Miracle-dz/UniFAR-FTUs huggingface dataset:
PHARMACODYNAMICS OF MYCOPHENOLIC ACID IN HEART ALLOGRAFT RECIPIENTS: CORRELATION OF LYMPHOCYTE PROLIFERATION AND ACTIVATION WITH PHARMACOKINETICS AND GRAFT HISTOLOGY1

Background. Assays of drug blood levels are used for therapeutic immunosuppressive drug monitoring (pharmacokinetics, PK). We monitored lymphocyte functions (pharmacodynamics, PD) in allograft recipients treated with mycophenolic acid (MPA) to determine its mechanisms and the relationships among dose levels, PK, PD, and histological severity of graft rejection. Methods. Lewis rats transplanted with Brown Norway (BN) rat hearts were treated with different dose levels of MPA for 8, 15, or 29 days at which times grafts were removed and scored for rejection grade. Blood was analyzed (high-performance liquid chromatography) for MPA plasma concentrations (area under the concentration-time curve 0–24 hr, C 6 hr, trough) and for lymphocyte functions using concanavalin A-stimulated whole blood assays to measure lymphocyte proliferation (tritium labled thymidine incorporation and flow cytometric bivariate proliferating nuclear cell antigen/DNA analysis) and activation (percent lymphocytes expressing CD25 or CD134). PD values were AUE 0–24 hr (area under the PD effect-time curve), maximum inhibition and trough. Results. MPA equipotently suppressed (by flow cytometry) both proliferation and activation and these effects correlated with MPA plasma levels (r2=0.80–0.91). Relationships among MPA dose levels, PK and PD were clear, direct, and reproducible. Correlation coefficients after 8 days of MPA treatment were: 0.90, 0.87, and 0.49 for MPA PK (AUC 0–24 hr, C 6 hr and trough) versus rejection scores; 0.80–0.89, 0.86–0.92, and 0.25–0.52 for PD flow cytometric assays (AUE 0–24 hr, maximum inhibition, and trough) versus rejection scores. Conclusions. MPA inhibits both lymphocyte proliferation and activation. PD by flow cytometry (FCM) correlates highly with severity of graft rejection, showing that PD of MPA measured in peripheral blood predicts immune cell activity in graft tissue.
Delivering integrated child development care in Pakistan: protocol for a clustered randomised trial

Background Early childhood developmental delay is associated with significant disadvantage in adult life. In Pakistan, high prevalence of developmental delay is associated with poverty, under-nutrition, and maternal depression. Aim To assess the effectiveness of an early child development counselling intervention delivered at private GP clinics, in poor urban communities. Design & setting A clustered randomised trial in Pakistan. Method The intervention was developed following a period of formative research, and in consultation with local experts. A total of 2112 mother–child pairs will be recruited at 32 clinics, from within the locality (cluster); 16 clinics per arm. A primary care counselling intervention (promoting child development, nutrition, and maternal mental health) will be delivered at 6 weeks, 3, 6, and 9 months of the child’s age. Monitoring, assessment, and treatment will also be performed at quarterly visits in intervention clinics. Primary outcome is the developmental delay at 12 months (ASQ-3 scores). Secondary outcomes are stunting rate, and maternal depression (PHQ-9 score). In addition, a process evaluation and costing study will be conducted. Discussion This trial will be the first to assess an early child development intervention, delivered in private GP clinics for poor urban communities in Pakistan. If found to be effective, this public–private model may offer a more sustainable, and feasible option for populations in poor urban settings, where private GP clinics are the most accessible provider of primary health care. There is scope for scale-up at provincial level, should the intervention be effective. Trial registration The trial has been registered with the Current Controlled Trials ISRCTN48032200.
Physically-based fluid-particle system using DirectCompute for use in real-time games

Context: Fluid-particle systems are seldom used in games, the apparent performance costs of simulating a fluid-particle system discourages the developer to implement a system of such. The processing power delivered by a modern GPU enables the developer to implement complex particle systems such as fluid-particle systems. Writing efficient fluid-particle systems is the key when striving for real-time fluid-particle simulations with good scalability. Objectives: This thesis ultimately tries to provide the reader with a well-performing and scalable fluid-particle system simulated in real-time using a great number of particles. The fluid-particle system implements two different fluid physics models for diversity and comparison purposes. The fluid-particle system will then be measured for each fluid physics model and provide results to educate the reader on how well the performance of a fluid-particle system might scale with the increase of active particles in the simulation. Finally, a performance comparison of the particle scalability is made by completely excluding the fluid physics calculations and simulate the particles using only gravity as an affecting force to be able to demonstrate how taxing the fluid physics calculations are on the GPU. Methods: The fluid-particle system has been run using different simulation scenarios, where each scenario is defined by the amount of particles being active and the dimensions of our fluid-particle simulation space. The performance results from each scenario has then been saved and put into a collection of results for a given simulation space. Results: The results presented demonstrate how well the fluid-particle system actually scales being run on a modern GPU. The system reached over a million particles while still running at an acceptable frame rate, for both of the fluid physics models. The results also shows that the performance is greatly reduced by simulating the particle system as a fluid-particle one, instead of only running it with gravity applied. Conclusions: With the results presented, we are able to conclude that fluid-particle systems scale well with the number of particles being active, while being run on a modern GPU. There are many optimizations to be done to be able to achieve a well-performing fluid-particle system, when developing fluid-particle system you should be wary of the many performance pitfalls that comes with it.
Quantum Dots-Based Multiplexed Fiber-Optic Temperature Sensors

Quantum dots (QDs)-based multiplexed fiber-optic temperature sensors are proposed for multi-point sensing, which are composed of hollow-core microstructured optical fibers filled with aqueous QDs solutions of different fluorescent wavelengths. A parallel reflective configuration is adopted to avoid the crosstalk of fluorescent emissions, and to construct practical probes. Temperature experiments show that the fluorescent peak wavelength and the self-referenced intensity of two sensors both change with temperature linearly in the range from -10 °C to 120 °C with favorable reversibility. At last, the crosstalk of both the fluorescent peak wavelength and the self-referenced intensity of two sensors is tested for in the range of the temperature measurements.
Effects of a brief intervention for reducing violence and alcohol misuse among adolescents: a randomized controlled trial.

CONTEXT Emergency department (ED) visits present an opportunity to deliver brief interventions to reduce violence and alcohol misuse among urban adolescents at risk of future injury. OBJECTIVE To determine the efficacy of brief interventions addressing violence and alcohol use among adolescents presenting to an urban ED. DESIGN, SETTING, AND PARTICIPANTS Between September 2006 and September 2009, 3338 patients aged 14 to 18 years presenting to a level I ED in Flint, Michigan, between 12 pm and 11 pm 7 days a week completed a computerized survey (43.5% male; 55.9% African American). Adolescents reporting past-year alcohol use and aggression were enrolled in a randomized controlled trial (SafERteens). INTERVENTION All patients underwent a computerized baseline assessment and were randomized to a control group that received a brochure (n = 235) or a 35-minute brief intervention delivered by either a computer (n = 237) or therapist (n = 254) in the ED, with follow-up assessments at 3 and 6 months. Combining motivational interviewing with skills training, the brief intervention for violence and alcohol included review of goals, tailored feedback, decisional balance exercise, role plays, and referrals. MAIN OUTCOME MEASURES Self-report measures included peer aggression and violence, violence consequences, alcohol use, binge drinking, and alcohol consequences. RESULTS About 25% (n = 829) of screened patients had positive results for both alcohol and violence; 726 were randomized. Compared with controls, participants in the therapist intervention showed self-reported reductions in the occurrence of peer aggression (therapist, -34.3%; control, -16.4%; relative risk [RR], 0.74; 95% confidence interval [CI], 0.61-0.90), experience of peer violence (therapist, -10.4%; control, +4.7%; RR, 0.70; 95% CI, 0.52-0.95), and violence consequences (therapist, -30.4%; control, -13.0%; RR, 0.76; 95% CI, 0.64-0.90) at 3 months. At 6 months, participants in the therapist intervention showed self-reported reductions in alcohol consequences (therapist, -32.2%; control, -17.7%; odds ratio, 0.56; 95% CI, 0.34-0.91) compared with controls; participants in the computer intervention also showed self-reported reductions in alcohol consequences (computer, -29.1%; control, -17.7%; odds ratio, 0.57; 95% CI, 0.34-0.95). CONCLUSION Among adolescents identified in the ED with self-reported alcohol use and aggression, a brief intervention resulted in a decrease in the prevalence of self-reported aggression and alcohol consequences. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00251212.
Blink recognition to detect the possibility of eye dystonia based on electrooculogram analysis

The present work proposes a system for detecting the possibility of eye dystonia from the analysis of eye movements. Eye movement data is recorded using an Electrooculogram signal acquisition system developed in the laboratory. Combinations of Hjorth parameters and Autoregressive (AR) parameters with Power Spectral Density (PSD) are used as signal features. Blinks are classified from other types of eye movements using Support Vector Machine (SVM) classifier with different kernel functions. We obtain a maximum average accuracy of 93.40% over all classes and participants using RBF-SVM classifier with a feature space of AR parameters of order 5 and PSD taken together. The system is designed to count the number of blinks in a particular interval of time thereby detecting the risk of eye dystonia, a neural disorder that causes a person to blink excessively.
Speciation is not necessarily easier in species with sexually monomorphic mating signals

Should we have different expectations regarding the likelihood and pace of speciation by sexual selection when considering species with sexually monomorphic mating signals? Two conditions that can facilitate rapid species divergence are Felsenstein's one‐allele mechanism and a genetic architecture that includes a genetic association between signal and preference loci. In sexually monomorphic species, the former can manifest in the form of mate choice based on phenotype matching. The latter can be promoted by selection acting upon genetic loci for divergent signals and preferences expressed simultaneously in each individual, rather than acting separately on signal loci in males and preference loci in females. Both sexes in the Chrysoperla carnea group of green lacewings (Insecta, Neuroptera, Chrysopidae) produce sexually monomorphic species‐specific mating signals. We hybridized the two species C. agilis and C. carnea to test for evidence of these speciation‐facilitating conditions. Hybrid signals were more complex than the parents and we observed a dominant influence of C. carnea. We found a dominant influence of C. agilis on preferences in the form of hybrid discrimination against C. carnea. Preferences in hybrids followed patterns predicting preference loci that determine mate choice rather than a one‐allele mechanism. The genetic association between signal and preference we detected in the segregating hybrid crosses indicates that speciation in these species with sexually monomorphic mating signals can have occurred rapidly. However, we need additional evidence to determine whether such genetic associations form more readily in sexually monomorphic species compared to dimorphic species and consequently facilitate speciation.
Dual effect of macroalgal extracts on growth of bacteria in Western Baltic Sea

It is assumed that the biological characteristics of the bacterial strains used in bioactivity tests have strong influences on their susceptibility against antibacterial compounds. Therefore, the selection of bacterial test strains may rush conclusions on the effect of macroalgal extracts and metabolites on bacteria. To proof this assumption, we have analysed the biological activities of crude extracts of 16 macroalgae from the coastal waters of Kiel Fjord (Germany), and tested their effect against a panel of 10 microorganisms comprising 5 standard test strains of bacteria and 5 macroalga-associated bacteria. Fourteen macroalgae (88%) displayed antibacterial activity against at least one of the test strains. Despite the high proportion of extracts exhibiting antimicrobial activity, only 3 strains of the standard set were susceptible to macroalgal extracts and the overall activities were low (less than 80% of inhibition). Most of active extracts inhibited Bacillus subtilis, while no inhibition effects were found against Erwinia amylovora, Escherichia coli, and the macroalga-associated bacteria. In contrast, all extracts produced stimulatory growth effects of at least two of the tested bacteria. While growth stimulation of standard set of bacteria was rare (22.5% of total tests) with exception of plant pathogen Erwinia amylovora and two cases of Staphylococcus lentus, it was common among bacteria associated with macroalgae (77.5%), especially Bacillus algicola, Pseudomonas marincola and both algal-pathogenic bacteria. This study demonstrates that macroalgal extracts can display different effects, i.e., inhibition or stimulation of bacterial growth depending on the origin of the test strains, which are derived from a standard panel or from the marine environment, respectively.
A Restriction Enzyme from Escherichia coli Purification and General Properties

An endonuclease restriction enzyme has been purified from E. coli about 40-fold with DNAse and RNAse recoveries of about 3%. The purification steps included precipitation of the enzyme with ammonium sulphate, and reclaimed it through Sephadex G-100 and DEAE-cellulose chromatography. The purified endonuclease was able to break lambda DNA into three bands. The enzyme has 5% of carbohydrate moiety which means it is a glycoprotein. Lastly, the comparison with other commercial restriction endonucleases proves that this enzyme is a restriction enzyme with enzymic activity dependent on Mg2+
Multisensory Integration Uses a Real-Time Unisensory–Multisensory Transform

The manner in which the brain integrates different sensory inputs to facilitate perception and behavior has been the subject of numerous speculations. By examining multisensory neurons in cat superior colliculus, the present study demonstrated that two operational principles are sufficient to understand how this remarkable result is achieved: (1) unisensory signals are integrated continuously and in real time as soon as they arrive at their common target neuron and (2) the resultant multisensory computation is modified in shape and timing by a delayed, calibrating inhibition. These principles were tested for descriptive sufficiency by embedding them in a neurocomputational model and using it to predict a neuron's moment-by-moment multisensory response given only knowledge of its responses to the individual modality-specific component cues. The predictions proved to be highly accurate, reliable, and unbiased and were, in most cases, not statistically distinguishable from the neuron's actual instantaneous multisensory response at any phase throughout its entire duration. The model was also able to explain why different multisensory products are often observed in different neurons at different time points, as well as the higher-order properties of multisensory integration, such as the dependency of multisensory products on the temporal alignment of crossmodal cues. These observations not only reveal this fundamental integrative operation, but also identify quantitatively the multisensory transform used by each neuron. As a result, they provide a means of comparing the integrative profiles among neurons and evaluating how they are affected by changes in intrinsic or extrinsic factors. SIGNIFICANCE STATEMENT Multisensory integration is the process by which the brain combines information from multiple sensory sources (e.g., vision and audition) to maximize an organism's ability to identify and respond to environmental stimuli. The actual transformative process by which the neural products of multisensory integration are achieved is poorly understood. By focusing on the millisecond-by-millisecond differences between a neuron's unisensory component responses and its integrated multisensory response, it was found that this multisensory transform can be described by two basic principles: unisensory information is integrated in real time and the multisensory response is shaped by calibrating inhibition. It is now possible to use these principles to predict a neuron's multisensory response accurately armed only with knowledge of its unisensory responses.
Level of Kidney Function Correlates with Cognitive Decline

Background: Early stage chronic kidney disease has been related to cognitive decline recently, while the association between them has never been explored in a Chinese population. Methods: This prospective study included a 1,351 community-based Chinese population >40 years and with estimated glomerular filtration rate (eGFR) >30 ml/min/ 1.73 m2. Kidney function was assessed by eGFR at baseline; cognitive function was evaluated by Mini-Mental State Examination (MMSE) both at baseline and 4 years later, and MMSE score decreased ≤2 was defined as cognitive decline using analysis of Reliable Change Indices. There were 1,243 participants (92.0%) with valid data of MMSE at the second visit. Results: Altogether there were 66 (5.3%) incident cognitive decline cases during 4 years of follow-up. After adjusting for potential confounders including urinary albumin-to-creatinine ratio, the odds ratio of developing cognitive decline was 1.35 (95% CI 0.69–2.65) among participants with eGFR 60–89 ml/min/1.73 m2 and was 2.73 (95% CI 1.00–7.56) among participants with eGFR 30–59 ml/min/1.73 m2, compared to those with eGFR ≧90 ml/min/1.73 m2. Conclusion: Our prospective study suggests that kidney function is associated with a cognitive decline in a Chinese population and the relation is independent of urinary albumin excretion.
TGF‐β down‐regulates IL‐6 signaling in intestinal epithelial cells: Critical role of SMAD‐2

Interleukin‐6 (IL‐6) is a pro‐inflammatory cytokine that plays an important role in the pathogenesis of inflammatory bowel disease. TGF‐β, a multifunctional cytokine, is a potent negative regulator of mucosal inflammation in the intestine. The aim of the present study is to determine possible cross‐talk between IL‐6 and TGF‐β signaling pathways. Model intestinal epithelial cell lines, Caco2‐BBE were used. We show that TGF‐β receptor Type II is predominantly present in the basolateral membrane of intestinal epithelial cells. TGF‐β1 induces a time‐dependent phosphorylation of Smad2 and co‐immunoprecipitation of SMAD‐2 with Smad‐4 and its subsequently translocation to the nucleus. We show that pretreatment of cells with TGF‐β1 is associated with a down‐regulation of IL‐6 induced tyrosine phosphorylation of STAT1 and STAT3 and suppression of ICAM‐1 expression. Furthermore, TGF‐β1 pretreatment resulted in a significant inhibition of IL‐6 induced ICAM‐1 promoter activity. TGF‐β mediated inhibition of IL‐6 induced ICAM‐1 expression was reversed by transfection with dominant negative Smad2 constructs. In conclusion, we show that: 1) TGF‐β receptor Type II is predominantly located on basolateral membrane and receptor stimulation activates Smad pathway; 2) TGF‐β1 down‐regulates IL‐6‐induced tyrosine phoshorylation of STAT1 and STAT3 and ICAM‐1 expression; and 3) Smad2 is required for the down‐regulation of IL‐6 signaling by TGF‐β. Collectively, our data demonstrate a cross‐talk between TGF‐β and IL‐6, and TGF‐β may play a role in the negative regulation of IL‐6 signaling in intestinal epithelial cells.
Alteration of polymorphonuclear leukocyte activity by viable Candida albicans

The response of human polymorphonuclear leukocytes (PMN) to blastospores and pseudo-hyphae of the opportunistic fungus Candida albicans has been studied in vitro and in vivo. Of the fungicidal mechanisms elucidated thus far, the myeloperoxidase-hydrogen peroxide-halide system appears to be most effective against cells of this fungus. In our studies on the interaction between murine PMN and blastospores, we assayed the release of H2O2 by PMN incubated with viable or killed, unopsonized or opsonized blastospores by using two assay systems, lysis of murine erythrocytes and oxidation of scopoletin. Our results showed that PMN released increasing amounts of H2O2 when incubated with increasing numbers of opsonized or unopsonized killed blastospores, but released decreasing amounts of H2O2 when incubated with increasing numbers of opsonized or unopsonized viable blastospores. The oxidative metabolic burst by PMN in the presence of viable or killed blastospores was also measured by using reduction of nitroblue tetrazolium and chemiluminescence. Viable blastospores stimulated a stronger metabolic burst than killed blastospores, suggesting that PMN respond to live blastospores more vigorously than killed blastospores; however, live blastospores appear to alter or inhibit the release of H2O2 by PMN.
Predicting Consumer Load Profiles  Using Commercial and Open Data

Automated Metering Infrastructure (AMI) has gradually become commonplace within the utilities industry and has brought with it numerous improvements in all related fields. Specifically in tariff setting and demand response models, classification of smart meter readings into load profiles helps in finding the right segments to target. This paper addresses the issue of assigning new customers, for whom no AMI readings are available, to one of these load profiles. This post-clustering phase has received little attention in the past. Our framework combines commercial, government and open data with the internal company data to accurately predict the load profile of a new customer using high performing classification models. The daily load profiles are generated using Spectral Clustering and are used as the dependent variable in our model. The framework was tested on over 6000 customers from GDF SUEZ in Belgium and six relevant load profiles were identified. The results show that the combination of internal data with commercial and cartographic data achieves the highest accuracy. Using external data alone, the model was still able to adequately place customers into their relevant load profile.