make the results of quantitative articles more informative and transparent. To illustrate our recommendations, we replicate the results of several published works, showing in each case how the authors' own conclusions can be expressed more sharply and informatively, and, without changing any data or statistical assumptions, how our approach reveals important new information about the research questions at hand. We also offer very easy-to-use Clarify software that implements our suggestions.
TL;DR: In this paper, the authors synthesize and explore the biological applications of nano-graphene oxide (NGO), i.e., single-layer graphene oxide sheets down to a few nanometers in lateral width.
Abstract: Two-dimensional graphene offers interesting electronic, thermal, and mechanical properties that are currently being explored for advanced electronics, membranes, and composites. Here we synthesize and explore the biological applications of nano-graphene oxide (NGO), i.e., single-layer graphene oxide sheets down to a few nanometers in lateral width. We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments. We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration. The NGO sheets are found to be photoluminescent in the visible and infrared regions. The intrinsic photoluminescence (PL) of NGO is used for live cell imaging in the near-infrared (NIR) with little background. We found that simple physisorption via π-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro. Owing to its small size, intrinsic optical properties, large specific surface area, low cost, and useful non-covalent interactions with aromatic drug molecules, NGO is a promising new material for biological and medical applications.
08 Dec 2008
TL;DR: A new symbolic execution tool, KLEE, capable of automatically generating tests that achieve high coverage on a diverse set of complex and environmentally-intensive programs, and significantly beat the coverage of the developers' own hand-written test suite is presented.
Abstract: We present a new symbolic execution tool, KLEE, capable of automatically generating tests that achieve high coverage on a diverse set of complex and environmentally-intensive programs. We used KLEE to thoroughly check all 89 stand-alone programs in the GNU COREUTILS utility suite, which form the core user-level environment installed on millions of Unix systems, and arguably are the single most heavily tested set of open-source programs in existence. KLEE-generated tests achieve high line coverage -- on average over 90% per tool (median: over 94%) -- and significantly beat the coverage of the developers' own hand-written test suite. When we did the same for 75 equivalent tools in the BUSYBOX embedded system suite, results were even better, including 100% coverage on 31 of them.We also used KLEE as a bug finding tool, applying it to 452 applications (over 430K total lines of code), where it found 56 serious bugs, including three in COREUTILS that had been missed for over 15 years. Finally, we used KLEE to crosscheck purportedly identical BUSYBOX and COREUTILS utilities, finding functional correctness errors and a myriad of inconsistencies.
TL;DR: These findings call into question the concept of a “glial” cell class as the gene profiles of astrocyte and oligodendrocytes are as dissimilar to each other as they are to neurons, for better understanding of neural development, function, and disease.
Abstract: Understanding the cell–cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100β promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin αvβ5 phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a “glial” cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified astrocytes, neurons, and oligodendrocytes provides a resource to the neuroscience community by providing improved cell-type-specific markers and for better understanding of neural development, function, and disease.
TL;DR: Results indicate South Asia and Southern Africa as two regions that, without sufficient adaptation measures, will likely suffer negative impacts on several crops that are important to large food-insecure human populations.
Abstract: Investments aimed at improving agricultural adaptation to climate change inevitably favor some crops and regions over others. An analysis of climate risks for crops in 12 food-insecure regions was conducted to identify adaptation priorities, based on statistical crop models and climate projections for 2030 from 20 general circulation models. Results indicate South Asia and Southern Africa as two regions that, without sufficient adaptation measures, will likely suffer negative impacts on several crops that are important to large food-insecure human populations. We also find that uncertainties vary widely by crop, and therefore priorities will depend on the risk attitudes of investment institutions.
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TL;DR: It is found that simple physisorption via π-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro.
Abstract: Two-dimensional graphene offers interesting electronic, thermal and mechanical properties that are currently explored for advanced electronics, membranes and composites. Here we synthesize and explore the biological application of nano-graphene oxide NGO, single-layer graphene oxide sheets down to a few nanometers in lateral width. We develop functionalization chemistry to impart solubility and compatibility of NGO in biological environments. We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration. The NGO sheets are found to be photoluminescent in the visible and infrared regions. The intrinsic photoluminescence of NGO is used for live cell imaging in the near-infrared with little background. We found that simple physisorption via pi-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective cancer cell killing in vitro. Owing to the small size, intrinsic optical properties, large specific surface area,low cost, and useful non-covalent interactions with aromatic drug molecules, NGO is a promising new material for biological and medical applications.
TL;DR: In this paper, it was shown that the fundamental time-reversal invariant (TRI) insulator exists in $4+1$ dimensions, where the effective field theory is described by the $(4 + 1)$-dimensional Chern-Simons theory and the topological properties of the electronic structure are classified by the second Chern number.
Abstract: We show that the fundamental time-reversal invariant (TRI) insulator exists in $4+1$ dimensions, where the effective-field theory is described by the $(4+1)$-dimensional Chern-Simons theory and the topological properties of the electronic structure are classified by the second Chern number. These topological properties are the natural generalizations of the time reversal-breaking quantum Hall insulator in $2+1$ dimensions. The TRI quantum spin Hall insulator in $2+1$ dimensions and the topological insulator in $3+1$ dimensions can be obtained as descendants from the fundamental TRI insulator in $4+1$ dimensions through a dimensional reduction procedure. The effective topological field theory and the ${Z}_{2}$ topological classification for the TRI insulators in $2+1$ and $3+1$ dimensions are naturally obtained from this procedure. All physically measurable topological response functions of the TRI insulators are completely described by the effective topological field theory. Our effective topological field theory predicts a number of measurable phenomena, the most striking of which is the topological magnetoelectric effect, where an electric field generates a topological contribution to the magnetization in the same direction, with a universal constant of proportionality quantized in odd multiples of the fine-structure constant $\ensuremath{\alpha}={e}^{2}∕\ensuremath{\hbar}c$. Finally, we present a general classification of all topological insulators in various dimensions and describe them in terms of a unified topological Chern-Simons field theory in phase space.
TL;DR: Knowing how organisms retain the ability to regenerate tissue throughout adult life might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
Abstract: The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
TL;DR: For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression and death are found.
Abstract: Background The improved prognosis for patients with human papillomavirus (HPV) – positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan – Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.
National Institutes of Health1, University of Arkansas for Medical Sciences2, University of Manchester3, University of Strasbourg4, Oregon Health & Science University5, Veterans Health Administration6, University of Minnesota7, Roswell Park Cancer Institute8, Duke University9, Santa Clara Valley Medical Center10, Stanford University11, University of Florida12, University of Texas Health Science Center at San Antonio13
TL;DR: This research presents a novel, scalable, scalable and scalable approach that allows for real-time evaluation of the impact of Epstein-Barr virus on the development and management of childhood cancer in rats.
Abstract: Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.
TL;DR: FMRI results indicate that the rFIC is likely to play a major role in switching between distinct brain networks across task paradigms and stimulus modalities, and have important implications for a unified view of network mechanisms underlying both exogenous and endogenous cognitive control.
Abstract: Cognitively demanding tasks that evoke activation in the brain's central-executive network (CEN) have been consistently shown to evoke decreased activation (deactivation) in the default-mode network (DMN). The neural mechanisms underlying this switch between activation and deactivation of large-scale brain networks remain completely unknown. Here, we use functional magnetic resonance imaging (fMRI) to investigate the mechanisms underlying switching of brain networks in three different experiments. We first examined this switching process in an auditory event segmentation task. We observed significant activation of the CEN and deactivation of the DMN, along with activation of a third network comprising the right fronto-insular cortex (rFIC) and anterior cingulate cortex (ACC), when participants perceived salient auditory event boundaries. Using chronometric techniques and Granger causality analysis, we show that the rFIC-ACC network, and the rFIC, in particular, plays a critical and causal role in switching between the CEN and the DMN. We replicated this causal connectivity pattern in two additional experiments: (i) a visual attention "oddball" task and (ii) a task-free resting state. These results indicate that the rFIC is likely to play a major role in switching between distinct brain networks across task paradigms and stimulus modalities. Our findings have important implications for a unified view of network mechanisms underlying both exogenous and endogenous cognitive control.