Showing papers by "Tel Aviv University published in 2014"

DeepFace: Closing the Gap to Human-Level Performance in Face Verification

Abstract: In modern face recognition, the conventional pipeline consists of four stages: detect => align => represent => classify. We revisit both the alignment step and the representation step by employing explicit 3D face modeling in order to apply a piecewise affine transformation, and derive a face representation from a nine-layer deep neural network. This deep network involves more than 120 million parameters using several locally connected layers without weight sharing, rather than the standard convolutional layers. Thus we trained it on the largest facial dataset to-date, an identity labeled dataset of four million facial images belonging to more than 4, 000 identities. The learned representations coupling the accurate model-based alignment with the large facial database generalize remarkably well to faces in unconstrained environments, even with a simple classifier. Our method reaches an accuracy of 97.35% on the Labeled Faces in the Wild (LFW) dataset, reducing the error of the current state of the art by more than 27%, closely approaching human-level performance.

Proximal alternating linearized minimization for nonconvex and nonsmooth problems

Abstract: We introduce a proximal alternating linearized minimization (PALM) algorithm for solving a broad class of nonconvex and nonsmooth minimization problems. Building on the powerful Kurdyka---?ojasiewicz property, we derive a self-contained convergence analysis framework and establish that each bounded sequence generated by PALM globally converges to a critical point. Our approach allows to analyze various classes of nonconvex-nonsmooth problems and related nonconvex proximal forward---backward algorithms with semi-algebraic problem's data, the later property being shared by many functions arising in a wide variety of fundamental applications. A by-product of our framework also shows that our results are new even in the convex setting. As an illustration of the results, we derive a new and simple globally convergent algorithm for solving the sparse nonnegative matrix factorization problem.

Zerocash: Decentralized Anonymous Payments from Bitcoin

Abstract: Bit coin is the first digital currency to see widespread adoption. While payments are conducted between pseudonyms, Bit coin cannot offer strong privacy guarantees: payment transactions are recorded in a public decentralized ledger, from which much information can be deduced. Zero coin (Miers et al., IEEE SaP 2013) tackles some of these privacy issues by unlinking transactions from the payment's origin. Yet, it still reveals payments' destinations and amounts, and is limited in functionality. In this paper, we construct a full-fledged ledger-based digital currency with strong privacy guarantees. Our results leverage recent advances in zero-knowledge Succinct Non-interactive Arguments of Knowledge (zk-SNARKs). First, we formulate and construct decentralized anonymous payment schemes (DAP schemes). A DAP scheme enables users to directly pay each other privately: the corresponding transaction hides the payment's origin, destination, and transferred amount. We provide formal definitions and proofs of the construction's security. Second, we build Zero cash, a practical instantiation of our DAP scheme construction. In Zero cash, transactions are less than 1 kB and take under 6 ms to verify - orders of magnitude more efficient than the less-anonymous Zero coin and competitive with plain Bit coin.

EltonTraits 1.0: Species-level foraging attributes of the world's birds and mammals

Abstract: Species are characterized by physiological, behavioral, and ecological attributes that are all subject to varying evolutionary and ecological constraints and jointly determine species' role and function in ecosystems. Attributes such as diet, foraging strata, foraging time, and body size, in particular, characterize a large portion of the “Eltonian” niches of species. Here we present a global species-level compilation of these key attributes for all 9993 and 5400 extant bird and mammal species derived from key literature sources. Global handbooks and monographs allowed the consistent sourcing of attributes for most species. For diet and foraging stratum we followed a defined protocol to translate the verbal descriptions into standardized, semiquantitative information about relative importance of different categories. Together with body size (continuous) and activity time (categorical) this enables a much finer distinction of species' foraging ecology than typical categorical guild assignments allow. Attri...

High-capacity millimetre-wave communications with orbital angular momentum multiplexing

Abstract: One property of electromagnetic waves that has been recently explored is the ability to multiplex multiple beams, such that each beam has a unique helical phase front. The amount of phase front ‘twisting’ indicates the orbital angular momentum state number, and beams with different orbital angular momentum are orthogonal. Such orbital angular momentum based multiplexing can potentially increase the system capacity and spectral efficiency of millimetre-wave wireless communication links with a single aperture pair by transmitting multiple coaxial data streams. Here we demonstrate a 32-Gbit s−1 millimetre-wave link over 2.5 metres with a spectral efficiency of ~16 bit s−1 Hz−1 using four independent orbital–angular momentum beams on each of two polarizations. All eight orbital angular momentum channels are recovered with bit-error rates below 3.8 × 10−3. In addition, we demonstrate a millimetre-wave orbital angular momentum mode demultiplexer to demultiplex four orbital angular momentum channels with crosstalk less than −12.5 dB and show an 8-Gbit s−1 link containing two orbital angular momentum beams on each of two polarizations. High speed data transmission using orbital angular momentum beams has been recently demonstrated. Here, Yan et al. demonstrate a 32 Gbit/s millimetre-wave communication link using eight coaxially propagating independent orbital angular momentum beams with four orbital angular momentum states on two orthogonal polarizations.

The PLATO 2.0 mission

Abstract: PLATO 2.0 has recently been selected for ESA’s M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4–16 mag). It focusses on bright (4–11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4–10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2–3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA’s Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.

Sex Determination: Why So Many Ways of Doing It?

Abstract: Sexual reproduction is an ancient feature of life on earth, and the familiar X and Y chromo- somes in humans and other model species have led to the impression that sex determination mecha- nisms are old and conserved. In fact, males and females are deter- mined by diverse mechanisms that evolve rapidly in many taxa. Yet this diversity in primary sex-deter- mining signals is coupled with conserved molecular pathways that trigger male or female develop- ment. Conflicting selection on dif- ferent parts of the genome and on the two sexes may drive many of these transitions, but few systems with rapid turnover of sex determi- nation mechanisms have been rig- orously studied. Here we survey our current understanding of how and why sex determination evolves in animals and plants and identify important gaps in our knowledge that present exciting research op- portunities to characterize the evo- lutionary forces and molecular pathways underlying the evolution of sex determination.

Decline in Estimated Glomerular Filtration Rate and Subsequent Risk of End-Stage Renal Disease and Mortality

Abstract: IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Does evolutionary theory need a rethink

Abstract: Nobel physicist talks plants with a waiter, then what? p.168 ENERGY Don't assume that renewable energies are problem-free p.168 AGEING Atul Gawande's call to action on end-of-life medical care p.167 HEALTH Lasting legacy of wartime battle against malaria p.166 Does evolutionary theory need a rethink? Researchers are divided over what processes should be considered fundamental. I n October 1881, just six months before he died, Charles Darwin published his final book. The Formation of Vegetable Mould, Through the Actions of Worms 11 sold briskly: Darwin's earlier publications had secured his reputation. He devoted an entire book to these humble creatures in part because they exemplify an interesting feedback process: earthworms are adapted to thrive in an environment that they modify through their own activities. Darwin learned about earthworms from conversations with gardeners and his own simple experiments. He had a genius for distilling penetrating insights about evolutionary processes — often after amassing years of observational and experimental data — and he drew on such disparate topics as agriculture, geology, embryol-ogy and behaviour. Evolutionary thinking ever since has followed Darwin's lead in its emphasis on evidence and in synthesizing information from other fields. A profound shift in evolutionary thinking began C harles Darwin conceived of evolution by natural selection without knowing that genes exist. Now mainstream evolutionary theory has come to focus almost exclusively on genetic inheritance and processes that change gene frequencies. Yet new data pouring out of adjacent fields are starting to undermine this narrow stance. An alternative vision of evolution is beginning to crystallize, in which the processes by which organisms grow and develop are recognized as causes of evolution. Some of us first met to discuss these advances six years ago. In the time since, as members of an interdisciplinary team, we have worked intensively to develop a broader framework, termed the extended evolutionary synthesis 1 (EES), and to flesh out its structure, assumptions and predictions. In essence, this synthesis maintains that important drivers of evolution, ones that cannot be reduced to genes, must be woven into the very fabric of evolutionary theory. We believe that the EES will shed new light on how POINT Yes, urgently Without an extended evolutionary framework, the theory neglects key processes, say Kevin Laland and colleagues.

International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

Abstract: Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145–176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee.

Rotation periods of 34,030 kepler main-sequence stars: the full autocorrelation sample

Abstract: We analyzed three years of data from the Kepler space mission to derive rotation periods of main-sequence stars below 6500 K. Our automated autocorrelation-based method detected rotation periods between 0.2 and 70 days for 34,030 (25.6%) of the 133,030 main-sequence Kepler targets (excluding known eclipsing binaries and Kepler Objects of Interest), making this the largest sample of stellar rotation periods to date. In this paper we consider the detailed features of the now well-populated period-temperature distribution and demonstrate that the period bimodality, first seen by McQuillan et al. in the M-dwarf sample, persists to higher masses, becoming less visible above 0.6 M {sub ☉}. We show that these results are globally consistent with the existing ground-based rotation-period data and find that the upper envelope of the period distribution is broadly consistent with a gyrochronological age of 4.5 Gyr, based on the isochrones of Barnes, Mamajek, and Hillenbrand and Meibom et al. We also performed a detailed comparison of our results to those of Reinhold et al. and Nielsen et al., who measured rotation periods of field stars observed by Kepler. We examined the amplitude of periodic variability for the stars with detection rotation periods, and found a typical range betweenmore » ∼950 ppm (5th percentile) and ∼22,700 ppm (95th percentile), with a median of ∼5600 ppm. We found typically higher amplitudes for shorter periods and lower effective temperatures, with an excess of low-amplitude stars above ∼5400 K.« less

PredictProtein—an open resource for online prediction of protein structural and functional features

Abstract: PredictProtein is a meta-service for sequence analysis that has been predicting structural and functional features of proteins since 1992. Queried with a protein sequence it returns: multiple sequence alignments, predicted aspects of structure (secondary structure, solvent accessibility, transmembrane helices (TMSEG) and strands, coiled-coil regions, disulfide bonds and disordered regions) and function. The service incorporates analysis methods for the identification of functional regions (ConSurf), homology-based inference of Gene Ontology terms (metastudent), comprehensive subcellular localization prediction (LocTree3), protein–protein binding sites (ISIS2), protein–polynucleotide binding sites (SomeNA) and predictions of the effect of point mutations (non-synonymous SNPs) on protein function (SNAP2). Our goal has always been to develop a system optimized to meet the demands of experimentalists not highly experienced in bioinformatics. To this end, the PredictProtein results are presented as both text and a series of intuitive, interactive and visually appealing figures. The web server and sources are available at http://ppopen.rostlab.org.

Mechanism for thermal relic dark matter of strongly interacting massive particles.

Abstract: A recent proposal is that dark matter could be a thermal relic of 3→2 scatterings in a strongly coupled hidden sector. We present explicit classes of strongly coupled gauge theories that admit this behavior. These are QCD-like theories of dynamical chiral symmetry breaking, where the pions play the role of dark matter. The number-changing 3→2 process, which sets the dark matter relic abundance, arises from the Wess-Zumino-Witten term. The theories give an explicit relationship between the 3→2 annihilation rate and the 2→2 self-scattering rate, which alters predictions for structure formation. This is a simple calculable realization of the strongly interacting massive-particle mechanism.

Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection

Abstract: Importance Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use. Objective To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C difficile infection. Design, Setting, and Participants Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C difficile infection requiring hospitalization were enrolled. Interventions Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at −80°C (−112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months. Main Outcomes and Measures The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements. Results No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 ( P = .001) and 1 (IQR, 1-2) at 8 weeks ( P P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02). Conclusions and Relevance This preliminary study among patients with relapsing C difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness. Trial Registration clinicaltrials.gov Identifier:NCT01914731

Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy

Abstract: BACKGROUND Polyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood. METHODS We carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and bio physical analysis of purified protein. RESULTS In all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein. CONCLUSIONS Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.)

The physical properties of supramolecular peptide assemblies: from building block association to technological applications.

Abstract: Bio-inspired nano-materials can be formed by the ordered assembly of elementary building blocks using recognition modules and structural elements. Among the biological sources, peptides and proteins are of special interest due to their role as major structural elements in all living systems, ranging from bacteria to humans in a continuum of magnitudes, from the nano-scale to the macro-scale. Peptides, as short as dipeptides, contain all the molecular information needed to form well-ordered structures at the nano-scale. Here, in light of the significant advancements in the field of peptide nanostructures in the last few years, we provide an updated overview of this subject. The use of these nanostructures was indeed recently demonstrated in various fields including the design of molecular motors based on nanostructure complexation with a metal-organic framework, the delivery of therapeutic agents, the development of energy storage devices and the fabrication of piezoelectric-based sensors.

Why Lead Methylammonium Tri-Iodide Perovskite-Based Solar Cells Require a Mesoporous Electron Transporting Scaffold (but Not Necessarily a Hole Conductor)

Abstract: CH3NH3PbI3-based solar cells were characterized with electron beam-induced current (EBIC) and compared to CH3NH3PbI3–xClx ones. A spatial map of charge separation efficiency in working cells shows p-i-n structures for both thin film cells. Effective diffusion lengths, LD, (from EBIC profile) show that holes are extracted significantly more efficiently than electrons in CH3NH3PbI3, explaining why CH3NH3PbI3-based cells require mesoporous electron conductors, while CH3NH3PbI3–xClx ones, where LD values are comparable for both charge types, do not.

Genome Sequencing Highlights the Dynamic Early History of Dogs

Abstract: To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11–16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary.

International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies

Abstract: Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.

A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes.

Abstract: RNA molecules transmit the information encoded in the genome and generally reflect its content. Adenosine-to-inosine (A-to-I) RNA editing by ADAR proteins converts a genomically encoded adenosine into inosine. It is known that most RNA editing in human takes place in the primate-specific Alu sequences, but the extent of this phenomenon and its effect on transcriptome diversity are not yet clear. Here, we analyzed large-scale RNA-seq data and detected ∼1.6 million editing sites. As detection sensitivity increases with sequencing coverage, we performed ultradeep sequencing of selected Alu sequences and showed that the scope of editing is much larger than anticipated. We found that virtually all adenosines within Alu repeats that form double-stranded RNA undergo A-to-I editing, although most sites exhibit editing at only low levels (<1%). Moreover, using high coverage sequencing, we observed editing of transcripts resulting from residual antisense expression, doubling the number of edited sites in the human genome. Based on bioinformatic analyses and deep targeted sequencing, we estimate that there are over 100 million human Alu RNA editing sites, located in the majority of human genes. These findings set the stage for exploring how this primate-specific massive diversification of the transcriptome is utilized.

100 Tbit/s free-space data link enabled by three-dimensional multiplexing of orbital angular momentum, polarization, and wavelength

Abstract: We investigate the orthogonality of orbital angular momentum (OAM) with other multiplexing domains and present a free-space data link that uniquely combines OAM-, polarization-, and wavelength-division multiplexing. Specifically, we demonstrate the multiplexing/demultiplexing of 1008 data channels carried on 12 OAM beams, 2 polarizations, and 42 wavelengths. Each channel is encoded with 100 Gbit/s quadrature phase-shift keying data, providing an aggregate capacity of 100.8 Tbit/s (12×2×42×100 Gbit/s).

Succinct non-interactive zero knowledge for a von Neumann architecture

Abstract: We build a system that provides succinct noninteractive zero-knowledge proofs (zk-SNARKs) for program executions on a von Neumann RISC architecture The system has two components: a cryptographic proof system for verifying satisfiability of arithmetic circuits, and a circuit generator to translate program executions to such circuits Our design of both components improves in functionality and efficiency over prior work, as follows Our circuit generator is the first to be universal: it does not need to know the program, but only a bound on its running time Moreover, the size of the output circuit depends additively (rather than multiplicatively) on program size, allowing verification of larger programs The cryptographic proof system improves proving and verification times, by leveraging new algorithms and a pairing library tailored to the protocol We evaluated our system for programs with up to 10,000 instructions, running for up to 32,000 machine steps, each of which can arbitrarily access random-access memory; and also demonstrated it executing programs that use just-in-time compilation Our proofs are 230 bytes long at 80 bits of security, or 288 bytes long at 128 bits of security Typical verification time is 5 ms, regardless of the original program's running time

Search for a dark photon in e(+)e(-) collisions at BABAR.

Abstract: Dark sectors charged under a new Abelian interaction have recently received much attention in the context of dark matter models. These models introduce a light new mediator, the so-called dark photon (A^{'}), connecting the dark sector to the standard model. We present a search for a dark photon in the reaction e^{+}e^{-}→γA^{'}, A^{'}→e^{+}e^{-}, μ^{+}μ^{-} using 514 fb^{-1} of data collected with the BABAR detector. We observe no statistically significant deviations from the standard model predictions, and we set 90% confidence level upper limits on the mixing strength between the photon and dark photon at the level of 10^{-4}-10^{-3} for dark photon masses in the range 0.02-10.2 GeV. We further constrain the range of the parameter space favored by interpretations of the discrepancy between the calculated and measured anomalous magnetic moment of the muon.

Rotation Periods of 34,030 Kepler Main-Sequence Stars: The Full Autocorrelation Sample

Abstract: We analyzed 3 years of data from the Kepler space mission to derive rotation periods of main-sequence stars below 6500 K. Our automated autocorrelation-based method detected rotation periods between 0.2 and 70 days for 34,030 (25.6%) of the 133,030 main-sequence Kepler targets (excluding known eclipsing binaries and Kepler Objects of Interest), making this the largest sample of stellar rotation periods to date. In this paper we consider the detailed features of the now well-populated period-temperature distribution and demonstrate that the period bimodality, first seen by McQuillan, Aigrain & Mazeh (2013) in the M-dwarf sample, persists to higher masses, becoming less visible above 0.6 M_sun. We show that these results are globally consistent with the existing ground-based rotation-period data and find that the upper envelope of the period distribution is broadly consistent with a gyrochronological age of 4.5 Gyrs, based on the isochrones of Barnes (2007), Mamajek & Hillenbrand (2008) and Meibom et al. (2009). We also performed a detailed comparison of our results to those of Reinhold et al. (2013) and Nielsen et al. (2013), who have measured rotation periods of field stars observed by Kepler. We examined the amplitude of periodic variability for the stars with detected rotation periods, and found a typical range between ~950 ppm (5th percentile) and ~22,700 ppm (95th percentile), with a median of ~5,600 ppm. We found typically higher amplitudes for shorter periods and lower effective temperatures, with an excess of low-amplitude stars above ~5400 K.

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.

Abstract: Background There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance.