Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic utility of serum GH, IGF-1 and IGFBP3 in patients of acromegaly with uncontrolled diabetes: a pilot study.

PURPOSE Diagnosis of acromegaly in presence of uncontrolled diabetes mellitus is not well validated. METHOD The study included 10 patients of active acromegaly with uncontrolled blood glucose, 10 patients of type 2 diabetes mellitus with poor glycemic control and 10 healthy subjects. The growth hormone level following oral glucose tolerance test and insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) were done at baseline in all the 3 groups and it was repeated after short term glycemic control in type 2 diabetics and acromegalics with diabetics RESULTS In the acromegalic group the basal GH value was very high (36.5 + 1.6) ng/ml and it was non-suppressible (32.5 + 1.43) ng/ml after OGTT. The mean IGF-1 and IGFBP-3 values were also high at baseline (208.38 + 38.51) ng/ml, and 7322 + 370 ng/ml respectively. In the non-acromegalic diabetic patients, the basal growth hormone value was marginally elevated (2.3 + 0.02) ng/ml. However, it was suppressible to 0.2 + 0.04 ng/ml after oral glucose load. In them the IGF-1 and IGFBP-3 values were not elevated and comparable to that of healthy controls. CONCLUSIONS Basal serum GH and IGFBP-3 levels are not influenced by degree of glycemic control however serum IGF-1 levels should be interpreted with caution in patients of acromegaly with diabetes. Oral glucose load test has discriminating ability to diagnose acromegaly even with poorly controlled diabetes.
The Staging of Venture Capital Financing: Milestone vs. Rounds

Venture capital funding is commonly provided to start-up firms on a piecemeal basis over numerous stages. One way in which this can be implemented is through milestone financing, where a venture capitalist commits upfront to providing additional future funding contingent upon the firm meeting certain conditions, or milestones. Alternately, the firm can operate without a firm commitment in place, still reasonably expecting to be able to receive additional rounds of funding after goals are met (round financing). We identify four dimensions which can affect the optimal contract and choice of financing method: entrepreneurial effort, venture capitalist effort, venture capitalist preference for liquid investments, and heterogeneous expectations about the feasibility of the underlying real technology. The effects of these on the optimal milestone and round financing contracts are examined. Firms that prefer milestone financing to round financing (and conversely) are characterized.
Covariance Tapering for Likelihood-Based Estimation in Large Spatial Data Sets

Maximum likelihood is an attractive method of estimating covariance parameters in spatial models based on Gaussian processes. But calculating the likelihood can be computationally infeasible for large data sets, requiring O(n3) calculations for a data set with n observations. This article proposes the method of covariance tapering to approximate the likelihood in this setting. In this approach, covariance matrixes are “tapered,” or multiplied element wise by a sparse correlation matrix. The resulting matrixes can then be manipulated using efficient sparse matrix algorithms. We propose two approximations to the Gaussian likelihood using tapering. One of these approximations simply replaces the model covariance with a tapered version, whereas the other is motivated by the theory of unbiased estimating equations. Focusing on the particular case of the Matérn class of covariance functions, we give conditions under which estimators maximizing the tapering approximations are, like the maximum likelihood estimator, strongly consistent. Moreover, we show in a simulation study that the tapering estimators can have sampling densities quite similar to that of the maximum likelihood estimator, even when the degree of tapering is severe. We illustrate the accuracy and computational gains of the tapering methods in an analysis of yearly total precipitation anomalies at weather stations in the United States.
Hepatoprotective activity of Colocasia antiquorum against experimentally induced liver injury in rats.

Colocasia antiquorum (Araceae) commonly known as ‘taro’, was claimed to have medicinal properties to treat hepatic ailments in ancient literature. The aim of this work was to study the hepatoprotective effect of crude ethanolic extracts of C. antiquorum. Ethanolic extract obtained from the corms of C. antiquorum (L.) Schott (Araceae), was evaluated for hepatoprotective activity using paracetamol and carbon tetrachloride (CCl4) intoxicated rats as experimental models. The protective effect was evident from serum biochemical parameters and histopathological analysis. Ethanolic extract of C. antiquorum significantly (P<0.5) prevented the elevation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in paracetamol and CCl4 treated rats as compared to silymarin, which was used as a positive control. These biochemical observations were supplemented by histopathological examination of liver sections showing the prevention of disarrangement and degeneration of hepatic cells induced by paracetamol and CCl4. The activity may be a result of the presence of anthocyanin compounds. Furthermore, acute toxicity studies showed no signs of toxicity up to a dose level of 1000 mg/kg. Thus, it may be concluded that ethanolic extract of C. antiquorum possesses significant hepatoprotective properties.
Usefulness of early dobutamine stress echocardiography for the assessment of risk of restenosis after percutaneous coronary interventions.

BACKGROUND The increasing role of percutaneous coronary interventions (PCI) in the treatment of coronary artery disease and relatively high restenosis rate following PCI require the introduction of available, easy to perform and cost-effective tests that would enable detection of restenosis after PTCA and identification of patients at particularly high risk of restenosis. AIM To estimate the predictive value of early dobutamine stress echocardiography (DSE) for the assessment of risk of coronary restenosis. METHODS Thirty-nine patients with a single coronary vessel disease after PCI were enrolled in this study. DSE was performed twice--2 to 3 days after the procedure and repeated after 8 to 12 months. All patients underwent coronary angiography after one-year follow-up. RESULTS Data analysis of direct pre- and postprocedural echocardiography showed that the wall motion score index decreased significantly (p <0.0001), whereas ejection fraction increased significantly after the intervention when compared with baseline (p <0.0001). Restenosis was detected in 8 out of 10 subjects with positive DSE test and in 3 out of 29 subjects with negative DSE test. In a group of 11 patients with restenosis confirmed in the coronary angiography, one-year follow-up DSE was found positive in 9 patients (80% test sensitivity) but in two cases results were false negative. Negative test was observed in 27 out of 28 individuals without restenosis (90% test specificity). CONCLUSIONS DSE is highly sensitive and specific in prediction and detection of restenosis after PCI. DSE performed early after PCI is safe.
INTERPOPULATION HYBRID BREAKDOWN MAPS TO THE MITOCHONDRIAL GENOME

Abstract Hybrid breakdown, or outbreeding depression, is the loss of fitness observed in crosses between genetically divergent populations. The role of maternally inherited mitochondrial genomes in hybrid breakdown has not been widely examined. Using laboratory crosses of the marine copepod Tigriopus californicus, we report that the low fitness of F3 hybrids is completely restored in the offspring of maternal backcrosses, where parental mitochondrial and nuclear genomic combinations are reassembled. Paternal backcrosses, which result in mismatched mitochondrial and nuclear genomes, fail to restore hybrid fitness. These results suggest that fitness loss in T. californicus hybrids is completely attributable to nuclear–mitochondrial genomic interactions. Analyses of ATP synthetic capacity in isolated mitochondria from hybrid and backcross animals found that reduced ATP synthesis in hybrids was also largely restored in backcrosses, again with maternal backcrosses outperforming paternal backcrosses. The strong fitness consequences of nuclear–mitochondrial interactions have important, and often overlooked, implications for evolutionary and conservation biology.
Discovering Denial Constraints

Integrity constraints (ICs) provide a valuable tool for enforcing correct application semantics. However, designing ICs requires experts and time. Proposals for automatic discovery have been made for some formalisms, such as functional dependencies and their extension conditional functional dependencies. Unfortunately, these dependencies cannot express many common business rules. For example, an American citizen cannot have lower salary and higher tax rate than another citizen in the same state. In this paper, we tackle the challenges of discovering dependencies in a more expressive integrity constraint language, namely Denial Constraints (DCs). DCs are expressive enough to overcome the limits of previous languages and, at the same time, have enough structure to allow efficient discovery and application in several scenarios. We lay out theoretical and practical foundations for DCs, including a set of sound inference rules and a linear algorithm for implication testing. We then develop an efficient instance-driven DC discovery algorithm and propose a novel scoring function to rank DCs for user validation. Using real-world and synthetic datasets, we experimentally evaluate scalability and effectiveness of our solution.
A Circuit Model for Saccadic Suppression in the Superior Colliculus

Attenuation of visual activity in the superficial layers (SLs), stratum griseum superficiale and stratum opticum, of the superior colliculus during saccades may contribute to reducing perceptual blur during saccades and also may help prevent subsequent unwanted saccades. GABAergic neurons in the intermediate, premotor, layer (SGI), stratum griseum intermedium, send an inhibitory input to SL. This pathway provided the basis for a model proposing that the SGI premotor cells that project to brainstem gaze centers and discharge before saccades also activate neighboring GABAergic neurons that suppress saccade-induced visual activity in SL. The in vitro method allowed us to test this model. We made whole-cell patch-clamp recordings in collicular slices from either rats or GAD67–GFP knock-in mice, in which GABAergic neurons could be identified by their expression of green fluorescence protein (GFP). Antidromic electrical stimulation of SGI premotor cells was produced by applying pulse currents in which their axons congregate after exiting the superior colliculus. The stimulation evoked monosynaptic EPSCs in SGI GABAergic neurons that project to SL, as would be predicted if these neurons receive excitatory input from the premotor cells. Second, IPSCs were evoked in SL neurons, some of which project to the visual thalamus. These IPSCs were polysynaptically mediated by the GABAergic neurons that were excited by the antidromically activated SGI neurons. These results support the hypothesis that collaterals of premotor neuron axons excite GABAergic neurons that inhibit SL visuosensory cells.
Adding Salt to Meals as a Risk Factor of Type 2 Diabetes Mellitus: A Case–Control Study

Objective: Type 2 diabetes mellitus (T2DM) is thought to arise from the complex interplay between genetic and environmental factors. It is important to identify modifiable risk factors that may help to reduce the risk of diabetes. Data on salt intake and the risk of type 2 diabetes are limited. The aim of this study was to assess the relationship between adding salt to prepared meals and the risk of type 2 diabetes. Methods: In a case–control study, we included 234 cases, all of whom were patients aged 35–86 years with a newly confirmed diagnosis of T2DM, and 468 controls that were free of the disease. Cases and controls (ratio 1:2) were matched by gender and age (±5 years). A questionnaire was used to collect information on possible risk factors for diabetes. Adding salt to prepared meals was assessed according to: Never, when there was not enough, or almost every time without tasting. The odds ratios (OR), and 95% confidence intervals (CI) for type 2 diabetes was calculated using a conditional logistic regression. Results: The cases had a higher body mass index and a significantly lower education level compared to the controls. Variables such as waist circumference, body mass index, eating speed, smoking, family history of diabetes, arterial hypertension, plasma triglycerides, educational level, occupational status, morning exercise, marital status, daily urine sodium excretion, and daily energy intake were retained in the models as confounders. After adjusting for possible confounders, an approximately two-fold increased risk of type 2 diabetes was determined in subjects who add salt to prepared meals when “it is not enough” or “almost every time without tasting” (1.82; 95% CI 1.19–2.78; p = 0.006) compared with never adding salt. Conclusion: Presented data suggest the possible relationship between additional adding of salt to prepared meals and an increased risk of type 2 diabetes.
Effects of Short- and Long-Term Variations in RLS Severity on Perceived Health Status – the COR-Study

In a cohort study among 2751 members (71.5% females) of the German and Swiss RLS patient organizations changes in restless legs syndrome (RLS) severity over time was assessed and the impact on quality of life, sleep quality and depressive symptoms was analysed. A standard set of scales (RLS severity scale IRLS, SF-36, Pittsburgh Sleep Quality Index and the Centre for Epidemiologic Studies Depression Scale) in mailed questionnaires was repeatedly used to assess RLS severity and health status over time and a 7-day diary once to assess short-term variations. A clinically relevant change of the RLS severity was defined by a change of at least 5 points on the IRLS scale. During 36 months follow-up minimal improvement of RLS severity between assessments was observed. Men consistently reported higher severity scores. RLS severity increased with age reaching a plateau in the age group 45–54 years. During 3 years 60.2% of the participants had no relevant (±5 points) change in RLS severity. RLS worsening was significantly related to an increase in depressive symptoms and a decrease in sleep quality and quality of life. The short-term variation showed distinctive circadian patterns with rhythm magnitudes strongly related to RLS severity. The majority of participants had a stable course of severe RLS over three years. An increase in RLS severity was accompanied by a small to moderate negative, a decrease by a small positive influence on quality of life, depressive symptoms and sleep quality.
Identification of germline BRCA1 and BRCA2 genetic alterations in Greek breast cancer moderate‐risk and low‐risk individuals – correlation with clinicopathological data

The current study was designed to evaluate the prevalence of BRCA1 and BRCA2 germline mutations in Greek moderate‐ and low‐risk individuals with respect to clinicopathological phenotype and clinical outcome of breast cancer. Ninety‐four consecutive individuals were prospectively recruited from two University Breast Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized as moderate‐risk and low‐risk individuals for carrying BRCA1/2 germline mutations. To identify the underlying mutations, protein‐truncation test and single‐strand conformation polymorphism methods were used, followed by direct sequencing. Three novel BRCA1 missense mutations, one novel BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating mutations, and one novel BRCA2 missense mutation were identified in the moderate‐risk group of individuals studied. The BRCA1/2 missense mutations as well as the single intronic variant identified were designated as unclassified genetic variants. Two BRCA1 unclassified genetic variants (missense mutations) were detected in two of the three (66.7%) male breast cancer patients analyzed, while the third one was identified in a sporadic (low‐risk) breast cancer patient. Clinicopathological characteristics of breast carcinomas originating from BRCA1/2 heterozygotes were consistent with those already reported and not different from those observed in BRCA1/2 mutation (–) breast cancer patients. Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5‐year overall survival (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status, genotype–phenotype correlations, and prognosis, in moderate‐ and low‐risk individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous syndrome in the Greek population.
The Relationship Between Deliberate Practice and Performance in Sports

Why are some people more skilled in complex domains than other people? According to one prominent view, individual differences in performance largely reflect individual differences in accumulated amount of deliberate practice. Here, we investigated the relationship between deliberate practice and performance in sports. Overall, deliberate practice accounted for 18% of the variance in sports performance. However, the contribution differed depending on skill level. Most important, deliberate practice accounted for only 1% of the variance in performance among elite-level performers. This finding is inconsistent with the claim that deliberate practice accounts for performance differences even among elite performers. Another major finding was that athletes who reached a high level of skill did not begin their sport earlier in childhood than lower skill athletes. This finding challenges the notion that higher skill performers tend to start in a sport at a younger age than lower skill performers. We conclude that to understand the underpinnings of expertise, researchers must investigate contributions of a broad range of factors, taking into account findings from diverse subdisciplines of psychology (e.g., cognitive psychology, personality psychology) and interdisciplinary areas of research (e.g., sports science).
Metabolic adaptations in a range‐expanding arthropod

Despite an increasing number of studies documenting life-history evolution during range expansions or shifts, we lack a mechanistic understanding of the underlying physiological processes. In this explorative study, we used a metabolomics approach to study physiological changes associated with the recent range expansion of the two-spotted spider mite (Tetranychus urticae). Mite populations were sampled along a latitudinal gradient from range core to edge and reared under benign common garden conditions for two generations. Using Gas Chromatography-Mass Spectrometry (GC-MS), we obtained metabolic population profiles, which showed a gradual differentiation along the latitudinal gradient, indicating (epi)genetic changes in the metabolome in association with range expansion. These changes seemed not related with shifts in the mites’ energetic metabolism, but rather with differential use of amino acids. Particularly, more dispersive northern populations showed lowered concentrations of several essential and non-essential amino acids, suggesting a potential downregulation of metabolic pathways associated with protein synthesis.
Enhancing students' activity in electrical engineering through Web and social networks

The paper explores Web technology, specifically social networking, which supports students' activity to enhance acquisition of Electrical Engineering disciplines. The results of the three-year study of the institutional learning management system, the thematic-oriented site, and the social network are presented. It was found that management of the learning content that combines various Internet services provides a suitable technology for students, being the social leverage to share and generate knowledge and experience.
Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish

ABSTRACT Protein tyrosine phosphatases (PTPs) are involved in hematopoiesis, but the function of many PTPs is not well characterized in vivo. Here, we have identified Ptpn9a, an ortholog of human PTPN9, as a crucial regulator of erythroid cell development in zebrafish embryos. ptpn9a, but not ptpn9b, was expressed in the posterior lateral plate mesoderm and intermediate cell mass – two primitive hematopoietic sites during zebrafish embryogenesis. Morpholino-mediated knockdown of ptpn9a caused erythrocytes to be depleted by inhibiting erythroid cell maturation without affecting erythroid proliferation and apoptosis. Consistently, both dominant-negative PTPN9 (with mutation C515S) and siRNA against PTPN9 inhibited erythroid differentiation in human K562 cells. Mechanistically, depletion of ptpn9 in zebrafish embryos in vivo or in K562 cells in vitro increased phosphorylated STAT3, and the hyper-phosphorylated STAT3 entrapped and prevented the transcription factors GATA1 and ZBP-89 (also known as ZNF148) from regulating erythroid gene expression. These findings imply that PTPN9 plays an important role in erythropoiesis by disrupting an inhibitory complex of phosphorylated STAT3, GATA1 and ZBP-89, providing new cellular and molecular insights into the role of ptpn9a in developmental hematopoiesis.
Conformational Analysis of the DFG-Out Kinase Motif and Biochemical Profiling of Structurally Validated Type II Inhibitors

Structural coverage of the human kinome has been steadily increasing over time. The structures provide valuable insights into the molecular basis of kinase function and also provide a foundation for understanding the mechanisms of kinase inhibitors. There are a large number of kinase structures in the PDB for which the Asp and Phe of the DFG motif on the activation loop swap positions, resulting in the formation of a new allosteric pocket. We refer to these structures as “classical DFG-out” conformations in order to distinguish them from conformations that have also been referred to as DFG-out in the literature but that do not have a fully formed allosteric pocket. We have completed a structural analysis of almost 200 small molecule inhibitors bound to classical DFG-out conformations; we find that they are recognized by both type I and type II inhibitors. In contrast, we find that nonclassical DFG-out conformations strongly select against type II inhibitors because these structures have not formed a large enough allosteric pocket to accommodate this type of binding mode. In the course of this study we discovered that the number of structurally validated type II inhibitors that can be found in the PDB and that are also represented in publicly available biochemical profiling studies of kinase inhibitors is very small. We have obtained new profiling results for several additional structurally validated type II inhibitors identified through our conformational analysis. Although the available profiling data for type II inhibitors is still much smaller than for type I inhibitors, a comparison of the two data sets supports the conclusion that type II inhibitors are more selective than type I. We comment on the possible contribution of the DFG-in to DFG-out conformational reorganization to the selectivity.