Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Exenatide Once Weekly Versus Metformin, Pioglitazone, and Sitagliptin Used as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

OBJECTIVE To test the safety and efficacy of exenatide once weekly (EQW) compared with metformin (MET), pioglitazone (PIO), and sitagliptin (SITA) over 26 weeks, in suboptimally treated (diet and exercise) drug-naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients were randomized to subcutaneous (SC) EQW 2.0 mg + oral placebo (n = 248), MET 2,000 mg/day + SC placebo (n = 246), PIO 45 mg/day + SC placebo (n = 163), or SITA 100 mg/day + SC placebo (n = 163) for 26 weeks. MET and PIO therapies were increased to maximum-tolerated dosages. Injections with EQW or placebo were administered weekly, while oral medication or placebo was administered daily. RESULTS Baseline characteristics were as follows: 59% men, 67% Caucasian, mean age 54 years, HbA1c 8.5%, fasting serum glucose 9.9 mmol/L, body weight 87.0 kg, and diabetes duration 2.7 years. HbA1c reductions (%) at 26 weeks (least-squares means) with EQW versus MET, PIO, and SITA were −1.53 vs. −1.48 (P = 0.620), −1.63 (P = 0.328), and −1.15 (P < 0.001), respectively. Weight changes (kg) were −2.0 vs. −2.0 (P = 0.892), +1.5 (P < 0.001), and −0.8 (P < 0.001), respectively. Common adverse events were as follows: EQW, nausea (11.3%) and diarrhea (10.9%); MET, diarrhea (12.6%) and headache (12.2%); PIO, nasopharyngitis (8.6%) and headache (8.0%); and SIT, nasopharyngitis (9.8%) and headache (9.2%). Minor (confirmed) hypoglycemia was rarely reported. No major hypoglycemia occurred. CONCLUSIONS EQW was noninferior to MET but not PIO and superior to SITA with regard to HbA1c reduction at 26 weeks. Of the agents studied, EQW and MET provided similar improvements in glycemic control along with the benefit of weight reduction and no increased risk of hypoglycemia.
Serotonin-induced brain glycogenolysis in rainbow trout (Oncorhynchus mykiss)

SUMMARY In this study, we evaluated the serotonin-mediated control of cerebral glycogen levels in the rainbow trout, Oncorhynchus mykiss. Intracerebroventricular (i.c.v.) administration of serotonin (5-HT) to normoglycemic trout (time and dose response) decreased glycogen levels in the brain and increased brain glycogen phosphorylase activity (time response). In hypoglycemic fish (that had been fasted for 5 and 10 days), there was a time-dependent decrease in brain glycogen levels; under these conditions, i.c. v. administration of 5-HT also reduced the brain glycogen content in fish that had been fasted for 5 days. In fish with local cerebral hypoglycemia (induced by 2-DG administration), the glycogen levels decreased and, as above, i.c. v. administration of 5-HT also lowered the glycogen content. In hyperglycemic fish, 5-HT did not affect glycogen levels. Administration of receptor agonists 5-HT1A (8-OH-DPAT), 5-HT1B (anpirtoline and CP93129) or 5-HT2 (α-m-5-HT) decreased the brain glycogen levels. This effect was antagonized by the administration of receptor antagonists 5-HT1A (WAY100135 and NAN190), 5-HT1B (NAS181) and 5-HT2B/C (SB206553). Administration of the receptor agonists (±)-DOI (5-HT2A/2C), m-CPP (5-HT2B/2C), BW723C86 (5-HT2B) and WAY 161503 (5-HT2C) led to decreases in the levels of brain glycogen. We found that 5-HT is involved in the modulation of brain glycogen homeostasis in the rainbow trout, causing a glycogenolytic effect when fish are in a normoglycemic or hypoglycemic state, but not when they are in a hyperglycemic state. 5-HT1A, 5-HT1B, 5HT2B and 5-HT2C-like receptors appeared to be involved in the glycogenolytic action of 5-HT, although the effect mediated by 5-HT1A or 5-HT1B was apparently stronger.
A rapid method for the isolation of functional thymus‐derived murine lymphocytes

A rapid method is described for effectively removing immunoglobulin‐bearing cells from either primed or unprimed mouse spleen and lymph node cell suspensions. Incubation of cell suspensions in nylon wool columns for 45 min at 37 °C resulted in a 9 to 100‐fold depletion of immunoglobulin‐bearing cells and a complementary 1.5 to 2‐fold enrichment of T cells in the column effluent populations.
Novel CDKL 5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy ( CDKL 5 / cyclin-dependent kinase-like 5 protein / early-onset epileptic encephalopathy / early-onset seizure variant of Rett syndrome )

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Received November 28, 2015. Accepted January 15, 2016. This work was supported by the grants UNCE 204011/12, RVOVFN64165/2012, and NT 13120-4/2012. Corresponding author: Daniela Záhoráková, Department of Pae­ diatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, Building E4, 128 08 Prague 2, Czech Republic. Phone: (+420) 224967758; Fax: (+420) 224967099; e-mail: da niela.zahorakova@lf1.cuni. cz Abbreviations: ATP – adenosine triphosphate, CDKL5 – cyclin­ dependent kinase­like 5 protein, EEG – electroencephalogram, HGMD – human gene mutation database, HRM – high­resolution melting, IVF – in vitro fertilization, MeCP2 – methyl-CpG-bind­ ing protein 2, MAP – mitogen-activated protein, MLPA – multi­ plex ligation-dependent probe amplification, NES – nuclear ex­ port signal, NLS – nuclear localization signal, PCR – polymerase chain reaction, RTT – Rett syndrome, XCI – X­chromosome in­ activation. Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation-dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c. 902_977+29del105, and c. 1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.
Amputation and prosthesis as definitive treatment in congenital absence of the fibula.

Sixty-two instances of congenital absence of the fibula occurring in forty-eight patients are reported. The transition of treatment from the conservative approach of correction of deformity, using plaster casts, bracing, platform braces, and built-up shoes, to the more radical approach of amputation and prosthesis is presented. End-bearing stumps are recommended for both boys and girls because of the utility of the stump, with or without the prosthesis; the more stable prosthetic gait with end-bearing; and the minimum prosthetic upkeep of these prostheses with few moving parts. Absence of complications in the stump is an important feature in these end-bearing amputations, with no revisions reported to date. The procedure of earlier amputation and fitting of a prosthesis is recommended.
iQ: An Efficient and Flexible Queue-Based Simulation Framework

Conventional system simulators are readily used by computer architects to design and evaluate their processor designs. These simulators provide reasonable levels of accuracy and execution detail but suffer from long simulation latencies and increased implementation complexity. In this work we propose iQ, a queue-based modeling technique that targets design space exploration and optimization studies at the core component level. iQ emulates processor elements by abstracting the implementation details into modular components composed of queue structures, delay parameters, probabilistic driven message generation and event control. Its easy reconfigurability makes iQ a highly flexible and powerful processor simulator. We have used iQ to build an Ivy Bridge and a Core 2 Duo processor model and have validated them against real hardware running SPEC CPU2006 Int achieving average error rates of 9.55% and 8.93%.
Exploring Corporate Lobbyists' Perceptions of Prospective Coalition Partners in Brussels

Using original data from a survey conducted in 2012, we apply theoretical insights from the literature on strategic alliances to explore Brussels-based corporate lobbyists' perceptions of prospective political partners. We find these perceptions to be driven primarily by strategic considerations. We also uncover instances where the size and nationality of respondents' firms influence their partner evaluations. Surprisingly, we find little evidence that respondents' assessments of lobbying partners are shaped by EU institutional arrangements. Whilst extant literature suggests information and relationships are important preconditions for successful EU lobbying, we expose the specific circumstances when seeking access to these—and other political resources—that can influence corporate lobbyists' perceptions of their partners. Combined, our findings respond to a concern that scholars of interest coalitions focus on why firms lobby in coalitions whilst overlooking how they select their lobbying partners.
Cost-Effectiveness of Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy: A Randomized Study

Background Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN. Methods Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs). Results Mean total costs from a healthcare perspective were $8935 for HARP and $8650 for LDN (P=0.25). Mean total costs from a societal perspective were $16,357 for HARP and $16,286 for LDN (P=0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P=0.65). LDN resulted in a gain of 0.005 QALYs. Conclusions Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN.
The Caspian Sea

Given the fact that the DRASTIC index is ineffective in addressing the saltwater uprising issue in coastal plains, in the present study, three factors including land use, distance to shoreline, and differences between groundwater and sea level were added to the DRASTIC index. The proposed modification to DRASTIC was validated using the measured electrical conductivity (EC) data gathered from groundwater monitoring wells throughout the Talesh Plain. The results showed that the coefficient of correlation between the map of EC over the region and the modified DRASTIC was 0.52, while for the original DRASTIC, the coefficient was 0.45, thereby implying a stronger relationship between EC and the modified DRASTIC in the Talesh Plain. Sensitivity analysis also showed that DRASTIC and the modified DRASTIC were the most sensitive to, respectively, depth to groundwater (D) and land use (Lu). According to the single-parameter sensitivity analysis results, depth to water table and net recharge were the most effective parameters in DRASTIC, whereas the modified DRASTIC was the most sensitive to land use and depth to groundwater. It could be concluded that modifying the DRASTIC index would result in decreasing the area of very high and high vulnerable classes, and the area classified as low and moderate vulnerable could be increased.
Location in distributed ad-hoc wireless sensor networks

Evolving networks of ad-hoc wireless sensing nodes rely heavily on the ability to establish position information. The algorithms presented herein rely on range measurements between pairs of nodes and the a priori coordinates of sparsely located anchor nodes. Clusters of nodes surrounding anchor nodes cooperatively establish confident position estimates through assumptions, checks, and iterative refinements. Once established, these positions are propagated to more distant nodes, allowing the entire network to create an accurate map of itself. Major obstacles include overcoming inaccuracies in range measurements as great as /spl plusmn/50%, as well as the development of initial guesses for node locations in clusters with few or no anchor nodes. Solutions to these problems are presented and discussed, using position error as the primary metric. Algorithms are compared according to position error, scalability, and communication and computational requirements. Early simulations yield average position errors of 5% in the presence of both range and initial position inaccuracies.
Acetylation-Deacetylation of the Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-related Factor 2) Regulates Its Transcriptional Activity and Nucleocytoplasmic Localization*

Activation of Nrf2 by covalent modifications that release it from its inhibitor protein Keap1 has been extensively documented. In contrast, covalent modifications that may regulate its action after its release from Keap1 have received little attention. Here we show that CREB-binding protein induced acetylation of Nrf2, increased binding of Nrf2 to its cognate response element in a target gene promoter, and increased Nrf2-dependent transcription from target gene promoters. Heterologous sirtuin 1 (SIRT1) decreased acetylation of Nrf2 as well as Nrf2-dependent gene transcription, and its effects were overridden by dominant negative SIRT1 (SIRT1-H355A). The SIRT1-selective inhibitors EX-527 and nicotinamide stimulated Nrf2-dependent gene transcription, whereas resveratrol, a putative activator of SIRT1, was inhibitory, mimicking the effect of SIRT1. Mutating lysine to alanine or to arginine at Lys588 and Lys591 of Nrf2 resulted in decreased Nrf2-dependent gene transcription and abrogated the transcription-activating effect of CREB-binding protein. Furthermore, SIRT1 had no effect on transcription induced by these mutants, indicating that these sites are acetylation sites. Microscope imaging of GFP-Nrf2 in HepG2 cells as well as immunoblotting for Nrf2 showed that acetylation conditions resulted in increased nuclear localization of Nrf2, whereas deacetylation conditions enhanced its cytoplasmic rather than its nuclear localization. We posit that Nrf2 in the nucleus undergoes acetylation, resulting in binding, with basic-region leucine zipper protein(s), to the antioxidant response element and consequently in gene transcription, whereas deacetylation disengages it from the antioxidant response element, thereby resulting in transcriptional termination and subsequently in its nuclear export.
Effect of hyperglycemia on in vitro tumor uptake of tritiated FDG, thymidine, L-methionine and L-leucine.

UNLABELLED We have previously demonstrated in vitro and in vivo that tumor uptake of FDG is markedly diminished by acute hyperglycemia. This in vitro study was designed to determine if tumor uptake of PET tracers (FDG, thymidine, L-methionine and L-leucine) is affected by acute or chronic hyperglycemia. METHODS Human ovarian adenocarcinoma (HTB 77 IP3) cells were grown in media containing 100 or 300 mg/dl of glucose. At 7, 20, 38, 51 and 72 days after initial culture, uptake of 3H-labeled FDG, thymidine, L-methionine and L-leucine into the cells was determined in the presence of 100 or 300 mg/dl of glucose. RESULTS With acute hyperglycemia (300 mg/dl of glucose), the percent decreases in uptake of FDG, thymidine, methionine and leucine were 76.7%, 22.4%, 7.4% and 11.1%, respectively, as compared to assay at 100 mg/dl of glucose (mean day 51 and day 72 data). Significant decreases were observed in FDG and thymidine uptake with acute hyperglycemia (p < 0.0005). When cells grown at 300 mg/dl of glucose for 51 and 72 days were assayed at 100 mg/dl of glucose, the mean percent decreases in uptake of these tracers were 10.4%, 7.8%, 8.0% and 16.8%, respectively, as compared to cells grown and assayed at 100 mg/dl of glucose. No significant decrease was observed in tumor uptake of these tracers, except for leucine (p < 0.05). CONCLUSION These human adenocarcinoma cells do not significantly change FDG uptake with chronic hyperglycemia while acute hyperglycemia markedly reduces uptake of FDG and thymidine. Neither methionine nor leucine uptake is significantly affected by acute hyperglycemia. To optimally evaluate tumor biology by PET, the fasting state seems necessary for FDG and thymidine studies, while methionine or leucine appears more suitable for hyperglycemic patients.
Prognostics and health management of electronics

In this paper, damage pre-cursors based residual life computation approach for various package elements to prognosticate electronic systems prior to appearance of any macro-indicators of damage has been presented. In order to implement the system-health monitoring system, precursor variables or leading indicators-of-failure have been identified for various package elements and failure mechanisms. Model-algorithms have been developed to correlate precursors with impending failure for computation of residual life. Package elements investigated include, first-level interconnects, dielectrics, chip interconnects, underfills and semiconductors. Examples of damage proxies include, phase growth rate of solder interconnects, intermetallics, normal stress at chip interface, and interfacial shear stress.
Internal Transfer Learning for Improving Performance in Human Action Recognition for Small Datasets

Human action recognition nowadays plays a key role in varieties of computer vision applications. Many computer vision methods focus on algorithms designing classifiers with handcrafted features which are complex and inflexible. In this paper, we focus on the human action recognition problem and utilize 3D convolutional neural networks to automatically extract both spatial and temporal features for classification. Specifically, in order to address the training problems with small data sets, we propose an internal transfer learning strategy adapted to this framework, by incorporating the sub-data classification method into transfer learning. We evaluate our method on several data sets and obtain promising results. With the proposed strategy, the performance of human action recognition is improved obviously.
Development of New Reactivators of Tabun Inhibited Acetylcholinesterase and the Evaluation of Their Efficacy by in Vitro and in Vivo Methods

Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. It differs from other highly toxic organophosphates by its chemical structure and by the fact that tabun-inhibited acetylcholinesterase is extraordinarily difficult to reactivate. The antidotal treatment of tabun acute poisonings still represents a serious problem and the development of new, more effective AChE reactivators to achieve the satisfactorily effective antidotal treatment of acute poisonings with tabun still represents very important goal. Since 2003, we have prepared around 200 new AChE reactivators. Their potency to reactivate tabun-inhibited acetylcholinesterase has been subsequently evaluated using our in vitro screening test. Afterwards, promising compounds were selected and kinetic parameters and reactivation constants were determined. Then, the best reactivators were subjected to the in vivo studies (toxicity test, the evaluation of therapeutical, reactivating and neuroprotective efficacy). According to the results obtained, all new oximes tested in vivo (K027, K048, K074, K075) were found to be relatively effective to eliminate acute lethal toxic effects in tabun poisoned mice and reactivate tabun-inhibited acetylcholinesterase in rats poisoned with tabun. In addition, newly developed oximes (K027, K048, K074, K075) combined with atropine seem to be sufficiently effective antidotes for a significant decrease in tabun-induced neurotoxicity in the case of sublethal poisonings of rats although they are not able to eliminate tabun-induced neurotoxicity completely. Our results also confirm that the reactivating efficacy of oximes evaluated by the methods in vitro correlates not only with the potency of oximes in reactivating tabun-inhibited acetylcholinesterase in vivo but also with the ability of oximes to protect rats poisoned with supralethal doses of tabun.
3D EIT image reconstruction with GREIT

Most applications of thoracic EIT use a single plane of electrodes on the chest from which a transverse image ‘slice’ is calculated. However, interpretation of EIT images is made difficult by the large region above and below the electrode plane to which EIT is sensitive. Volumetric EIT images using two (or more) electrode planes should help compensate, but are little used currently. The Graz consensus reconstruction algorithm for EIT (GREIT) has become popular in lung EIT. One shortcoming of the original formulation of GREIT is its restriction to reconstruction onto a 2D planar image. We present an extension of the GREIT algorithm to 3D and develop open-source tools to evaluate its performance as a function of the choice of stimulation and measurement pattern. Results show 3D GREIT using two electrode layers has significantly more uniform sensitivity profiles through the chest region. Overall, the advantages of 3D EIT are compelling.