Miracle-dz/UniFAR-FTUs huggingface dataset:
THE IMPACT OF A FAMILY EMPOWERMENT INTERVENTION ON JUVENILE OFFENDER HEAVY DRINKING: A LATENT GROWTH MODEL ANALYSIS*

We report the results of a growth model analysis of the impact of a Family Empowerment Intervention (FEI) on the heavy drinking over a 36-month follow-up period among youths processed at the Hillsborough County Juvenile Assessment Center. Families involved in the project were randomly assigned to either receive an Extended Services Intervention (ESI) or the FEI. Families in the ESI group received monthly phone contacts and, if indicated, referral information; FEI families received three one-hour, home-based meetings per week for approximately 10 weeks from a clinician-trained paraprofessional. By seeking to improve family functioning by empowering parents, it was hypothesized that target youths' behavior and psychosocial functioning would improve. Although the difference between FEI and ESI was not significant, the reported frequency of getting very high or drunk on alcohol declined more over time for FEI completers than FEI noncompleters. The results provide support for the impact of the FEI services.
CMOS SPADs selection, modeling and characterization towards image sensors implementation

The selection, modeling and characterization of Single Photon Avalanche Diodes (SPADs) are presented. Working with the standard 180nm UMC CMOS process, different SPAD structures are proposed in combination with several quenching circuits in order to compare their relative performances. Various configurations for the active region and the prevention of the premature edge breakdown are tested, looking for a miniaturization of the devices to implement image sensor arrays without loses in their performance.
Effect of antibrowning dips and controlled atmosphere storage on the physico-chemical, visual and nutritional quality of minimally processed “Rojo Brillante” persimmons

The combined effect of antibrowning dips and controlled atmosphere storage on fresh-cut “Rojo Brillante” persimmon quality was investigated. Persimmon slices were dipped in 10 g L−1 ascorbic acid, 10 g L−1 citric acid or water and were stored in different controlled atmospheres at 5 ℃. Controlled atmosphere conditions were 21 kPa O2 + 10 kPa CO2 (Atm-B), 21 kPa O2 + 20 kPa CO2 (Atm-C), 5 kPa O2 + 10 kPa CO2 (Atm-D) and 5 kPa O2 in the absence of CO2 (Atm-E). Air (Atm-A) was used as a control. Atmospheres with high CO2 concentrations induced darkening, associated with a flesh disorder known as “internal flesh browning”. Only the samples placed in Atm-E, and treated with 10 g L−1 ascorbic acid or 10 g L−1 citric acid, controlled enzymatic browning, reduced firmness loss and prevented the “internal flesh browning” disorder. The maximum limit of marketability was achieved in the samples treated with 10 g L−1 citric acid and stored in Atm-E for nine storage days at 5 ℃. The total vitamin C, free radical scavenging activity, total phenolic content and total carotenoids of the fresh-cut “Rojo Brillante” persimmons were affected by maturity stage at harvest, whereas antibrowning dips and controlled atmosphere storage had no clear effect.
Efficient Multioutput Gaussian Processes through Variational Inducing Kernels

Interest in multioutput kernel methods is increasing, whether under the guise of multitask learning, multisensor networks or structured output data. From the Gaussian process perspective a multioutput Mercer kernel is a covariance function over correlated output functions. One way of constructing such kernels is based on convolution processes (CP). A key problem for this approach is efficient inference. Alvarez and Lawrence recently presented a sparse approximation for CPs that enabled efficient inference. In this paper, we extend this work in two directions: we introduce the concept of variational inducing functions to handle potential non-smooth functions involved in the kernel CP construction and we consider an alternative approach to approximate inference based on variational methods, extending the work by Titsias (2009) to the multiple output case. We demonstrate our approaches on prediction of school marks, compiler performance and financial time series.
Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back

Abstract The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon-encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin–antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7-like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the “guns for hire” paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense.
Molecular Epidemiology and Evolution of Human Enterovirus Serotype 68 in Thailand, 2006–2011

Background Publications worldwide have reported on the re-occurrence of human enterovirus 68 (EV68), a rarely detected pathogen usually causing respiratory illness. However, epidemiological data regarding this virus in particular on the Asian continent has so far been limited. Methodology/Findings We investigated the epidemiology and genetic variability of EV68 infection among Thai children with respiratory illnesses from 2006–2011 (n = 1810). Semi-nested PCR using primer sets for amplification of the 5′-untranslated region through VP2 was performed for rhino-enterovirus detection. Altogether, 25 cases were confirmed as EV68 infection indicating a prevalence of 1.4% in the entire study population. Interestingly, the majority of samples were children aged >5 years (64%). Also, co-infection with other viruses was found in 28%, while pandemic H1N1 influenza/2009 virus was the most common co-infection. Of EV68-positive patients, 36% required hospitalizations with the common clinical presentations of fever, cough, dyspnea, and wheezing. The present study has shown that EV68 was extremely rare until 2009 (0.9%). An increasing annual prevalence was found in 2010 (1.6%) with the highest detection frequency in 2011 (4.3%). Based on analysis of the VP1 gene, the evolutionary rate of EV68 was estimated at 4.93×10−3 substitutions/site/year. Major bifurcation of the currently circulating EV68 strains occurred 66 years ago (1945.31 with (1925.95–1960.46)95% HPD). Among the current lineages, 3 clusters of EV68 were categorized based on the different molecular signatures in the BC and DE loops of VP1 combined with high posterior probability values. Each cluster has branched off from their common ancestor at least 36 years ago (1975.78 with (1946.13–1984.97)95% HPD). Conclusion Differences in epidemiological characteristic and seasonal profile of EV68 have been found in this study. Results from Bayesian phylogenetic investigations also revealed that EV68 should be recognized as a genetically diverse virus with a substitution rate identical to that of enterovirus 71 genotype B (4.2×10−3 s/s/y).
Influence of Phosphate Starvation on Cultures of Pseudomonas aeruginosa

Hou, Cynthia I. (University of British Columbia, Vancouver, B.C., Canada), Audrey F. Gronlund, and J. J. R. Campbell. Influence of phosphate starvation on cultures of Pseudomonas aeruginosa. J. Bacteriol. 92:851–855. 1966. —The changes occurring in Pseudomonas aeruginosa during phosphate starvation in a phosphate-deficient medium were assessed by measuring alterations in optical density, viable-cell count, chemical composition, and ribosome patterns. After a 24-hr period of starvation, optical density, protein, and deoxyribonucleic acid per milliliter of culture increased, whereas ribonucleic acid decreased. Extensive ribosomal degradation was apparent from sucrose density gradient centrifugation patterns. The induction of an alkaline phosphomonoesterase during phosphate starvation was observed. A linear response of phosphate-starved cells to low levels of phosphate supplied exogenously was evident from optical-density measurements, and a threshold requirement for phosphate analogous to the “energy of maintenance” was not detected.
Relationship of F-actin distribution to development of polar shape in human polymorphonuclear neutrophils

Polymerization of actin has been associated with development of polar shape in human neutrophils (PMN). To examine the relation of filamentous actin (F-actin) distribution to shape change in PMN, we developed a method using computerized video image analysis and fluorescence microscopy to quantify distribution of F-actin in single cells. PMN were labeled with fluorescent probe NBD-phallicidin to measure filamentous actin and Texas red to assess cell thickness. We show that Texas red fluorescence is a reasonable measure of cell thickness and that correction of the NBD-phallicidin image for cell thickness using the Texas red image permits assessment of focal F-actin content. Parameters were derived that quantify total F-actin content, movement of F-actin away from the center of the cell, asymmetry of F- actin distribution, and change from round to polar shape. The sequence of change in F-actin distribution and its relation to development of polar shape in PMN was determined using these parameters. After stimulation with chemotactic peptide at 25 degrees C, F-actin polymerized first at the rim of the PMN. This was followed by development of asymmetry of F-actin distribution and change to polar shape. The dominant pseudopod developed first in the region of lower F- actin concentration followed later by polymerization of actin in the end of the developed pseudopod. Asymmetric F-actin distribution was detected in round PMN before development of polar shape. Based upon these data, asymmetric distribution of F-actin is coincident with and probably precedes development of polar shape in PMN stimulated in suspension by chemotactic peptide.
University of Birmingham Methods for evaluating gene expression from Affymetrix microarray datasets

Background: Affymetrix high density oligonucleotide expression arrays are widely used across all fields of biological research for measuring genome-wide gene expression. An important step in processing oligonucleotide microarray data is to produce a single value for the gene expression level of an RNA transcript using one of a growing number of statistical methods. The challenge for the researcher is to decide on the most appropriate method to use to address a specific biological question with a given dataset. Although several research efforts have focused on assessing performance of a few methods in evaluating gene expression from RNA hybridization experiments with different datasets, the relative merits of the methods currently available in the literature for evaluating genome-wide gene expression from Affymetrix microarray data collected from real biological experiments remain actively debated. Results: The present study reports a comprehensive survey of the performance of all seven commonly used methods in evaluating genome-wide gene expression from a well-designed experiment using Affymetrix microarrays. The experiment profiled eight genetically divergent barley cultivars each with three biological replicates. The dataset so obtained confers a balanced and idealized structure for the present analysis. The methods were evaluated on their sensitivity for detecting differentially expressed genes, reproducibility of expression values across replicates, and consistency in calling differentially expressed genes. The number of genes detected as differentially expressed among methods differed by a factor of two or more at a given false discovery rate (FDR) level. Moreover, we propose the use of genes containing single feature polymorphisms (SFPs) as an empirical test for comparison among methods for the ability to detect true differential gene expression on the basis that SFPs largely correspond to cis -acting expression regulators. The PDNN method demonstrated superiority over all other methods in every comparison, whilst the default Affymetrix MAS5.0 method was clearly inferior. Conclusion: A comprehensive assessment of seven commonly used data extraction methods based on an extensive barley Affymetrix gene expression dataset has shown that the PDNN method has superior performance for the detection of differentially expressed genes.
Highly efficient production of the Alzheimer's γ‐Secretase integral membrane protease complex by a multi‐gene stable integration approach

Inefficient production of membrane‐embedded multi‐protein complexes by conventional methods has largely prevented the generation of high‐resolution structural information and the performance of high‐throughput drug discovery screens for this class of proteins. Not exempt from this rule is γ‐secretase, an intramembrane‐cleaving protease complex regulating a multitude of signaling pathways and biological processes by influencing gene transcription. γ‐Secretase is also implicated in the pathogenesis of Alzheimer's disease and several types of cancer. As an additional challenge, the reconstitution of the protease complex in its active form requires an intricate assembly and maturation process, including a highly regulated endoproteolytic processing of its catalytic component. In this article we report the application of a transposon‐mediated multigene stable integration technology to produce active γ‐secretase in mammalian cells in amounts adequate for crystallization studies and drug screening. Our strategy is expected to help elucidate the molecular mechanisms of intramembrane proteolysis. It is further expected to be widely used for the production of other multi‐protein complexes for applications in structural biology and drug development. Biotechnol. Bioeng. 2013; 110: 1995–2005. © 2013 Wiley Periodicals, Inc.
Hamartin and Tuberin Interaction With the G2/M Cyclin‐Dependent Kinase CDK1 and Its Regulatory Cyclins A and B

Tuberous sclerosis (TSC) is a multi-system disorder characterized by hamartomatous tumors and abnormal brain development, with multiple foci of disrupted neuronal migration and giant dysmorphic neurons within cortical tubers. TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. The functions of these proteins have yet to be determined. Recently, the Drosophila homologue of TSC2, gigas, has been shown to be required for the G2/M transition of the cell cycle. However, the mechanism of this action remains unknown. Because the cyclin-dependent kinase CDK1 forms a complex with cyclin B1 to trigger the G2/M transition, we hypothesized that tuberin interacts with CDK1 to regulate its activity. In the study reported in this paper, we have used co-immunoprecipitation and confocal microscopy to demonstrate that tuberin interacts with and co-localizes with CDK1 and its binding partner cyclin B1 in multiple cell types. We also demonstrate that hamartin interacts with CDK1 and cyclin B1. We further present evidence that tuberin interacts with the other regulatory subunit of CDK1, cyclin A. These findings suggest a direct role for tuberin and hamartin in modulating the activity of CDK1 during G2 and the G2/M transition. This is the first description of a role for both tuberin and hamartin in a common cellular function, providing a potential mechanism for the identical clinicopathologic manifestations that result when either of these proteins are inactivated.
Understanding clinical reasoning: the next step in working out how it really works

Educ 2011;16:311–29. 8 Ericsson KA. The influence of experience and deliberate practice on the development of superior expert performance. In: Ericsson KA, Charness N, Feltovich P, Hoffman RR, eds. Cambridge Handbook of Expertise and Expert Performance. Cambridge: Cambridge University Press 2006;685–706. 9 Hodges BD. A tea-steeping or i-Doc model for medical education? Acad Med 2010;9 (Suppl):34–44. 10 ten Cate O, Snell L, Carraccio C. Medical competence: the interplay between individual ability and the health care environment. Med Teach 2010;32 (8):669–75.
Responses of an Amazonian Teleost, the Tambaqui (Colossoma macropomum), to Low pH in Extremely Soft Water

Our goal was to compare the internal physiological responses to acid challenge in an acidophilic tropical teleost endemic to dilute low-pH waters with those in nonacidophilic temperate species such as salmonids, which have been the subject of most previous investigations. The Amazonian tambaqui (Colossoma macropomum), which migrates between circumneutral water and dilute acidic “blackwater” of the Rio Negro, was exposed to a graded low-pH and recovery regime in representative soft water (Na+ = 15, Cl− = 16, Ca2+ = 20 μmol L−1). Fish were fitted with arterial catheters for repetitive blood sampling. Water pH was altered from 6.5 (control) to 5.0, 4.0, 3.0, and back to 6.5 (recovery) on successive days. Some deaths occurred at pH 3.0. Throughout the regime, there were no disturbances of blood gases (O2 and CO2 tensions and contents) or lactate levels, and only very minor changes in acid-base status of plasma and red cells. However, erythrocytic guanylate and ade-nylate levels increased at pH's less than or equal to 5.0. Down to pH 4.0, plasma glucose, cortisol, and total ammonia levels remained constant, but all increased at pH 3.0, denoting a stress response. Plasma Na+ and Cl− levels declined and plasma protein concentration increased at pH 3.0, indicative of ionore-gulatory and fluid volume disturbance, and neither recovered upon return to pH 6.5. Cortisol and ammonia elevations also persisted. Transepithelial potential changed progressively from highly negative values (inside) at pH 6.5 to highly positive values at pH 3.0; these alterations were fully reversible. Experimental elevations in water calcium levels drove the transepithe-lial potential positive at circumneutral pH, attenuated or prevented changes in transepithelial potential at low pH, and reduced Na+ and Cl− loss rates to the water during acute low-pH challenges. In general, tambaqui exhibited responses to low pH that were qualitatively similar but quantitatively more resistant than those previously documented in salmonids.
'Well, It's the Risk of the Unknown… Right?': A Qualitative Study of Perceived Risks and Benefits of HIV Cure Research in the United States

Introduction Biomedical research towards an HIV cure is advancing in the United States and elsewhere, yet little is known about perceptions of risks and benefits among potential study participants and other stakeholders. We conducted a qualitative study to explore perceived risks and benefits of investigational HIV cure research among people living with HIV (PLWHIV), biomedical HIV cure researchers, policy-makers and bioethicists. Methods We conducted a qualitative research study using in-depth interviews with a purposive sample of PLWHIV, biomedical HIV cure researchers, policy-makers and bioethicists in 2015–2016. We analysed interview transcripts using thematic analysis anchored in grounded theory. Results We conducted and analyzed 36 key informant interviews. Qualitative analysis revealed four main findings. 1) Potential HIV cure study volunteers noted needing more information and education about the potential risks of HIV cure research. 2) Biomedical HIV cure researchers, policy-makers and bioethicists showed less awareness of social and financial risks of HIV cure research than PLWHIV. 3) Most respondents across the different categories of informants identified some risks that were too great to be acceptable in HIV cure research, although a subset of PLWHIV did not place an upper limit on acceptable risk. 4) PLWHIV showed a better awareness of potential psychological benefits of participating in HIV cure research than other groups of stakeholders. Conclusion Our research suggests that PLWHIV have a variable understanding of the individual risks, sometimes substantial, associated with participating in biomedical HIV cure research studies. Community engagement and increased research literacy may help improve community understanding. Intensive informed consent procedures will be necessary for ethical study implementation. The current state of HIV cure research offers greater potential benefits to society than to participants. There is likely to be disagreement among regulators, researchers, clinicians, and potential participants about what constitutes acceptable risk for HIV cure studies.
Budesonide/formoterol maintenance and reliever therapy: impact on airway inflammation in asthma

The aim of the present study was to compare the effectiveness, safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada. After 2 weeks of usual therapy, 1,538 patients were randomised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 μg twice daily and as needed, or to guideline-based conventional best practice. Severe asthma exacerbations, reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub-study of 115 patients. No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate. There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy (4.4 versus 7.5 events per 100 patients·yr−1, 41% reduction); however, this did not reach statistical significance. Mean total inhaled corticosteroid dose, reliever use, asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy. Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups. In conclusion, budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice, with significantly lower total inhaled corticosteroid dose and lower cost, while maintaining similar control of eosinophilic inflammation.