1,913 research outputs found
Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate non-nucleoside inhibitors
No full textO-Phthalimidoethyl-N-arylthiocarbamates (TCs) have been recently identified as a new class of potent HIV-1 reverse transcriptase (RT) non-nucleoside inhibitors (NNRTIs), by means of computer-aided drug design techniques [Ranise A. Spallarossa, S. Cesarini, F. Bondavalli. S. Schenone, O. Bruno, G. Menozzi, P. Fossa, L. Mosti, M. La Colla, et al., Structure-based design, parallel synthesis, structure-activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriplase inhibitor isosteres of phenethylthiazolylthiourea derivatives, J. Med. Chem. 48 (2005) 3858-3873]. To elucidate the atomic details of RT/TC interaction and validate an earlier TC docking model, the structures of three RT/TC complexes were determined at 2.8-3.0 angstrom resolution by X-ray crystallography. The conformations adopted by the enzyme-bound TCs were analyzed and compared with those of bioisosterically related NNRTIs
Toward marine environmental predictions in the Mediterranean Sea coastal areas: a monitoring approach
No full textPerception of Reproductive Health in Women with Inflammatory Bowel Disease (vol 10, pg 886, 2016)
No full textAs inflammatory bowel diseases [IBD] affect female patients almost exclusively during their reproductive age, issues related to fertility, fecundity, pregnancy, delivery, and lactation are of utmost importance. Lack of education and misconceptions regarding the effect of disease and/or treatment on reproductive outcome may lead to voluntary childlessness and/or development of unwanted cervical pathologies which may impact tremendously on patients' welfare and quality of life. The aims of this study were to assess the perspectives of IBD patients on fertility, pregnancy and its outcomes, and lactation, as well as their awareness of human papillomavirus [HPV]-related pathologies and screening for cervical cancer. This prospective study was performed across nine different Mediterranean IBD centres between 2014 and 2015 and included consecutive female IBD patients between the ages of 16 and 50 years. All patients responded to a questionnaire based on ECCO guidelines. A total of 348 IBD female patients with a mean age of 37.4 (standard deviation [SD] +/- 2.1) years were recruited 50% had a diagnosis of ulcerative colitis, 49.4% had Crohn`s disease, and 0.6% patients had a diagnosis of indeterminate colitis [IC]. A significant proportion of patients [ > 60%] were afraid that IBD may lead to a complicated pregnancy and that the disease itself and/or its medications can cause fetal harm. Patients had similar concerns that IBD can be transmitted to their offspring as well as with regard to breastfeeding. Counselling from health care professionals with regard to fertility, pregnancy, and lactation was associated positively with the highest number of pregnancies and inversely with the lowest number of patients who considered voluntary childlessness [p < 0.0001]. Patients with a higher level of education were more likely to get pregnant [p = 0.004]. There was a low uptake of the HPV vaccine. However, there was a reasonably good uptake of cervical cancer screening. Our study demonstrates that women with IBD have misperceptions about fertility, pregnancy, and health maintenance. We also show that education by physicians has a positive influence. We thus conclude that improved multidisciplinary approaches should be used to educate and implement European guidelines for women with IBD
Visual processing in Noonan syndrome: dorsal and ventral stream sensitivity
No full textGlobal spatial and motion processing abilities were assessed in 18 patients with Noonan syndrome (NS) and in 43 matched controls using form and motion coherence testing, respectively. We observed a discrepancy between the two groups since the study group had significantly lower performances than the control group for form coherence while there was no impairment on motion coherence. All the patients were also assessed on the Movement Assessment Battery for Children (M-ABC) to evaluate visuomotor skills. Thirteen of the 18 (72%) also had global poor performances on the M-ABC. The results show that children with NS have a specific impairment in the global processing of visuospatial information and are likely to have a specific ventral stream deficit as also suggested by the frequent visuomotor perceptual difficulties. Testing form and motion coherence thresholds may be a useful diagnostic tool for this group of patients, despite their normal cognitive abilities, since aspects of global form processing and visuomotor perceptual difficulties can be identified and potentially targeted for a specific rehabilitation program
Measurement of the production cross-section of J/ψ and ψ(2S) mesons in pp collisions at √s=13 TeV with the ATLAS detector
No full textMeasurements of the differential production cross-sections of prompt and non-prompt J/ψ and ψ(2S) mesons with transverse momenta between 8 and 360 GeV and rapidity in the range |y|<2 are reported. Furthermore, measurements of the non-prompt fractions of J/ψ and ψ(2S), and the prompt and non-prompt ψ(2S)-to-J/ψ production ratios, are presented. The analysis is performed using 140 fb-1 of s=13 TeV pp collision data recorded by the ATLAS detector at the LHC during the years 2015–2018
e-EVN monitoring of M87
No full textM87 is a privileged laboratory for a detailed study of the properties of jets, owing to its proximity (D=16.7 Mpc, 1 mas = 0.080 pc), its massive black hole (~6.0 x 10^9M) and its conspicuous emission at radio wavelengths and above. We started on November 2009 a monitoring program with the e-EVN at 5 GHz, in correspondence of the season of Very High Energy (VHE) observations. Indeed, two episodes of VHE activity have been reported in February and April 2010. We present here the main results of these multi-epoch observations: the inner jet and HST-1 are both detected and resolved in our datasets. We study the apparent velocity of HST-1, which seems to be increasing since 2005, and the flux density variability in the inner jet. All in all, the radio counterpart to this year’s VHE event seems to be different from the ones in 2005 and 2008, opening new scenario for the radio-high energy connection
No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences
No full textBackground
Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare.
Methodology/Principal Findings
We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games.
Conclusion
We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant
Structure-based design, parallel synthesis, structure-activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives
No full textIn this paper we describe our structure-based ligand design, synthetic strategy, and structure-activity relationship (SAR) studies that led to the identification of thiocarbamates (TCs), a novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), isosteres of phenethylthiazolylthiourea (PETT) derivatives. Assuming as a lead compound O-[2-(phthalimido)ethyl] phenylthiocarbamate 12, one of the precursors of the previously described acylthiocarbamates (Ranise, A.; et al. J. Med. Chem. 2003, 46, 768-781), two targeted solution-phase TC libraries were prepared by parallel synthesis. The lead optimization strategy led to para-substituted TCs 31, 33, 34, 39, 40, 41, 44, 45, and 50, which were active against wild-type HIV-1 in MT-4-based assays at nanomolar concentrations (EC50 range: 0.04-0.01 μM). The most potent congener 50 (EC50 = 0.01 μM) bears a methyl group at position 4 of the phthalimide moiety and a nitro group at the para position of the N-phenyl ring. Most of the TCs showed good selectivity indices, since no cytotoxic effect was detected at concentrations as high as 100 μM. TCs 31, 37, 39, 40, and 44 significantly reduced the multiplication of the Y181C mutant, but they were inactive against K103R and K103N + Y181C mutants. Nevertheless, the fold increase in resistance of 41 was not greater than that of efavirenz against the K103R mutant in enzyme assays. The docking model predictions were consistent with in vitro biological assays of the anti-HIV-1 activity of the TCs and related compounds synthesized. © 2005 American Chemical Society
Observation of Markarian 421 in TeV gamma rays over a 14-year time span
No full textThe variability of the blazar Markarian 421 in TeV gamma rays over a 14-year time period has been explored with the Whipple 10 m telescope. It is shown that the dynamic range of its flux variations is large and similar to that in X-rays. A correlation between the X-ray and TeV energy bands is observed during some bright flares and when the complete data sets are binned on long timescales. The main database consists of 878.4 hours of observation with the Whipple telescope, spread over 783 nights. The peak energy response of the telescope was 400 GeV with 20% uncertainty. This is the largest database of any TeV-emitting active galactic nucleus (AGN) and hence was used to explore the variability profile of Markarian 421. The time-averaged flux from Markarian 421 over this period was 0.4460.008 Crab flux units. The flux exceeded 10 Crab flux units on three separate occasions. For the 2000-2001 season the average flux reached 1.86 Crab units, while in the 1996-1997 season the average flux was only 0.23 Crab units.Fil: Acciari, V. A.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Arlen, T.. University of California; Estados UnidosFil: Aune, T.. University of California; Estados UnidosFil: Benbow, W.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Bird, R.. University College Dublin; IrlandaFil: Bouvier, A.. University of California; Estados UnidosFil: Bradbury, S. M.. University of Leeds; Reino UnidoFil: Buckley, J. H.. University of Washington; Estados UnidosFil: Bugaev, V.. University of Washington; Estados UnidosFil: de la Calle Perez, I.. European Space Astronomy Center; EspañaFil: Carter Lewis, D. A.. University of Iowa; Estados UnidosFil: Cesarini, A.. National University of Ireland Galway; IrlandaFil: Ciupik, L.. Adler Planetarium and Astronomy Museum; Estados UnidosFil: Collins Hughes, E.. University College Dublin; IrlandaFil: Connolly, M. P.. National University of Ireland Galway; IrlandaFil: Cui, W.. Purdue University; Estados UnidosFil: Duke, C.. Grinnell College; Estados UnidosFil: Dumm, J.. University Of Minnesota; Estados UnidosFil: Falcone, A.. State University Of Pennsylvania; Estados UnidosFil: Federici, S.. University of Potsdam; AlemaniaFil: Fegan, D. J.. University College Dublin; IrlandaFil: Fegan, S. J.. University College Dublin; IrlandaFil: Finley, J. P.. Purdue University; Estados UnidosFil: Finnegan, G.. University of Utah; Estados UnidosFil: Fortson, L.. University Of Minnesota; Estados UnidosFil: Gaidos, J.. Purdue University; Estados UnidosFil: Galante, N.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Gall, D.. University of Iowa; Estados UnidosFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: The Veritas Collaboration
SEEMP: A Networked Marketplace for Employment Services
No full textThe purpose of this chapter is to introduce the SEEMP marketplace of employment mediators, detailing the business objectives and main features of the SEEMP integrated technology platform. The purpose of SEEMP is to enable the meeting of Job Offers from employers and CVs of job seekers by developing an e-marketplace, improving the business activity of brokers in an employment market currently characterised by: Multiplicity of the players on the market and diversity of the distribution networks: Job Seekers and CVs are distributed across many online databases, brokers and intermediaries. In order to be sufficiently visible, a candidate or an enterprise has to contact several intermediaries, for example temporary work agencies, employment websites, with a redundancy of information and multiplication of the effort needed to correctly classify, qualify and maintain their data. Lack of common standard for Job Offer and CV: The lack of standardized descriptions and search criteria shared by the intermediaries prevents them to exchange information easily and effectively. Insufficient information sharing among the players on the labour market: Inspite of various existing information systems for e-employment, data sharing between entities of intermediary networks remains insufficient. The same holdsfor the cooperation aspects among players in the market, which need cooperative information systems technology. This paper is organized as follows. In Sect. 2, we state the overall objectives of the SEEMP project and state the market vision of the project. In Sect. 3, we present the methodologies adopted in SEEMP in terms of minimal shared commitment that drives the SEEMP policies, and we describe the adopted best practices which help to clarify the agreement levels established for SEEMP and the SEEMP architecture used to implement the interoperability framework. In Sect. 4, we provide a demonstrative use case of the elements described in the paper; this use case is rather simple but proves difficult to solve at a European scale. Finally, in Sect. 5 we introduce some elements of discussion such as a comparison between SEEMP with EURES and other job boards and employment search engines, and set the stage for evaluating the SEEMP benefits for its intended actors; finally we give the concluding remarks
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