NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.

This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S007961071400087X.Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets.The authors are very grateful to the organizations that funded their research: the UK Biotechnology and Biological Sciences Research Council (BBSRC, grants BB/J001201/1 and David Phillips Fellowship BB/G023123/1 to A.C.), the European Research Council (ERC-2012-StG-311460 DrugE3CRLs, Starting Grant to A.C.) the European Commission (Bio-NMR, Project 261863), and the Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/81735/2011 Studentship to D.M.D.)

Smart Property Valuation. Problem Solving for Industry

The analysis of this project it is used the CRISP-DM method. Smart Property Valuation (SPV) is a fictional company created by David Silva, Luiz Dias, and Raul Fuzita to analyse, explore, and prove the conception of a model capable of predicting or estimating prices for properties. They believe they can benefit common people, realtors, and construction companies with their solutions. This research is for educational purposes and should be treated as such

34. Grip strength across Europe –North/ South and East/West divides

info:eu-repo/semantics/publishedVersio

Pando: Personal Volunteer Computing in Browsers

The large penetration and continued growth in ownership of personal electronic devices represents a freely available and largely untapped source of computing power. To leverage those, we present Pando, a new volunteer computing tool based on a declarative concurrent programming model and implemented using JavaScript, WebRTC, and WebSockets. This tool enables a dynamically varying number of failure-prone personal devices contributed by volunteers to parallelize the application of a function on a stream of values, by using the devices' browsers. We show that Pando can provide throughput improvements compared to a single personal device, on a variety of compute-bound applications including animation rendering and image processing. We also show the flexibility of our approach by deploying Pando on personal devices connected over a local network, on Grid5000, a French-wide computing grid in a virtual private network, and seven PlanetLab nodes distributed in a wide area network over Europe.Comment: 14 pages, 12 figures, 2 table

Natural pigments of anthocyanin and betalain for coloring soy-based yogurt alternative

The aim of this work was to evaluate the color stability of betalain- and anthocyanin-rich extracts in yogurt-like fermented soy, in order to develop a preliminary understanding of how these pigments behave in this type of food system during storage for 21 days at 4 °C. Thus, the extracts of red beetroot, opuntia, hibiscus and red radish were integrated into the yogurt-like fermented soy in two different ways—directly after lyophilization, and encapsulated in nanosystems based in soybean lecithin—as this approach has never been used to further increase the value and potential of the dairy-free alternatives of yogurt-like fermented soy. The results showed that non-encapsulated betalain-rich extracts from red radish are the most promising for coloring yogurt-like fermented soy. However, encapsulated opuntia extracts can also be an alternative to supplement the soy fermented beverages with betalains, without changing significantly the color of the system but giving all its health benefits, due to the protection of the pigments by nanoencapsulation.This research was funded by COMPETE 2020 program, co-financed by the FEDER and the European Union, PTDC/ASP-AGR/30154/2017 (POCI-01-0145-FEDER-030154). Foundation for Science and Technology (FCT, Portugal), and FEDER-COMPETE-QREN-EU funded research centers CQ-UM (UID/QUI/00686/2019), CF-UM-UP (UID/FIS/04650/2019) and REQUIMTE (UIDB/50006/2020)

Exploring the Impact of a Gamified Exercise Platform to Support Healthy Ageing:Home-Based Study with Older Adults

Active ageing is an increasingly important concept within society due to the ageing of the world population and search for enhanced quality of life. Technological resources such as serious games can be used as a means to promote healthier lifestyle and ageing, particularly in older adults. This study intended to explore the effects of using a digital approach composed of serious games to support physical and cognitive exercise at home, to support healthy ageing. Eleven older adults voluntarily participated in an eight-day home-based study. The aim of the study was to explore the feasibility of the digital approach in autonomous sessions at home, by measuring satisfaction and motivation, and assessing the impact of different gamification strategies. The results showed that participants exercised autonomously on average on 5.5 out of the 8 days. Each session had an average duration of 35 minutes. Moreover, participants reported an average satisfaction of 80.0% throughout the sessions. Yet, the findings indicate that system usability should still be improved. Participants provided suggestions towards an easier user experience, pointing for example to the importance of personalized exercise plans. The findings suggest that gamification strategies focused on multi-joint and dynamic exercises were preferred over single limb and more monotonous exercises. The current study highlights the potential of home-based digital solutions to support healthy ageing in older adults and provide suggestions for future endeavors in this area.</p

Beetroot as a source of natural dyes for ham

Beetroot (Beta vulgaris L.) was subjected to extraction procedures in order to obtain the respective extracts containing the natural dyes and subjected to cytotoxicity assays in AGS cell line. Encapsulation of the extracts in nanosystems based on soybean lecithin and maltodextrin was performed. Lyophilized extracts before and after encapsulation in maltodextrin were applied in the formulation of leg ham and used in pilot scale of production. The colour of ham samples from the different assays was evaluated visually and by colorimetry.Dias, S.; Pereira, D.M.; Castanheira, E.M.S.; Fortes, A.G.; Pereira, R.; Gonçalves, a.M.S.T. Beetroot as a Source of Natural Dyes for Ham. Proceedings 2019, 41, 82. https://doi.org/10.3390/ecsoc-23-0662

Rethinking Leahy’s Emotional Schema Scale (LESS): Results from the Portuguese Adaptation of the LESS

This study aims to contribute to the study of emotional schemas, through the adaptation of the Leahy Emotional Schema Scale (LESS) to Portuguese. The LESS is a 50 item self-report with 14 theoretical dimensions, representing concepts, evaluations, attributions of emotions, and strategies of emotion regulation (Leahy in Cognit Behav Pract 9(3):177–190, 2002. https://doi.org/10.1016/S1077-7229(02)80048- 7). Translation, back-translation and pilot assessment of LESS’s Portuguese version were completed. Data was collected online with 396 participants. An exploratory principal component analysis was conducted. Parallel analysis revealed a 5-component structure, which after the deletion of eight items generated a fnal solution explaining 48% of the variance. Components internal consistency was adequate and convergent validity supported with signifcant correlations with difculties in emotional regulation and emotional processing, and psychopathology. It presents dimensions that are highly relevant for assessment, case conceptualization and clinical decision making. Although this scale is related to a specifc cognitive theory, the construct and its subscales may be useful beyond the psychotherapeutic model, stressing the transtheoretical potential of the scale.info:eu-repo/semantics/publishedVersio

The Cost Effectiveness of Psychological and Pharmacological Interventions for Social Anxiety Disorder:A Model-Based Economic Analysis

Background Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder. Methods A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs) of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion. Results Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT), phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs. Conclusion Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately the long-term comparative benefits and harms of psychological and pharmacological interventions for social anxiety disorder and establish their relative cost effectiveness with greater certainty

Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis

SummaryBackgroundSocial anxiety disorder—a chronic and naturally unremitting disease that causes substantial impairment—can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults.MethodsWe did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and unpublished sources between 1988 and Sept 13, 2013. We analysed interventions by class and individually. Outcomes were validated measures of social anxiety, reported as standardised mean differences (SMDs) compared with a waitlist reference. This study is registered with PROSPERO, number CRD42012003146.FindingsWe included 101 trials (13 164 participants) of 41 interventions or control conditions (17 classes) in the analyses. Classes of pharmacological interventions that had greater effects on outcomes compared with waitlist were monoamine oxidase inhibitors (SMD −1·01, 95% credible interval [CrI] −1·56 to −0·45), benzodiazepines (−0·96, −1·56 to −0·36), selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors (SSRIs and SNRIs; −0·91, −1·23 to −0·60), and anticonvulsants (−0·81, −1·36 to −0·28). Compared with waitlist, efficacious classes of psychological interventions were individual cognitive–behavioural therapy (CBT; SMD −1·19, 95% CrI −1·56 to −0·81), group CBT (−0·92, −1·33 to −0·51), exposure and social skills (−0·86, −1·42 to −0·29), self-help with support (−0·86, −1·36 to −0·36), self-help without support (−0·75, −1·25 to −0·26), and psychodynamic psychotherapy (−0·62, −0·93 to −0·31). Individual CBT compared with psychological placebo (SMD −0·56, 95% CrI −1·00 to −0·11), and SSRIs and SNRIs compared with pill placebo (−0·44, −0·67 to −0·22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD −0·56, 95% CrI −1·03 to −0·11) and interpersonal psychotherapy, mindfulness, and supportive therapy (−0·82, −1·41 to −0·24).InterpretationIndividual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit.FundingNational Institute for Health and Care Excellence