Showing papers by "Stanford University published in 2012"

Comprehensive molecular portraits of human breast tumours

Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

Biodiversity loss and its impact on humanity

Abstract: The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.

Review of Particle Physics: Particle data group

Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, V-cb & V-ub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.

Landscape of transcription in human cells

Abstract: Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

The Atmospheric Imaging Assembly (AIA) on the Solar Dynamics Observatory (SDO)

Abstract: The Atmospheric Imaging Assembly (AIA) provides multiple simultaneous high-resolution full-disk images of the corona and transition region up to 0.5 R ⊙ above the solar limb with 1.5-arcsec spatial resolution and 12-second temporal resolution. The AIA consists of four telescopes that employ normal-incidence, multilayer-coated optics to provide narrow-band imaging of seven extreme ultraviolet (EUV) band passes centered on specific lines: Fe xviii (94 A), Fe viii, xxi (131 A), Fe ix (171 A), Fe xii, xxiv (193 A), Fe xiv (211 A), He ii (304 A), and Fe xvi (335 A). One telescope observes C iv (near 1600 A) and the nearby continuum (1700 A) and has a filter that observes in the visible to enable coalignment with images from other telescopes. The temperature diagnostics of the EUV emissions cover the range from 6×104 K to 2×107 K. The AIA was launched as a part of NASA’s Solar Dynamics Observatory (SDO) mission on 11 February 2010. AIA will advance our understanding of the mechanisms of solar variability and of how the Sun’s energy is stored and released into the heliosphere and geospace.

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Comprehensive genomic characterization of squamous cell lung cancers

Abstract: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Genome Regulation by Long Noncoding RNAs

Abstract: The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs), provides an important new perspective on the centrality of RNA in gene regulation. Here, we discuss genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, lncRNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs for proper gene control across all kingdoms of life.

The Design of CMOS Radio-Frequency Integrated Circuits

Abstract: This book, first published in 2004, is an expanded and thoroughly revised edition of Tom Lee's acclaimed guide to the design of gigahertz RF integrated circuits. A new chapter on the principles of wireless systems provides a bridge between system and circuit issues. The chapters on low-noise amplifiers, oscillators and phase noise have been significantly expanded. The chapter on architectures now contains several examples of complete chip designs, including a GPS receiver and a wireless LAN transceiver, that bring together the theoretical and practical elements involved in producing a prototype chip. Every section has been revised and updated with findings in the field and the book is packed with physical insights and design tips, and includes a historical overview that sets the whole field in context. With hundreds of circuit diagrams and homework problems this is an ideal textbook for students taking courses on RF design and a valuable reference for practising engineers.

Engineering the surface structure of MoS2 to preferentially expose active edge sites for electrocatalysis

Abstract: Controlling surface structure at the atomic scale is paramount to developing effective catalysts. For example, the edge sites of MoS(2) are highly catalytically active and are thus preferred at the catalyst surface over MoS(2) basal planes, which are inert. However, thermodynamics favours the presence of the basal plane, limiting the number of active sites at the surface. Herein, we engineer the surface structure of MoS(2) to preferentially expose edge sites to effect improved catalysis by successfully synthesizing contiguous large-area thin films of a highly ordered double-gyroid MoS(2) bicontinuous network with nanoscaled pores. The high surface curvature of this catalyst mesostructure exposes a large fraction of edge sites, which, along with its high surface area, leads to excellent activity for electrocatalytic hydrogen evolution. This work elucidates how morphological control of materials at the nanoscale can significantly impact the surface structure at the atomic scale, enabling new opportunities for enhancing surface properties for catalysis and other important technological applications.

A cross-platform toolkit for mass spectrometry and proteomics

Abstract: Mass-spectrometry-based proteomics has become an important component of biological research. Numerous proteomics methods have been developed to identify and quantify the proteins in biological and clinical samples1, identify pathways affected by endogenous and exogenous perturbations2, and characterize protein complexes3. Despite successes, the interpretation of vast proteomics datasets remains a challenge. There have been several calls for improvements and standardization of proteomics data analysis frameworks, as well as for an application-programming interface for proteomics data access4,5. In response, we have developed the ProteoWizard Toolkit, a robust set of open-source, software libraries and applications designed to facilitate proteomics research. The libraries implement the first-ever, non-commercial, unified data access interface for proteomics, bridging field-standard open formats and all common vendor formats. In addition, diverse software classes enable rapid development of vendor-agnostic proteomics software. Additionally, ProteoWizard projects and applications, building upon the core libraries, are becoming standard tools for enabling significant proteomics inquiries.

Network Information Theory

Abstract: This comprehensive treatment of network information theory and its applications provides the first unified coverage of both classical and recent results. With an approach that balances the introduction of new models and new coding techniques, readers are guided through Shannon's point-to-point information theory, single-hop networks, multihop networks, and extensions to distributed computing, secrecy, wireless communication, and networking. Elementary mathematical tools and techniques are used throughout, requiring only basic knowledge of probability, whilst unified proofs of coding theorems are based on a few simple lemmas, making the text accessible to newcomers. Key topics covered include successive cancellation and superposition coding, MIMO wireless communication, network coding, and cooperative relaying. Also covered are feedback and interactive communication, capacity approximations and scaling laws, and asynchronous and random access channels. This book is ideal for use in the classroom, for self-study, and as a reference for researchers and engineers in industry and academia.

Annotation of functional variation in personal genomes using RegulomeDB

Abstract: As the sequencing of healthy and disease genomes becomes more commonplace, detailed annotation provides interpretation for individual variation responsible for normal and disease phenotypes. Current approaches focus on direct changes in protein coding genes, particularly nonsynonymous mutations that directly affect the gene product. However, most individual variation occurs outside of genes and, indeed, most markers generated from genome-wide association studies (GWAS) identify variants outside of coding segments. Identification of potential regulatory changes that perturb these sites will lead to a better localization of truly functional variants and interpretation of their effects. We have developed a novel approach and database, RegulomeDB, which guides interpretation of regulatory variants in the human genome. RegulomeDB includes high-throughput, experimental data sets from ENCODE and other sources, as well as computational predictions and manual annotations to identify putative regulatory potential and identify functional variants. These data sources are combined into a powerful tool that scores variants to help separate functional variants from a large pool and provides a small set of putative sites with testable hypotheses as to their function. We demonstrate the applicability of this tool to the annotation of noncoding variants from 69 full sequenced genomes as well as that of a personal genome, where thousands of functionally associated variants were identified. Moreover, we demonstrate a GWAS where the database is able to quickly identify the known associated functional variant and provide a hypothesis as to its function. Overall, we expect this approach and resource to be valuable for the annotation of human genome sequences.

Exact matrix completion via convex optimization

Abstract: Suppose that one observes an incomplete subset of entries selected from a low-rank matrix. When is it possible to complete the matrix and recover the entries that have not been seen? We demonstrate that in very general settings, one can perfectly recover all of the missing entries from most sufficiently large subsets by solving a convex programming problem that finds the matrix with the minimum nuclear norm agreeing with the observed entries. The techniques used in this analysis draw upon parallels in the field of compressed sensing, demonstrating that objects other than signals and images can be perfectly reconstructed from very limited information.

Metal–Oxide RRAM

Abstract: In this paper, recent progress of binary metal-oxide resistive switching random access memory (RRAM) is reviewed. The physical mechanism, material properties, and electrical characteristics of a variety of binary metal-oxide RRAM are discussed, with a focus on the use of RRAM for nonvolatile memory application. A review of recent development of large-scale RRAM arrays is given. Issues such as uniformity, endurance, retention, multibit operation, and scaling trends are discussed.

The Helioseismic and Magnetic Imager (HMI) Investigation for the Solar Dynamics Observatory (SDO)

Abstract: The Helioseismic and Magnetic Imager (HMI) instrument and investigation as a part of the NASA Solar Dynamics Observatory (SDO) is designed to study convection-zone dynamics and the solar dynamo, the origin and evolution of sunspots, active regions, and complexes of activity, the sources and drivers of solar magnetic activity and disturbances, links between the internal processes and dynamics of the corona and heliosphere, and precursors of solar disturbances for space-weather forecasts. A brief overview of the instrument, investigation objectives, and standard data products is presented.

New insights into the electrochemical reduction of carbon dioxide on metallic copper surfaces

Abstract: We report new insights into the electrochemical reduction of CO2 on a metallic copper surface, enabled by the development of an experimental methodology with unprecedented sensitivity for the identification and quantification of CO2 electroreduction products. This involves a custom electrochemical cell designed to maximize product concentrations coupled to gas chromatography and nuclear magnetic resonance for the identification and quantification of gas and liquid products, respectively. We studied copper across a range of potentials and observed a total of 16 different CO2 reduction products, five of which are reported here for the first time, thus providing the most complete view of the reaction chemistry reported to date. Taking into account the chemical identities of the wide range of C1–C3 products generated and the potential-dependence of their turnover frequencies, mechanistic information is deduced. We discuss a scheme for the formation of multicarbon products involving enol-like surface intermediates as a possible pathway, accounting for the observed selectivity for eleven distinct C2+ oxygenated products including aldehydes, ketones, alcohols, and carboxylic acids.

Stable cycling of double-walled silicon nanotube battery anodes through solid-electrolyte interphase control

Abstract: Although the performance of lithium ion-batteries continues to improve, their energy density and cycle life remain insufficient for applications in consumer electronics, transport and large-scale renewable energy storage. Silicon has a large charge storage capacity and this makes it an attractive anode material, but pulverization during cycling and an unstable solid-electrolyte interphase has limited the cycle life of silicon anodes to hundreds of cycles. Here, we show that anodes consisting of an active silicon nanotube surrounded by an ion-permeable silicon oxide shell can cycle over 6,000 times in half cells while retaining more than 85% of their initial capacity. The outer surface of the silicon nanotube is prevented from expansion by the oxide shell, and the expanding inner surface is not exposed to the electrolyte, resulting in a stable solid-electrolyte interphase. Batteries containing these double-walled silicon nanotube anodes exhibit charge capacities approximately eight times larger than conventional carbon anodes and charging rates of up to 20C (a rate of 1C corresponds to complete charge or discharge in one hour).

Emergent phenomena at oxide interfaces

Abstract: Recent technical advances in the atomic-scale synthesis of oxide heterostructures have provided a fertile new ground for creating novel states at their interfaces. Different symmetry constraints can be used to design structures exhibiting phenomena not found in the bulk constituents. A characteristic feature is the reconstruction of the charge, spin and orbital states at interfaces on the nanometre scale. Examples such as interface superconductivity, magneto-electric coupling, and the quantum Hall effect in oxide heterostructures are representative of the scientific and technological opportunities in this rapidly emerging field.

Two-Year Outcomes after Transcatheter or Surgical Aortic-Valve Replacement

Abstract: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P = 0.41) and at 2 years (Kaplan–Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P = 0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P = 0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P = 0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). Conclusions A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)

Design and Ground Calibration of the Helioseismic and Magnetic Imager (HMI) Instrument on the Solar Dynamics Observatory (SDO)

Abstract: The Helioseismic and Magnetic Imager (HMI) investigation (Solar Phys. doi: 10.1007/s11207-011-9834-2, 2011) will study the solar interior using helioseismic techniques as well as the magnetic field near the solar surface. The HMI instrument is part of the Solar Dynamics Observatory (SDO) that was launched on 11 February 2010. The instrument is designed to measure the Doppler shift, intensity, and vector magnetic field at the solar photosphere using the 6173 A Fe i absorption line. The instrument consists of a front-window filter, a telescope, a set of waveplates for polarimetry, an image-stabilization system, a blocking filter, a five-stage Lyot filter with one tunable element, two wide-field tunable Michelson interferometers, a pair of 40962 pixel cameras with independent shutters, and associated electronics. Each camera takes a full-disk image roughly every 3.75 seconds giving an overall cadence of 45 seconds for the Doppler, intensity, and line-of-sight magnetic-field measurements and a slower cadence for the full vector magnetic field. This article describes the design of the HMI instrument and provides an overview of the pre-launch calibration efforts. Overviews of the investigation, details of the calibrations, data handling, and the science analysis are provided in accompanying articles.

Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types

Abstract: Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.

The Institutional Logics Perspective: A New Approach to Culture, Structure and Process

Abstract: 1. Introduction to the Institutional Logics Perspective 2. Precursors to the Institutional Logics Perspective 3. Defining the Inter-institutional System 4. The Emergence, Stability and Change of the Inter-institutional System 5. Micro-Foundations of Institutional Logics 6. The Dynamics of Organizational Practices and Identities 7. The Emergence and Evolution of Field-Level Logics 8. Implications for Future Research

Leveled) fully homomorphic encryption without bootstrapping

Abstract: We present a novel approach to fully homomorphic encryption (FHE) that dramatically improves performance and bases security on weaker assumptions. A central conceptual contribution in our work is a new way of constructing leveled fully homomorphic encryption schemes (capable of evaluating arbitrary polynomial-size circuits), without Gentry's bootstrapping procedure.Specifically, we offer a choice of FHE schemes based on the learning with error (LWE) or ring-LWE (RLWE) problems that have 2λ security against known attacks. For RLWE, we have:• A leveled FHE scheme that can evaluate L-level arithmetic circuits with O(λ · L3) per-gate computation -- i.e., computation quasi-linear in the security parameter. Security is based on RLWE for an approximation factor exponential in L. This construction does not use the bootstrapping procedure.• A leveled FHE scheme that uses bootstrapping as an optimization, where the per-gate computation (which includes the bootstrapping procedure) is O(λ2), independent of L. Security is based on the hardness of RLWE for quasi-polynomial factors (as opposed to the sub-exponential factors needed in previous schemes).We obtain similar results to the above for LWE, but with worse performance.Based on the Ring LWE assumption, we introduce a number of further optimizations to our schemes. As an example, for circuits of large width -- e.g., where a constant fraction of levels have width at least λ -- we can reduce the per-gate computation of the bootstrapped version to O(λ), independent of L, by batching the bootstrapping operation. Previous FHE schemes all required Ω(λ3.5) computation per gate.At the core of our construction is a much more effective approach for managing the noise level of lattice-based ciphertexts as homomorphic operations are performed, using some new techniques recently introduced by Brakerski and Vaikuntanathan (FOCS 2011).