Bayesian Optimization with Dimension Scheduling: Application to Biological Systems

Bayesian Optimization (BO) is a data-efficient method for global black-box optimization of an expensive-to-evaluate fitness function. BO typically assumes that computation cost of BO is cheap, but experiments are time consuming or costly. In practice, this allows us to optimize ten or fewer critical parameters in up to 1,000 experiments. But experiments may be less expensive than BO methods assume: In some simulation models, we may be able to conduct multiple thousands of experiments in a few hours, and the computational burden of BO is no longer negligible compared to experimentation time. To address this challenge we introduce a new Dimension Scheduling Algorithm (DSA), which reduces the computational burden of BO for many experiments. The key idea is that DSA optimizes the fitness function only along a small set of dimensions at each iteration. This DSA strategy (1) reduces the necessary computation time, (2) finds good solutions faster than the traditional BO method, and (3) can be parallelized straightforwardly. We evaluate the DSA in the context of optimizing parameters of dynamic models of microalgae metabolism and show faster convergence than traditional BO

Leukotriene inhibition in hamster periodontitis. A histochemical and morphometric study

The effects of leukotriene (LT) inhibition on gingival and adjacent bone compartments were assessed by using phenidone (100 mg/kg/d) and ketoconazole (50 mg/kg/d) given for 4 weeks to periodontitis-affected hamsters. In the gingiva the two agents significantly decreased PMNL recruitment and migration and increased the vascular lumen. At the bone level, they reduced significantly preosteoclast and osteoclast numbers but did not affect osteoclast activity. Phenidone had no action on periodontitis induced inhibition of bone formation; in contrast ketoconazole enhanced formation. As both phenidone and ketoconazole are unspecific LT inhibitors it cannot be ascertained that the effects observed were actually due to LT inhibition. However, phenidone and ketoconazole induced changes different from indomethacin used in previous studies to inhibit the cyclooxygenase pathway. These discrepancies suggest that LT inhibition occurred in the present study and that they participate in gingival inflammation and osteoclastic destruction during hamster periodontitis

Genes2WordCloud: a quick way to identify biological themes from gene lists and free text

<p>Abstract</p> <p>Background</p> <p>Word-clouds recently emerged on the web as a solution for quickly summarizing text by maximizing the display of most relevant terms about a specific topic in the minimum amount of space. As biologists are faced with the daunting amount of new research data commonly presented in textual formats, word-clouds can be used to summarize and represent biological and/or biomedical content for various applications.</p> <p>Results</p> <p>Genes2WordCloud is a web application that enables users to quickly identify biological themes from gene lists and research relevant text by constructing and displaying word-clouds. It provides users with several different options and ideas for the sources that can be used to generate a word-cloud. Different options for rendering and coloring the word-clouds give users the flexibility to quickly generate customized word-clouds of their choice.</p> <p>Methods</p> <p>Genes2WordCloud is a word-cloud generator and a word-cloud viewer that is based on WordCram implemented using Java, Processing, AJAX, mySQL, and PHP. Text is fetched from several sources and then processed to extract the most relevant terms with their computed weights based on word frequencies. Genes2WordCloud is freely available for use online; it is open source software and is available for installation on any web-site along with supporting documentation at <url>http://www.maayanlab.net/G2W</url>.</p> <p>Conclusions</p> <p>Genes2WordCloud provides a useful way to summarize and visualize large amounts of textual biological data or to find biological themes from several different sources. The open source availability of the software enables users to implement customized word-clouds on their own web-sites and desktop applications.</p

“We Don’t Understand this Present”: Shimon Adaf’s Shadrach and the Possibilities of Hebrew Language

In this article, I wish to present Shimon Adaf’s post‑apocalyptic novella, Shadrach, and the two ways in which it represents Hebrew language: as a memory or relic of the past on one hand, and as a source of constant renewal on the other. What I would like to claim is that only through meaningful encounter with an Other, a synthesis between the past and the future can occur, making innovation of Hebrew language possible.Je souhaite présenter dans cet article le court roman post‑apocalyptique de Shimon Adaf, Shadrach, ainsi que les deux aspects sous lesquels y est représentée la langue hébraïque : d’une part comme souvenir et vestige du passé et d’autre part, comme source de renouvellement. Mon propos est de montrer que seule une rencontre significative avec l’Autre permet une synthèse entre le passé et l’avenir, rendant ainsi possible le renouvellement de la langue hébraïque.במאמר זה אני אציג את הנובלה הפוסט-אפוקליפטית שדרך של שמעון אדף, ואת שתי הדרכים בהן מיוצגת בה השפה העברית: כזיכרון או כשריד מן העבר מצד אחד, וכמקור להתחדשות ומטאמורפוזה מצד שני. טענתי היא, שרק דרך מפגש משמעותי עם האחר ועם האחרוּת, יכולה להיווצר סינתזה בין העבר והעתיד, סינתזה שהופכת את התחדשותה של השפה העברית לאפשרית

Bayesian Optimization with Dimension Scheduling: Application to Biological Systems

Bayesian Optimization (BO) is a data-efficient method for global black-box optimization of an expensive-to-evaluate fitness function. BO typically assumes that computation cost of BO is cheap, but experiments are time consuming or costly. In practice, this allows us to optimize ten or fewer critical parameters in up to 1,000 experiments. But experiments may be less expensive than BO methods assume: In some simulation models, we may be able to conduct multiple thousands of experiments in a few hours, and the computational burden of BO is no longer negligible compared to experimentation time. To address this challenge we introduce a new Dimension Scheduling Algorithm (DSA), which reduces the computational burden of BO for many experiments. The key idea is that DSA optimizes the fitness function only along a small set of dimensions at each iteration. This DSA strategy (1) reduces the necessary computation time, (2) finds good solutions faster than the traditional BO method, and (3) can be parallelized straightforwardly. We evaluate the DSA in the context of optimizing parameters of dynamic models of microalgae metabolism and show faster convergence than traditional BO

Association between carrier screening and incidence of cystic fibrosis

Context A downward trend in cystic fibrosis (CF) birth incidence has been reported in some areas. Objective To evaluate the association between carrier screening and CF birth incidence. Design, Setting, and Participants In northeastern Italy, CF birth incidence is monitored by means of a long-standing neonatal screening program. In the same area, 2 sections using different carrier detection approaches were identified—the western region, in which CF carrier tests are offered only to relatives of patients or to couples planning in vitro fertilization; and the eastern region, in which carrier testing is offered to relatives and carrier screening to infertile couples and to couples of reproductive age. A total of 779 631 newborns underwent CF neonatal screening between January 1993 and December 2007, of whom 195 had CF detected. Main Outcome Measure Cystic fibrosis birth incidence in the 2 regions. Results A time-related decrease in birth incidence was found, with a mean annual percentage decrease of 0.16 per 10 000 neonates (P &lt; .001). In the western region, 2559 carrier tests were performed, 314 carriers were identified, and 9 carrier couples were detected. In the eastern region, 87 025 carrier tests were performed, 3650 carriers were identified, and 82 carrier couples were detected. The birth rate decrease was greater in the eastern region (decrease rate, 0.24; 95% confidence interval [CI], 0.12-0.36) than in the western region (decrease rate, 0.04; 95% CI, –0.16 to 0.08; P = .01). The increase in the number of screened carriers over time was significantly correlated with the decrease in CF birth incidence (correlation coefficient = −0.53; 95% CI, –0.20 to –0.74; P = .003). Conclusion In northeastern Italy, carrier screening was associated with a decrease in the incidence of CF

Gestão Esportiva: O Planejamento Estratégico da FECARU

TCC (graduação) - Universidade Federal de Santa Catarina, Centro Sócio Econômico, Curso de Administração.O presente trabalho tem como objetivo à análise do planejamento estratégico da Federação Catarinense de Rugby (FECARU) e, descrever a percepção dos atletas catarinenses deste esporte sobre essa técnica de gestão. A FECARU foi fundada em 2011, visando a atender a urgência da Confederação Brasileira de Rugby para a disputa dos Jogos Olímpicos - RIO 2016. O estudo de caso foi realizado durante o segundo semestre de 2016, através de entrevistas, questionários e coleta de dados secundários disponibilizados pela referida federação. Foram realizadas as análises do Planejamento Estratégico do período de 2012 a 2016. Complementou-se o estudo com aplicação de questionário com os atletas de todas as macro-regiões catarinenses e, entrevistas gravadas em áudio com as gestões atual e anterior, com intuito de se fazer a triangulação destes dados. Depois desta etapa, efetivou-se o levantamento dos pontos definidos no Planejamento Estratégico da FECARU, no período supramencionado, investigando-se os pontos críticos apontados pelos atletas e pela Gestão da FECARU. Com isso foi possível se fazer a triangulação de dados e se verificar a real situação da federação no processo de gestão esportiva. Concluiu-se que há o amadorismo na gestão deste esporte no Estado de Santa Catarina, refletindo-se na Gestão dos clubes e da FECARU. Sugere-se urgência na revisão do Planejamento Estratégico desta Federação em parceria com seus clubes catarinenses afiliados que possibilite consolidar a gestão integrada e transparente.The present work aims to analyze the strategic planning of the Catarinense Federation of Rugby (FECARU) and to describe the perception of the athletes from Santa Catarina of this sport on this technique of management. FECARU was founded in 2011, aiming to meet the urgency of the Brazilian Rugby Confederation for the Olympic Games - RIO 2016. The case study was conducted during the second half of 2016 through interviews, questionnaires and secondary data collection Provided by the said federation. The analyzes of the Strategic Planning for the period from 2012 to 2016 were carried out. The study was completed with a questionnaire with the athletes from all the regions of Santa Catarina and audio interviews with the current and previous management, in order to triangulate of these data. After this stage, the points defined in the Strategic Planning of FECARU, during the aforementioned period, were surveyed, investigating the critical points pointed out by the athletes and the Management of FECARU. With this it was possible to do the triangulation of data and verify the real situation of the federation in the process of sports management. It was concluded that there is the amateurism in the management of this sport in the State of Santa Catarina, reflected in the Management of the clubs and FECARU. It is suggested that it is urgent to review the Strategic Planning of this Federation in partnership with its affiliated Santa Catarina clubs that will make it possible to consolidate integrated and transparent management

Bronchiectases at early chest computed tomography in children with cystic fibrosis are associated with increased risk of subsequent pulmonary exacerbations and chronic pseudomonas infection

AbstractBackgroundChildren with cystic fibrosis (CF) are often Pseudomonas aeruginosa (PsA) free and exhibit normal spirometry between the ages of 5 and 7. It is reported that computed tomography (CT) is more sensitive than FEV1 as an instrument in the identification of pulmonary disease. It is not known whether CF-CT scores in childhood may be used to highlight children at risk of developing severe disease.Aims1 — To assess the number of respiratory exacerbations (RTEs) during a follow-up period of 6years and their correlation with the CF-CT scores in young CF children. 2 — To assess whether PsA-negative CF children with high chest CF-CT scores are more likely to develop chronic PsA lung infection.Methods68 chest CT performed in patients without chronic PsA infection were scored. All patients (median age 7.8years) had at least 4 clinical, functional and microbiologic assessments/year in the subsequent 6years. RTE was defined as hospitalization and IV antibiotic treatment for respiratory symptoms.Results86.8% patients had <3 RTEs in the 6year follow-up period. The number of RTEs in the 6years subsequent to the CT scan was correlated to the bronchiectasis CT score (BCTS) (r=0.612; p<0.001) and to FEV1 at baseline (r=−0.495, p<0.001). A BCTS ≥17.5 identified patients with >3 RTEs during follow-up (sensitivity: 100%, specificity: 85%), while FEV1 did not. Only BCTS was significant in a logistic multivariate model (RR 1.15). BCTS was significantly lower and FEV1 higher in patients who did not develop chronic PsA infection by the end of the study.ConclusionIn CF children free from chronic PsA, both CT scores and FEV1 values demonstrate significant correlation with disease severity in the subsequent 6years but CT score has higher predictive value in the identification of patients at risk

Impaired CFTR function in mild cystic fibrosis associated with the S977F/T5TG12complex allele in trans with F508del mutation

AbstractBackgroundThe S977F mutation (c.2930C>T) in the CFTR gene (CFTR/ABCC7) is extremely rare. We describe the case of an adult patient carrying the complex allele S977F/T5TG12 in trans with the F508del mutation. Mild respiratory manifestations arose in adulthood associated with azoospermia, acute pancreatitis, minor hemoptysis and Cl− levels ranging from 40 to 42mEq/L.MethodDiagnosis was confirmed by repeated NPD measurements, genetic DHPLC analysis and a recently described functional assay measuring cAMP-dependent cell depolarization in peripheral blood monocytes.ResultsNPD measurements, DHPLC and monocyte functional assay (CF index=−18). Results were consistent with a CF phenotype.ConclusionsThe combined application of DHPLC and NPD analysis in the algorithm for CF diagnosis appears useful for the management of similar cases. In addition, the novel monocyte functional assay might contribute to improve our diagnostic capability, counseling and better treatment of these challenging clinical cases