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

Introduction to G2\mathrm{G}_2 geometry

These notes give an informal and leisurely introduction to $\mathrm{G}_2$ geometry for beginners. A special emphasis is placed on understanding the special linear algebraic structure in $7$ dimensions that is the pointwise model for $\mathrm{G}_2$ geometry, using the octonions. The basics of $\mathrm{G}_2$-structures are introduced, from a Riemannian geometric point of view, including a discussion of the torsion and its relation to curvature for a general $\mathrm{G}_2$-structure, as well as the connection to Riemannian holonomy. The history and properties of torsion-free $\mathrm{G}_2$ manifolds are considered, and we stress the similarities and differences with Kahler and Calabi-Yau manifolds. The notes end with a brief survey of three important theorems about compact torsion-free $\mathrm{G}_2$ manifolds.Comment: 37 pages. To appear in a forthcoming volume of the Fields Institute Communications, entitled "Lectures and Surveys on G2 manifolds and related topics". Version 2: Corrected the references. No other change

Portuguese validation of the Internet Gaming Disorder Scale–Short-Form

In the latest (fifth) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Internet Gaming Disorder (IGD) was included as a tentative disorder worthy of future research. Since then, several psychometric instruments to assess IGD have emerged in the literature, including the 9-item Internet Gaming Disorder Scale–Short-Form (IGDS9-SF), the most brief tool available to date. Research on the effects of IGD in Portugal has been minimal and may be due the lack of psychometrically validated tool to assess this construct within this particular cultural background. Therefore, the aim of the present study was to develop and examine the psychometric properties the Portuguese IGDS9-SF. A total of 509 adolescents were recruited to the present study. Construct validity of the IGDS9-SF was assessed in two ways. Firstly, confirmatory factor analysis (CFA) was performed to investigate the factorial structure of the IGDS9-SF in the sample and the uni-dimensional structure of the IGDS9-SF fitted the data well. Secondly, nomological validation of the IGDS9-SF was carried out and the nomological network analyzed was replicated as expected, further supporting the construct validity of the IGDS9-SF. Criterion validity of the IGDS9-SF was also established using key criterion variables. Finally, the IGDS9-SF also showed satisfactory levels of reliability using several indicators of internal consistency. Based on the results found, the IGDS9-SF appears to be a valid and reliable instrument to assess IGD amongst Portuguese adolescents and further research on IGD in Portugal is warranted

Boride Coating on Titanium Alloys as Biomaterial in Wear and Fretting Applications

The issue taken into account is the lifespan and potential toxicity of arthroprostheses with a focus on metal-polyethylene coupling. The gold standard for hip prostheses is a femoral component made of Ti6Al4V alloy, a head made of Co-Cr-Mo alloy and an insert made of UHMWPE while for knee prostheses the gold standard is a tibial component made of Co-Cr-Mo alloy, a femoral component made of Ti6Al4V and an insert made of UHMWPE. Open issues are wear of UHMWPE, toxicity of Co alloys and low fretting/wear resistance of Ti alloys. The aim of this research is to focus on the most biocompatible material (Ti6Al4V alloy) in order to improve its bio-tribological characteristics. A ceramic surface conversion by thermal treatment was used to obtain a borided coating on the titanium alloy surface in order to combine high hardness, good wettability and lubricant behavior of ceramics with good mechanical properties of Ti metal alloys. The coatings were characterized by means of optical microscope observation, FESEM analysis, XRD analysis, microindentation, scratch, friction and wear tests in order to identify the thermal treatment most suitable to obtain a coating with the required properties (thickness, hardness, roughness, wear resistance, friction coefficient and scratch resistance, surface lubrication ability in contact with human fluids) without significant modification of the microstructure of the substrate

"Particle Informatics": Advancing Our Understanding of Particle Properties through Digital Design

We introduce a combination of existing and novel approaches to the assessment and prediction of particle properties intrinsic to the formulation and manufacture of pharmaceuticals. Naturally following on from established solid form informatics methods, we return to the drug lamotrigine, re-evaluating its context in the Cambridge Structural Database (CSD). We then apply predictive digital design tools built around the CSD-System suite of software, including Synthonic Engineering methods that focus on intermolecular interaction energies, to analyze and understand important particle properties and their effects on several key stages of pharmaceutical manufacturing. We present a new, robust workflow that brings these approaches together to build on the knowledge gained from each step and explain how this knowledge can be combined to provide resolutions at decision points encountered during formulation design and manufacturing processes

Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins

We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins

A protective role for BRCA2 at stalled replication forks

The hereditary breast and ovarian cancer predisposition genes BRCA1 and BRCA2 account for the lion's share of heritable breast cancer risk in the human population. Loss of function of either gene results in defective homologous recombination (HR) and triggers genomic instability, accelerating breast tumorigenesis. A long-standing hypothesis proposes that BRCA1 and BRCA2 mediate HR following attempted replication across damaged DNA, ensuring error-free processing of the stalled replication fork. A recent paper describes a new replication fork protective function of BRCA2, which appears to collaborate with its HR function to suppress genomic instability

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Muscle Fiber Viability, a Novel Method for the Fast Detection of Ischemic Muscle Injury in Rats

Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury