Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical Characterization of the High Affinity Binding between the Glycine Receptor and Gephyrin*

Gephyrin is an essential and instructive molecule for the formation of inhibitory synapses. Gephyrin binds directly to the large cytoplasmic loop located between transmembrane helices three and four of the β-subunit of the glycine receptor and to microtubules, thus promoting glycine receptor (GlyR) anchoring to the cytoskeleton and clustering in the postsynaptic membrane. Besides its structural role, gephyrin is involved in the biosynthesis of the molybdenum cofactor that is essential for all molybdenum-dependent enzymes in mammals. Gephyrin can be divided into an N-terminal trimeric G domain and a C-terminal E domain, which are connected by a central linker region. Here we have studied the in vitro interaction of gephyrin and its domains with the large cytoplasmic loop of the GlyR β-sub-unit (GlyRβ-loop). Binding of gephyrin to the GlyR is exclusively mediated by the E domain, and the binding site was mapped to one of its sub-domains (residues 496–654). By using isothermal titration calorimetry, a high affinity (Kd = 0.2–0.4 μm) and low affinity (Kd = 11–30 μm) binding site for the GlyRβ-loop was found on holo-gephyrin and the E domain, respectively, with a binding stoichiometry of two GlyRβ-loops per E domain in both cases. Binding of the GlyRβ-loop does not change the oligomeric state of either full-length gephyrin or the isolated E domain.
Conflict-Directed Backjumping Revisited

In recent years, many improvements to backtracking algorithms for solving constraint satisfaction problems have been proposed. The techniques for improving backtracking algorithms can be conveniently classified as look-ahead schemes and look-back schemes. Unfortunately, look-ahead and look-back schemes are not entirely orthogonal as it has been observed empirically that the enhancement of look-ahead techniques is sometimes counterproductive to the effects of look-back techniques. In this paper, we focus on the relationship between the two most important look-ahead techniques--using a variable ordering heuristic and maintaining a level of local consistency during the backtracking search--and the look-back technique of conflict-directed backjumping (CBJ). We show that there exists a "perfect" dynamic variable ordering such that CBJ becomes redundant. We also show theoretically that as the level of local consistency that is maintained in the backtracking search is increased, the less that backjumping will be an improvement. Our theoretical results partially explain why a backtracking algorithm doing more in the look-ahead phase cannot benefit more from the backjumping look-back scheme. Finally, we show empirically that adding CBJ to a backtracking algorithm that maintains generalized arc consistency (GAC), an algorithm that we refer to as GAC-CBJ, can still provide orders of magnitude speedups. Our empirical results contrast with Bessiere and Regin's conclusion (1996) that CBJ is useless to an algorithm that maintains arc consistency.
Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells

Glutamine metabolism is crucial for cancer cell growth via the generation of intermediate molecules in the tricarboxylic acid (TCA) cycle, antioxidants and ammonia. The goal of the current study was to evaluate the effects of glutamine on metabolism in the breast cancer tumor microenvironment, with a focus on autophagy and cell death in both epithelial and stromal compartments. For this purpose, MCF7 breast cancer cells were cultured alone or co-cultured with non-transformed fibroblasts in media containing high glutamine and low glucose (glutamine +) or under control conditions, with no glutamine and high glucose (glutamine –). Here, we show that MCF7 cells maintained in co-culture with glutamine display increased mitochondrial mass, as compared with control conditions. Importantly, treatment with the autophagy inhibitor chloroquine abolishes the glutamine-induced augmentation of mitochondrial mass. It is known that loss of caveolin-1 (Cav-1) expression in fibroblasts is associated with increased autophagy and an aggressive tumor microenvironment. Here, we show that Cav-1 downregulation which occurs in fibroblasts maintained in co-culture specifically requires glutamine. Interestingly, glutamine increases the expression of autophagy markers in fibroblasts, but decreases expression of autophagy markers in MCF7 cells, indicating that glutamine regulates the autophagy program in a compartment-specific manner. Functionally, glutamine protects MCF7 cells against apoptosis, via the upregulation of the anti-apoptotic and anti-autophagic protein TIGAR. Also, we show that glutamine cooperates with stromal fibroblasts to confer tamoxifen-resistance in MCF7 cancer cells. Finally, we provide evidence that co-culture with fibroblasts (1) promotes glutamine catabolism, and (2) decreases glutamine synthesis in MCF7 cancer cells. Taken together, our findings suggest that autophagic fibroblasts may serve as a key source of energy-rich glutamine to fuel cancer cell mitochondrial activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion.
Taking off to the Third Dimension, Schematization of Virtual Environments

Virtual environments are increasingly popular in different areas in both research and industry. However, interaction with these environments is challenging, posing a variety of difficulties to human users. In this paper, we explore how well known principles of abstraction and information reduction for 2D spatial representations, which we term schematization, can be transferred to the 3D representations of virtual environments in order to ease interaction and to increase their utility.
A Report of High Triglyceride Level in Cord Blood of Iranian Newborns

Background: Since cord blood triglyceride level have been reported very different in recent articles, the purpose of this study is determination of triglyceride level in cord blood of Iranian newborns and compare it with other reports. Methods: In this study, cord blood of 174 healthy term newborn infants (97 girls, 77 boys) born from healthy mothers have been used. Triglyceride level has been measured by calorie metric method Statistical analysis was performed by independent t test, Mann-Whitney regression test and Spearman correlation coefficient method using SPSS 16 . 0 software (SPSS, USA). Results: The mean of cord blood triglyceride was 1.37 ± 4.81 mg /dl and there was no statistical difference between two sexes. There was not exist linear relationship between triglyceride and weight, height, head circumference, body mass index and sex of the babies. In 8.6% of our new born infants, triglyceride levels were more than 95th percentile of triglyceride level reported in Iranian population. In 33.9% of our cases, triglyceride levels were more than 95th percentile of triglyceride level reported in the Nelson text book of Pediatrics. In this study, the 95th percentile of triglyceride level in cord blood was 132.5 mg /dl. Conclusion: The mean and 95th percentiles of triglyceride levels in cord blood of our newborn infants were higher than other reports. We recommend that larger studies should be conducted in this area to establish preventive ways for increasing epidemic of the metabolic syndrome.
Two Gamma Interferon-Activated Site-Like Elements in the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer Are Important for Viral Replication

ABSTRACT Human cytomegalovirus (HCMV) infection directly initiates a signal transduction pathway that leads to activation of a large number of cellular interferon-stimulated genes (ISGs). Our previous studies demonstrated that two interferon response elements, the interferon-stimulated response element and gamma interferon-activated site (GAS), in the ISG promoters serve as HCMV response sites (VRS). Interestingly, two GAS-like VRS elements (VRS1) were also present in the HCMV major immediate-early promoter-enhancer (MIEP/E). In this study, the importance of these VRS elements in viral replication was investigated. We demonstrate that the expression of the major IE genes, IE1 and IE2, is interferon inducible. To understand the biological significance of this signal transduction pathway in HCMV major IE expression, the two VRS1 in the MIEP/E were mutated. Mutant HCMVs in which the VRS elements were deleted or that contained point mutations grew dramatically more slowly than wild-type virus at a low multiplicity of infection (MOI). Insertion of wild-type VRS1 into the mutant viral genome rescued the slow growth phenotype. Furthermore, the expression levels of major IE RNAs and proteins were greatly reduced during infection with the VRS mutants at a low MOI. HCMV microarray analysis indicated that infection of host cells with the VRS mutant virus resulted in a global reduction in the expression of viral genes. Collectively, these data demonstrate that the two VRS elements in the MIEP/E are necessary for efficient viral gene expression and replication. This study suggests that although the HCMV-initiated signal transduction pathway results in induction of cellular antiviral genes, it also functions to stimulate viral major IE gene expression. This might be a new viral strategy in which the pathway is used to regulate gene expression and play a role in reactivation.
External schemas in a schema-evolution environment for OODBs

External schemas are derived from the database conceptual schema; they can be used to simulate changes in it. Sometimes the final users' information requirements change: they need new information which cannot be derived from the information in the database. The solution put forward here is the definition of partially derived classes (capacity augmenting classes) which may contain non-derived information in the intension and moreover, unlike other systems, in the extension. When an external schema with partially derived classes is to be defined, the conceptual schema has to be modified in order to include the non-derived information. In order to avoid unnecessary modifications of the conceptual schema the use of a test environment for the definition of temporal external schemas is also proposed.
Chagas Disease Vector Control in a Hyperendemic Setting: The First 11 Years of Intervention in Cochabamba, Bolivia

Background Chagas disease has historically been hyperendemic in the Bolivian Department of Cochabamba. In the early 2000s, an extensive vector control program was implemented; 1.34 million dwelling inspections were conducted to ascertain infestation (2000–2001/2003–2011), with blanket insecticide spraying in 2003–2005 and subsequent survey-spraying cycles targeting residual infestation foci. Here, we assess the effects of this program on dwelling infestation rates (DIRs). Methodology/Principal Findings Program records were used to calculate annual, municipality-level aggregate DIRs (39 municipalities); very high values in 2000–2001 (median: 0.77–0.69) dropped to ∼0.03 from 2004 on. A linear mixed model (with municipality as a random factor) suggested that infestation odds decreased, on average, by ∼28% (95% confidence interval [CI95] 6–44%) with each 10-fold increase in control effort. A second, better-fitting mixed model including year as an ordinal predictor disclosed large DIR reductions in 2001–2003 (odds ratio [OR] 0.11, CI95 0.06–0.19) and 2003–2004 (OR 0.22, CI95 0.14–0.34). Except for a moderate decrease in 2005–2006, no significant changes were detected afterwards. In both models, municipality-level DIRs correlated positively with previous-year DIRs and with the extent of municipal territory originally covered by montane dry forests. Conclusions/Significance Insecticide-spraying campaigns had very strong, long-lasting effects on DIRs in Cochabamba. However, post-intervention surveys consistently detected infestation in ∼3% of dwellings, underscoring the need for continuous surveillance; higher DIRs were recorded in the capital city and, more generally, in municipalities dominated by montane dry forest – an eco-region where wild Triatoma infestans are widespread. Traditional strategies combining insecticide spraying and longitudinal surveillance are thus confirmed as very effective means for area-wide Chagas disease vector control; they will be particularly beneficial in highly-endemic settings, but should also be implemented or maintained in other parts of Latin America where domestic infestation by triatomines is still commonplace.
Inappropriate drug use among older persons: is it time for action?

o u r c e : h t t p s : / / d o i . o r g / 1 0 . 7 8 9 2 / b o r i s . 6 7 5 6 4 | d o w n l o a d e d : 2 2 . 9 . 2 0 2 3 On the basis of the findings of this review, the authors propose that clinicians consider screening for sarcopenia in community and geriatric settings. However, this is premature in the absence of unequivocal evidence of short and long-term benefit for the existing interventions. Nevertheless as geriatricians we should have a high index of suspicion for sarcopenia in our patients across healthcare settings, be willing to measure as well as interpret gait speed , muscle strength and mass, and consider how best we can institute exercise programmes where indicated, together with dietary advice. It is time to translate existing research findings into clinical practice.
The influence of demonstration sites and field days on adoption of conservation practices

For more than 100 years, demonstrations have been used by university extension programs and other conservation professionals to increase knowledge, awareness, and adoption of agricultural practices and technologies. However, there has been no systematic, empirical examination of the effect demonstrations have on adoption of agricultural innovations nor conservation practices. We examined the relationship between producer attendance at demonstration sites and field days of four conservation practices and the subsequent adoption of these practices using a mail survey (n = 513) and in-person interviews (n = 24) with agricultural producers in three regions of Indiana. Results show that there is a significant, moderate relationship between attendance and adoption of cover crops, nutrient management, and filter strips and a significant, weak relationship for two-stage ditches. Interviews with agricultural producers suggest that cover crop demonstration sites and field days allow for learning about practices from persons outside their regular social and professional network and provide tailored advice that allow producers to understand what to consider when making a decision to adopt a conservation practice. Results indicate that demonstration sites and field days do influence adoption of conservation practices; however, data do not control for the probability that those who attend are more likely to adopt regardless of attendance.
Automatic Grading of Evidence: the 2011 ALTA Shared Task

The ALTA shared tasks are programming competitions where all participants attempt to solve the same problem, and the winner is the system with the best results. The 2011 ALTA shared task is the second in the series and it focuses on trying to automatically grade the level of clinical evidence in medical research papers. In this paper we describe the task, present the results of several baselines, and the results of our method. We apply a sequence of high precision machine learning classifiers with varying feature sets for each. In addition to usingn-grams, we incorporate domain knowledge by representing specific medical concepts using their semantic categories. We also apply a specialised rule-based approach for automatically identifying the publication types of articles, which is then used as a feature set. Our approach obtains an accuracy of 62.84% which is a significant improvement over the baselines.
Robust speech recognition with speech enhanced deep neural networks

We propose a signal pre-processing front-end to enhance speech based on deep neural networks (DNNs) and use the enhanced speech features directly to train hidden Markov models (HMMs) for robust speech recognition. As a comprehensive study, we examine its effectiveness for different acoustic features, acoustic models, and training-testing combinations. Tested on the Aurora4 task the experimental results indicate that our proposed framework consistently outperform the state-of-the-art speech recognition systems in all evaluation conditions. To our best knowledge, this is the ﬁrst showcase on the Aurora4 task yielding performance gains by using only an enhancement pre-processor without any adaptation or compensation post-processing on top of the best DNN-HMM system. The word error rate reduction from the baseline system is up to 50% for clean-condition training and 15% for multi-condition training. We believe the system performance could be improved further by incorporating post-processing techniques to work coher-ently with the proposed enhancement pre-processing scheme.
Analyses of Lunar Orbiter Laser Altimeter 1,064‐nm Albedo in Permanently Shadowed Regions of Polar Crater Flat Floors: Implications for Surface Water Ice Occurrence and Future In Situ Exploration

Potential water ice concentrated within the permanently shadowed regions (PSRs) near lunar poles is both scientifically significant and of value for future explorations. However, after decades of observations, the existence and characteristics of PSR water ice remain controversial. The 1,064‐nm laser reflectance measurements collected by the Lunar Orbiter Laser Altimeter (LOLA) onboard the Lunar Reconnaissance Orbiter (LRO) provide a unique opportunity to detect and characterize PSR water ice. In this work, we focus on all major PSRs on the flat floors of lunar polar craters and analyze their detailed LOLA 1,064‐nm albedo and then compare this with the adjacent flat non‐PSRs. We find that the LOLA albedo of the majority of these PSRs is systematically higher than their adjacent non‐PSRs. Potential contributions of various factors to the observed LOLA albedo are individually quantitatively evaluated; we show that each of them is unable to account for the observed LOLA albedo anomalies and that the presence of surface water ice is the most likely explanation. Combined characterization of LOLA albedo and substrate impact cratering records (crater populations and depths) reveals that the inferred PSR water ices are in very small quantity (probably in the form of a surface frost layer or admixture with regolith) and are laterally heterogeneous in model ice concentration, ranging from negligible to ~6%. We recommend that these PSRs as priority targets for future surface in situ exploration endeavors, and a case assessment of Amundsen crater is presented.
Gestational Diabetes Mellitus in Early Pregnancy: Evidence for Poor Pregnancy Outcomes Despite Treatment

OBJECTIVE Recent guidelines recommend testing at <24 weeks of gestation for maternal dysglycemia in “high-risk” women. Evidence to support the early identification and treatment of gestational diabetes mellitus (GDM) is, however, limited. We examined the prevalence, clinical characteristics, and pregnancy outcomes of high-risk women with GDM diagnosed at <24 weeks of gestation (early GDM) and those with pre-existing diabetes compared with GDM diagnosed at ≥24 weeks of gestation, in a large treated multiethnic cohort. RESEARCH DESIGN AND METHODS Outcomes from 4,873 women attending a university hospital antenatal diabetes clinic between 1991 and 2011 were examined. All were treated to standardized glycemic targets. Women were stratified as pre-existing diabetes (n = 65) or GDM diagnosed at <12 weeks of gestation (n = 68), at 12–23 weeks of gestation (n = 1,247), or at ≥24 weeks of gestation (n = 3,493). RESULTS Hypertensive disorders in pregnancy including pre-eclampsia, preterm delivery, cesarean section, and neonatal jaundice (all P < 0.001) were more prevalent in women with pre-existing diabetes and early GDM. Macrosomia (21.8% vs. 20.3%, P = 0.8), large for gestational age (39.6% vs. 32.8%, P = 0.4), and neonatal intensive care admission (38.5% vs. 39.7%, P = 0.9) in women in whom GDM was diagnosed at <12 weeks of gestation were comparable to rates seen in women with pre-existing diabetes. CONCLUSIONS Despite early testing and current best practice treatment, early GDM in high-risk women remains associated with poorer pregnancy outcomes. Outcomes for those in whom GDM was diagnosed at <12 weeks of gestation approximated those seen in pre-existing diabetes. These findings indicate the need for further studies to establish the efficacy of alternative management approaches to improve outcomes in these high-risk pregnancies.
R1R2R3-Myb proteins positively regulate cytokinesis through activation of KNOLLE transcription in Arabidopsis thaliana

G2/M phase-specific gene transcription in tobacco cells is mediated by R1R2R3-Myb transcriptional activators, NtmybA1 and NtmybA2, which bind to mitosis-specific activator (MSA) elements. We show here that two structurally related genes, MYB3R1 and MYB3R4, which encode homologs of NtmybA1 and NtmybA2, play a partially redundant role in positively regulating cytokinesis in Arabidopsis thaliana. The myb3r1 myb3r4 double mutant often fails to complete cytokinesis, resulting in multinucleate cells with gapped walls and cell wall stubs in diverse tissues. These defects correlate with the selective reduction of transcript levels of several G2/M phase-specific genes, which include B2-type cyclin (CYCB2), CDC20.1 and KNOLLE (KN). These genes contain MSA-like motifs in their promoters and were activated by MYB3R4 in transient expression assays in tobacco cells. The KN gene encodes a cytokinesis-specific syntaxin that is essential for cell plate formation. The cytokinesis defects of myb3r1 myb3r4 double mutants were partially rescued by KN gene expression from heterologous promoters. In addition, a kn heterozygous mutation enhanced cytokinesis defects resulting from heterozygous or homozygous mutations in the MYB3R1 and MYB3R4 genes. Our results suggest that a pair of structurally related R1R2R3-Myb transcription factors may positively regulate cytokinesis mainly through transcriptional activation of the KN gene.
Improved intensive care unit survival for critically ill allogeneic haematopoietic stem cell transplant recipients following reduced intensity conditioning

The use of allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) is a standard treatment option for many patients with haematological malignancies. Historically, patients requiring intensive care unit (ICU) admission for transplant‐related toxicities have fared extremely poorly, with high ICU mortality rates. Little is known about the impact of reduced intensity Allo‐HSCT conditioning regimens in older patients on the ICU and subsequent long‐term outcomes. A retrospective analysis of data collected from 164 consecutive Allo‐HSCT recipients admitted to ICU for a total of 213 admissions, at a single centre over an 11·5‐year study period was performed. Follow‐up was recorded until 31 March 2011. Autologous HSCT recipients were excluded. In this study we report favourable ICU survival following Allo‐HSCT and, for the first time, demonstrate significantly better survival for patients who underwent Allo‐HSCT with reduced intensity conditioning compared to those treated with myeloablative conditioning regimens. In addition, we identified the need for ventilation (invasive or non‐invasive) as an independently significant adverse factor affecting short‐term ICU outcome. For patients surviving ICU admission, subsequent long‐term overall survival was excellent; 61% and 51% at 1 and 5 years, respectively. Reduced intensity Allo‐HSCT patients admitted to ICU with critical illness have improved survival compared to myeloablative Allo‐HSCT recipients.