Word-level Symbolic Trajectory Evaluation

Symbolic trajectory evaluation (STE) is a model checking technique that has been successfully used to verify industrial designs. Existing implementations of STE, however, reason at the level of bits, allowing signals to take values in {0, 1, X}. This limits the amount of abstraction that can be achieved, and presents inherent limitations to scaling. The main contribution of this paper is to show how much more abstract lattices can be derived automatically from RTL descriptions, and how a model checker for the general theory of STE instantiated with such abstract lattices can be implemented in practice. This gives us the first practical word-level STE engine, called STEWord. Experiments on a set of designs similar to those used in industry show that STEWord scales better than word-level BMC and also bit-level STE.Comment: 19 pages, 3 figures, 2 tables, full version of paper in International Conference on Computer-Aided Verification (CAV) 201

Obfuscator Synthesis for Privacy and Utility

We consider the problem of synthesizing an obfuscation policy that enforces privacy while preserving utility with formal guarantees. Specifically, we consider plants modeled as finite automata with predefined secret behaviors. A given plant generates event strings for some useful computation, but meanwhile wants to hide its secret behaviors from any outside observer. We formally capture the privacy and utility specifications using the automaton model of the plant. To enforce both specifications, we propose an obfuscation mechanism where an edit function “edits” the plant’s output in a reactive manner. We develop algorithmic procedures that synthesize a correct-by-construction edit function satisfying both privacy and utility specifications. To address the state explosion problem, we encode the synthesis algorithm symbolically using Binary Decision Diagrams. We present EdiSyn, an implementation of our algorithms, along with experimental results demonstrating its performance on illustrative examples. This is the first work, to our knowledge, to successfully synthesize controllers satisfying both privacy and utility requirements

DWSB in heterotic flux compactifications

We address the construction of non-supersymmetric vacua in heterotic compactifications with intrinsic torsion and background fluxes. In particular, we implement the approach of domain-wall supersymmetry breaking (DWSB) previously developed in the context of type II flux compactifications. This approach is based on considering backgrounds where probe NS5-branes wrapping internal three-cycles and showing up as four-dimensional domain-walls do not develop a BPS bound, while all the other BPS bounds characterizing the N=1 supersymmetric compactifications are preserved at tree-level. Via a scalar potential analysis we provide the conditions for these backgrounds to solve the ten-dimensional equations of motion including order \alpha' corrections. We also consider backgrounds where some of the NS5-domain-walls develop a BPS bound, show their relation to no-scale SUSY-breaking vacua and construct explicit examples via elliptic fibrations. Finally, we consider backgrounds with a non-trivial gaugino condensate and discuss their relation to supersymmetric and non-supersymmetric vacua in the present context.Comment: 56 pages, 1 figur

Ovarian Activity and Oestrous Signs among Group-Housed, Lactating Sows: Influence of Behaviour, Environment and Production

Animal welfare concerns require the development of housing systems that allow the animals to express their natural behaviour. One example of this is the group-housing system for lactating sows. The present study aimed at exploring ovarian activity in such a system. Thirty-eight sows farrowing individually outdoors during spring and summer, and indoors during autumn and winter, and group-housed in groups of four during weeks 3–7 of the lactation period, were monitored regarding reproductive functions, behaviour and production during their first to fourth lactation period. Average ovulation frequency during lactation was 47%. Only 50% of these ovulating cases were accompanied by a standing oestrus. Lactational ovulation frequency was higher in later parities (p < 0.001). Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%), than during summer (10%) and autumn (23%). Occurrence of lactational ovulation was associated with some aspects of suckling behaviour and also with litter weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations occurred during the seventh week of lactation. Timing of ovulation seemed positively (p = 0.08) associated with weight loss during lactation. Compared with the sows that were anoestrus during lactation, oestradiol-17β values were higher (p < 0.05) only in the week before occurrence of lactational ovulation. Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that ovulated during lactation. The present study identifies several factors influencing ovarian activity among group-housed sows, thereby providing tools for the control of lactational ovulation in group-housing systems

Heterotic Black Horizons

We show that the supersymmetric near horizon geometry of heterotic black holes is either an AdS_3 fibration over a 7-dimensional manifold which admits a G_2 structure compatible with a connection with skew-symmetric torsion, or it is a product R^{1,1} * S^8, where S^8 is a holonomy Spin(7) manifold, preserving 2 and 1 supersymmetries respectively. Moreover, we demonstrate that the AdS_3 class of heterotic horizons can preserve 4, 6 and 8 supersymmetries provided that the geometry of the base space is further restricted. Similarly R^{1,1} * S^8 horizons with extended supersymmetry are products of R^{1,1} with special holonomy manifolds. We have also found that the heterotic horizons with 8 supersymmetries are locally isometric to AdS_3 * S^3 * T^4, AdS_3 * S^3 * K_3 or R^{1,1} * T^4 * K_3, where the radii of AdS_3 and S^3 are equal and the dilaton is constant.Comment: 35 pages, latex. Minor alterations to equation (3.11) and section 4.1, the conclusions are not affecte

Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

The pseudo McMillan degree of implicit transfer functions of RLC networks

We study the structure of a given RLC network without sources. Since the McMillan degree of the implicit transfer function is not a suitable measure of complexity of the network, we introduce the pseudo McMillan degree to overcome these shortcomings.Using modified nodal analysis models, which are linked directly to the natural network topology, we shaw that the pseudo-McMillan degree equals the sum of the number of capacitors and inductors minus the number of fundamental loops of capacitors and fundamental cutsets of inductors; this is the number of independent dynamic elements in the network. Exploiting this representation we derive a minimal realization of the given RLC network, that is one where the number of independent differential equations equals the pseudo McMillan degree

Diversity and Strain Specificity of Plant Cell Wall Degrading Enzymes Revealed by the Draft Genome of Ruminococcus flavefaciens FD-1

Peer reviewedPublisher PD