Miracle-dz/UniFAR-FTUs huggingface dataset:
A social model for health promotion for an aging population: Initial evidence on the experience corps model

This report evaluates whether a program for older volunteers, designed for both benerativity and health promotion, leads to short-term improvements inmultiple behavioral risk factors and positive effects on intermediary risk factors for disability and other morbidities. The Experience Corps® places older volunteers in public elementary schools in roles designed to meet schools’ needs and increase the social, physical, and cognitive activity of the volunteers. This article reports on a pilot randomized trial in Baltimore, Maryland. The 128 volunteers were 60–86 years old; 95% were African American. At follow-up of 4–8 months, physical activity, strength, people one could turn to for help, and cognitive activity increased significantly, and walking speed decreased significantly less, in participants compared to controls. In this pilot trial, physical, cognitive, and social activity increased, suggesting the potential for the Experience Corps to improve health for an aging population and simultaneously improve educational outcomes for children.
DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals

Significance We developed and applied nanogold labels for DNA complexes with proteins examined by small angle X-ray scattering (SAXS) to follow DNA conformations acting in error detection by the mismatch repair (MMR) system in solution. This technique can examine short or long pieces of DNA and in most solution conditions, including those closest to cellular environments. Thus, we expect the technique to be useful for many biologically important systems involving DNA complexes and conformations. Specifically, we reveal DNA bending followed by straightening by the repair protein MutS at the site of a mismatch as a suitable mechanism for error detection and signaling needed to avoid mutations and cancers and to control microbial stability and evolution in response to environmental stress. DNA metabolism and processing frequently require transient or metastable DNA conformations that are biologically important but challenging to characterize. We use gold nanocrystal labels combined with small angle X-ray scattering to develop, test, and apply a method to follow DNA conformations acting in the Escherichia coli mismatch repair (MMR) system in solution. We developed a neutral PEG linker that allowed gold-labeled DNAs to be flash-cooled and stored without degradation in sample quality. The 1,000-fold increased gold nanocrystal scattering vs. DNA enabled investigations at much lower concentrations than otherwise possible to avoid concentration-dependent tetramerization of the MMR initiation enzyme MutS. We analyzed the correlation scattering functions for the nanocrystals to provide higher resolution interparticle distributions not convoluted by the intraparticle distribution. We determined that mispair-containing DNAs were bent more by MutS than complementary sequence DNA (csDNA), did not promote tetramer formation, and allowed MutS conversion to a sliding clamp conformation that eliminated the DNA bends. Addition of second protein responder MutL did not stabilize the MutS-bent forms of DNA. Thus, DNA distortion is only involved at the earliest mispair recognition steps of MMR: MutL does not trap bent DNA conformations, suggesting migrating MutL or MutS/MutL complexes as a conserved feature of MMR. The results promote a mechanism of mismatch DNA bending followed by straightening in initial MutS and MutL responses in MMR. We demonstrate that small angle X-ray scattering with gold labels is an enabling method to examine protein-induced DNA distortions key to the DNA repair, replication, transcription, and packaging.
Methionine Sulfoxide Reductase from the Hyperthermophilic Archaeon Thermococcus kodakaraensis, an Enzyme Designed To Function at Suboptimal Growth Temperatures

ABSTRACT Methionine sulfoxide reductase (Msr) catalyzes the thioredoxin-dependent reduction and repair of methionine sulfoxide (MetO). Although Msr genes are not present in most hyperthermophile genomes, an Msr homolog encoding an MsrA-MsrB fusion protein (MsrABTk) was present on the genome of the hyperthermophilic archaeon Thermococcus kodakaraensis. Recombinant proteins corresponding to MsrABTk and the individual domains (MsrATk and MsrBTk) were produced, purified, and biochemically examined. MsrATk and MsrBTk displayed strict substrate selectivity for Met-S-O and Met-R-O, respectively. MsrABTk, and in particular the MsrB domain of this protein, displayed an intriguing behavior for an enzyme from a hyperthermophile. While MsrABTk was relatively stable at temperatures up to 80°C (with a half-life of ∼30 min at 80°C), a 75% decrease in activity was observed after 2.5 min at 85°C, the optimal growth temperature of this archaeon. Moreover, maximal levels of MsrB activity of MsrABTk were observed at the strikingly low temperature of 30°C, which also was observed for MsrBTk. Consistent with the low-temperature-specific biochemical properties of MsrABTk, the presence of the protein was greater in T. kodakaraensis cells grown at suboptimal temperatures (60 to 70°C) and could not be detected at 80 to 90°C. We found that the amount of intracellular MsrABTk protein increased with exposure to higher dissolved oxygen levels, but only at suboptimal growth temperatures. While measuring background rates of the Msr enzyme reactions, we observed significant levels of MetO reduction at high temperatures without enzyme. The occurrence of nonenzymatic MetO reduction at high temperatures may explain the specific absence of Msr homologs in most hyperthermophiles. Together with the fact that the presence of Msr in T. kodakaraensis is exceptional among the hyperthermophiles, the enzyme may represent a novel strategy for this organism to deal with low-temperature environments in which the dissolved oxygen concentrations increase.
Cache consistency and concurrency control in a client/server DBMS architecture

This, paper. examines five application cache consistency algorithms m a cltent/server database system: two-phase locking, certification, callback locking, no-wait locking, and no-wait locking with notification. A simulator was developed to compare the average transaction respnse time and server throughput for these algorithms under different workloads and system configurations. Two-phase locking and callback locking dominate no-wait locking and no-wait locking with notification when the server or the network is a bottleneck. Callback locking is better than two-phase locking when the inter-transaction locality is high or when intertrensaction locality is medium and the probability of object update is low. When there is no network delay and the server is very fast, no-wait locking with notification end callback locking dominate two-phase and no-wait locking.
Ex Vivo Effect of Varespladib on Secretory Phospholipase A2 Alveolar Activity in Infants with ARDS

Background Secretory phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available. Methods We studied varespladib in broncho-alveolar lavage (BAL) fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10–40–100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance. Results Varespladib reduces sPLA2 activity (p<0.0001) at 10,40 and 100 µM; both sPLA2 activity reduction and its ratio to total proteins significantly raise with increasing varespladib concentrations (p<0.001). IC50 was 80 µM. Western blotting revealed the presence of sPLA2-IIA and –IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity reduction/proteins ratio and PaO2 (rho = 0.63;p<0.001), PaO2/FiO2 (rho = 0.7; p<0.001), oxygenation (rho = −0.6; p<0.001) and ventilation (rho = −0.4;p = 0.038) indexes. Conclusions Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to be inversely related to the severity of gas exchange impairment.
Star formation and nuclear activity in close pairs of early-type galaxies

We extract from the Sloan Digital Sky Survey a sample of 347 systems involving early type galaxies separated by less than 30 kpc, in projection, and 500 km/s in radial velocity. These close pairs are likely progenitors of dry mergers. The (opti cal) spectra is used to determine how the interaction affects the star formation history and n uclear activity of the galaxies. The emission lines (or lack thereof) are used to classify the sam ple into AGN, star forming or quiescent. Increased AGN activity and reduced star formation in early-type pairs that already appear to be interacting indicate that the merging process changes the nature of nebular activity, a finding that is also supported by an increase in AGN l uminosity with decreasing pair separation. Recent star formation is studied on the absorpt ion line spectra, both through principal component analysis as well as via a comparison of the spectra with composite stellar population models. We find that the level of recent star forma tion in close pairs is raised relative to a control sample of early-type galaxies. This excess of residual star formation is found throughout the sample of close pairs and does not correlate with pair separation or with visual signs of interaction. Our findings are consistent with a scen ario whereby the first stage of the encounter (involving the outer parts of the halos) trigger r esidual star formation, followed by a more efficient inflow towards the centre ‐ switching to an AGN phase ‐ after which the systems are quiescent.
Spotting Design Problems with Smell Agglomerations

Design problems are structures that indicate violations of key design principles or rules. The main difficulty to identify them in the source code is due to the fact they are scattered through several code elements. Thus, code smells - microstructures in the program - have been used to reveal surface indications of a design problem. However, individually, each code smell represents only a partial embodiment of a design problem. Since design problem is scattered through several program elements, we are investigating a strategy to select a group of code smells that is likely to help developers to find design problems. We call \textit{agglomeration} this group of code smells. Our main goal is to summarize smell agglomerations that better indicate the occurrence of design problems. Our strategy to derive agglomerations is based on capturing semantic relations among closely-related code smells. We will assess to what extent code smell agglomerations help developers to locate and prioritize design problems.
Immune regulation of ovarian development: programming by neonatal immune challenge

Neonatal immune challenge by administration of lipopolysaccharide (LPS) produces enduring alterations in the development and activity of neuroendocrine, immune and other physiological systems. We have recently reported that neonatal exposure to an immune challenge by administration of LPS results in altered reproductive development in the female Wistar rat. Specifically, LPS-treated animals exhibited diminished ovarian reserve and altered reproductive lifespan. In the current study, we examined the cellular mechanisms that lead to the previously documented impaired ovulation and reduced follicular pool. Rats were administered intraperitoneally either 0.05 mg/kg of LPS (Salmonella Enteritidis) or an equivalent volume of non-pyrogenic saline on postnatal days (PNDs) 3 and 5, and ovaries were obtained on PND 7. Microarray analysis revealed a significant upregulation in transcript expression (2-fold change; p < 0.05) for a substantial number of genes in the ovaries of LPS-treated animals, implicated in immune cell signaling, inflammatory responses, reproductive system development and disease. Several canonical pathways involved in immune recognition were affected by LPS treatment, such as nuclear factor-κB (NF-κB) activation and LPS-stimulated mitogen-activated protein kinase (MAPK) signaling. Quantitative Real-time PCR analysis supported the microarray results. Protein expression analysis of several components of the MAPK signaling pathway revealed a significant upregulation in the expression of Toll-like receptor 4 (TLR4) in the neonatal ovary of LPS-treated animals. These results indicate that neonatal immune challenge by administration of LPS has a direct effect on the ovary during the sensitive period of follicular formation. Given the pivotal role of inflammatory processes in the regulation of reproductive health, our findings suggest that early life immune activation via TLR signaling may have significant implications for the programming of ovarian development and fertility.
Histoplasma capsulatum Endocarditis

AbstractInfective endocarditis is an uncommon manifestation of infection with Histoplasma capsulatum. The diagnosis is frequently missed, and outcomes historically have been poor. We present 14 cases of Histoplasma endocarditis seen in the last decade at medical centers throughout the United States. All patients were men, and 10 of the 14 had an infected prosthetic aortic valve. One patient had an infected left atrial myxoma. Symptoms were present a median of 7 weeks before the diagnosis was established. Blood cultures yielded H. capsulatum in only 6 (43%) patients. Histoplasma antigen was present in urine and/or serum in all but 3 of the patients and provided the first clue to the diagnosis of histoplasmosis for several patients. Antibody testing was positive for H. capsulatum in 6 of 8 patients in whom the test was performed.Eleven patients underwent surgery for valve replacement or myxoma removal. Large, friable vegetations were noted at surgery in most patients, confirming the preoperative transesophageal echocardiography findings. Histopathologic examination of valve tissue and the myxoma revealed granulomatous inflammation and large numbers of organisms in most specimens. Four of the excised valves and the atrial myxoma showed a mixture of both yeast and hyphal forms on histopathology.A lipid formulation of amphotericin B, administered for a median of 29 days, was the initial therapy in 11 of the 14 patients. This was followed by oral itraconazole therapy, in all but 2 patients. The length of itraconazole suppressive therapy ranged from 11 months to lifelong administration. Three patients (21%) died within 3 months of the date of diagnosis. All 3 deaths were in patients who had received either no or minimal (1 day and 1 week) amphotericin B.
Impacts of federal ephedrine and pseudoephedrine regulations on methamphetamine-related hospital admissions.

AIMS To determine whether the federal regulation of ephedrine and pseudoephedrine, precursors used in illicit methamphetamine production, reduced methamphetamine-related acute care hospital admissions. DESIGN ARIMA-intervention time-series analysis. SETTING California (1983-2000), Arizona and Nevada (1991-2000), USA. MEASUREMENTS Monthly counts of methamphetamine-related acute care hospital admissions. INTERVENTIONS Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Products containing pseudoephedrine: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines), used mainly by small-scale producers: regulated October 1996. FINDINGS In California, the bulk powder regulation stopped a 7-year rise in admissions (1983-89) and reduced them by 35% (P < 0.01). The single ingredient ephedrine regulation stopped a 4-year rise (1992-95) in California, Arizona and Nevada, with 48% (P < 0.01), 71% (P < 0.01) and 52% (P < 0.01) reductions, respectively. The pseudoephedrine products regulation stopped a 2-year rise (1996-97) in California, Arizona and Nevada, with 38% (P < 0.01), 41% (P < 0.05) and 61% (P < 0.01) reductions, respectively. Admissions rose at the end of the study period but were still well below peak 1990s levels. The regulation of ephedrine combined with other active medicinal ingredients had no significant impact in any of the three states. CONCLUSIONS Regulations targeting precursors used by large-scale producers reduced admissions substantially during the study period. However, the regulation of precursors used primarily by small-scale producers had little, if any, effect.
The BARD1 C-Terminal Domain Structure and Interactions with Polyadenylation Factor CstF-50

The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF-50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins. Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.
Epidural Analgesia in the Postoperative Period

Abstract : Postoperative pain is an unwanted side effect of surgery, and is associated with many postoperative complications. This descriptive study was conducted to determine which surgical patients experienced the most analgesia with the fewest side effects when receiving epidural analgesia in the postoperative period. A retrospective chart audit of 200 surgical patients who received epidural medications for pain management was conducted. The sample was obtained from a 90-bed hospital. A description of the patients age, gender, type of surgery, type of epidural medication, side effects, incidence of breakthrough pain, and treatments were recorded and cross-tabulated. The following surgical categories emerged: abdominal, orthopedic, thoracic, and lower extremity/vascular. Breakthrough pain was reported in 27% of the cases. Lower extremity/vascular surgery patients had the lowest incidence of side effects. Thoracic surgery patients had the highest incidence of breakthrough pain, and abdominal surgery had the highest incidence of nausea/vomiting, pruritis, and respiratory depression. Morphine and bupivacaine provided the best analgesia, but had the highest incidence of side effects.
Conserved Motifs and Prediction of Regulatory Modules in Caenorhabditis elegans

Transcriptional regulation, a primary mechanism for controlling the development of multicellular organisms, is carried out by transcription factors (TFs) that recognize and bind to their cognate binding sites. In Caenorhabditis elegans, our knowledge of which genes are regulated by which TFs, through binding to specific sites, is still very limited. To expand our knowledge about the C. elegans regulatory network, we performed a comprehensive analysis of the C. elegans, Caenorhabditis briggsae, and Caenorhabditis remanei genomes to identify regulatory elements that are conserved in all genomes. Our analysis identified 4959 elements that are significantly conserved across the genomes and that each occur multiple times within each genome, both hallmarks of functional regulatory sites. Our motifs show significant matches to known core promoter elements, TF binding sites, splice sites, and poly-A signals as well as many putative regulatory sites. Many of the motifs are significantly correlated with various types of experimental data, including gene expression patterns, tissue-specific expression patterns, and binding site location analysis as well as enrichment in specific functional classes of genes. Many can also be significantly associated with specific TFs. Combinations of motif occurrences allow us to predict the location of cis-regulatory modules and we show that many of them significantly overlap experimentally determined enhancers. We provide access to the predicted binding sites, their associated motifs, and the predicted cis-regulatory modules across the whole genome through a web-accessible database and as tracks for genome browsers.
Robust Data-Driven Inference for Density-Weighted Average Derivatives

This paper presents a novel data-driven bandwidth selector compatible with the small bandwidth asymptotics developed in Cattaneo, Crump, and Jansson (2009) for density-weighted average derivatives. The new bandwidth selector is of the plug-in variety, and is obtained based on a mean squared error expansion of the estimator of interest. An extensive Monte Carlo experiment shows a remarkable improvement in performance when the bandwidth-dependent robust inference procedures proposed by Cattaneo, Crump, and Jansson (2009) are coupled with this new data-driven bandwidth selector. The resulting robust data-driven confidence intervals compare favorably to the alternative procedures available in the literature. The online supplemental material to this paper contains further results from the simulation study.