Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Analysis Reveals Loci Encoding Anti-Macrophage Factors in the Human Pathogen Burkholderia pseudomallei K96243

Burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. The bacterium is endemic to tropical regions, including South East Asia and Northern Australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages. However despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterized to date. Here we perform a genome-wide gain of function screen of B. pseudomallei strain K96243 to identify loci encoding factors with anti-macrophage activity. We identify a total of 113 such loci scattered across both chromosomes, with positive gene clusters encoding transporters and secretion systems, enzymes/toxins, secondary metabolite, biofilm, adhesion and signal response related factors. Further phenotypic analysis of four of these regions shows that the encoded factors cause striking cellular phenotypes relevant to infection biology, including apoptosis, formation of actin ‘tails’ and multi-nucleation within treated macrophages. The detailed analysis of the remaining host of loci will facilitate genetic dissection of the interaction of this important pathogen with host macrophages and thus further elucidate this critical part of its infection cycle.
Bioinsecticide and Leaf Litter Combination Increases Oviposition and Reduces Adult Recruitment to Create an Effective Ovitrap for Culex Mosquitoes

ABSTRACT: Mosquito egg traps, aquatic habitats baited with oviposition attractant and insecticide, are important tools for surveillance and control efforts in integrated vector management programs. The bioinsecticide Bacillus thuringiensis subsp. israelensis (Bti) is increasingly used as an environmentally friendly alternative to chemical insecticides and the combination of Bti with a simple oviposition attractant like leaf litter to create an effective egg trap seems appealing. However, previous research suggests that Bti may itself alter oviposition, and that leaf litter may dramatically reduce Bti toxicity. Here we present results from field experiment designed to link the effects of litter and Bti on mosquito oviposition habitat selection and post-colonization survival to production of adult mosquitoes. Tripling litter increased Culex spp. oviposition nearly nine-fold, while Bti had no effect on oviposition. Neither factor altered egg survival, thus larval abundance reflected the effects of litter on oviposition. Both Bti and litter reduced larval survival by ∼60%. We found no evidence that increased litter reduced Bti toxicity. Adult production was dependent upon both litter and Bti. In the absence of Bti, effects of litter on oviposition translated into three-fold more adults. However, in the presence of Bti, initial increases in oviposition were erased by the combined negative effects of Bti and litter on post-colonization survival. Thus, our study provides field evidence that combined litter and Bti application creates an effective ovitrap. This combined treatment had the highest oviposition and the lowest survival, and thus removed the greatest number of mosquitoes from the landscape.
Current Collapse-Free and Self-Heating Performances in Normally Off GaN Nanowire GAA-MOSFETs

Normally off lateral GaN nanowire gate-all-around MOSFETs have been fabricated on the GaN-on-insulator substrate. The dynamic measurement proved that the devices with various nanowire heights exhibit current collapse-free characteristics implying that the electrons in the isolated nanowire channel do not suffer from trapping effects. However, the dc current level measured at high drain and gate voltage is reduced to approximately one half of the value measured in dynamic mode. This is attributed to the difficulty in heat dissipation because the suspended lateral nanowire channel is thermally isolated from the substrate. However, the heat dissipation is mitigated as the nanowire size increases.
Analysis of multi‐gigabits signal integrity through clock H‐tree

The H‐tree interconnect network is frequently used for the clock signal sharing in the microelectronic systems. Due to the increase of complexity and operating processing data speed, these interconnect effects can bottleneck the technological advancement. Hence, more accurate interconnect modelling methods are necessary for electronic designers. For this reason, a simple and accurate ultra‐wide band (UWB) model of multilevel distributed interconnection clock trees as a single input multiple outputs (SIMO) system is developed in this article. Very accurate single input single output (SISO) model transfer functions are derived. This method allows the signal integrity prediction regarding the distributed H‐tree characteristics including the source and load impedances. In order to demonstrate the relevance of model developed, analyses of two‐ and three‐level tree networks were performed. Distributed H‐tree realistic devices formed by sub‐millimetre physical length lines for applications for standardised Printed Circuit Board (PCB) interconnections were experimented numerically. The piece of lines constituting the trees is modelled by UWB RLCG network from DC to 8 GHz which takes into account the frequency dispersions and dielectric loss effects. Thus, excellent correlations between simulations and the results from the models proposed were observed both in frequency and time domains regarding 2.5 Gbits/s clock input. Copyright © 2012 John Wiley & Sons, Ltd.
Molecular dynamics simulations reveal the influence of dextran sulfate in nanoparticle formation with calcium alginate to encapsulate insulin

Molecular dynamics simulations reveal the influence of dextran sulfate in nanoparticle formation with calcium alginate to encapsulate insulin Daniela Nadvorny* , José Lamartine Soares-Sobrinho, Monica F. de La Roca Soares, Antônio José Ribeiro , Francisco Veiga and Gustavo M. Seabra Núcleo de Controle de Qualidade de Medicamentos e Correlatos, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, Brazil; Faculdade de Farmácia, Universidade de Coimbra, Coimbra, Portugal; Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, Brazil
The systematic analysis of ultraconserved genomic regions in the budding yeast

Motivation In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment. However, the UCSs are still regarded as mysterious genetic sequences so far. Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast. Results Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed up by the previous observation. Besides that, we also find the highly unchanged genes are enriched in some other pathways, such as the nutrient‐sensitive signaling pathway. To facilitate the investigation of unique UCSs, the UCSC Genome Browser was utilized to visualize the chromosomal position and related annotations of UCSs in S.cerevisiae genome. Availability and implementation For more details on UCSs, please refer to the Supplementary information online, and the custom code is available on request.
Evaluating activities of daily living using an infrared depth sensor: KINECTTM

Abstract Purpose: With a growing proportion of elderly people in the population, the maintenance of activities of daily living (ADLs) in elderly people is crucial to keep medical costs down. We investigated the ADL measurement accuracy of KINECTTM and Kinect Studio. To eliminate the subjectivity of conventional methods, we numerically assessed motions with computer analysis. Methods: Eighteen actions that repeated “move” and “stationary” phases, including movement of arms, legs, head and torso were measured using KINECTTM. Errors and standard deviations of joint coordinates at the stationary points outputted from KINECT Studio were evaluated. Simultaneous measurements were performed with KINECTTM using conventional high-performance motion capture, and the output was treated as a true value for comparison. Results: In most motions, errors of the joint coordinates were within 100 mm; however, there were two cases where errors due to the skeleton-model estimation by KINECT Studio increased. Firstly, when a part of the body unexpectedly moved out of the infrared measurable area, and secondly, when parts of the body overlapped each other on the KINECTTM image. Conclusions: KINECTTM and Kinect Studio are effective for ADL assessment when positions that cause large errors are excluded. Since KINECTTM has sufficient precision, it should also be possible to develop a more appropriate ADL evaluation system with a new algorithm of skeleton-model estimation that does not depend on KINECT Studio. Implications for Rehabilitation The KINECTTM and Kinect Studio are effective for ADL assessment when positions that cause large errors are excluded With an increasing proportion of elderly people in the population, the maintenance of activities of daily living (ADLs) in elderly people is crucial to keep medical costs down Systems such as the KINECTTM can support these goals
Evidence for strategies that improve recruitment and retention of adults aged 65 years and over in randomised trials and observational studies: a systematic review

Background adults aged ≥65 years are often excluded from health research studies. Lack of representation reduces generalisability of treatments for this age group. Objective to evaluate the effectiveness of strategies that improve recruitment and retention of adults aged ≥65 in observational studies and randomised controlled trials (RCTs). Methods searches conducted in 10 databases for RCTs of recruitment and retention strategies in RCTs or observational studies. Two reviewers screened abstracts and full-text articles for eligibility and extracted data. Studies without separate data for adults aged ≥65 were discarded. Risk of bias assessed using the Cochrane Risk of Bias tool. Results were synthesised narratively. Results thirty-two studies were included in the review (n = 75,444). Twelve studies had low risk of bias, of which 10 had successful strategies including: Opt-out versus opt-in increased recruitment (13.6% (n = 261)-18.7% (n = 36) difference; two studies); Advance notification increased retention (1.6% difference, OR 1.45; 95% CI 1.01, 2.10, one study (n = 2,686); 9.1% difference at 4 months, 1.44; 1.08, 1.92, one study (n = 753)); Hand-delivered versus postal surveys increased response (25.1% difference; X2 = 11.40, P < 0.01; one study (n = 139)); Open randomised design versus blinded RCT increased recruitment (1.56; 1.05, 2.33) and retention (13.9% difference; 3.1%, 24.6%) in one study (n = 538). Risk of bias was high/unclear for studies in which incentives or shorter length questionnaires increased response. Discussion in low risk of bias studies, few of the strategies that improved participation in older adults had been tested in ≥1 study. Opt-out and advance notification strategies improved recruitment and retention, respectively, although an opt-out approach may have ethical limitations. Evidence from single studies limits the generalisability of other strategies.
Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure

Many enzymes form homooligomers, yet the functional significance of self‐association is seldom obvious. Herein, we examine the connection between oligomerization and catalytic function for proline utilization A (PutA) enzymes. PutAs are bifunctional enzymes that catalyze both reactions of proline catabolism. Type A PutAs are the smallest members of the family, possessing a minimal domain architecture consisting of N‐terminal proline dehydrogenase and C‐terminal l‐glutamate‐γ‐semialdehyde dehydrogenase modules. Type A PutAs form domain‐swapped dimers, and in one case (Bradyrhizobium japonicum PutA), two of the dimers assemble into a ring‐shaped tetramer. Whereas the dimer has a clear role in substrate channeling, the functional significance of the tetramer is unknown. To address this question, we performed structural studies of four‐type A PutAs from two clades of the PutA tree. The crystal structure of Bdellovibrio bacteriovorus PutA covalently inactivated by N‐propargylglycine revealed a fold and substrate‐channeling tunnel similar to other PutAs. Small‐angle X‐ray scattering (SAXS) and analytical ultracentrifugation indicated that Bdellovibrio PutA is dimeric in solution, in contrast to the prediction from crystal packing of a stable tetrameric assembly. SAXS studies of two other type A PutAs from separate clades also suggested that the dimer predominates in solution. To assess whether the tetramer of B. japonicum PutA is necessary for catalytic function, a hot spot disruption mutant that cleanly produces dimeric protein was generated. The dimeric variant exhibited kinetic parameters similar to the wild‐type enzyme. These results implicate the domain‐swapped dimer as the core structural and functional unit of type A PutAs.
Proximal Aberrant Crypt Foci Associate with Synchronous Neoplasia and Are Primed for Neoplastic Progression

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12–6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas. Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma–carcinoma sequence but remain below the detection limit of conventional endoscopy. Visual Overview: http//mcr.accrjournals. org/content/molcanres/16/3/486/F1.large. jpg. Mol Cancer Res; 16(3); 486–95. ©2017 AACR. Visual Overview
#WhyWeTweetMH: Understanding Why People Use Twitter to Discuss Mental Health Problems

Background Use of the social media website Twitter is highly prevalent and has led to a plethora of Web-based social and health-related data available for use by researchers. As such, researchers are increasingly using data from social media to retrieve and analyze mental health-related content. However, there is limited evidence regarding why people use this emerging platform to discuss mental health problems in the first place. Objectives The aim of this study was to explore the reasons why individuals discuss mental health on the social media website Twitter. The study was the first of its kind to implement a study-specific hashtag for research; therefore, we also examined how feasible it was to circulate and analyze a study-specific hashtag for mental health research. Methods Text mining methods using the Twitter Streaming Application Programming Interface (API) and Twitter Search API were used to collect and organize tweets from the hashtag #WhyWeTweetMH, circulated between September 2015 and November 2015. Tweets were analyzed thematically to understand the key reasons for discussing mental health using the Twitter platform. Results Four overarching themes were derived from the 132 tweets collected: (1) sense of community; (2) raising awareness and combatting stigma; (3) safe space for expression; and (4) coping and empowerment. In addition, 11 associated subthemes were also identified. Conclusions The themes derived from the content of the tweets highlight the perceived therapeutic benefits of Twitter through the provision of support and information and the potential for self-management strategies. The ability to use Twitter to combat stigma and raise awareness of mental health problems indicates the societal benefits that can be facilitated via the platform. The number of tweets and themes identified demonstrates the feasibility of implementing study-specific hashtags to explore research questions in the field of mental health and can be used as a basis for other health-related research.
Ieee Transactions on Parallel and Distributed Systems Secure Outsourced Attribute-based Signatures

—Attribute-based signature (ABS) enables users to sign messages over attributes without revealing any information other than the fact that they have attested to the messages. However, heavy computational cost is required during signing in existing work of ABS, which grows linearly with the size of the predicate formula. As a result, this presents a significant challenge for resource-constrained devices (such as mobile devices or RFID tags) to perform such heavy computations independently. Aiming at tackling the challenge above, we first propose and formalize a new paradigm called Outsourced ABS, i.e., OABS, in which the computational overhead at user side is greatly reduced through outsourcing intensive computations to an untrusted signing-cloud service provider (S-CSP). Furthermore, we apply this novel paradigm to existing ABS schemes to reduce the complexity. As a result, we present two concrete OABS schemes: i) in the first OABS scheme, the number of exponentiations involving in signing is reduced from O(d) to O(1) (nearly three), where d is the upper bound of threshold value defined in the predicate; ii) our second scheme is built on Herranz et al.'s construction with constant-size signatures. The number of exponentiations in signing is reduced from O(d 2) to O(d) and the communication overhead is O(1). Security analysis demonstrates that both OABS schemes are secure in terms of the unforgeability and attribute-signer privacy definitions specified in the proposed security model. Finally, to allow for high efficiency and flexibility, we discuss extensions of OABS and show how to achieve accountability as well.
The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process

Background Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. Objective This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. Methods In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. Results Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to guarantee data privacy of patients posting on Internet, (3) took into account pharmacovigilance expert requirements with use case diagrams and scenarios, (4) built domain-specific knowledge resources embeding a lexicon, morphological rules, context rules, semantic rules, syntactic rules, and post-analysis processing, and (5) proposed a component-based architecture that allows storage of big data and accessibility to third-party applications through Web services. Conclusions We demonstrated the feasibility of implementing a component-based architecture that allows collection of patient posts on the Internet, near real-time processing of those posts including annotation, and storage in big data structures. In the next steps, we will evaluate the posts identified by the system in social media to clarify the interest and relevance of such approach to improve conventional pharmacovigilance processes based on spontaneous reporting.
Extracellular Signal-regulated Kinases (ERKs) Phosphorylate Lin28a Protein to Modulate P19 Cell Proliferation and Differentiation*

Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 microRNA (miRNA) and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at the post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. By editing lin28a gene with the CRISPR/Cas9-based method, we generated P19 mouse embryonic carcinoma stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants, respectively, to study the functional impact of Ser-200 phosphorylation. Lin28a-S200D-expressing cells, but not Lin28a-S200A-expressing or control P19 embryonic carcinoma cells, displayed impaired inhibition of let-7 miRNA and resulted in decreased cyclin D1, whereas Lin28a-S200A knock-in cells expressed less let-7 miRNA, proliferated faster, and exhibited differentiation defect upon retinoic acid induction. Therefore our results support that ERK kinase-mediated Lin28a phosphorylation may be an important mechanism for pluripotent cells to facilitate the escape from the self-renewal cycle and start the differentiation process.