3,640 research outputs found
Evaluation of academic stress among medical students using graphology and machine learning algorithm in correlation with salivary cortisol
Background: Stress is a part of the academic life of graduates. Young adults are especially susceptible to academic stress based on their subjective commitment towards academic goals, and social pressure for superior academic performance. Recognizing academic stress is crucial for planning successful management, and to prevent mental illness. The aim of the study was to develop methods to identify stress using graphology, machine learning algorithm and salivary cortisol.Methods: The study included a mixed method research design and enrolled 43 medical students (19 males and 24 females) between 18-23 years of age were taken in the present study. The Kessler psychological distress scale (K10) was used to ascertain distress among the study subjects.Results: Students written manuscript images were taken for artificial intelligence training and analysis. The written manuscript was evaluated for positive and negative personality traits using graphology techniques. One of the negative traits identified by graphology, i.e.; dejection, it was used to train a machine learning tool to identify the negative trait of dejection.Conclusions: This study suggests that mental health professionals can train machine learning algorithms, using graphology tools, to function as a screening tool to determine stress levels. This may help to plan for management and recovery of stressed individuals and help them in future academic performance
Upper-rim functionalised calix[4]arenes for chemoselective Au3+ detection
A unique, readily synthesised, upper-rim 1,3-difunctionalised calix[4]arene is reported; equipped with a fluorophore and an alkyne it mediates the efficient chemoselective detection of Au3+. Its ability to detect Au3+ is not perturbed by Au+ or excess competing and or contaminating metal e.g. platinum, cadmium, mercury, silver, sodium, magnesium or potassium cations
Formation of finite antiferromagnetic clusters and the effect of electronic phase separation in Pr{_0.5}Ca{_0.5}Mn{_0.975}Al{_0.025}O{_3}
We report the first experimental evidence of a magnetic phase arising due to
the thermal blocking of antiferromagnetic clusters in the weakened charge and
orbital ordered system Pr{_0.5}Ca{_0.5}Mn{_0.975}Al{_0.025}O{_3}. The third
order susceptibility (\chi_3) is used to differentiate this transition from a
spin or cluster glass like freezing mechanism. These clusters are found to be
mesoscopic and robust to electronic phase separation which only enriches the
antiphase domain walls with holes at the cost of the bulk, without changing the
size of these clusters. This implies that Al substitution provides sufficient
disorder to quench the length scales of the striped phases.Comment: 4 Post Script Figure
Pac13 is a small, monomeric dehydratase that mediates the formation of the 3′-deoxy nucleoside of pacidamycins
This work was supported by the EPSRC council (Grant number 1398501), Wellcome Trust (Investigator Award) and GlaxoSmithKline.The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3′-deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine-5’-aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme’s mechanism demonstrating that H42 is critical to the enzyme’s activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3′-deoxy pacidamycin moiety with the synthetic anti-retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds.Publisher PDFPeer reviewe
A marine viral halogenase that iodinates diverse substrates
We thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no. 614779 GenoChemetics to R.J.M.G.), Syngenta and Wellcome ISSF (grant no. 204821/Z/16/Z to D.S.G.) for generous financial support.Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage. Notably, halogenases have been previously associated with secondary metabolism, tailoring natural products. Exploration of this viral halogenase reveals it capable of regioselective halogenation of a diverse range of substrates with a preference for forming aryl iodide species; this has potential implications for the metabolism of the infected host. Until recently, a flavin-dependent halogenase that is capable of iodination in vitro had not been reported. VirX1 is interesting from a biocatalytic perspective as it shows strikingly broad substrate flexibility and a clear preference for iodination, as illustrated by kinetic analysis. These factors together render it an attractive tool for synthesis.PostprintPeer reviewe
Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers
Introduction
Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents.
Methods
Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed.
Results
By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator.
Conclusions
These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC
Short Prolegomena of a »Right to a Home« in the Consumer Bankruptcy Act
Kriza identiteta modela »socijalne države« otvorila je niz pitanja za teoretičare i praktičare. Ovi problemi, naravno, nisu zaobišli niti sustav potrošačko stečajne zaštite kojoj je primarni cilj ekonomska i socijalna »rehabilitacija« potrošača što je differentia specifica u odnosu na primarni cilj korporativnog stečaja, namirenje vjerovnika. Prostor koji ovdje imamo ne dopušta detaljnu raščlambu ove problematike, pa smo prinuđeni ograničiti se isključivo na jedno od ključnih pitanja novog potrošačko stečajnog zakonodavstva: prava na dom. Pritom se posebno analizira praksa Europskog suda za ljudska prava (dalje: Europski sud) u postupcima prema čl. 8. Europske konvencije za zaštitu ljudskih prava i temeljnih sloboda (»Pravo na dom«) jer polazimo od pretpostavke da saznanja o ovome mogu biti ključna za razumijevanje problematike rada, kao i za pravilnu primjenu instituta prava na dom. U cilju što sveobuhvatnijeg odgovora na samu temu, uz uvažavanje prethodno navedenog, struktura i koncept rada je tome morao biti prilagođen. Ovaj rad mogao je biti podijeljen na tri dijela što će se i vidjeti tijekom njegovog čitanja, ali to formalno nije učinjeno.The identity crisis of a »welfare state» model has raised a number of questions for theorists and practitioners. These problems, of course, have not surpassed the system of consumer bankruptcy protection which has the primary objective - economic and social »rehabilitation« of consumers and which is differentia specifica in relation to the primary objective of corporate bankruptcy − settlement of creditors. The scope of this paper does not permit a detailed analysis of these issues, and we are forced to limit ourselves exclusively to one of the key issues of the new consumer bankruptcy law: the right to a home. We specifically analyze the practice of the European Court of Human Rights (hereinafter: European Court) in proceedings under Art. 8 of the European Convention for the Protection of Human Rights and Fundamental Freedoms ("Right to a Home") because we assume that it is a key to understanding the paper subject, as well as to the proper application of the institute of “right to a home”. With respect to the foregoing, in order to have a comprehensive answer to the subject, the structure and concept of paper had to be adjusted. This paper could have been divided into three parts, but it has not been formally done
Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts
Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia.
Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased.
Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia
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