Miracle-dz/UniFAR-FTUs huggingface dataset:
Olanzapine in the treatment of pathological gambling: a negative randomized placebo-controlled trial.

OBJECTIVE Pathological gambling is associated with bipolar disorder and dopamine dysfunction. Olanzapine is a second-generation antipsychotic with mood-stabilizing properties and antagonistic activity at several dopamine receptors. The purpose of this study was to evaluate olanzapine in the treatment of pathological gambling. METHOD In this 12-week, single-center, randomized, double-blind, placebo-controlled, flexible-dose (2.5-15 mg/day) trial, 42 outpatients with pathological gambling by DSM-IV-TR criteria received olanzapine (N = 21) or placebo (N = 21). The primary outcome measure was the Pathological Gambling Adaptation of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS). The primary analysis of efficacy was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the effect measure. Subjects were enrolled from June 2, 2000, through November 28, 2005. RESULTS Compared with placebo, olanzapine was associated with a similar rate of reduction in total scores on the PG-YBOCS scale, as well as in gambling episodes/week, hours gambled/week, and Clinical Global Impressions-Severity of Illness scale scores. The mean (SD) olanzapine daily dose at endpoint evaluation was 8.9 (5.2) mg/day. Eleven subjects (52%) receiving olanzapine and 6 (29%) receiving placebo discontinued prematurely; 3 subjects receiving olanzapine and 2 receiving placebo discontinued because of adverse events. Events causing olanzapine discontinuation were pneumonia, sedation, and hypomania. CONCLUSION Olanzapine was not superior to placebo in the short-term treatment of pathological gambling. It was also associated with a high discontinuation rate. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00438776 (http://www.clinicaltrials.gov).
Prediction of michael-type acceptor reactivity toward glutathione.

A model has been developed to predict the kinetic rate constants (k(GSH)) of α,β-unsaturated Michael acceptor compounds for their reaction with glutathione (GSH). The model uses the local charge-limited electrophilicity index ω(q) [Wondrousch, D. , et al. (2010) J. Phys. Chem. Lett. 1, 1605-1610] at the β-carbon atom as a descriptor of reactivity, a descriptor for resonance stabilization of the transition state, and one for steric hindrance at the reaction sites involved. Overall, the Michael addition model performs well (r² = 0.91; rms = 0.34). It includes various classes of compounds with double and triple bonds, linear and cyclic systems, and compounds with and without substituents in the α-position. Comparison of experimental and predicted rate constants demonstrates even better performance of the model for individual classes of compounds (e.g., for aldehydes, r² = 0.97 and rms = 0.15; for ketones, r² = 0.95 and rms = 0.35). The model also allows for the prediction of the RC₅₀ values from the Schultz chemoassay, the accuracy being close to the interlaboratory experimental error. Furthermore, k(GSH) and associated RC₅₀ values can be predicted in cases where experimental measurements are not possible or restricted, for example, because of low solubility or high volatility. The model has the potential to provide information to assist in the assessment and categorization of toxicants and in the application of integrated testing strategies.
Evaluation of Innate Immunity Biomarkers on Admission and at Discharge From an Acute Heart Failure Episode

The involvement of the immune system in heart failure (HF) has been demonstrated. Evidence shows that innate immunity can have a role in the remodeling process and progression of HF. With previous studies showing the prognostic value of some innate immunity markers and their relevance in this condition, we aim to evaluate how these markers vary on hospitalization due to an acute episode of HF and at discharge.
Novel star-shaped fractal design of rectangular patch antenna for improved gain and bandwidth

A novel fractal design of conventional microstrip rectangular patch antenna is proposed. Gain and bandwidth of microstrip rectangular patch antenna is improved by addition of Star-shaped fractals at two sides and four corners of rectangular patch. A linearly polarized antenna is designed for 10 GHz and has directionality. Introduction of fractal geometry improved the gain from 5.479dB to 11dB and bandwidth from 550MHz to 5GHz with respect to simple rectangular patch. Bandwidth of 9GHz-14GHz has achieved covering X band and Ku band (according to IEEE standards). Likely applications areas for proposed design are radars, amateur radio operations, motion detectors, satellites, aerospace and communication systems.
Genetic transformation in Staphylococcus aureus: isolation and characterization of a competence-conferring factor from bacteriophage 80 alpha lysates

The competence-conferring activity in crude lysates of the staphylococcal bacteriophage 80 alpha was concentrated and purified by (NH4)2SO4 precipitation, differential ultracentrifugation and rate-zonal centrifugation through Ficoll. This concentrated preparation exhibited lytic activity toward assay cells of Staphylococcus aureus 8325-4 that could not be attributed to the residual 80 alpha infectious particles present. Electron microscopic examination of the concentrated competence-conferring activity revealed an occasional intact but empty virion and large numbers of free phage tails. Sodium dodecyl sulfate-polyacrylamide gel analysis of this material confirmed that the competence-conferring activity contained only some, but not all, of the major virion proteins. The competence-conferring activity exhibited single-hit kinetics when assay cells and 80 alpha transfecting deoxyribonucleic acid were present in excess. The competence-conferring activity thus seems to be a unique morphogenic precursor of the 80 alpha virion that mediates transfection and transformation in the presence of 0.1 M CaCl2.
Semistatic and sparse variance‐optimal hedging

We consider the problem of hedging a contingent claim with a “semistatic” strategy composed of a dynamic position in one asset and static (buy‐and‐hold) positions in other assets. We give general representations of the optimal strategy and the hedging error under the criterion of variance optimality and provide tractable formulas using Fourier integration in case of the Heston model. We also consider the problem of optimally selecting a sparse semistatic hedging strategy, i.e., a strategy that only uses a small subset of available hedging assets and discuss parallels to the variable‐selection problem in linear regression. The methods developed are illustrated in an extended numerical example where we compute a sparse semistatic hedge for a variance swap using European options as static hedging assets.
Patterns of population subdivision, gene flow and genetic variability in the African wild dog (Lycaon pictus)

African wild dogs are large, highly mobile carnivores that are known to disperse over considerable distances and are rare throughout much of their geographical range. Consequently, genetic variation within and differentiation between geographically separated populations is predicted to be minimal. We determined the genetic diversity of mitochondrial DNA (mtDNA) control region sequences and microsatellite loci in seven populations of African wild dogs. Analysis of mtDNA nucleotide diversity suggests that, historically, wild dog populations have been small relative to other large carnivores. However, population declines due to recent habitat loss have not caused a dramatic reduction in genetic diversity. We found one historical and eight recent mtDNA genotypes in 280 individuals that defined two highly divergent clades. In contrast to a previous, more limited, mtDNA analysis, sequences from these clades are not geographically restricted to eastern or southern African populations. Rather, we found a large admixture zone spanning populations from Botswana, Zimbabwe and south‐eastern Tanzania. Mitochondrial and microsatellite differentiation between populations was significant and unique mtDNA genotypes and alleles characterized the populations. However, gene flow estimates (Nm) based on microsatellite data were generally greater than one migrant per generation. In contrast, gene flow estimates based on the mtDNA control region were lower than expected given differences in the mode of inheritance of mitochondrial and nuclear markers which suggests a male bias in long‐distance dispersal.
Cytoskeleton elements mediate the inhibition of the (Na++K+)atpase activity by PKC in Rhodnius prolixus malpighian tubules during hyperosmotic shock.

In a previous paper, we observed that the specific activity of (Na++K+)ATPase of the isolated Malpighian tubules from Rhodnius prolixus is inhibited by protein kinase C (PKC) during hyperosmotic shock [Arenstein et al., J Membr Biol 146:47-57 [1995]; Caruso-Neves et al., Z Naturforsch 53c:911-917 [1998]). In the present paper, we study the involvement of the cytoskeleton in this process using isolated Malpighian tubules of Rhodnius prolixus. We observed that pre-incubation of the Malpighian tubule cells in hyperosmotic media decreases the specific activity of (Na++K+)ATPase by 90%. This effect was completely reversed when colchicine, which disrupts microtubules, or cytochalasin B, an inhibitor of actin microfilament polymerization, were added to the media in a dose-dependent manner. The maximal reversion was obtained with colchicine 7.0 microM or cytochalasin B 5.0 microM. The simultaneous addition of sphingosine 50 ng/mL, an inhibitor of PKC, to 10 microM colchicine or 5 microM cytochalasin B, in hyperosmotic media, did not change the stimulatory effect of these drugs on the specific activity of (Na++K+)ATPase. On the other hand, the co-incubation of TPA 20 ng/mL, an activator of PKC, to colchicine or cytochalasin B within hyperosmotic media, abolished the stimulatory effect of these drugs on the specific activity of (Na++K+)ATPase to a similar extent as hyperosmotic shock. These results suggest that inhibition of the (Na++K+)ATPase of the isolated Malpighian tubules from Rhodnius prolixus by PKC during hyperosmotic shock is mediated by cytoskeletal elements.
Left and right superior parietal lobule in tactile object discrimination

Tactile object discrimination is one of the major manual skills of humans. While the exploring finger movements are not perceived explicitly, attention to the movement‐evoked kinaesthetic information gates the tactile perception of object form. Using event‐related functional magnetic resonance imaging in seven healthy subjects we found one area in the right superior parietal cortex, which was specifically activated by kinaesthetic attention during tactile object discrimination. Another area with similar location in the left hemisphere was related to the maintenance of tactile information for subsequent object discrimination. We conclude that kinaesthetic information is processed in the anterior portion of the superior parietal cortex (aSPL) with a right hemispheric predominance for discrimination and a left hemispheric predominance for information maintenance.
Haemodialysis for post-traumatic acute renal failure - factors predicting outcome.

BACKGROUND Post-traumatic acute renal failure requiring renal replacement therapy in an intensive care unit (ICU) is associated with high mortality. OBJECTIVE To assess indicators of improved survival. METHODS This was a retrospective cohort study of 64 consecutive trauma patients (penetrating and blunt trauma and burns) who underwent haemodialysis (HD) over a period of 5 years. Information on pre-hospital and in-hospital resuscitation, trauma scores and physiological scores and daily ICU records were collected. The majority of the patients were dialysed with continuous venovenous haemofiltration in the early years of the study and later with sustained low-efficiency dialysis. RESULTS Of the 64 patients 47 died, giving an overall mortality rate of 73%. Mortality was highest in the burns patients (84%). Survival in all patients, irrespective of injury, was unrelated to the Revised Trauma Score, Injury Severity Score, Acute Physiology and Chronic Health Evaluation Score or Trauma Injury Severity Score. The duration of HD did not differ significantly between the three trauma groups, and age was not a significant predictor of survival. Patients who were polyuric at the time of the initiation of HD had a lower mortality rate than those who were oliguric, anuric or normouric, although this did not reach statistical significance (p=0.09). CONCLUSIONS Acute renal failure in trauma patients is associated with a low survival rate. Controversial conclusions have been presented in the literature. In this study, none of the parameters previously reported to affect survival proved to be valid, although the number of patients was comparable with those in other studies. Since understanding of the predictors and course of renal failure in trauma patients is still at an early stage, there is a need for multicentre prospective studies.
On the Transformational Potential of ‘Eating Local’: Insights for Socially Just Local Food System and Social Sustainability Theory and Practice

The gradual restructuring of international food and agriculture (or agri-food) systems over the past several decades has established industrialisation, productivism, and corporatisation as overriding imperatives governing contemporary food provisioning. The resultant interrelated adverse social and ecological impacts have led many commentators to argue that a global ‘food crisis’ is evident. These impacts include the loss of small farmer livelihoods, patenting of biological resources, increased soil, air, and water pollution, and heighted levels of food insecurity. An oft promoted strategy to combat this crisis and ensure agri-food sustainability is the shortening of food supply chains and the increased consumption of locally produced food through community- based food systems. The social dimension of sustainability is central to the development of sustainability strategies, such as local food systems. An explicit social focus highlights that to be transformative and address the root causes of socio-ecological change, sustainability is best understood as a socially negotiated process and not just a project for setting reformist goals and indicators. A primary component of this process-based approach to sustainability is social justice. In particular, procedural social justice emphasises the importance of including disadvantaged individuals and social groups when developing equitable actions for sustainability, which help mitigate the social inequalities that often lie at the heart of sustainability challenges. Problematically, local food systems have been found to inadequately address representations of social injustice faced by citizen- consumers. A deficit of social justice in local food practice results in a myriad of possible problems, including the (often unwitting) exclusion of socially marginalised community members, the development of ineffectual market-driven consumer-based sustainability interventions, or the devaluation of minority perspectives on food and eating. These problems call into question the possibility that ‘eating local’ can develop beyond a niche social practice to present a viable transition pathway toward more just and sustainable agri-food systems.
BAMBI Promotes C2C12 Myogenic Differentiation by Enhancing Wnt/β-Catenin Signaling

Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) is regarded as an essential regulator of cell proliferation and differentiation that represses transforming growth factor-β and enhances Wnt/β-catenin signaling in various cell types. However, its role in skeletal muscle remains largely unknown. In the current study, we found that the expression level of BAMBI peaked in the early differentiation phase of the C2C12 rodent myoblast cell line. Knockdown of BAMBI via siRNA inhibited C2C12 differentiation, indicated by repressed MyoD, MyoG, and MyHC expression as well as reductions in the differentiation and fusion indices. BAMBI knockdown reduced the activity of Wnt/β-catenin signaling, as characterized by the decreased nuclear translocation of β-catenin and the lowered transcription of Axin2, which is a well-documented target gene of the Wnt/β-catenin signaling pathway. Furthermore, treatment with LiCl, an activator of Wnt/β-catenin signaling, rescued the reduction in C2C12 differentiation caused by BAMBI siRNA. Taken together, our data suggest that BAMBI is required for normal C2C12 differentiation, and that its role in myogenesis is mediated by the Wnt/β-catenin pathway.
Degradation of Microtubule‐Associated Protein 2 and Brain Spectrin by Calpain: A Comparative Study

Abstract: The in vitro degradation of microtubule‐associated protein 2 (MAP‐2) and spectrin by the calcium‐dependent neutral protease calpain was studied. Five major results are reported. First, MAP‐2 isolated from twice‐cycled microtubules (2XMT MAP‐2) was extremely sensitive to calpain‐induced hydrolysis. Even at an enzyme‐to‐substrate ratio (wt/wt) of 1:200, 2XMT MAP‐2 was significantly degraded by calpain. Second, MAP‐2 purified from the total brain heat‐stable fraction (total MAP‐2) was significantly more resistant to calpain‐induced hydrolysis compared with 2XMT MAP‐2. Third, MAP‐2a and MAP‐2b were proteolyzed similarly by calpain, although some relative resistance of MAP‐2b was observed. Fourth, the presence of calmodulin significantly increased the extent of calpain‐induced hydrolysis of the α‐subunit of spectrin. Fifth, the two neuronal isoforms of brain spectrin (240/235 and 240/235E, referred to as α/βN and α/βE, respectively) showed different sensitivities to calpain. αN‐spectrin was significantly more sensitive to calpain‐induced degradation compared to αE‐spectrin. Among other things, these results suggest a role for the calpain‐induced degradation of MAP‐2, as well as spectrin, in such physiological processes as alterations in synaptic efficacy, dendritic remodeling, and in pathological processes associated with neurodegeneration.
Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice

Hemophilia B is a bleeding disorder caused by defective factor IX (FIX), currently treated by regular infusions of plasma‐derived or recombinant FIX. We propose a gene therapy strategy based on the implantation of cells secreting FIX enclosed in alginate microcapsules as a highly desirable alternative treatment. We have reported sustained delivery of human factor IX (hFIX) in immunocompetent mice implanted with encapsulated primary mouse myoblasts engineered to secrete hFIX. As a step towards the treatment of human patients, in this study we report the implantation of encapsulated human primary myoblasts secreting hFIX in hemophilia B mice.
Hybrid model for water demand prediction based on fuzzy cognitive maps and artificial neural networks

In this study, we propose a new hybrid approach for time series prediction based on the efficient capabilities of fuzzy cognitive maps (FCMs) with structure optimization algorithms and artificial neural networks (ANNs). The proposed structure optimization genetic algorithm (SOGA) for automatic construction of FCM is used for modeling complexity based on historical time series, and artificial neural networks (ANNs) which are used at the final process for making time series prediction. The suggested SOGA-FCM method is used for selecting the most important nodes (attributes) and interconnections among them which in the next stage are used as the input data to ANN used for time series prediction after training. The FCM with efficient learning algorithms and ANN have been already proved as sufficient methods for making time series forecasting. The performance of the proposed approach is presented through the analysis of real data of daily water demand and the corresponding prediction. The multivariate analysis of historical data is held for nine variables, season, month, day or week, holiday, mean and high temperature, rain average, touristic activity and water demand. The whole approach was implemented in an intelligent software tool initially deployed for FCM prediction. Through the experimental analysis, the usefulness of the new hybrid approach in water demand prediction is demonstrated, by calculating the mean absolute error (as one of the well known prediction measures). The results are promising for future work to this direction.
sgs1: a neomorphic nac52 allele impairing post‐transcriptional gene silencing through SGS3 downregulation

Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) sources. Genetic screens based on the reactivation of silenced transgenes have long been used to identify cellular components and regulators of PTGS. Here we show that the first isolated PTGS-deficient mutant, sgs1, is impaired in the transcription factor NAC52. This mutant exhibits striking similarities to a mutant impaired in the H3K4me3 demethylase JMJ14 isolated from the same genetic screen. These similarities include increased transgene promoter DNA methylation, reduced H3K4me3 and H3K36me3 levels, reduced PolII occupancy and reduced transgene mRNA accumulation. It is likely that increased DNA methylation is the cause of reduced transcription because the effect of jmj14 and sgs1 on transgene transcription is suppressed by drm2, a mutation that compromises de novo DNA methylation, suggesting that the JMJ14-NAC52 module promotes transgene transcription by preventing DNA methylation. Remarkably, sgs1 has a stronger effect than jmj14 and nac52 null alleles on PTGS systems requiring siRNA amplification, and this is due to reduced SGS3 mRNA levels in sgs1. Given that the sgs1 mutation changes a conserved amino acid of the NAC proteins involved in homodimerization, we propose that sgs1 corresponds to a neomorphic nac52 allele encoding a mutant protein that lacks wild-type NAC52 activity but promotes SGS3 downregulation. Together, these results indicate that impairment of PTGS in sgs1 is due to its dual effect on transgene transcription and SGS3 transcription, thus compromising siRNA amplification.
Stabilized‐Cycle Strategy for Capacitated Lot Sizing with Multiple Products: Fill‐Rate Constraints in Rolling Schedules

In practice, deterministic, multi‐period lot‐sizing models are implemented in rolling schedules since this allows the revision of decisions beyond the frozen horizon. Thus, rolling schedules are able to take realizations and updated forecasts of uncertain data (e.g., customer demands) into account. Furthermore, it is common to hold safety stocks to ensure given service levels (e.g., fill rate). As we will show, this approach, implemented in rolling schedules, often results in increased setup and holding costs while (over‐)accomplishing given fill rates. A well‐known alternative to deterministic planning models are stochastic, static, multi‐period planning models used in the static uncertainty strategy, which results in stable plans. However, these models have a lack of flexibility to react to the realization of uncertain data. As a result, actual costs may differ widely from planned costs, and downside deviations of actual fill rates from those given are very high. We propose a new strategy, namely the stabilized cycle. This combines and expands upon ideas from the literature for minimizing setup and holding costs in rolling schedules, while controlling actual product‐specific fill rates for a finite reporting period. A computational study with a multi‐item capacitated medium‐term production planning model has been executed in rolling schedules. On the one hand, it demonstrates that the stabilized‐cycle strategy yields a good compromise between costs and downside deviations. Furthermore, the stabilized‐cycle strategy weakly dominates the order‐based strategy for both constant and seasonal demands.