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

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

Challenging the diagnosis of Cystic Fibrosis in a patient carrying the 186-8T/C allelic variant in the CF Transmembrane Conductance Regulator gene

BACKGROUND: This report describe for the first time a clinical case with a CFTR allelic variant 186-8T/C (c.54-8 T/C) in intron 1 of CFTR and underline the importance of applying a combination of genetic and functional tests to establish or exclude a diagnosis of Cystic Fibrosis. In this case the diagnostic algorithm proposed for CF has been successfully applied at our Center and previous CF diagnosis assigned in a different Center was not confirmed.Case report: A 38 year-old Italian woman had been treated as affected by CF since 2010, following diagnosis based on sweat tests (reported values of 73 and 57 mEq/L) and a clinical history consistent with CF. No mutations were identified by first level of genetic analysis. Afterwards the patient referred to our center for assessing the relevance of these findings. The genetic variant 186-8T/C (c.54-8 T/C) in intron 1 of the CFTR gene was detected by sequencing. Low-level interstitial-alveolar infiltration was recorded by high-resolution computerized tomography. Lung function was normal and sputum and Broncho Alveolar Lavage cultures resulted bacteriologically negative. Sweat chloride levels was re-assessed and resulted with values of 57 and 35 mEq/L, with a borderline range between 40 and 60 mEq/L. Nasal Potential Difference measurements resulted in three reliable measurements consistent with a non-CF phenotype. Differential diagnosis with ciliary dyskinesia was excluded, as was exon 2 skipping of CFTR gene that might have caused a CFTR functional defect. Furthermore, single cell fluorescence analysis in response to cAMP agonists performed in patient's monocytes overlapped those obtained in healthy donors. CONCLUSION: We concluded that this patient was not affected by CF. This case highlights the need for referrals to highly specialized centers and the importance of combined functional and genetic tests in making a correct diagnosis. Moreover, we confirmed a correlation between NPD tracings and cell depolarization in monocytes providing a rationale for proposing the use of leukocytes as a potential support for CF diagnosis

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

MMX, The Next Generation of In-Situ Exploration Mission

The JAXA MMX (Martian Moons eXploration) mission has the objectives to study Phobos, the largest moon of Mars, and to bring back to Earth a sample from its surface, to answer one main question: what is the origin of the Martian moons? This mission will be launched in 2026 and will last five years. MMX spacecraft, the orbiter, developed by JAXA will travel from Earth to Mars and then study Phobos and Deimos moons with a foreseen sample collection of Phobos soil. MMX will carry and drop a small rover, developed by CNES and DLR, on Phobos surface. This rover, called Idefix, delivered close to the sample collection area will perform soil characterization in order to secure MMX spacecraft landing It\u27s designed to drive in very low gravity and low power availability for a hundred days, moving thanks to four wheels and carrying a couple of instruments to study Phobos composition. The electronic elements of the rover are in a nanosat size stack. CNES was in charge of most of the rover internal subsystems, the flight software, the mission analysis and thermal and mechanical architectures. DLR was in charge of the rover chassis, shutters, separation and locomotion systems. CNES and DLR share the system, operations and project lead. The RF communication between the rover and the orbiter is performed thanks to an intersatellite link using two S-band transponders. Their design is a heritage of the Rosetta-Philae mission combined to the needs brought by the nanosatellite markets. The article will present in a first part the development logic and the characteristics of these equipment. The communications during the mission will go through three different phases, each one associated to specific constraints. A second part of the article will focus on these phases and the impacts on the RF link. A third part will focus on the ISL qualifications, tests and measurements performed to comply with the mission and planning constraints

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01&nbsp;Hz to 50&nbsp;Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1&nbsp;sps and a continuous compound VBB/SP vertical axis at 10&nbsp;sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1&nbsp;Hz and ∼ 200 000 at 0.1&nbsp;Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users

MicroRNA-19b downregulates insulin 1 through targeting transcription factor NeuroD1

AbstractMiR-17-92 cluster miRNAs are disclosed to contribute to the development of multiple organs and tumorigenesis, but their roles in pancreas development remains unclear. In this study, we found that miR-19b, a member of miR-17-92, was highly expressed in the pancreatic progenitor cells, and miR-19b could target the 3′ UTR of NeuroD1 mRNA to decrease its protein and mRNA levels. Functional analysis showed that miR-19b exerted little effect on the proliferation of pancreatic progenitors, whereas it inhibited the expression of insulin 1, but not insulin 2 in MIN6 cells. These results suggest that miR-19b can downregulate insulin 1 expression through targeting transcription factor NeuroD1, and thus regulate the differentiation and function of β-cells