Protocol-based verification of message-passing parallel programs

© 2015 ACM.We present ParTypes, a type-based methodology for the verification of Message Passing Interface (MPI) programs written in the C programming language. The aim is to statically verify programs against protocol specifications, enforcing properties such as fidelity and absence of deadlocks. We develop a protocol language based on a dependent type system for message-passing parallel programs, which includes various communication operators, such as point-to-point messages, broadcast, reduce, array scatter and gather. For the verification of a program against a given protocol, the protocol is first translated into a representation read by VCC, a software verifier for C. We successfully verified several MPI programs in a running time that is independent of the number of processes or other input parameters. This contrasts with alternative techniques, notably model checking and runtime verification, that suffer from the state-explosion problem or that otherwise depend on parameters to the program itself. We experimentally evaluated our approach against state-of-the-art tools for MPI to conclude that our approach offers a scalable solution

A study of the Scrum Master’s role

Scrum is an increasingly common approach to software development adopted by organizations around the world. However, as organizations transition from traditional plan-driven development to agile development with Scrum, the question arises as to which Scrum role (Product Owner, Scrum Master, or Scrum Team Member) corresponds to a Project Manager, or conversely which Scrum role should the Project Managers adopt? In an attempt to answer this question, we adopted a mixed-method research approach comprising a systematic literature review and embedded case study of a commercial software development team. Our research has identified activities that comprise the Scrum Master role, and which additional roles are actually performed by Scrum Masters in practice. We found nine activities that are performed by Scrum Masters. In addition, we found that Scrum Masters also perform other roles, most importantly as Project Managers. This latter situation results in tension and conflict of interest that could have a negative impact on the performance of the team as a whole. These results point to the need to re-assess the role of Project Managers in organizations that adopt Scrum as a development approach. We hypothesize that it might be better for Project Managers to become Product Owners, as aspects of this latter role are more consistent with the traditional responsibilities of a Project Manager

Obesity, diabetes and OSAS induce of sleep disorders: Exercise as therapy

Sleep is an integral part of good health. Sleep disorders and variations in sleep habits are associated with a low-grade inflammatory status, which may be either a cause or consequence of other conditions, including obesity, diabetes and cardiovascular disease. Several strategies are available to counteract these conditions including continuous positive airway pressure (CPAP), pharmacological and nutritional interventions, and even surgery. At present, our group is investigating the effect of chronic endurance exercise on sleep alterations

Exercise Intensity Modulation of Hepatic Lipid Metabolism

Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer

Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations. Understanding how these mutations impact on ER function is a prerequisite for identifying methods to treat breast cancer patients featuring such mutations. Towards this end, we used CRISPR-Cas9 genome editing to make a single allele knock-in of the most commonly mutated amino acid residue, tyrosine 537, in the estrogen-responsive MCF7 breast cancer cell line. Genomic analyses using RNA-seq and ER ChIP-seq demonstrated that the Y537S mutation promotes constitutive ER activity globally, resulting in estrogen-independent growth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen and fulvestrant. Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. These studies confirm the functional importance of ER mutations in endocrine resistance, demonstrate the utility of knock-in mutational models for investigating alternative therapeutic approaches and highlight CDK7 inhibition as a potential therapy for endocrine-resistant breast cancer mediated by ER mutations

Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~1020 W/cm2. The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear

Clinical and hematological findings in Leishmania braziliensis-infected dogs from Pernambuco, Brazil

Canine cutaneous leishmaniasis by Leishmania braziliensis is a neglected, but widespread disease of dogs in South America. This paper describes clinical and hematological alterations in 17 L. braziliensis-infected dogs from Brazil. The most common hematological findings were thrombocytopenia (82.4%), anemia (70.6%), low packed cell volume (52.9%) and eosinophilia (41.2%). Twelve (70.6%) dogs displayed at least one evident physical alteration; 11 dogs (64.7%) presented skin lesions, four (23.5%) had weight loss and two (11.8%) onychogryphosis. L. braziliensis-infected dogs present clinical and hematological signs often observed in dogs infected by other pathogens. This indicates that veterinarians and public health workers should not consider the presence of non-specific clinical signs as diagnostic criteria for visceral leishmaniasis in dogs living endemic areas to avoid misdiagnosis and subsequent elimination of dogs infected by L. braziliensis

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

Cognivitra, a digital solution to support dual-task rehabilitation training

This article focuses on an eHealth application, CogniViTra, to support cognitive and physical training (i.e., dual-task training), which can be done at home with supervision of a health care provider. CogniViTra was designed and implemented to take advantage of an existing Platform of Services supporting a Cognitive Health Ecosystem and comprises several components, including the CogniViTra Box (i.e., the patient terminal equipment), the Virtual Coach to provide assistance, the Game Presentation for the rehabilitation exercises, and the Pose and Gesture Recognition to quantify responses during dual-task training. In terms of validation, a functional prototype was exposed in a highly specialized event related to healthy and active ageing, and key stakeholders were invited to test it and share their insights. Fifty-seven specialists in information-technology-based applications to support healthy and active ageing were involved and the results and indicated that the functional prototype presents good performance in recognizing poses and gestures such as moving the trunk to the left or to the right, and that most of the participants would use or suggest the utilization of CogniViTra. In general, participants considered that CogniViTra is a useful tool and may represent an added value for remote dual-task training.This study has received funding from the European Union under the AAL programme through project CogniViTra (Grant No. AAL-2018-5-115-CP), with national funding support from FCT, ISCIII, and FNR. This presentation reflects the authors’ views, and neither AAL nor the National Funding Agencies are responsible for any use that may be made of the information