Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
The ggpS Gene from Synechocystis sp. Strain PCC 6803 Encoding Glucosyl-Glycerol-Phosphate Synthase Is Involved in Osmolyte Synthesis

ABSTRACT A salt-sensitive mutant of Synechocystis sp. strain PCC 6803 defective in the synthesis of the compatible solute glucosylglycerol (GG) was used to search for the gene encoding GG-phosphate synthase (GGPS), the key enzyme in GG synthesis. Cloning and sequencing of the mutated region and the corresponding wild-type region revealed that a deletion of about 13 kb occurred in the genome of mutant 11. This deletion affected at least 10 open reading frames, among them regions coding for proteins showing similarities to trehalose (otsA homolog)- and glycerol-3-phosphate-synthesizing enzymes. After construction and characterization of mutants defective in these genes, it became obvious that an otsA homolog (sll1566) (T. Kaneko et al., DNA Res. 3:109–136, 1996) encodes GGPS, since only the mutant affected in sll1566 showed salt sensitivity combined with a complete absence of GG accumulation. Furthermore, the overexpression ofsll1566 in Escherichia coli led to the appearance of GGPS activity in the heterologous host. The overexpressed protein did not show the salt dependence that is characteristic for the GGPS in crude protein extracts of Synechocystis.
Thermal Contact Conductance in Bolted Joints

Determining thermal contact conductance in bolted joints is a major challenge when designing for space application. The lack of heat transfer through convection enforces the need for full understanding of thermal contact conductance, and the influencing physical parameters. Due to the uncertain variance of pressure distribution in a bolted joint, determination of thermal contact conductance becomes difficult. At the time of this thesis, models describing thermal contact conductance in bolted joints, were limited. In accordance with RUAG Space, vacuum experiments on generic rods as well as bolted joints were executed. Measured interface temperature drops were used as reference in iterative finite volume analyses, developed to estimate the thermal contact conductance. Results were achieved for the relationship between interface pressure and thermal contact conductance in nickel-plated aluminum joints. Available theoretical models were found to vary strongly in estimation of thermal contact conductance. Performing experiments adapted to the specific application was therefore found to be essential for gaining knowledge about the actual thermal contact conductance. Experiments on bolted joints gave information about the total thermal contact conductance and its dependence on several important design parameters, including bolt torque, number of bolt, surface roughness and joint material. The overall results coincided with theory. In conclusion, the thesis puts forth a new method of thermal contact conductance estimations in bolted joints by a combination of empirical test data and finite volume analyses. This method was concluded to result in more accurate estimation of thermal contact conductance in bolted joints, compared to older studies.
Bevacizumab for glioblastoma

Glioblastoma is the most common type of malignant primary brain tumor and has a median survival of only 14.6–16 months.1,2 For patients whose tumors progress after standard radiotherapy with concomitant and adjuvant temozolomide chemotherapy, the treatment options are limited. Because glioblastomas are highly vascular tumors, therapies that target angiogenesis have generated substantial interest. In 2009, bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, received accelerated approval from the US Food and Drug Administration for treatment of recurrent glioblastomas based on 2 phase II trials showing improved response rates and 6-month progression-free survival (PFS) compared to historical controls.3,4 However, the benefits of bevacizumab are transient, and tumors progress after a median of only 3–5 months.3,4 Once tumors progress on bevacizumab, further treatments are of little or no benefit.5
TROY, a Newly Identified Member of the Tumor Necrosis Factor Receptor Superfamily, Exhibits a Homology with Edar and Is Expressed in Embryonic Skin and Hair Follicles*

In a signal sequence trap screening of the murine brain, we identified a new member of the tumor necrosis factor receptor superfamily designated TROY. TROY is a type I membrane protein of 416 amino acids with characteristic cysteine-rich motifs in the extracellular domain and a tumor necrosis factor receptor-associated factor (TRAF) 2 binding sequence in the cytoplasmic domain of 223 amino acids. In fact, activation of nuclear factor κB was induced by the overexpression of TROY and inhibited by dominant negative forms of TRAF2, TRAF5, and TRAF6, indicating that TRAFs and nuclear factor κB are involved in the signal transduction of TROY. We also cloned a cDNA for a human counterpart, which showed a 75% homology with mouse TROY at the amino acid level. The extracellular domain of TROY exhibits an extensive homology with that of Edar, a receptor that specifies hair follicle fate. TROY mRNA is strongly expressed in brain and embryo and moderately expressed in the heart, lung, and liver but not the spleen. In the embryo, the expression level is particularly strong in the skin. Interestingly, in situ hybridization analysis of the embryo showed that TROY mRNA was exclusively expressed in the epithelium of many tissues. On the other hand, in neonatal mice, TROY is expressed in hair follicles like Edar as well as in the cerebrum, suggesting pleiotropic functions of TROY in development as well as in the adult mice. The Troy gene is located near the waved coat (Wc) locus, a mutant related to abnormalities in skin and hair.
Common Melanocytic Nevi in 7-Year-Old Schoolchildren Residing at Different Latitudes in Sweden

Background: Current epidemiologic research shows consistently that increased number of acquired common melanocytic nevi (CMN) is an important risk factor for cutaneous malignant melanoma. The purpose of this study was to investigate the number of CMN in relation to tanning habits and complexion among 7-year-old children residing at different latitudes in Sweden. Methods: Two municipalities were chosen at latitude 65°N to 68°N in the north of Sweden and two at latitude 57°N in the south. Children born in 1994 and registered in the municipalities were to be included (N = 1,676). A questionnaire was sent to their parents asking about the child's tanning habits. A body examination of CMN of size ≥2 mm was done by the same trained nurse in 1,380 (82.3%) of the children. Results: CMN was significantly less prevalent among children living in the north with a prevalence of 5.6 [95% confidence interval (95% CI), 4.8-6.5] inland and 6.2 (95% CI, 5.3-7.2) coastal compared with the south with a prevalence of 9.5 (95% CI, 8.2-11.0) inland and 10.4 (95% CI, 8.9-12.0) coastal. In addition, blond hair, blue/gray/green eyes, holidays at seaside resorts abroad, more frequent sunburns, and parents fancying tanning were significant predictors of higher prevalence of CMN. Conclusions: These findings support previous evidence that the development of CMN is related to the level of sun exposure in childhood expressed as latitude of residence, holidays at seaside resort abroad, and number of sunburns. To reduce the incidence of cutaneous malignant melanoma, a change in attitude and behavior must start with young children and their parents. (Cancer Epidemiol Biomarkers Prev 2007;16(1):122–7)
WRB and CAML Are Necessary and Sufficient to Mediate Tail-Anchored Protein Targeting to the ER Membrane

Tail-Anchored (TA) proteins are inserted into the endoplasmic reticulum (ER) membrane of yeast cells via the posttranslational Guided Entry of Tail-Anchored protein (GET) pathway. The key component of this targeting machinery is the ATPase Get3 that docks to the ER membrane by interacting with a receptor complex formed by the proteins Get1 and Get2. A conserved pathway is present in higher eukaryotes and is mediated by TRC40, homolog of Get3, and the recently identified membrane receptors WRB and CAML. Here, we used yeast lacking the GET1 and GET2 genes and substituted them with WRB and CAML. This rescued the growth phenotypes of the GET receptor mutant. We demonstrate that WRB and CAML efficiently recruit Get3 to the ER membrane and promote the targeting of the TA proteins in vivo. Our results show that the membrane spanning segments of CAML are essential to create a functional receptor with WRB and to ensure TA protein membrane insertion. Finally, we determined the binding parameters of TRC40 to the WRB/CAML receptor. We conclude that together, WRB and CAML are not only necessary but also sufficient to create a functional membrane receptor complex for TRC40. The yeast complementation assay can be used to further dissect the structure-function relationship of the WRB/CAML heteromultimer in the absence of endogenous receptor proteins.
Recognition of the Class Ib Molecule Qa-1b by Putative Activating Receptors Cd94/Nkg2c and Cd94/Nkg2e on Mouse Natural Killer Cells

The heterodimeric CD94/NKG2A receptor, expressed by mouse natural killer (NK) cells, transduces inhibitory signals upon recognition of its ligand, Qa-1b, a nonclassical major histocompatibility complex class Ib molecule. Here we clone and express two additional receptors, CD94/NKG2C and CD94/NKG2E, which we show also bind to Qa-1b. Within their extracellular carbohydrate recognition domains, NKG2C and NKG2E share extensive homology with NKG2A (93–95% amino acid similarity); however, NKG2C/E receptors differ from NKG2A in their cytoplasmic domains (only 33% similarity) and contain features that suggest that CD94/NKG2C and CD94/NKG2E may be activating receptors. We employ a novel blocking anti-NKG2 monoclonal antibody to provide the first direct evidence that CD94/NKG2 molecules are the only Qa-1b receptors on NK cells. Molecular analysis reveals that NKG2C and NKG2E messages are extensively alternatively spliced and ∼20-fold less abundant than NKG2A message in NK cells. The organization of the mouse Cd94/Nkg2 gene cluster, presented here, shows striking similarity with that of the human, arguing that the entire CD94/NKG2 receptor system is relatively primitive in origin. Analysis of synonymous substitution frequencies suggests that within a species, NKG2 genes may maintain similarities with each other by concerted evolution, possibly involving gene conversion–like events. These findings have implications for understanding NK cells and also raise new possibilities for the role of Qa-1 in immune responses.
Trajectory of disability and quality-of-life in non-geriatric and geriatric survivors after severe traumatic brain injury

ABSTRACT Objective: The objective was to investigate disability and health-related quality-of-life (HRQoL) 3, 6 and 12 months after traumatic brain injury (TBI) in non-geriatric (≤ 65 years) and geriatric patients (> 65 years). Methods: Patients ≥ 16 years who sustained a severe TBI (Abbreviated Injury Scale of the head region > 3) were included in this prospective, multi-centre study. Outcome measures were Glasgow Outcome Scale Extended (GOSE; disability), SF-12 (HRQoL). Mixed linear model analyses were performed. Results: Three hundred and fifty-one patients (median age = 50 years; interquartile range (IQR) = 27–67) were included; 73.2% were male and 27.6% were geriatric patients. Median GOSE at 3, 6 and 12 months was 5 (IQR = 3–7), 6 (IQR = 4–8) and 7 (IQR = 5–8); this increase (slopetime = 0.22, p < 0.0001) was age dependent (slopeage*time = –0.06, p = 0.003). Median SF-12 physical component scale score at 3, 6 and 12 months was 42.1 (IQR = 33.6–50.7), 46.6 (IQR = 37.4–53.9) and 50.4 (IQR = 39.2–55.1); this increase (slopetime = 1.52, p < 0.0001) was not age dependent (slopeage*time = –0.30, p = 0.083). SF-12 mental component scale scores were unchanged. Conclusions: Disability decreased and HRQoL improved after TBI between 3–12 months. In geriatric patients this improvement was relevant for HRQoL only.
Increased High-Density Lipoprotein Cholesterol Predicts the Pioglitazone-Mediated Reduction of Carotid Intima-Media Thickness Progression in Patients With Type 2 Diabetes Mellitus

Background— Measurement of carotid intima-media thickness (CIMT) has been validated as a measure of atherosclerosis and as a predictor of future cardiovascular events. Compared with glimepiride, pioglitazone has been shown to slow the progression of atherosclerosis measured by CIMT in patients with type 2 diabetes mellitus. Methods and Results— We evaluated individual cardiovascular risk factors as predictors of the change in CIMT produced by pioglitazone treatment by determining whether their addition to a baseline model resulted in loss of significance for the treatment effect on CIMT. Pioglitazone treatment led to improvement in levels of multiple cardiovascular risk markers, including high-sensitivity C-reactive protein, apolipoprotein B, apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, triglyceride, insulin, and free fatty acid. At 24 weeks, there were significant differences in HDL cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin, body mass index, hip circumference, and high-sensitivity C-reactive protein between the pioglitazone and glimepiride treatment groups. After adjustment for 24-week on-treatment values of cardiovascular risk factors, only inclusion of the changes in HDL cholesterol and insulin significantly impacted the magnitude and significance of the treatment effect on CIMT. Furthermore, irrespective of treatment assignment, increased HDL cholesterol at 24 weeks was a significant predictor of reduced CIMT progression at 72 weeks. Conclusions— The beneficial effect of pioglitazone on HDL cholesterol at 24 weeks predicted its beneficial effect for reducing CIMT progression at 72 weeks. Changes in HDL cholesterol at 24 weeks, irrespective of treatment, predicted less progression of CIMT at 72 weeks. These results suggest that suppression of atherosclerosis with pioglitazone therapy is linked to its ability to raise HDL cholesterol.
Forecasting Techniques for Time Series from Sensor Data

Forecasting has always been of interest. Whether one's field is finance, health or seismology, being able to predict future values based on previously gathered data proves to be invaluable when taking decisions concerning the future. In this paper, we research machine learning techniques for predictions on time series and choose the best models that fit our use case, Smart Farms, in which we distributedly analyze time series received from farm-monitoring sensors. On time series with short term dependencies, like temperature or pressure, we make predictions with Hidden Markov Models, whilst for those with long range dependencies, like ground wind speeds orprecipitations, we use Recurrent Neural Networks with Long Short-Term Memory architecture.
Bacteriophage φ6: a Lipid-Containing Virus of Pseudomonas phaseolicola

The purification and properties of a lipid-containing bacteriophage, φ6, are described. The phage contains a lipid envelope which is probably essential for infection. Infectivity of φ6 was lost in the presence of organic solvents, sodium deoxycholate, and phospholipase A. The fatty acid composition of the phage lipid was similar to that of the Pseudomonas phaseolicola host cells. The phage was composed of about 25% lipid, 13% RNA, and 62% protein. The buoyant density of φ6 was 1.27 g/ml in cesium chloride. The morphology of φ6 was unusual; it had a polyhedral head of about 60 nm surrounded by a membranous, compressible envelope which appeared to assume an elongated configuration upon attachment to pili. The adsorption rate constant was 3.3 × 10−10 ml/min in a semi-synthetic medium and 3.8 × 10−10 ml/min in a nutrient broth-yeast extract medium. The latent period was shorter in the former medium (80-115 min compared with 120-160 min), and the average burst size was larger (250-400 compared with 125-150). The eclipse period coincided with the latent period.
DNA Barcoding for the Identification of Sand Fly Species (Diptera, Psychodidae, Phlebotominae) in Colombia

Sand flies include a group of insects that are of medical importance and that vary in geographic distribution, ecology, and pathogen transmission. Approximately 163 species of sand flies have been reported in Colombia. Surveillance of the presence of sand fly species and the actualization of species distribution are important for predicting risks for and monitoring the expansion of diseases which sand flies can transmit. Currently, the identification of phlebotomine sand flies is based on morphological characters. However, morphological identification requires considerable skills and taxonomic expertise. In addition, significant morphological similarity between some species, especially among females, may cause difficulties during the identification process. DNA-based approaches have become increasingly useful and promising tools for estimating sand fly diversity and for ensuring the rapid and accurate identification of species. A partial sequence of the mitochondrial cytochrome oxidase gene subunit I (COI) is currently being used to differentiate species in different animal taxa, including insects, and it is referred as a barcoding sequence. The present study explored the utility of the DNA barcode approach for the identification of phlebotomine sand flies in Colombia. We sequenced 700 bp of the COI gene from 36 species collected from different geographic localities. The COI barcode sequence divergence within a single species was <2% in most cases, whereas this divergence ranged from 9% to 26.6% among different species. These results indicated that the barcoding gene correctly discriminated among the previously morphologically identified species with an efficacy of nearly 100%. Analyses of the generated sequences indicated that the observed species groupings were consistent with the morphological identifications. In conclusion, the barcoding gene was useful for species discrimination in sand flies from Colombia.
Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry, enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors.
Segregated failures model for availability evaluation of fault-tolerant systems

This paper presents a method of estimating the availability of fault-tolerant computer systems with several recovery procedures. A segregated failures model has been proposed recently for this purpose. This paper provides further analysis and extension of this model. The segregated failures model is compared with a Markov chain model and is extended for the situation when the coverage factor is unknown and failure escalation rates must be used instead. This situation is illustrated in detail by estimating availability of a Lucent Technologies Reliable Clustered Computing architecture. For this example, numeric values are provided for availability indexes and the contribution of each recovery procedure to total system availability is analysed.
Effects of strength training on endurance capacity in top‐level endurance athletes

The effect of concurrent strength (S) and endurance (E) training on adaptive changes in aerobic capacity, endurance performance, maximal muscle strength and muscle morphology is equivocal. Some data suggest an attenuated cardiovascular and musculoskeletal response to combined E and S training, while other data show unimpaired or even superior adaptation compared with either training regime alone. However, the effect of concurrent S and E training only rarely has been examined in top‐level endurance athletes. This review describes the effect of concurrent SE training on short‐term and long‐term endurance performance in endurance‐trained subjects, ranging from moderately trained individuals to elite top‐level athletes. It is concluded that strength training can lead to enhanced long‐term (>30 min) and short‐term (<15 min) endurance capacity both in well‐trained individuals and highly trained top‐level endurance athletes, especially with the use of high‐volume, heavy‐resistance strength training protocols. The enhancement in endurance capacity appears to involve training‐induced increases in the proportion of type IIA muscle fibers as well as gains in maximal muscle strength (MVC) and rapid force characteristics (rate of force development), while likely also involving enhancements in neuromuscular function.