A Water-Bridged Cysteine-Cysteine Redox Regulation Mechanism in Bacterial Protein Tyrosine Phosphatases

The emergence of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains highlights the need to develop more efficacious and potent drugs. However, this goal is dependent on a comprehensive understanding of Mtb virulence protein effectors at the molecular level. Here, we used a post-expression cysteine (Cys)-to-dehydrolanine (Dha) chemical editing strategy to identify a water-mediated motif that modulates accessibility of the protein tyrosine phosphatase A (PtpA) catalytic pocket. Importantly, this water-mediated Cys-Cys non-covalent motif is also present in the phosphatase SptpA from Staphylococcus aureus, which suggests a potentially preserved structural feature among bacterial tyrosine phosphatases. The identification of this structural water provides insight into the known resistance of Mtb PtpA to the oxidative conditions that prevail within an infected host macrophage. This strategy could be applied to extend the understanding of the dynamics and function(s) of proteins in their native state and ultimately aid in the design of small-molecule modulators.e thank CNPq Brazil (fellowship 200456/2015-6 to J.B.B. and grants 454507/2014-3 and 300606/2010-9 to H.T.), the Fundação para a Ciência e a Tecnologia (FCT Investigator award IF/00624/2015 to G.J.L.B.), the European Union (Marie-Sklodowska Curie Innovative Training Network Protein Conjugates; Marie Skłodowska-Curie Individual Fellowship 743640 to T.R.; Marie-Curie Intra-European Fellowship 626890 to O.B.), the Ministerio de Economía, Industria, y Competitividad (project CTQ2015-67727-R to F.C.), and the Biotechnology and Biological Sciences Research Council (PhD studentship to L.D.) for funding. G.J.L.B. is a Royal Society University Research Fellow and the recipient of a European Research Council Starting Grant (TagIt, 676832 ). We also acknowledge funding by LISBOA-01-0145-FEDER-007391, co-financed by FEDER through the Programa Operacional Regional de Lisboa (Lisboa 2020) of PORTUGAL 2020 and by FCT Portugal

Assessment of pollution risk ascribed to Santa Margarida Military Camp activities (Portugal)

Santa Margarida Military Camp (S.M.M.C.) is the only one Portuguese military training area, including firing ranges for tactical military manoeuvres of mechanised divisions. For this reason, various negative effects on the environment were expected due to the military activities, as the Military Camp’s area is classified as a high vulnerability area to pollution of its multilayer porous aquifers. The aim of this study was to identify and characterise local/regional geochemical impacts caused by the continuing military training activities performed at S.M.M.C. in the course of 52 years. An overview of the geochemical research issues as a basis for risk assessment is presented. A special attention has been put on the quality of local and regional surface waters, shallow groundwaters and groundwaters. Local soils and sediments as well as fragments of shells and bullets were sampled and analysed. The results so far obtained, indicated that none pollution effects were a consequence of the military training activities. Till now, the geochemical signatures such as, high levels of K, Cl and NO3 in waters, detected in particular sites, should be faced as tracers of diffuse pollution ascribed to urban waste disposal and cattle breading

An investigation of the predictability of the Brazilian three-modal hand-based behavioural biometric: a feature selection and feature-fusion approach

Abstract: New security systems, methods or techniques need to have their performance evaluated in conditions that closely resemble a real-life situation. The effectiveness with which individual identity can be predicted in different scenarios can benefit from seeking a broad base of identity evidence. Many approaches to the implementation of biometric-based identification systems are possible, and different configurations are likely to generate significantly different operational characteristics. The choice of implementational structure is, therefore, very dependent on the performance criteria, which is most important in any particular task scenario. The issue of improving performance can be addressed in many ways, but system configurations based on integrating different information sources are widely adopted in order to achieve this. Thus, understanding how each data information can influence performance is very important. The use of similar modalities may imply that we can use the same features. However, there is no indication that very similar (such as keyboard and touch keystroke dynamics, for example) basic biometrics will perform well using the same set of features. In this paper, we will evaluate the merits of using a three-modal hand-based biometric database for user prediction focusing on feature selection as the main investigation point. To the best of our knowledge, this is the first thought-out analysis of a database with three modalities that were collected from the same users, containing keyboard keystroke, touch keystroke and handwritten signature. First, we will investigate how the keystroke modalities perform, and then, we will add the signature in order to understand if there is any improvement in the results. We have used a wide range of techniques for feature selection that includes filters and wrappers (genetic algorithms), and we have validated our findings using a clustering technique

The Acceptability of Internet-Based Treatment and Characteristics of an Adult Sample with Obsessive Compulsive Disorder: An Internet Survey

Background: Obsessive-compulsive disorder (OCD) is a disabling anxiety disorder, but most individuals delay seeking treatment. Internet-based cognitive behavioural therapy (iCBT) is an innovative service delivery method that may help to improve access to care, but the acceptability to consumers of such programs has not yet been established. Methodology: People with symptoms of OCD were invited to complete an online survey enquiring about demographic characteristics, symptom severity, and acceptability of Internet-based treatment. Demographic and symptom severity data were compared with people with OCD identified in a national epidemiological survey and with a sample of patients with OCD from a specialist outpatient anxiety clinic. Participants: 129 volunteers to an online Internet survey, 135 patients at a specialist anxiety disorders outpatient clinic, and 297 cases identified in a national epidemiological survey. Main Measures: Demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale, the 12-item World Health Organisation Disability Assessment Schedule - Second Edition and the Yale Brown Obsessive Compulsive Scale - Self Report Version. Principal Findings: The Internet sample was similar demographically but reported more severe symptoms than the comparison groups, although had similar severity of symptoms of OCD compared with other clinical samples reported in the literature. Participants reported Internet-based treatment for OCD would be highly acceptable. Conclusions: Internet-based treatment may reduce barriers to accessing treatment to people with OCD. Individuals in this study were similar demographically to other samples and had similar severity of symptoms as those identified in other clinical samples, suggesting that Internet-based treatment using techniques employed in face-to-face treatment may be effective in this group. Internet-based treatments for OCD need to be developed and evaluated

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV