Miracle-dz/UniFAR-FTUs huggingface dataset:
Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder.

BACKGROUND An analysis of the relationship between clinical features and allele sharing could clarify the issue of genetic linkage between bipolar affective disorder (BPAD) and chromosome 18q, contributing to the definition of genetically valid clinical subtypes. METHODS Relatives ascertained through a proband who had bipolar I disorder (BPI) were interviewed by a psychiatrist, assigned an all-sources diagnosis, and genotyped with 32 markers on 18q21-23. Exploratory findings from the first 28 families (n = 247) were tested prospectively in an additional 30 families (n = 259), and the effect of confirmed findings on the linkage evidence was assessed. RESULTS In exploratory analyses, paternal allele sharing on 18q21 was significantly (P =.03) associated with a diagnostic subtype, and was greatest in pairs where both siblings had bipolar II disorder (BPII). Prospective analysis confirmed the finding that BPII-BPII sibling pairs showed significantly (P =.016) greater paternal allele sharing. Paternal allele sharing across 18q21-23 was also significantly greater in families with at least one BPII-BPII sibling pair. In these families, multipoint affected sibling-pair linkage analysis produced a peak paternal lod score of 4.67 (1-lod confidence interval, 12 centimorgans [cM]) vs 1.53 (1-lod confidence interval, 44 cM) in all families. CONCLUSIONS Affected sibling pairs with BPII discriminated between families who showed evidence of linkage to 18q, and families who did not. Families with a BPII sibling pair produced an increased lod score and improved linkage resolution. These findings, limited by the small number of BPII-BPII sibling pairs, strengthen the evidence of genetic linkage between BPAD and chromosome 18q, and provide preliminary support for BPII as a genetically valid subtype of BPAD.
Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia

Background Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. Methods We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran’s Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Results Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27–0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36–1.87) or overall mortality (RR 0.95, 95% CI 0.46–1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Conclusions Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.
Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK)

Madin-Darby canine kidney (MDCK) cells grown in tissue culture have the morphological properties of distal tubular epithelial cells, form tight junctions, and lack several proximal tubular enzyme markers. Adenylate cyclase in these cells was stimulated by vasopressin, oxytocin, prostaglandins E1 and E2, glucagon, and cholera toxin. Hormone- stimulated adenylate cyclase activity in isolated membrane preparations was dependent on low concentrations of GTP and had the MgCl2 and pH optima expected for the kidney enzyme. The results, as well as the demonstration of enhanced hemicyst formation induced by cyclic AMP, suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cell of origin. When MDCK cells were injected into baby nude mice, continuous nodule growth was observed until adulthood was attained. Histological studies revealed the presence of two cell types: normal mouse fibroblasts which comprise 80--90% of the solid nodule mass, and MDCK cells, which formed epithelial sheets lining internal fluid-filled glands. Electron microscope analysis showed that the mucosal surfaces of the cells were characterized by microvilli which faced the lumen of the glands, that adjacent MDCK cells were joined by tight junctions, and that the serosal surfaces of the epithelial sheets were characterized by smooth plasma membranes which were lined by a continuous basement membrane. These observations lead to the conclusion that the MDCK cells retain regional differentiation of their plasma membranes and the ability to regenerate kidney tubule-like structures in vivo.
Tucking RCC in Cyc's ontological bed

Formalisms and axiomatic theories are designed to support reasoning, they are often intended with a preferred interpretation and a targeted ontology. Questions of proper interpretations and of the possible challenge of an intended interpretation arise when integrating a particular theory in pre-existing formal and ontological settings. This paper reports on an instance of this general problem of ontological engineering. The case study is that of the integration of the Region Connection Calculus for spatial reasoning in the Cyc knowledge base. We show that given the assumptions on the Cyc ontology, RCC had to be interpreted within a substantivalist metaphysic of space as a Boolean algebra of spatial regions which are distinct from their occupants. The RCC literature suggests such an intended interpretation, and this paper intends to show that this was a necessary condition of integration in Cyc's ontology. This led to the enrichment of the Cyc knowledge base, rather than to a radical modification of the upper-level ontology.
The Importance of Technology Trust for B2B Electronic Commerce

Whereas the traditional notion of trust primarily focuses on trust in a trading partner, trust in e-business also incorporates the notion of trust in the infrastructure and the underlying control mechanisms (technology trust), which deals with transaction integrity, authentication, confidentiality, and non-repudiation. We argue that value creation in B2B e-commerce is heavily dependent on technology trust. Given the absence of adequate metrics to capture the technology trust in B2B e-commerce, this research develops and validates measures for technology trust, captured both as perceived benefits and also as B2B e-commerce performance. Our empirical results strongly support the hypothesis that technology trust is essential for successful B2B e-commerce.
Update on the management of severe hypertriglyceridemia – focus on free fatty acid forms of omega-3

: High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases, often associated with anomalies in other lipids or lipoproteins. Hypertriglyceridemia (HTG), particularly at very high levels, significantly increases also the risk of acute pancreatitis. Thus, interventions to lower TG levels are required to reduce the risk of pancreatitis and cardiovascular disease. Several strategies may be adopted for TG reduction, including lifestyle changes and pharmacological interventions. Among the available drugs, the most commonly used for HTG are fibrates, nicotinic acid, and omega-3 polyunsaturated fatty acids (usually a mixture of eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA). These last are available under different concentrated formulations containing high amounts of omega-3 fatty acids, including a mixture of EPA and DHA or pure EPA. The most recent formulation contains a free fatty acid (FFA) form of EPA and DHA, and exhibits a significantly higher bioavailability compared with the ethyl ester forms contained in the other formulations. This is due to the fact that the ethyl ester forms, to be absorbed, need to be hydrolyzed by the pancreatic enzymes that are secreted in response to fat intake, while the FFA do not. This higher bioavailability translates into a higher TG-lowering efficacy compared with the ethyl ester forms at equivalent doses. Omega-3 FFA are effective in reducing TG levels and other lipids in hypertriglyceridemic patients as well as in high cardiovascular risk patients treated with statins and residual HTG. Currently, omega-3 FFA formulation is under evaluation to establish whether, in high cardiovascular risk subjects, the addition of omega-3 to statin therapy may prevent or reduce major cardiovascular events.
Infants with Intrauterine Growth Restriction Have Impaired Formation of Docosahexaenoic Acid in Early Neonatal Life: A Stable Isotope Study

This study evaluated the arachidonic acid (AA) and docosahexaenoic acid (DHA) formation from d5-labeled linoleic acid (d5-LA) and α-linolenic acid (d5-LNA) precursors in infants with intrauterine growth restriction (IUGR) compared with control groups matched by gestational age (GA) or birth weight. We compared DHA and AA formation from deuterated precursors d5-LA and d5-LNA in 11 infants with IUGR with 13 and 25 control subjects who were appropriate for GA and matched by GA and by birth weight, respectively. After an enteral administration of d5-LA and d5-LNA, we determined unlabeled and d5-labeled fatty acids at 24, 48, and 96 h in plasma. Absolute concentrations and area under the curve (AUC) over the 96-h study were used for analysis. Absolute concentration of d5-DHA and the product/precursor ratio of the d5-labeled AUCs indicated a less active DHA formation from LNA in infants with IUGR compared with their GA-matched (2-fold) and birth weight–matched (3-fold) control subjects. The ratios of eicosapentaenoic and n-3 docosapentaenoic acid to DHA were also affected. Similar evaluation for the n-6 series was not significant. DHA metabolism is affected in infants with IUGR; the restricted DPA to DHA conversion step seems to be principally responsible for this finding.
Existential consistency: measuring and understanding consistency at Facebook

Replicated storage for large Web services faces a trade-off between stronger forms of consistency and higher performance properties. Stronger consistency prevents anomalies, i.e., unexpected behavior visible to users, and reduces programming complexity. There is much recent work on improving the performance properties of systems with stronger consistency, yet the flip-side of this trade-off remains elusively hard to quantify. To the best of our knowledge, no prior work does so for a large, production Web service. We use measurement and analysis of requests to Facebook's TAO system to quantify how often anomalies happen in practice, i.e., when results returned by eventually consistent TAO differ from what is allowed by stronger consistency models. For instance, our analysis shows that 0.0004% of reads to vertices would return different results in a linearizable system. This in turn gives insight into the benefits of stronger consistency; 0.0004% of reads are potential anomalies that a linearizable system would prevent. We directly study local consistency models---i.e., those we can analyze using requests to a sample of objects---and use the relationships between models to infer bounds on the others. We also describe a practical consistency monitoring system that tracks φ-consistency, a new consistency metric ideally suited for health monitoring. In addition, we give insight into the increased programming complexity of weaker consistency by discussing bugs our monitoring uncovered, and anti-patterns we teach developers to avoid.
SEU Tolerant Latch Based on Error Detection

This paper presents an SEU hardened latch that can mitigate SEU based on an error detection circuit and a multiplexer. During the hold phase, an SEU on an internal node may upset the logic state of the latch. But the error detection circuit can detect this fault and generate fault indication signals via precharge and discharge operations. The fault indication signals control a multiplexer to select a correct output. Therefore, each latch has some error detection and correction capability.
Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures

We have defined a signal responsible for the morphological differentiation of human umbilical vein and human dermal microvascular endothelial cells in vitro. We find that human umbilical vein endothelial cells deprived of growth factors undergo morphological differentiation with tube formation after 6-12 wk, and that human dermal microvascular endothelial cells differentiate after 1 wk of growth factor deprivation. Here, we report that morphological differentiation of both types of endothelial cells is markedly accelerated by culture on a reconstituted gel composed of basement membrane proteins. Under these conditions, tube formation begins in 1-2 h and is complete by 24 h. The tubes are maintained for greater than 2 wk. Little or no proliferation occurs under these conditions, although the cells, when trypsinized and replated on fibronectin-coated tissue culture dishes, resume division. Ultrastructurally, the tubes possess a lumen surrounded by endothelial cells attached to one another by junctional complexes. The cells possess Weibel-Palade bodies and factor VIII-related antigens, and take up acetylated low density lipoproteins. Tubule formation does not occur on tissue culture plastic coated with laminin or collagen IV, either alone or in combination, or on an agarose or a collagen I gel. However, endothelial cells cultured on a collagen I gel supplemented with laminin form tubules, while supplementation with collagen IV induces a lesser degree of tubule formation. Preincubation of endothelial cells with antibodies to laminin prevented tubule formation while antibodies to collagen IV were less inhibitory. Preincubation of endothelial cells with synthetic peptides derived from the laminin B1 chain that bind to the laminin cell surface receptor or incorporation of these peptides into the gel matrix blocked tubule formation, whereas control peptides did not. These observations indicate that endothelial cells can rapidly differentiate on a basement membrane-like matrix and that laminin is the principal factor in inducing this change.
Tracing the geographic origin of the cosmopolitan parthenogenetic insect pest Liposcelis bostrychophila (Psocoptera: Liposcelididae)

Abstract The randomly amplified polymorphic DNA technique was used to trace the geographic origin of Liposcelis bostrychophila Badonnel populations in Australia from unknown geographic sources internationally. Haplotype (or clonal) diversity was high, with 474 unique haplotypes found from 616 individuals genotyped. Gene diversity estimates (0.10–0.28) and percent polymorphic loci (38.1–88.1%) were moderate to high for most populations. This resulted in genetic distance estimates that ranged from 0.04 to 0.26 and were significantly different for most pairwise population combinations. GST values for all populations were also moderate (0.04–0.54) and again were significantly different for most pairwise population comparisons. Analysis of molecular variance revealed that the majority of variation was apportioned among individuals within populations regardless of the level at which they were grouped. Gene flow (Nm) was mostly low for all pairwise populations comparisons with an average Nm = 1.8. A non-significant negative correlation between genetic distance and geographic distance was found for worldwide populations. In contrast, within Australian populations a significant positive correlation between genetic distance and geographic distance was detected. Genetic relationships explored using unweighted pair group method analysis and non-metric multidimensional scaling indicated a mixed pattern of genetic similarities among all populations. Multiple introductions, from a wide range of international source populations, have obscured the ability to accurately determine the geographic origin of L. bostrychophila in Australia.
Whispering dysphonia in an Australian family (DYT4): A clinical and genetic reappraisal

The designation, DYT4, was assigned to an Australian family with whispering dysphonia. The role of known causes of dystonia has not been comprehensively investigated in this family, nor has the possible relationship with Wilson disease (WND) in 2 siblings. Eighteen family members were neurologically examined, and DNA samples were obtained. Linkage analysis was performed to DYT1, DYT6, DYT7, DYT11, DYT13, DYT15, and ATP7B with microsatellite markers and the THAP1 (DYT6), PRKRA (DYT16), and ATP7B (WND) genes were sequenced. Reevaluation of the family identified 9 living affected family members, 6 of whom are newly affected. Phenotypic expression was variable, ranging from isolated spasmodic dysphonia (often with mild craniocervical dystonia) to severe generalized dystonia. Two newly described features included an extrusional tongue dystonia and a unique “hobby horse gait. ” Genetic analyses excluded all tested loci. Haplotype analysis of the ATP7B region resulted in three different combinations of the two parental alleles in the 8 investigated siblings of the 2 deceased WND patients, indicating that the fourth combination (of two mutated alleles) had occurred only in the deceased WND patients. On these two alleles, we identified a missense (c.2297C>G; p.T766R) and a splice‐site mutation (IVS5+1G>T). The c.2297C>G mutation was detected in 3 affected and 4 unaffected family members, whereas the IVS5+1G>T mutation was detected in 1 affected and unaffected family member. Five DYT4 patients carried neither mutation. DYT4 is a familial form of dystonia unrelated to known dystonia genes and loci. ATP7B mutations do not segregate with the dystonia phenotype, indicating two independent genetic diseases in this family. © 2011 Movement Disorder Society
The Influence of Drought Stress on Nutrients Uptake and Physiological Responses in Rapeseed ( Brassica napus L.) Lines

To study the effect of drought stress on nutrients uptake and physiological traits of seven rapeseed advanced lines, a two year experiment was conducted under greenhouse condition. The experiments were laid out in CRD factorial with three replications. A highly significant decline was observed in chlorophyll a and b content, relative water content, and biomass of oilseed rape lines under drought stress, while total soluble sugars content enhanced in this condition. The results showed that phosphate was the most abundant ion in leaves under both stress and non-stress conditions. The concentration of nutrients was also affected by drought and mostly diminished under stress condition. Water deficit significantly reduced nitrate, phosphate, sulfate, ammonium, calcium and manganese ions uptake, which was greater for phosphate than the other ions. In contrast, the concentration of nitrite increased. Also among inorganic forms of nitrogen (nitrate, nitrite and ammonium), the highest and the lowest sensitivity to soil moisture content was observed in ammonium and nitrate, respectively. In conclusion, improving nutritional status of rapeseed lines under drought stress condition is essential to diminish detrimental effects of water deficit.
Socieconomic and demographic characteristics and retirement: a descriptive study

This paper assesses the correlation between socioeconomic and demographic variables and the individuals’ perceptions about retirement. Using data from the “Raio X do investidor”, a survey conducted by the Brazilian Association of Financial and Capital Markets Entities (ANBIMA) in partnership with Datafolha, we use descriptive analysis and logistic regressions to study the perception of individuals regarding retirement. Our main results suggest that the genders have different perceptions about retirement. The study also reinforces that individuals with lower education and income levels are more likely to choose the social retirement system in Brazil, INSS, as a strategy. The findings support the existing inequalities in the country and are useful for political agents and future strategies of social security evaluation. This research contributes to personal finance studies, such as Potrich, Vieira, and Kirch (2015), with innovations focused on retirement.
Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool

Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by increases not only in release probability (Pr) but also in the readily releasable pool size estimated from a cumulative plot of excitatory post-synaptic current amplitudes (RRPcum), which contribute to the augmentation phase and the late phase of PTP, respectively. The vesicle pool dynamics underlying the latter has not been investigated, because PTP is abolished by presynaptic whole-cell patch clamp. We found that supplement of recombinant calmodulin to the presynaptic pipette solution rescued the increase in the RRPcum after high-frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in Pr. Release-competent synaptic vesicles (SVs) are heterogeneous in their releasing kinetics. To investigate post-tetanic changes of fast and slowly releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before and 40 s after HFS using the deconvolution method. After HFS, the FRP size increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP and SRP sizes did not increase. Similar changes in the RRP were induced by a single long depolarizing pulse (100 ms). The post-tetanic complementary changes of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in the SRP size provides the first line of evidence for the idea that a slowly releasing SV can be converted to a fast releasing one.