Power Connector

A pair of mating connectors includes a receptacle having an insulative housing and at least one conductive receptacle contact with a pair of spaced walls forming a plug contact receiving space. The plug connector has an insulative housing and at least one conductive contact having a pair of spaced walls which converge to form a projection engageable in the plug receiving space of the receptacle contact. In each case, the spaced walls are joined by a bridging structure that unites the walls. The plug and receptacle contacts are retained in the respective housings by engagement of opposed lateral edge portions of the contacts with the housings in a manner to enhance heat dissipation by convection by maintaining substantial portions of the contacts spaced from the housing walls and from each other. The bridging structure may include a retention element for engaging respective connector housings to retain the contact in the housings. The open structure of both the receptacle and plug contacts enhances heat dissipation and allows flexibility in achieving desired contact normal forces. The contact construction is especially useful for electronic power connectors

Influence of a football match on landing biomechanics and jump performance in female football players

This study aimed to assess the acute effect of a competitive football match on jump performance and kinematic parameters during jump landing in semiprofessional female football players. Twenty-two semiprofessional players (20 ± 3 years) underwent a drop jump task for a posterior video analysis of the landing phase. These measurements were obtained at (1) baseline, (2) after, and (3) 48 h after a competitive football match. A one-way ANOVA with repeated measures was employed to detect differences over the time. There was a main effect of time for maximal knee flexion angle during drop landing (p = 0.001). In comparison with baseline, maximal knee flexion angle was reduced immediately post-match and was still reduced 48 h after the match (63.4 ± 8.6 vs 57.0 ± 11.7 vs 48.9 ± 19.1, p ≤ 0.038). There was also a main effect of time for drop jump height (p < 0.001). Drop jump height was reduced immediately post-match and remained low 48 h after the match in comparison with baseline (27.3 ± 3.6 vs 24.5 ± 2.8 ~ 25.5 ± 3.0 cm, p ≤ 0.002). There was a main effect of time on hip flexion angle during landing (p = 0.001), but the pairwise comparison revealed that this variable was not affected immediately post-match but was lower 48 h after the match than at baseline (50.1 ± 10.1 ~ 50.8 ± 13.2 vs 38.1 ± 17.8 °, p ≤ 0.005). A competitive football match worsened jump performance and several landing biomechanical parameters in female football players, which were still decreased in comparison with baseline even 48 h after the match

Distinct ubiquitin binding modes exhibited by SH3 domains: Molecular determinants and functional implications

SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination. © 2013 Ortega Roldan et al

Massless particles in three-dimensional Lorentzian warped products

The model of a massless relativistic particle with curvature-dependent Lagrangian is well known in (d+1)-dimensional Minkowski space. For other gravitational fields less rigid than those with constant (zero) curvature only a few results are known. In this paper, we give a geometric approach in order to solve the field equations associated with that Lagrangian in the setting of an interesting three-dimensional background, namely, a three-dimensional warped product with Lorentzian fibers. When some rigidity conditions are imposed to the fiber (constant Gauss curvature), the trajectories can be totally described. Several examples help us clarify this.Ministerio de Educación y CienciaFondo Europeo de Desarrollo RegionalJunta de Andalucí

Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery

Factors affecting the performance of P22 ELISA for the diagnosis of caprine tuberculosis in milk samples

Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB eradication programmes are based mainly on intradermal tuberculin tests and slaughterhouse surveillance. However, the use of serological test has been extended as a potential diagnostic tool in goats through the use of serum, plasma, or even milk samples. Milk production and the antibodies (Ab) present in milk can vary depending on several circumstances. In the present study, different factors that may affect the performance of humoral TB diagnosis were analysed using goat milk samples: 1) lactation stage, 2) a recent previous skin test (booster effect) and 3) the effect of freeze-thaw cycles on milk samples preserved with azidiol. TB-infected animals (n = 44) were selected to evaluate the evolution of the Ab levels during the 6-month lactation period, along with its potential effect on the P22 ELISA results. In general, no significant changes (p = 0.079) were observed throughout the study as regards Ab levels in milk samples between consecutive analysis although the reactivity to P22 ELISA decreased when samplings were performed at the last two months of the lactation. Regarding the booster effect, the quantitative results showed a significant variation (p < 0.001) for both milk and serum samples when serological tests were carried out 15 days after the skin test. Finally, there were no significant differences (p = 0.99) in the P22 ELISA results when using milk samples preserved with azidiol that had undergone freeze-thaw cycles.This study was funded by the Spanish Ministry of Science and Innovation through the project “Análisis del proceso de erradicación de la tuberculosis caprina a largo plazo y desarrollo de pruebas de diagnóstico y medidas de control para su mejora (GoaTBfree-UCM, reference PID2019-105155RB-C31) and the Spanish Ministry of Agriculture, Fisheries and Food. JO was supported by an FPU (Formación de Profesorado Universitario) contract-fellowship provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (FPU18/05197).S

Enhancing a de novo enzyme activity by computationally-focused ultra-low-throughput screening

Directed evolution has revolutionized protein engineering. Still, enzyme optimization by random library screening remains sluggish, in large part due to futile probing of mutations that are catalytically neutral and/or impair stability and folding. FuncLib is a novel approach which uses phylogenetic analysis and Rosetta design to rank enzyme variants with multiple mutations, on the basis of predicted stability. Here, we use it to target the active site region of a minimalist-designed, de novo Kemp eliminase. The similarity between the Michaelis complex and transition state for the enzymatic reaction makes this system particularly challenging to optimize. Yet, experimental screening of a small number of active-site variants at the top of the predicted stability ranking leads to catalytic efficiencies and turnover numbers ( 2 104 M 1 s 1 and 102 s 1) for this anthropogenic reaction that compare favorably to those of modern natural enzymes. This result illustrates the promise of FuncLib as a powerful tool with which to speed up directed evolution, even on scaffolds that were not originally evolved for those functions, by guiding screening to regions of the sequence space that encode stable and catalytically diverse enzymes. Empirical valence bond calculations reproduce the experimental activation energies for the optimized eliminases to within 2 kcal mol 1 and indicate that the enhanced activity is linked to better geometric preorganization of the active site. This raises the possibility of further enhancing the stabilityguidance of FuncLib by computational predictions of catalytic activity, as a generalized approach for computational enzyme designKnut and Alice Wallenberg Foundation (Wallenberg Academy Fellowship) 2018.0140Human Frontier Science Program RGP0041/2017FEDER Funds/Spanish Ministry of Science, Innovation and Universities BIO2015-66426-R RTI2018-097142-B-100FEDER/Junta de Andalucia - Consejeria de Economia y Conocimiento E.FQM.113.UGR18Swedish National Infrastructure for computing (SNAC) 2018/2-3 2019/2-

Do ResearchGate Scores create ghost academic reputations?

[EN] The academic social network site ResearchGate (RG) has its own indicator, RG Score, for its members. The high profile nature of the site means that the RG Score may be used for recruitment, promotion and other tasks for which researchers are evaluated. In response, this study investigates whether it is reasonable to employ the RG Score as evidence of scholarly reputation. For this, three different author samples were investigated. An outlier sample includes 104 authors with high values. A Nobel sample comprises 73 Nobel winners from Medicine and Physiology, Chemistry, Physics and Economics (from 1975 to 2015). A longitudinal sample includes weekly data on 4 authors with different RG Scores. The results suggest that high RG Scores are built primarily from activity related to asking and answering questions in the site. In particular, it seems impossible to get a high RG Score solely through publications. Within RG it is possible to distinguish between (passive) academics that interact little in the site and active platform users, who can get high RG Scores through engaging with others inside the site (questions, answers, social networks with influential researchers). Thus, RG Scores should not be mistaken for academic reputation indicators.Alberto Martin-Martin enjoys a four-year doctoral fellowship (FPU2013/05863) granted by the Ministerio de Educacion, Cultura, y Deporte (Spain). Enrique Orduna-Malea holds a postdoctoral fellowship (PAID-10-14), from the Polytechnic University of Valencia (Spain).Orduña Malea, E.; Martín-Martín, A.; Thelwall, M.; Delgado-López-Cózar, E. (2017). Do ResearchGate Scores create ghost academic reputations?. Scientometrics. 112(1):443-460. https://doi.org/10.1007/s11192-017-2396-9S4434601121Bosman, J. & Kramer, B. (2016). Innovations in scholarly communication—data of the global 2015–2016 survey. Available at: http://zenodo.org/record/49583 #. Accessed December 11, 2016.González-Díaz, C., Iglesias-García, M., & Codina, L. (2015). Presencia de las universidades españolas en las redes sociales digitales científicas: Caso de los estudios de comunicación. El profesional de la información, 24(5), 1699–2407.Goodwin, S., Jeng, W., & He, D. (2014). Changing communication on ResearchGate through interface updates. Proceedings of the American Society for Information Science and Technology, 51(1), 1–4.Hicks, D., Wouters, P., Waltman, L., de Rijcke, S., & Rafols, I. (2015). The Leiden Manifesto for research metrics. Nature, 520(7548), 429–431.Hoffmann, C. P., Lutz, C., & Meckel, M. (2015). A relational altmetric? Network centrality on ResearchGate as an indicator of scientific impact. Journal of the Association for Information Science and Technology, 67(4), 765–775.Jiménez-Contreras, E., de Moya Anegón, F., & Delgado López-Cózar, E. (2003). The evolution of research activity in Spain: The impact of the National Commission for the Evaluation of Research Activity (CNEAI). Research Policy, 32(1), 123–142.Jordan, K. (2014a). Academics’ awareness, perceptions and uses of social networking sites: Analysis of a social networking sites survey dataset (December 3, 2014). Available at: http://dx.doi.org/10.2139/ssrn.2507318 . Accessed December 11, 2016.Jordan, K. (2014b). Academics and their online networks: Exploring the role of academic social networking sites. First Monday, 19(11). Available at: http://dx.doi.org/10.5210/fm.v19i11.4937 . Accessed December 11, 2016.Jordan, K. (2015). Exploring the ResearchGate score as an academic metric: reflections and implications for practice. Quantifying and Analysing Scholarly Communication on the Web (ASCW’15), 30 June 2015, Oxford. Available at: http://ascw.know-center.tugraz.at/wp-content/uploads/2015/06/ASCW15_jordan_response_kraker-lex.pdf . Accessed December 11, 2016.Kadriu, A. (2013). Discovering value in academic social networks: A case study in ResearchGate. Proceedings of the ITI 2013—35th Int. Conf. on Information Technology Interfaces Information Technology Interfaces, pp. 57–62.Kraker, P. & Lex, E. (2015). A critical look at the ResearchGate score as a measure of scientific reputation. Proceedings of the Quantifying and Analysing Scholarly Communication on the Web workshop (ASCW’15), Web Science conference 2015. Available at: http://ascw.know-center.tugraz.at/wp-content/uploads/2016/02/ASCW15_kraker-lex-a-critical-look-at-the-researchgate-score_v1-1.pdf . Accessed December 11, 2016.Li, L., He, D., Jeng, W., Goodwin, S. & Zhang, C. (2015). Answer quality characteristics and prediction on an academic Q&A Site: A case study on ResearchGate. Proceedings of the 24th International Conference on World Wide Web Companion, pp. 1453–1458.Martín-Martín, A., Orduna-Malea, E., Ayllón, J. M. & Delgado López-Cózar, E. (2016). The counting house: measuring those who count. Presence of Bibliometrics, Scientometrics, Informetrics, Webometrics and Altmetrics in the Google Scholar Citations, ResearcherID, ResearchGate, Mendeley & Twitter. Available at: https://arxiv.org/abs/1602.02412 . Accessed December 11, 2016.Martín-Martín, A., Orduna-Malea, E. & Delgado López-Cózar, E. (2016). The role of ego in academic profile services: Comparing Google Scholar, ResearchGate, Mendeley, and ResearcherID. Researchgate, Mendeley, and Researcherid. The LSE Impact of Social Sciences blog. Available at: http://blogs.lse.ac.uk/impactofsocialsciences/2016/03/04/academic-profile-services-many-mirrors-and-faces-for-a-single-ego . Accessed December 11, 2016.Matthews, D. (2016). Do academic social networks share academics’ interests?. Times Higher Education. Available at: https://www.timeshighereducation.com/features/do-academic-social-networks-share-academics-interests . Accessed December 11, 2016.Memon, A. R. (2016). ResearchGate is no longer reliable: leniency towards ghost journals may decrease its impact on the scientific community. Journal of the Pakistan Medical Association, 66(12), 1643–1647.Mikki, S., Zygmuntowska, M., Gjesdal, Ø. L. & Al Ruwehy, H. A. (2015). Digital presence of norwegian scholars on academic network sites-where and who are they?. Plos One 10(11). Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142709 . Accessed December 11, 2016.Nicholas, D., Clark, D., & Herman, E. (2016). ResearchGate: Reputation uncovered. Learned Publishing, 29(3), 173–182.Orduna-Malea, E., Martín-Martín, A., & Delgado López-Cózar, E. (2016). The next bibliometrics: ALMetrics (Author Level Metrics) and the multiple faces of author impact. El profesional de la información, 25(3), 485–496.Ortega, Jose L. (2015). Relationship between altmetric and bibliometric indicators across academic social sites: The case of CSIC’s members. Journal of informetrics, 9(1), 39–49.Ortega, Jose L. (2016). Social network sites for scientists. Cambridge: Chandos.Ovadia, S. (2014). ResearchGate and Academia. edu: Academic social networks. Behavioral & Social Sciences Librarian, 33(3), 165–169.Thelwall, M., & Kousha, K. (2015). ResearchGate: Disseminating, communicating, and measuring Scholarship? Journal of the Association for Information Science and Technology, 66(5), 876–889.Thelwall, M. & Kousha, K. (2017). ResearchGate articles: Age, discipline, audience size and impact. Journal of the Association for Information Science and Technology, 68(2), 468–479.Van Noorden, R. (2014). Online collaboration: Scientists and the social network. Nature, 512(7513), 126–129.Wilsdon, J., Allen, L., Belfiore, E., Campbell, P., Curry, S., Hill, S. et al. (2015). The Metric Tide: Independent Review of the Role of Metrics in Research Assessment and Management. HEFCE. Available at: http://doi.org/10.13140/RG.2.1.4929.1363 . Accessed December 11, 2016

Effect of the topical administration of corticosteroids and tuberculin pre-sensitisation on the diagnosis of tuberculosis in goats

Background: Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals. In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed. Methods: The animals (n = 151) were distributed into three groups: (1) a group topically treated with corticosteroids 48 h after intradermal tuberculin tests (n = 53); (2) a group pre-sensitised with bovine and avian purified protein derivatives (PPDs) 3 days before the intradermal tuberculin test used for TB diagnosis (n = 48); and (3) a control group (n = 50). All the animals were tested using single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, an interferon-gamma release assay (IGRA) and a P22 ELISA. Results: The number of SIT test reactors was significantly lower in the group treated with corticosteroids when compared to the pre-sensitised (p 0.05). No significant effect was observed on IGRA and P22 ELISA due to corticosteroids administration. Nevertheless, a previous PPD injection affected the IGRA performance in some groups. Conclusions: The application of topical corticosteroid 24 h before reading the SIT and CIT tests can reduce the increase in skin fold thickness and subsequently significantly decrease the number of positive reactors. Corticosteroids used can be detected in hair samples. A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs.This study was funded by the “Analysis of the long-term caprine tuberculosis eradication process and development of diagnostic tests and control measures for its improvement (GoaTBfree-UCM)” Project (PID2019-105155RB-C31, Ministry of Science and Innovation of Spain) and the Ministry of Agriculture, Fisheries and Food of Spain. JO was supported by an FPU contract-fellowship (Formación de Profesorado Universitario) from the Spanish Ministerio de Ciencia, Innovación y Universidades (FPU18/05197).S

Membrane insertion of soluble CLIC1 into active chloride channels is triggered by specific divalent cations

The CLIC family of proteins display the unique feature of altering their structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, can be found in the cytoplasm or in nuclear, ER and plasma membranes, with membrane overexpression linked to tumour proliferation. The molecular switch promoting CLIC1 membrane insertion has been related to environmental factors, but still remains unclear. Here, we use solution NMR studies to confirm that both the soluble and membrane bound forms are in the same oxidation state. Our data from fluorescence assays and chloride efflux assays indicate that Ca2+ and Zn2+ trigger association to the membrane into active chloride channels. We use fluorescence microscopy to confirm that an increase of the intracellular Ca2+ leads to re-localisation of CLIC1 to both plasma and internal membranes. Finally, we show that soluble CLIC1 adopts an equilibrium of oligomeric species, and Ca2+/Zn2+ mediated membrane insertion promotes the formation of a tetrameric assembly. Thus, our results identify Ca2+ and Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion.SIGNIFICANCE STATEMENT CLIC1, a member of the CLIC family of proteins, is expressed as a soluble protein in cells but can insert in the membrane forming a chloride channel. This chloride channel form is upregulated in different types of cancers including glioblastoma and promote tumour invasiveness and metastasis. The factors promoting CLIC1 membrane insertion nor the mechanism of this process are yet understood. Here, we use a combination of solution NMR, biophysics and fluorescence microscopy to identify Ca2+ and Zn2+ binding as the switch to promote CLIC1 insertion into the membrane to form active chloride channels. We also provide a simple mechanism how such transition to the membrane occurs. Such understanding will enable subsequent studies on the structure of the chloride channel form and its inhibition