Showing papers by "University of Washington published in 2011"

Scikit-learn: Machine Learning in Python

Abstract: Scikit-learn is a Python module integrating a wide range of state-of-the-art machine learning algorithms for medium-scale supervised and unsupervised problems. This package focuses on bringing machine learning to non-specialists using a general-purpose high-level language. Emphasis is put on ease of use, performance, documentation, and API consistency. It has minimal dependencies and is distributed under the simplified BSD license, encouraging its use in both academic and commercial settings. Source code, binaries, and documentation can be downloaded from http://scikit-learn.sourceforge.net.

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Abstract: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

FIMO: scanning for occurrences of a given motif.

Abstract: Summary: A motif is a short DNA or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix. Results: We describe Find Individual Motif Occurrences (FIMO), a software tool for scanning DNA or protein sequences with motifs described as position-specific scoring matrices. The program computes a log-likelihood ratio score for each position in a given sequence database, uses established dynamic programming methods to convert this score to a P-value and then applies false discovery rate analysis to estimate a q-value for each position in the given sequence. FIMO provides output in a variety of formats, including HTML, XML and several Santa Cruz Genome Browser formats. The program is efficient, allowing for the scanning of DNA sequences at a rate of 3.5 Mb/s on a single CPU. Availability and Implementation: FIMO is part of the MEME Suite software toolkit. A web server and source code are available at

Trophic Downgrading of Planet Earth

Abstract: Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind's most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of their disappearance in marine, terrestrial, and freshwater ecosystems worldwide. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles. These findings emphasize the urgent need for interdisciplinary research to forecast the effects of trophic downgrading on process, function, and resilience in global ecosystems.

Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma

Abstract: MicroRNAs (miRNAs) circulate in the bloodstream in a highly stable, extracellular form and are being developed as blood-based biomarkers for cancer and other diseases. However, the mechanism underlying their remarkable stability in the RNase-rich environment of blood is not well understood. The current model in the literature posits that circulating miRNAs are protected by encapsulation in membrane-bound vesicles such as exosomes, but this has not been systematically studied. We used differential centrifugation and size-exclusion chromatography as orthogonal approaches to characterize circulating miRNA complexes in human plasma and serum. We found, surprisingly, that the majority of circulating miRNAs cofractionated with protein complexes rather than with vesicles. miRNAs were also sensitive to protease treatment of plasma, indicating that protein complexes protect circulating miRNAs from plasma RNases. Further characterization revealed that Argonaute2 (Ago2), the key effector protein of miRNA-mediated silencing, was present in human plasma and eluted with plasma miRNAs in size-exclusion chromatography. Furthermore, immunoprecipitation of Ago2 from plasma readily recovered non–vesicle-associated plasma miRNAs. The majority of miRNAs studied copurified with the Ago2 ribonucleoprotein complex, but a minority of specific miRNAs associated predominantly with vesicles. Our results reveal two populations of circulating miRNAs and suggest that circulating Ago2 complexes are a mechanism responsible for the stability of plasma miRNAs. Our study has important implications for the development of biomarker approaches based on capture and analysis of circulating miRNAs. In addition, identification of extracellular Ago2–miRNA complexes in plasma raises the possibility that cells release a functional miRNA-induced silencing complex into the circulation.

Sdss-iii: massive spectroscopic surveys of the distant universe, the milky way, and extra-solar planetary systems

Abstract: Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z 100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)

International standards for neurological classification of spinal cord injury (Revised 2011)

Abstract: This article represents the content of the booklet, International Standards for Neurological Classification of Spinal Cord Injury, revised 2011, published by the American Spinal Injury Association (ASIA). For further explanation of the clarifications and changes in this revision, see the accompanying article (Kirshblum S., et al. J Spinal Cord Med. 2011:doi 10.1179/107902611X13186000420242 The spinal cord is the major conduit through which motor and sensory information travels between the brain and body. The spinal cord contains longitudinally oriented spinal tracts (white matter) surrounding central areas (gray matter) where most spinal neuronal cell bodies are located. The gray matter is organized into segments comprising sensory and motor neurons. Axons from spinal sensory neurons enter and axons from motor neurons leave the spinal cord via segmental nerves or roots. In the cervical spine, there are 8 nerve roots. Cervical roots of C1-C7 are named according to the vertebra above which they exit (i.e. C1 exits above the C1 vertebra, just below the skull and C6 nerve roots pass between the C5 and C6 vertebrae) whereas C8 exists between the C7 and T1 vertebra; as there is no C8 vertebra. The C1 nerve root does not have a sensory component that is tested on the International Standards Examination. The thoracic spine has 12 distinct nerve roots and the lumbar spine consists of 5 distinct nerve roots that are each named accordingly as they exit below the level of the respective vertebrae. The sacrum consists of 5 embryonic sections that have fused into one bony structure with 5 distinct nerve roots that exit via the sacral foramina. The spinal cord itself ends at approximately the L1-2 vertebral level. The distal most part of the spinal cord is called the conus medullaris. The cauda equina is a cluster of paired (right and left) lumbosacral nerve roots that originate in the region of the conus medullaris and travel down through the thecal sac and exit via the intervertebral foramen below their respective vertebral levels. There may be 0, 1, or 2 coccygeal nerves but they do not have a role with the International Standards examination in accordance with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Each root receives sensory information from skin areas called dermatomes. Similarly each root innervates a group of muscles called a myotome. While a dermatome usually represents a discrete and contiguous skin area, most roots innervate more than one muscle, and most muscles are innervated by more than one root. Spinal cord injury (SCI) affects conduction of sensory and motor signals across the site(s) of lesion(s), as well as the autonomic nervous system. By systematically examining the dermatomes and myotomes, as described within this booklet, one can determine the cord segments affected by the SCI. From the International Standards examination several measures of neurological damage are generated, e.g., Sensory and Motor Levels (on right and left sides), NLI, Sensory Scores (Pin Prick and Light Touch), Motor Scores (upper and lower limb), and ZPP. This booklet also describes the ASIA (American Spinal Injury Association) Impairment Scale (AIS) to classify the severity (i.e. completeness) of injury. This booklet begins with basic definitions of common terms used herein. The section that follows describes the recommended International Standards examination, including both sensory and motor components. Subsequent sections cover sensory and motor scores, the AIS classification, and clinical syndromes associated with SCI. For ease of reference, a worksheet (Appendix 1) of the recommended examination is included, with a summary of steps used to classify the injury (Appendix 2). A full-size version for photocopying and use in patient records has been included as an enclosure and may also be downloaded from the ASIA website (www.asia-spinalinjury.org). Additional details regarding the examination and e-Learning training materials can also be obtained from the website15.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules.

Abstract: We have recently completed a full re-architecturing of the ROSETTA molecular modeling program, generalizing and expanding its existing functionality. The new architecture enables the rapid prototyping of novel protocols by providing easy-to-use interfaces to powerful tools for molecular modeling. The source code of this rearchitecturing has been released as ROSETTA3 and is freely available for academic use. At the time of its release, it contained 470,000 lines of code. Counting currently unpublished protocols at the time of this writing, the source includes 1,285,000 lines. Its rapid growth is a testament to its ease of use. This chapter describes the requirements for our new architecture, justifies the design decisions, sketches out central classes, and highlights a few of the common tasks that the new software can perform.

Exome sequencing as a tool for Mendelian disease gene discovery

Abstract: Exome sequencing — the targeted sequencing of the subset of the human genome that is protein coding — is a powerful and cost-effective new tool for dissecting the genetic basis of diseases and traits that have proved to be intractable to conventional gene-discovery strategies. Over the past 2 years, experimental and analytical approaches relating to exome sequencing have established a rich framework for discovering the genes underlying unsolved Mendelian disorders. Additionally, exome sequencing is being adapted to explore the extent to which rare alleles explain the heritability of complex diseases and health- related traits. These advances also set the stage for applying exome and whole-genome sequencing to facilitate clinical diagnosis and personalized disease-risk profiling.

Analysis, Experimental Results, and Range Adaptation of Magnetically Coupled Resonators for Wireless Power Transfer

Abstract: Wireless power technology offers the promise of cutting the last cord, allowing users to seamlessly recharge mobile devices as easily as data are transmitted through the air. Initial work on the use of magnetically coupled resonators for this purpose has shown promising results. We present new analysis that yields critical insight into the design of practical systems, including the introduction of key figures of merit that can be used to compare systems with vastly different geometries and operating conditions. A circuit model is presented along with a derivation of key system concepts, such as frequency splitting, the maximum operating distance (critical coupling), and the behavior of the system as it becomes undercoupled. This theoretical model is validated against measured data and shows an excellent average coefficient of determination of 0.9875. An adaptive frequency tuning technique is demonstrated, which compensates for efficiency variations encountered when the transmitter-to-receiver distance and/or orientation are varied. The method demonstrated in this paper allows a fixed-load receiver to be moved to nearly any position and/or orientation within the range of the transmitter and still achieve a near-constant efficiency of over 70% for a range of 0-70 cm.

The aligned rank transform for nonparametric factorial analyses using only anova procedures

Abstract: Nonparametric data from multi-factor experiments arise often in human-computer interaction (HCI). Examples may include error counts, Likert responses, and preference tallies. But because multiple factors are involved, common nonparametric tests (e.g., Friedman) are inadequate, as they are unable to examine interaction effects. While some statistical techniques exist to handle such data, these techniques are not widely available and are complex. To address these concerns, we present the Aligned Rank Transform (ART) for nonparametric factorial data analysis in HCI. The ART relies on a preprocessing step that "aligns" data before applying averaged ranks, after which point common ANOVA procedures can be used, making the ART accessible to anyone familiar with the F-test. Unlike most articles on the ART, which only address two factors, we generalize the ART to N factors. We also provide ARTool and ARTweb, desktop and Web-based programs for aligning and ranking data. Our re-examination of some published HCI results exhibits advantages of the ART.

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

Abstract: The Sloan Digital Sky Survey (SDSS) started a new phase in 2008 August, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Lyα forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the SDSS imaging to 14,555 deg2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Exploration (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameter pipeline, which has better determination of metallicity for high-metallicity stars.

Dynamic DNA nanotechnology using strand-displacement reactions

Abstract: The programmable and reliable hybridization of DNA strands has enabled the preparation of a wide variety of structures. This Review discusses how, in addition to these static assemblies, the process of displacing — and ultimately replacing — strands also makes possible the construction of dynamic systems such as logic gates or autonomous walkers.

High‐resolution mapping of the world's reservoirs and dams for sustainable river‐flow management

Abstract: Despite the recognized importance of reservoirs and dams, global datasets describing their characteristics and geographical distribution are largely incomplete. To enable advanced assessments of th ...

A large-scale hierarchical multi-view RGB-D object dataset

Abstract: Over the last decade, the availability of public image repositories and recognition benchmarks has enabled rapid progress in visual object category and instance detection. Today we are witnessing the birth of a new generation of sensing technologies capable of providing high quality synchronized videos of both color and depth, the RGB-D (Kinect-style) camera. With its advanced sensing capabilities and the potential for mass adoption, this technology represents an opportunity to dramatically increase robotic object recognition, manipulation, navigation, and interaction capabilities. In this paper, we introduce a large-scale, hierarchical multi-view object dataset collected using an RGB-D camera. The dataset contains 300 objects organized into 51 categories and has been made publicly available to the research community so as to enable rapid progress based on this promising technology. This paper describes the dataset collection procedure and introduces techniques for RGB-D based object recognition and detection, demonstrating that combining color and depth information substantially improves quality of results.

A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

Abstract: The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.

Genome structural variation discovery and genotyping

Abstract: Comparisons of human genomes show that more base pairs are altered as a result of structural variation — including copy number variation — than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some global discovery biases remain, but the integration of experimental and computational approaches is proving fruitful for accurate characterization of the copy, content and structure of variable regions. We argue that the long-term goal should be routine, cost-effective and high quality de novo assembly of human genomes to comprehensively assess all classes of structural variation.

Comparing photosynthetic and photovoltaic efficiencies and recognizing the potential for improvement.

Abstract: Comparing photosynthetic and photovoltaic efficiencies is not a simple issue. Although both processes harvest the energy in sunlight, they operate in distinctly different ways and produce different types of products: biomass or chemical fuels in the case of natural photosynthesis and nonstored electrical current in the case of photovoltaics. In order to find common ground for evaluating energy-conversion efficiency, we compare natural photosynthesis with present technologies for photovoltaic-driven electrolysis of water to produce hydrogen. Photovoltaic-driven electrolysis is the more efficient process when measured on an annual basis, yet short-term yields for photosynthetic conversion under optimal conditions come within a factor of 2 or 3 of the photovoltaic benchmark. We consider opportunities in which the frontiers of synthetic biology might be used to enhance natural photosynthesis for improved solar energy conversion efficiency.

PILCO: A Model-Based and Data-Efficient Approach to Policy Search

Abstract: In this paper, we introduce PILCO, a practical, data-efficient model-based policy search method. PILCO reduces model bias, one of the key problems of model-based reinforcement learning, in a principled way. By learning a probabilistic dynamics model and explicitly incorporating model uncertainty into long-term planning, PILCO can cope with very little data and facilitates learning from scratch in only a few trials. Policy evaluation is performed in closed form using state-of-the-art approximate inference. Furthermore, policy gradients are computed analytically for policy improvement. We report unprecedented learning efficiency on challenging and high-dimensional control tasks.

Dark silicon and the end of multicore scaling

Abstract: Since 2005, processor designers have increased core counts to exploit Moore's Law scaling, rather than focusing on single-core performance. The failure of Dennard scaling, to which the shift to multicore parts is partially a response, may soon limit multicore scaling just as single-core scaling has been curtailed. This paper models multicore scaling limits by combining device scaling, single-core scaling, and multicore scaling to measure the speedup potential for a set of parallel workloads for the next five technology generations. For device scaling, we use both the ITRS projections and a set of more conservative device scaling parameters. To model single-core scaling, we combine measurements from over 150 processors to derive Pareto-optimal frontiers for area/performance and power/performance. Finally, to model multicore scaling, we build a detailed performance model of upper-bound performance and lower-bound core power. The multicore designs we study include single-threaded CPU-like and massively threaded GPU-like multicore chip organizations with symmetric, asymmetric, dynamic, and composed topologies. The study shows that regardless of chip organization and topology, multicore scaling is power limited to a degree not widely appreciated by the computing community. Even at 22 nm (just one year from now), 21% of a fixed-size chip must be powered off, and at 8 nm, this number grows to more than 50%. Through 2024, only 7.9x average speedup is possible across commonly used parallel workloads, leaving a nearly 24-fold gap from a target of doubled performance per generation.

Comprehensive experimental analyses of automotive attack surfaces

Abstract: Modern automobiles are pervasively computerized, and hence potentially vulnerable to attack. However, while previous research has shown that the internal networks within some modern cars are insecure, the associated threat model--requiring prior physical access--has justifiably been viewed as unrealistic. Thus, it remains an open question if automobiles can also be susceptible to remote compromise. Our work seeks to put this question to rest by systematically analyzing the external attack surface of a modern automobile. We discover that remote exploitation is feasible via a broad range of attack vectors (including mechanics tools, CD players, Bluetooth and cellular radio), and further, that wireless communications channels allow long distance vehicle control, location tracking, in-cabin audio exfiltration and theft. Finally, we discuss the structural characteristics of the automotive ecosystem that give rise to such problems and highlight the practical challenges in mitigating them.

The resurgence of covalent drugs

Abstract: Covalent drugs have proved to be successful therapies for various indications, but largely owing to safety concerns, they are rarely considered when initiating a target-directed drug discovery project. There is a need to reassess this important class of drugs, and to reconcile the discordance between the historic success of covalent drugs and the reluctance of most drug discovery teams to include them in their armamentarium. This review surveys the prevalence and pharmacological advantages of covalent drugs, discusses how potential risks and challenges may be addressed through innovative design, and presents the broad opportunities provided by targeted covalent inhibitors.