Towards Verifying Nonlinear Integer Arithmetic

We eliminate a key roadblock to efficient verification of nonlinear integer arithmetic using CDCL SAT solvers, by showing how to construct short resolution proofs for many properties of the most widely used multiplier circuits. Such short proofs were conjectured not to exist. More precisely, we give n^{O(1)} size regular resolution proofs for arbitrary degree 2 identities on array, diagonal, and Booth multipliers and quasipolynomial- n^{O(\log n)} size proofs for these identities on Wallace tree multipliers.Comment: Expanded and simplified with improved result

Deciding Quantifier-Free Presburger Formulas Using Parameterized Solution Bounds

Given a formula in quantifier-free Presburger arithmetic, if it has a satisfying solution, there is one whose size, measured in bits, is polynomially bounded in the size of the formula. In this paper, we consider a special class of quantifier-free Presburger formulas in which most linear constraints are difference (separation) constraints, and the non-difference constraints are sparse. This class has been observed to commonly occur in software verification. We derive a new solution bound in terms of parameters characterizing the sparseness of linear constraints and the number of non-difference constraints, in addition to traditional measures of formula size. In particular, we show that the number of bits needed per integer variable is linear in the number of non-difference constraints and logarithmic in the number and size of non-zero coefficients in them, but is otherwise independent of the total number of linear constraints in the formula. The derived bound can be used in a decision procedure based on instantiating integer variables over a finite domain and translating the input quantifier-free Presburger formula to an equi-satisfiable Boolean formula, which is then checked using a Boolean satisfiability solver. In addition to our main theoretical result, we discuss several optimizations for deriving tighter bounds in practice. Empirical evidence indicates that our decision procedure can greatly outperform other decision procedures.Comment: 26 page

Culture clash: Appearance concerns in black and minority ethnic groups

Around the world, men and women of all cultures and ethnicities are being exposed to Western appearance ideals. Paired with a lack of representation of black and minority ethnic (BME) men and women in the mainstream media, the public's appreciation of ethnic diversity is being threatened. Nicola Stock examines the growing trend of appearance-altering practice among those from BME communities

Collaborative development of diffraction-limited beamline optical systems at US DOE light sources

An ongoing collaboration among four US Department of Energy (DOE) National Laboratories has demonstrated key technology prototypes and software modeling tools required for new high-coherent flux beamline optical systems. New free electron laser (FEL) and diffraction-limited storage ring (DLSR) light sources demand wavefront preservation from source to sample to achieve and maintain optimal performance. Fine wavefront control was achieved using a novel, roomtemperature cooled mirror system called REAL (resistive element adjustable length) that combines cooling with applied, spatially variable auxiliary heating. Single-grating shearing interferometry (also called Talbot interferometry) and Hartmann wavefront sensors were developed and used for optical characterization and alignment on several beamlines, across a range of photon energies. Demonstrations of non-invasive hard x-ray wavefront sensing were performed using a thin diamond single-crystal as a beamsplitter

The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

Preadaptation of pandemic GII.4 noroviruses in unsampled virus reservoirs years before emergence

The control of re-occurring pandemic pathogens requires understanding the origins of new pandemic variants and the factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have hypothesized that new GII.4 pandemic viruses arise when previously circulating pandemic or pre-pandemic variants undergo substitutions in antigenic regions that enable evasion of host population immunity, as described by conventional models of antigenic drift. In contrast, we show here that the acquisition of new genetic and antigenic characteristics cannot be the proximal driver of new pandemics. Pandemic GII.4 viruses diversify and spread over wide geographical areas over several years prior to simultaneous pandemic emergence of multiple lineages, indicating that the necessary sequence changes must have occurred before diversification, years prior to pandemic emergence. We confirm this result through serological assays of reconstructed ancestral virus capsids, demonstrating that by 2003, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics

Influence of climatic variables on crown condition in pine forests of Northern Spain

Producción CientíficaThe aim of this study was to find relationships between crown condition and some climatic parameters to identify which are those having a main influence on crown condition, and how this influence is shown in the tree (crown transparency), and to contribute to the understanding of how these parameters will affect under future climate change scenarios

Nanobodies raised against monomeric alpha-synuclein inhibit fibril formation and destabilize toxic oligomeric species

BACKGROUND: The aggregation of the protein ɑ-synuclein (ɑS) underlies a range of increasingly common neurodegenerative disorders including Parkinson’s disease. One widely explored therapeutic strategy for these conditions is the use of antibodies to target aggregated ɑS, although a detailed molecular-level mechanism of the action of such species remains elusive. Here, we characterize ɑS aggregation in vitro in the presence of two ɑS-specific single-domain antibodies (nanobodies), NbSyn2 and NbSyn87, which bind to the highly accessible C-terminal region of ɑS. RESULTS: We show that both nanobodies inhibit the formation of ɑS fibrils. Furthermore, using single-molecule fluorescence techniques, we demonstrate that nanobody binding promotes a rapid conformational conversion from more stable oligomers to less stable oligomers of ɑS, leading to a dramatic reduction in oligomer-induced cellular toxicity. CONCLUSIONS: The results indicate a novel mechanism by which diseases associated with protein aggregation can be inhibited, and suggest that NbSyn2 and NbSyn87 could have significant therapeutic potential

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Re-examination of the Controversial Coexistence of Traumatic Brain Injury and Posttraumatic Stress Disorder: Misdiagnosis and Self-Report Measures

The coexistence of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) remains a controversial issue in the literature. To address this controversy, we focused primarily on the civilian-related literature of TBI and PTSD. Some investigators have argued that individuals who had been rendered unconscious or suffered amnesia due to a TBI are unable to develop PTSD because they would be unable to consciously experience the symptoms of fear, helplessness, and horror associated with the development of PTSD. Other investigators have reported that individuals who sustain TBI, regardless of its severity, can develop PTSD even in the context of prolonged unconsciousness. A careful review of the methodologies employed in these studies reveals that investigators who relied on clinical interviews of TBI patients to diagnose PTSD found little or no evidence of PTSD. In contrast, investigators who relied on PTSD questionnaires to diagnose PTSD found considerable evidence of PTSD. Further analysis revealed that many of the TBI patients who were initially diagnosed with PTSD according to self-report questionnaires did not meet the diagnostic criteria for PTSD upon completion of a clinical interview. In particular, patients with severe TBI were often misdiagnosed with PTSD. A number of investigators found that many of the severe TBI patients failed to follow the questionnaire instructions and erroneously endorsed PTSD symptoms because of their cognitive difficulties. Because PTSD questionnaires are not designed to discriminate between PTSD and TBI symptoms or determine whether a patient's responses are accurate or exaggerated, studies that rely on self-report questionnaires to evaluate PTSD in TBI patients are at risk of misdiagnosing PTSD. Further research should evaluate the degree to which misdiagnosis of PTSD occurs in individuals who have sustained mild TBI