935 resultados para Gemstone Team PANACEA: Promoting A Novel Approach to Cellular (gene) Expression Alteration
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Agile methodologies have become the standard approach to software development. The most popular and used one is Scrum. Scrum is a very simple and flexible framework that respond to unpredictability in a really effective way. However, his implementation must be correct, and since Scrum tells you what to do but not how to do it, this is not trivial. In this thesis I will describe the Scrum Framework, how to implement it and a tool that can help to do this. The thesis is divided into three parts. The first part is called Scrum. Here I will introduce the framework itself, its key concepts and its components. In Scrum there are three components: roles, meetings and artifacts. Each of these is meant to accomplish a series of specific tasks. After describing the “what to do”, in the second part, Best Practices, I will focus on the “how to do it”. For example, how to decide which items should be included in the next sprint, how to estimate tasks, and how should the team workspace be. Finally, in the third part called Tools, I will introduce Visual Studio Online, a cloud service from Microsoft that offers Git and TFVC repositories and the opportunity to manage projects with Scrum. == Versione italiana: I metodi Agile sono diventati l’approccio standard per lo sviluppo di software. Il più famoso ed utilizzato è Scrum. Scrum è un framework molto semplice e flessibile che risponde ai cambiamenti in una maniera molto efficace. La sua implementazione deve però essere corretta, e visto che Scrum ci dice cosa fare ma non come farlo, questo non risulta essere immediato. In questa tesi descriverò Scrum, come implementarlo ed uno strumento che ci può aiutare a farlo. La tesi è divisa in tre parti. La prima parte è chiamata Scrum. Qui introdurrò il framework, i suoi concetti base e le sue componenti. In Scrum ci sono tre componenti: i ruoli, i meeting e gli artifact. Ognuno di questi è studiato per svolgere una serie di compiti specifici. Dopo aver descritto il “cosa fare”, nella seconda parte, Best Practices, mi concentrerò sul “come farlo”. Ad esempio, come decidere quali oggetti includere nella prossima sprint, come stimare ogni task e come dovrebbe essere il luogo di lavoro del team. Infine, nella terza parte chiamata Tools, introdurrò Visual Studio Online, un servizio cloud della Microsoft che offre repository Git e TFVC e l’opportunità di gestire un progetto con Scrum.
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The treatment of amelogenesis imperfecta (AI) with an anterior open bite (AOB) is a challenge for the clinician and often requires a multidisciplinary team of specialists. Most often, patients suffering from these conditions are young and a good functional and esthetic long-term result must be aspired. This clinical report illustrates the orthodontic, maxillofacial, restorative, and prosthodontic rehabilitation of a 20-year-old woman with a hypoplastic form of AI and an AOB malocclusion, having received treatment for the last 6 years. It included adhesive resin composite restorations, orthodontical and maxillofacial surgery with a one-piece Le Fort I osteotomy, and a genioplasty. Subsequent prosthodontic therapy consisted of 28 all-ceramic crowns whereby a solid interdigitation, a canine guidance, and consistent and regular contacts between tooth crowns could be achieved to assure a good functional and esthetic oral situation. The tooth preparation techniques guaranteed minimally invasive treatment. The patient was affected very positively. CLINICAL SIGNIFICANCE: This article describes an interdisciplinary approach to the successful treatment of a patient with a hypoplastic form of amelogenesis imperfecta over a period of 6 years. It starts with a discussion of the conservative steps taken during adolescence and concludes with the final prosthetic rehabilitation with all-ceramic crowns after reaching adulthood.
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Epileptic seizures are due to the pathological collective activity of large cellular assemblies. A better understanding of this collective activity is integral to the development of novel diagnostic and therapeutic procedures. In contrast to reductionist analyses, which focus solely on small-scale characteristics of ictogenesis, here we follow a systems-level approach, which combines both small-scale and larger-scale analyses. Peri-ictal dynamics of epileptic networks are assessed by studying correlation within and between different spatial scales of intracranial electroencephalographic recordings (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant epilepsy. Epileptiform activity as recorded by a single iEEG electrode is determined objectively by the signal derivative and then subjected to a multivariate analysis of correlation between all iEEG channels. We find that during seizure, synchrony increases on the smallest and largest spatial scales probed by iEEG. In addition, a dynamic reorganization of spatial correlation is observed on intermediate scales, which persists after seizure termination. It is proposed that this reorganization may indicate a balancing mechanism that decreases high local correlation. Our findings are consistent with the hypothesis that during epileptic seizures hypercorrelated and therefore functionally segregated brain areas are re-integrated into more collective brain dynamics. In addition, except for a special sub-group, a highly significant association is found between the location of ictal iEEG activity and the location of areas of relative decrease of localised EEG correlation. The latter could serve as a clinically important quantitative marker of the seizure onset zone (SOZ).
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Profiling miRNA expression in cells that directly contribute to human disease pathogenesis is likely to aid the discovery of novel drug targets and biomarkers. However, tissue heterogeneity and the limited amount of human diseased tissue available for research purposes present fundamental difficulties that often constrain the scope and potential of such studies. We established a flow cytometry-based method for isolating pure populations of pathogenic T cells from bronchial biopsy samples of asthma patients, and optimized a high-throughput nano-scale qRT-PCR method capable of accurately measuring 96 miRNAs in as little as 100 cells. Comparison of circulating and airway T cells from healthy and asthmatic subjects revealed asthma-associated and tissue-specific miRNA expression patterns. These results establish the feasibility and utility of investigating miRNA expression in small populations of cells involved in asthma pathogenesis, and set a precedent for application of our nano-scale approach in other human diseases. The microarray data from this study (Figure 7) has been submitted to the NCBI Gene Expression Omnibus (GEO; http://ncbi.nlm.nih.gov/geo) under accession no. GSE31030.
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The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine. Approximately 600 million users of areca nut products, for example, betel quid chewers, are exposed to these alkaloids, principally arecoline and arecaidine. Metabolism of arecoline (20 mg/kg p.o. and i.p.) and arecaidine (20 mg/kg p.o. and i.p.) was investigated in the mouse using a metabolomic approach employing ultra-performance liquid chromatography-time-of-flight mass spectrometric analysis of urines. Eleven metabolites of arecoline were identified, including arecaidine, arecoline N-oxide, arecaidine N-oxide, N-methylnipecotic acid, N-methylnipecotylglycine, arecaidinylglycine, arecaidinylglycerol, arecaidine mercapturic acid, arecoline mercapturic acid, and arecoline N-oxide mercapturic acid, together with nine unidentified metabolites. Arecaidine shared six of these metabolites with arecoline. Unchanged arecoline comprised 0.3-0.4%, arecaidine 7.1-13.1%, arecoline N-oxide 7.4-19.0%, and N-methylnipecotic acid 13.5-30.3% of the dose excreted in 0-12 h urine after arecoline administration. Unchanged arecaidine comprised 15.1-23.0%, and N-methylnipecotic acid 14.8%-37.7% of the dose excreted in 0-12 h urine after arecaidine administration. The major metabolite of both arecoline and arecaidine, N-methylnipecotic acid, is a novel metabolite arising from carbon-carbon double-bond reduction. Another unusual metabolite found was the monoacylglyceride of arecaidine. What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known. However, the enhanced understanding of the metabolic transformation of arecoline and arecaidine should contribute to further research into the clinical toxicology of the areca alkaloids.
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During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.
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In this study, we present a novel genotyping scheme to classify German wild-type varicella-zoster virus (VZV) strains and to differentiate them from the Oka vaccine strain (genotype B). This approach is based on analysis of four loci in open reading frames (ORFs) 51 to 58, encompassing a total length of 1,990 bp. The new genotyping scheme produced identical clusters in phylogenetic analyses compared to full-genome sequences from well-characterized VZV strains. Based on genotype A, D, B, and C reference strains, a dichotomous identification key (DIK) was developed and applied for VZV strains obtained from vesicle fluid and liquor samples originating from 42 patients suffering from varicella or zoster between 2003 and 2006. Sequencing of regions in ORFs 51, 52, 53, 56, 57, and 58 identified 18 single-nucleotide polymorphisms (SNPs), including two novel ones, SNP 89727 and SNP 92792 in ORF51 and ORF52, respectively. The DIK as well as phylogenetic analysis by Bayesian inference showed that 14 VZV strains belonged to genotype A, and 28 VZV strains were classified as genotype D. Neither Japanese (vaccine)-like B strains nor recombinant-like C strains were found within the samples from Germany. The novel genotyping scheme and the DIK were demonstrated to be practical and simple and allow the highly efficient replication of phylogenetic patterns in VZV initially derived from full-genome DNA sequence analyses. Therefore, this approach may allow us to draw a more comprehensive picture of wild-type VZV strains circulating in Germany and Central Europe by high-throughput procedures in the future.
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Pulse wave velocity (PWV) is a surrogate of arterial stiffness and represents a non-invasive marker of cardiovascular risk. The non-invasive measurement of PWV requires tracking the arrival time of pressure pulses recorded in vivo, commonly referred to as pulse arrival time (PAT). In the state of the art, PAT is estimated by identifying a characteristic point of the pressure pulse waveform. This paper demonstrates that for ambulatory scenarios, where signal-to-noise ratios are below 10 dB, the performance in terms of repeatability of PAT measurements through characteristic points identification degrades drastically. Hence, we introduce a novel family of PAT estimators based on the parametric modeling of the anacrotic phase of a pressure pulse. In particular, we propose a parametric PAT estimator (TANH) that depicts high correlation with the Complior(R) characteristic point D1 (CC = 0.99), increases noise robustness and reduces by a five-fold factor the number of heartbeats required to obtain reliable PAT measurements.
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The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis. The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method (Chou and Talalay, 1984). The Median-Effect Principle/Combination Index method leads to inefficiency by ignoring important sources of variation inherent in dose-response data and discarding data points that do not fit the Median-Effect Principle. Previous work has shown that the conventional method yields a high rate of false positives (Boik, Boik, Newman, 2008; Hennessey, Rosner, Bast, Chen, 2010) and, in some cases, low power to detect synergy. There is a great need for improving the current methodology. We developed a Bayesian framework for dose-response modeling and drug-drug interaction analysis. First, we developed a hierarchical meta-regression dose-response model that accounts for various sources of variation and uncertainty and allows one to incorporate knowledge from prior studies into the current analysis, thus offering a more efficient and reliable inference. Second, in the case that parametric dose-response models do not fit the data, we developed a practical and flexible nonparametric regression method for meta-analysis of independently repeated dose-response experiments. Third, and lastly, we developed a method, based on Loewe additivity that allows one to quantitatively assess interaction between two agents combined at a fixed dose ratio. The proposed method makes a comprehensive and honest account of uncertainty within drug interaction assessment. Extensive simulation studies show that the novel methodology improves the screening process of effective/synergistic agents and reduces the incidence of type I error. We consider an ovarian cancer cell line study that investigates the combined effect of DNA methylation inhibitors and histone deacetylation inhibitors in human ovarian cancer cell lines. The hypothesis is that the combination of DNA methylation inhibitors and histone deacetylation inhibitors will enhance antiproliferative activity in human ovarian cancer cell lines compared to treatment with each inhibitor alone. By applying the proposed Bayesian methodology, in vitro synergy was declared for DNA methylation inhibitor, 5-AZA-2'-deoxycytidine combined with one histone deacetylation inhibitor, suberoylanilide hydroxamic acid or trichostatin A in the cell lines HEY and SKOV3. This suggests potential new epigenetic therapies in cell growth inhibition of ovarian cancer cells.
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Derivation of probability estimates complementary to geophysical data sets has gained special attention over the last years. Information about a confidence level of provided physical quantities is required to construct an error budget of higher-level products and to correctly interpret final results of a particular analysis. Regarding the generation of products based on satellite data a common input consists of a cloud mask which allows discrimination between surface and cloud signals. Further the surface information is divided between snow and snow-free components. At any step of this discrimination process a misclassification in a cloud/snow mask propagates to higher-level products and may alter their usability. Within this scope a novel probabilistic cloud mask (PCM) algorithm suited for the 1 km × 1 km Advanced Very High Resolution Radiometer (AVHRR) data is proposed which provides three types of probability estimates between: cloudy/clear-sky, cloudy/snow and clear-sky/snow conditions. As opposed to the majority of available techniques which are usually based on the decision-tree approach in the PCM algorithm all spectral, angular and ancillary information is used in a single step to retrieve probability estimates from the precomputed look-up tables (LUTs). Moreover, the issue of derivation of a single threshold value for a spectral test was overcome by the concept of multidimensional information space which is divided into small bins by an extensive set of intervals. The discrimination between snow and ice clouds and detection of broken, thin clouds was enhanced by means of the invariant coordinate system (ICS) transformation. The study area covers a wide range of environmental conditions spanning from Iceland through central Europe to northern parts of Africa which exhibit diverse difficulties for cloud/snow masking algorithms. The retrieved PCM cloud classification was compared to the Polar Platform System (PPS) version 2012 and Moderate Resolution Imaging Spectroradiometer (MODIS) collection 6 cloud masks, SYNOP (surface synoptic observations) weather reports, Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical feature mask version 3 and to MODIS collection 5 snow mask. The outcomes of conducted analyses proved fine detection skills of the PCM method with results comparable to or better than the reference PPS algorithm.
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We present a novel approach for the reconstruction of spectra from Euclidean correlator data that makes close contact to modern Bayesian concepts. It is based upon an axiomatically justified dimensionless prior distribution, which in the case of constant prior function m(ω) only imprints smoothness on the reconstructed spectrum. In addition we are able to analytically integrate out the only relevant overall hyper-parameter α in the prior, removing the necessity for Gaussian approximations found e.g. in the Maximum Entropy Method. Using a quasi-Newton minimizer and high-precision arithmetic, we are then able to find the unique global extremum of P[ρ|D] in the full Nω » Nτ dimensional search space. The method actually yields gradually improving reconstruction results if the quality of the supplied input data increases, without introducing artificial peak structures, often encountered in the MEM. To support these statements we present mock data analyses for the case of zero width delta peaks and more realistic scenarios, based on the perturbative Euclidean Wilson Loop as well as the Wilson Line correlator in Coulomb gauge.
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Mental color imagery abilities are commonly measured using paradigms that involve naming, judging, or comparing the colors of visual mental images of well-known objects (e.g., “Is a sunflower darker yellow than a lemon”?). Although this approach is widely used in patient studies, differences in the ability to perform such color comparisons might simply reflect participants’ general knowledge of object colors rather than their ability to generate accurate visual mental images of the colors of the objects. The aim of the present study was to design a new color imagery paradigm. Participants were asked to visualize a color for 3 s and then to determine a visually presented color by pressing 1 of 6 keys. The authors reasoned that participants would react faster when the imagined and perceived colors were congruent than when they were incongruent. In Experiment 1, participants were slower in incongruent than congruent trials but only when they were instructed to visualize the colors. The results in Experiment 2 demonstrate that the congruency effect reported in Experiment 1 cannot be attributed to verbalization of the color that had to be visualized. Finally, in Experiment 3, the congruency effect evoked by mental imagery correlated with performance in a perceptual version of the task. The authors discuss these findings with respect to the mechanisms that underlie mental imagery and patients suffering from color imagery deficits.
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The north-eastern escarpment of Madagascar has been deemed a global hotspot of biodiversity due to its high levels of endemic speciesbeing heavily threatened by accelerated deforestation rates and landscape changes. The main concern for conservation of the remaining humid primary forests is the shifting cultivation practices of local smallholder farmers for rice production. According to the mainstream narrative, human population growth leads to a shortening of crop-fallow cycles and thus to the accelerated conversion of forests to agricultural land. However, little is currently known about the dynamic changes between forest and shifting cultivation systems at the regional level. Existing land cover change analyses in this area have so far only focused on binary forest to non-forest changes and have therefore failed to account for the dynamic nature of the change processes between forest and different agriculture land use systems. This can be partly explained by the significant challenge to delineate shifting cultivation systems on land cover maps using traditional remote sensing classification approaches. To address this gap we therefore applied a novel GIS approach, that was originally developed for the assessment of shifting cultivation dynamics in Laos and has so far never been applied elsewhere, to map shifting cultivation of different crop-fallow lengths as well as permanent agriculture land use at the regional level. Change analyses of land use maps between 1995 and 2011 allowed us to comprehend the general trends of land use trajectories and their spatial variation. This more detailed understanding of land use change dynamics is key to plan for successful interventions to slow forest loss while at the same time improving local livelihoods. We further believe that this approach holds great potential for conservation monitoring in this resource-rich but povertyprone conservation hotspot.
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Introduction: According to the ecological view, coordination establishes byvirtueof social context. Affordances thought of as situational opportunities to interact are assumed to represent the guiding principles underlying decisions involved in interpersonal coordination. It’s generally agreed that affordances are not an objective part of the (social) environment but that they depend on the constructive perception of involved subjects. Theory and empirical data hold that cognitive operations enabling domain-specific efficacy beliefs are involved in the perception of affordances. The aim of the present study was to test the effects of these cognitive concepts in the subjective construction of local affordances and their influence on decision making in football. Methods: 71 football players (M = 24.3 years, SD = 3.3, 21 % women) from different divisions participated in the study. Participants were presented scenarios of offensive game situations. They were asked to take the perspective of the person on the ball and to indicate where they would pass the ball from within each situation. The participants stated their decisions in two conditions with different game score (1:0 vs. 0:1). The playing fields of all scenarios were then divided into ten zones. For each zone, participants were asked to rate their confidence in being able to pass the ball there (self-efficacy), the likelihood of the group staying in ball possession if the ball were passed into the zone (group-efficacy I), the likelihood of the ball being covered safely by a team member (pass control / group-efficacy II), and whether a pass would establish a better initial position to attack the opponents’ goal (offensive convenience). Answers were reported on visual analog scales ranging from 1 to 10. Data were analyzed specifying general linear models for binomially distributed data (Mplus). Maximum likelihood with non-normality robust standard errors was chosen to estimate parameters. Results: Analyses showed that zone- and domain-specific efficacy beliefs significantly affected passing decisions. Because of collinearity with self-efficacy and group-efficacy I, group-efficacy II was excluded from the models to ease interpretation of the results. Generally, zones with high values in the subjective ratings had a higher probability to be chosen as passing destination (βself-efficacy = 0.133, p < .001, OR = 1.142; βgroup-efficacy I = 0.128, p < .001, OR = 1.137; βoffensive convenience = 0.057, p < .01, OR = 1.059). There were, however, characteristic differences in the two score conditions. While group-efficacy I was the only significant predictor in condition 1 (βgroup-efficacy I = 0.379, p < .001), only self-efficacy and offensive convenience contributed to passing decisions in condition 2 (βself-efficacy = 0.135, p < .01; βoffensive convenience = 0.120, p < .001). Discussion: The results indicate that subjectively distinct attributes projected to playfield zones affect passing decisions. The study proposes a probabilistic alternative to Lewin’s (1951) hodological and deterministic field theory and enables insight into how dimensions of the psychological landscape afford passing behavior. Being part of a team, this psychological landscape is not only constituted by probabilities that refer to the potential and consequences of individual behavior, but also to that of the group system of which individuals are part of. Hence, in regulating action decisions in group settings, informers are extended to aspects referring to the group-level. References: Lewin, K. (1951). In D. Cartwright (Ed.), Field theory in social sciences: Selected theoretical papers by Kurt Lewin. New York: Harper & Brothers.
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This paper presents a formal initiative for monitoring the competence acquisition by a team of students with different backgrounds facing the experience of being working by projects and in a project. These students are inexperienced in the project management field and they play this game on a time-shared manner along with other activities. The goal of this experience is to make some improvements in determining the competence levels acquired by means of how the work is being done. The use of this information, which is out of the scope of this particular work, could make possible to bring additional information to the students involved in terms of their individual competencies and the identification of new opportunities of personal improvement.