Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and Genetic Studies of the Initiation of Human Rhinovirus 2 RNA Replication: Purification and Enzymatic Analysis of the RNA-Dependent RNA Polymerase 3Dpol

ABSTRACT The replication of human rhinovirus 2 (HRV2), a positive-stranded RNA virus belonging to the Picornaviridae, requires a virus-encoded RNA polymerase. We have expressed in Escherichia coli and purified both a glutathioneS-transferase fusion polypeptide and an untagged form of the HRV2 RNA polymerase 3Dpol. Using in vitro assay systems previously described for poliovirus RNA polymerase 3Dpol(J. B. Flanegan and D. Baltimore, Proc. Natl. Acad. Sci. USA 74:3677–3680, 1977; A. V. Paul, J. H. van Boom, D. Filippov, and E. Wimmer, Nature 393:280–284, 1998), we have analyzed the biochemical properties of the two different enzyme preparations. HRV2 3Dpol is both template and primer dependent, and it catalyzes two types of synthetic reactions in the presence of UTP, Mn2+, and a poly(A) template. The first consists of an elongation reaction of an oligo(dT)15 primer into poly(U). The second is a protein-priming reaction in which the enzyme covalently links UMP to the hydroxyl group of tyrosine in the terminal protein VPg, yielding VPgpU. This precursor is elongated first into VPgpUpU and then into VPg-linked poly(U), which is identical to the 5′ end of picornavirus minus strands. The two forms of the enzyme are about equally active both in the oligonucleotide elongation and in the VPg-primed reaction. Various synthetic mutant VPgs were tested as substrates in the VPg uridylylation reaction.
Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation

Hypoparathyroidism, mental retardation and facial dysmorphism (HRD) is a fatal developmental disease caused by mutations in tubulin-specific chaperone E (TBCE). A mouse Tbce mutation causes progressive motor neuronopathy. To dissect the functions of TBCE and the pathogenesis of HRD, we generated mutations in Drosophila tbce, and manipulated its expression in a tissue-specific manner. Drosophila tbce nulls are embryonic lethal. Tissue-specific knockdown and overexpression of tbce in neuromusculature resulted in disrupted and increased microtubules, respectively. Alterations in TBCE expression also affected neuromuscular synapses. Genetic analyses revealed an antagonistic interaction between TBCE and the microtubule-severing protein Spastin. Moreover, treatment of muscles with the microtubule-depolymerizing drug nocodazole implicated TBCE as a tubulin polymerizing protein. Taken together, our results demonstrate that TBCE is required for the normal development and function of neuromuscular synapses and that it promotes microtubule formation. As defective microtubules are implicated in many neurological and developmental diseases, our work on TBCE may offer novel insights into their basis.
Disassociation of Muscle Insulin Signaling and Insulin-Stimulated Glucose Uptake during Endotoxemia

Lipopolysaccharide (LPS) elicits a strong immune response, which leads to the release of inflammatory cytokines. Increased cytokine production has been shown to impair insulin-mediated glucose disposal. LPS can alter other factors, such as muscle blood flow and insulin signaling in the myocyte,that can influence glucose disposal. We hypothesize that LPS induced impairments in cardiovascular function contribute to the associated impairments in insulin action in vivo. Male wild-type C57BL/6J mice had a catheter implanted in the jugular vein for infusions and the carotid artery for sampling 5 days prior to the hyperinsulinemic-euglycemic clamp. Mice were treated with vehicle, low-(1 ug/gBW) or high-dose (10 ug/gBW) LPS 4 hours prior to the clamp. Muscle glucose uptake (MGU) was assessed using [2-14C] deoxyglucose. While both low- and high-dose LPS inhibited insulin-stimulated MGU compared to vehicle-treated mice, the impairment was more significant with the high-dose treatment (∼25% in soleus and ∼70% in both gastrocnemius and vastus lateralis). Interestingly, insulin signaling through the PI3-kinase pathway in the muscle was not affected by this treatment suggesting that the decrease in MGU is not directly due to impairments in muscle insulin action. Echocardiography demonstrated that high-dose LPS treatment significantly decreased stroke volume (∼30%), heart rate (∼35%), and cardiac output (∼50%). These observations were not seen with vehicle or low-dose LPS treatment. High-dose LPS treatment also significantly decreased muscle blood flow (∼70%) and whole body oxygen consumption (∼50%). Thus, in vivo acute endotoxemia does not impair insulin signaling through the PI3-kinase pathway in skeletal muscle and decreased tissue blood flow likely plays a central role in the impairment of glucose uptake in the muscle.
Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin.

Pharmacokinetic relationships have been developed to characterize a multicompartment drug distribution and elimination model which includes a saturable renal tubular reabsorption process. The derived expressions have been applied to serum concentration and urinary excretion data obtained after rapid intravenous administration of riboflavin to man and dog. The mathematical relationships and experimental data demonstrate the dependence of renal clearance on the serum concentration of the drug and on urine flow rate. The results of this study indicate that the renal excretion of riboflavin, like that of several other water-soluble vitamins, involves saturable tubular reabsorption as well as tubular secretion.
P3-166 THE USE OF QUANTITATIVE EEG AS A POTENTIAL BIOMARKER FOR COGNITIVE ENHANCERS

marker of neurodegeneration). All measures were related to clinical disease progression. Standardized plasma samples were collected from 318 subjects (mean age1⁄476.1 [6 3.5]; MMSE1⁄428.7 [60.95]; FCSRT1⁄446.05 [62.0]; APOE genotype: ε2/ε2 [0.3%], ε2/ε3 [13.9%], ε2/ε4 [1.3%], ε3/ε3 [67.5%], ε3/ε4 [16.1%], ε4/ε4 [0.9%]). These samples were investigated for NFL, Ab1-40, Ab142, and tau protein by using the ultrasensitive Single-Molecule Array (Simoa) technology. Results:All data and results will be presented at the conference. Conclusions:We present a comprehensive panel of novel plasma candidate biomarkers reflecting different pathophysiological mechanisms during the preclinical stage of AD. This will help characterize initiated pathophysiological mechanisms of action driving amyloid accumulation and AD progression during the preclinical stage and support early disease detection and identification of molecular mechanisms as targets for therapeutic intervention.
Making Neural QA as Simple as Possible but not Simpler

Recent development of large-scale question answering (QA) datasets triggered a substantial amount of research into end-to-end neural architectures for QA. Increasingly complex systems have been conceived without comparison to simpler neural baseline systems that would justify their complexity. In this work, we propose a simple heuristic that guides the development of neural baseline systems for the extractive QA task. We find that there are two ingredients necessary for building a high-performing neural QA system: first, the awareness of question words while processing the context and second, a composition function that goes beyond simple bag-of-words modeling, such as recurrent neural networks. Our results show that FastQA, a system that meets these two requirements, can achieve very competitive performance compared with existing models. We argue that this surprising finding puts results of previous systems and the complexity of recent QA datasets into perspective.
Static Hedging of Geometric Average Asian Options with Standard Options

In this article, we first establish a theorem that represents the price of an Asian option in terms of standard European options with a shorter term and different strikes. Then using Gauss–Hermite numerical integration, we discretize our theorem so as to use Monte Carlo simulation to examine the error of the static hedging under the Black–Scholes model and the Merton jump-diffusion model. For ease of comparison, we also provide the error of the dynamic hedging. The numerical results show that the static hedging strategy performs better than the dynamic one under both models.
Frequency adaptive phase-sequence separation method based on a generalized delayed signal cancelation method

A new frequency adaptive method for detecting the Fundamental Frequency Positive Sequence (FFPS) voltage vector is proposed in this paper. The analytical developments demonstrate that the proposed method allows obtaining the FFPS αβ voltage vector canceling the effects of fundamental-frequency negative-sequence components, as well as the influences of all harmonic voltage vectors up to 24th order and also dc offsets. A high bandwidth output synchronous reference frame phase locked loop (SRF-PLL) is then used for obtaining the amplitude and position of the fundamental frequency vector. A scheme for making the proposed method adaptive to input frequency variations is also presented. The proposed method performance is verified through simulations and experiments.
Functional invariant natural killer T-cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy

Invariant natural killer T cells recognize glycolipid antigens such as α-galactosylceramide presented by CD1d. In preclinical models of B-cell malignancies, α-galactosylceramide is an adjuvant to tumor vaccination, enhancing tumor-specific T-cell responses and prolonging survival. However, numerical and functional invariant natural killer T-cell defects exist in patients with some cancers. Our aim was to assess this axis in patients with chronic lymphocytic leukemia. The numbers of circulating invariant natural killer T cells and the expression of CD1d on antigen-presenting cells were evaluated in patients with chronic lymphocytic leukemia and age-matched controls. Cytokine profile and in vitro proliferative capacity were determined. Patient- and control-derived invariant natural killer T-cell lines were generated and characterized, and allogeneic and autologous responses to α-galactosylce-ramide-treated leukemia cells were assessed. Absolute numbers and phenotype of invariant natural killer T cells were normal in patients with untreated chronic lymphocytic leukemia, and cytokine profile and proliferative capacity were intact. Chemotherapy-treated patients had reduced numbers of invariant natural killer T cells and myeloid dendritic cells, but α-galactosylceramide-induced proliferation was preserved. Invariant natural killer T-cell lines from patients lysed CD1d-expressing targets. Irradiated α-galactosylceramide-treated leukemic cells elicited allogeneic and autologous invariant natural killer T-cell proliferation, and α-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor. In conclusion, the invariant natural killer T-cell and CD1d axis is fundamentally intact in patients with early-stage chronic lymphocytic leukemia and, despite reduced circulating numbers, function is retained in fludarabine-treated patients. Immunotherapies exploiting the adjuvant effect of α-galactosylceramide may be feasible.
Habitat of the Corn Leafhopper (Hemiptera: Cicadellidae) During the Dry (Winter) Season in Mexico

Abstract Although the corn leafhopper Dalbulus maidis (DeLong and Wolcott) is the most important vector of maize pathogens in Latin America, little is known about how and where it overwinters (passes the dry season), particularly in Mexico. The objectives of this study were (1) to monitor the abundance of D. maidis adults throughout the dry season in maize and maize-free habitats and (2) to determine where and how D. maidis adults, exposed or nonexposed to the maize pathogen Spiroplasma kunkelii Whitcomb, overwinter in a maize-free habitat. Work for the first objective was done during the two consecutive dry seasons of 1999–2000 and 2000–2001; the second objective was done during the dry seasons of 2003–2004 and 2005–2006. During the dry winter seasons, D. maidis was prevalent as long as maize was present in irrigated areas. The leafhopper was found in 52 of the 58 irrigated maize fields sampled in Mexico at the end of the dry seasons of 1999–2000 and 2000–2001. However, leafhopper adults were not found in nonirrigated maize-free habitats at high elevation during the dry winter season (February, March, and April), although leafhopper adults were prevalent on perennial wild grasses in January after maize harvest. Additional experiments revealed, however, that corn leafhopper adults, although few in number, survived the entire dry season in these nonirrigated maize-free fields. Also, no detectable difference in survival existed between leafhoppers exposed and those not exposed to S. kunkelli during the two dry seasons in the maize-free habitat.
Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes

A significant proportion of endogenously processed CD8+ T cell epitopes are derived from newly synthesized proteins and rapidly degrading polypeptides (RDPs). It has been hypothesized that the generation of rapidly degrading polypeptides and CD8+ T cell epitopes from these RDP precursors may be influenced by the efficiency of protein translation. Here we address this hypothesis by using the Epstein-Barr virus–encoded nuclear antigen 1 protein (EBNA1), with or without its internal glycine-alanine repeat sequence (EBNA1 and EBNA1ΔGA, respectively), which display distinct differences in translation efficiency. We demonstrate that RDPs constitute a significant proportion of newly synthesized EBNA1 and EBNA1ΔGA and that the levels of RDPs produced by each of these proteins directly correlate with the translation efficiency of either EBNA1 or EBNA1ΔGA. As a consequence, a higher number of major histocompatibility complex–peptide complexes can be detected on the surface of cells expressing EBNA1ΔGA, and these cells are more efficiently recognized by virus-specific cytotoxic T lymphocytes compared to the full-length EBNA1. More importantly, we also demonstrate that the endogenous processing of these CD8+ T cell epitopes is predominantly determined by the rate at which the RDPs are generated rather than the intracellular turnover of these proteins.
Performance of pultruded GFRP composites under tropical climate

Glass fibre reinforced polymer (GFRP) is a composite material, which consists of polyester thermosetting resin as matrix and glass fibres as reinforcement. GFRP is mainly used as structural sections and as structural rehabilitation and repair material. It is observed that the current required technical and design data of pultruded GFRP sections is rather limited especially with regard to material properties and its performance in the tropical climate. Therefore, this study is conducted experimentally to investigate the engineering properties of the GFRP material and sections, and its performance to the local tropical climate. Special observations on the effects of the fibre orientations and stacking sequences in laminates are also made. Testing procedures are basically in accordance with the requirements of the American Standard of Testing and Materials (ASTM), and the British Standards (BS). There are six different fibre orientations of GFRP plates and two different fibre orientations of GFRP box sections of 6.35 mm nominal thickness with different stacking sequence selected for the test samples. They were fabricated by local manufacturer according to the commercial quality requirements. A total of 2304 GFRP samples were tested, 1 152 of the samples were exposed to the outdoor environment, while the other 1 152 samples were kept in the laboratory environment as control samples. The samples were tested for physical and mechanical performance. Among the visual observations made were the surface appearance, thickness variation and weight gain. Samples were also tested for tension, compression and in-plane shear to indicate the mechanical performance. Measurements were taken at 3,6, 12 and 24 months period of exposure to weathering. Four point bending tests were also conducted on 900 mm span of GFRP box section beams to investigate the structural performance under tropical weather. Twenty-four beams were tested for this purpose after being exposed to the outdoor environment and the other twenty-four beams were tested under controlled environment. The statistical test data were analysed using Weibull distribution. The test results showed that the GFRP material is significantly affected by tropical weather conditions. In general, surface degradation was significant after 12 months exposure due to fungal attack. Surface roughness and discoloration on the top surface of the samples were also observed with the bottom surface not affected by the exposure at all. The effect of tropical weather conditions on mechanical performance of the exposed GFRP samples was significant, but varied with fibre quantity. The reduction in flexural capacity of GFRP box beams was also observed due to weathering after a period of 24 months. Ultimately, the mechanical properties and structural beam performance with respect to the period of exposure under tropical weather was formulated and presented at the end of this study.
On the robustness of OLSR in a mobile tactical scenario in rural terrain

This paper investigates the robustness of the optimized link state routing (OLSR) protocol when used for unicast traffic in a highly dynamic military tactical scenario. The importance of the channel model in ad hoc network simulations is shown, as a radio channel model considering terrain effects and real radio transmission behaviour is employed. Results show, among other things, that using an advanced channel model has a large influence on the robustness of OLSR, compared with results obtained with a plane earth model which can produce misleading results. The robustness is evaluated for different network sizes and over different network connectivity. Different system aspects are considered, such as the link metric used by OLSR and the ability to manage small-scale fading. Results show the gain, in terms of robustness of OLSR, from utilizing some kind of diversity at the data link layer to reduce small-scale fading. Moreover, the results show the benefit of using a link metric based on information provided by the physical layer, as the fast link feedback from the physical layer is needed to handle the dynamic channel.
Loss of low-density lipoprotein utilization by regressing porcine luteal cells: effects of protein kinase C activation.

We recently reported a decline in low-density lipoprotein (LDL) uptake by regressing porcine luteal cells that correlated with diminished LDL stimulation of progesterone (P) production. The objectives of the present study were to determine 1) whether loss of LDL utilization is a specific lesion in the steroidogenic pathway in regressing luteal cells and 2) whether in vitro activation of protein kinase C (PKC) in mid-cycle luteal cells acutely suppresses LDL utilization. Dispersed cells (4 x 10(4)/0.2 ml) from mid-(Days 6-10, estrus = Day 0; n = 5) or late-(Days 15-18; n = 7) cycle porcine CL were cultured in Dulbecco's Modified Eagle/F-12 medium supplemented with insulin, transferrin, sodium selenite, and aprotinin for 24 h with human (h) LDL (0-100 micrograms/ml), 22(R)-hydroxycholesterol (22[OH]-C;-0-25 micrograms/ml), or pregnenolone (0-1000 nM). P production by mid-cycle luteal cells was dose-dependently increased (p < 0.05) by LDL (up to 2.8-fold), 22(OH)-C (up to 3.2-fold), and pregnenolone (> 3-fold). In contrast, LDL (10-100 micrograms/ml) failed to stimulate P production by late-cycle luteal cells. But 22(OH)-C (up to 4-fold) and pregnenolone (> 10-fold) were as effective in promoting (p < 0.05) steroidogenesis relative to basal levels in late luteal cells as in mid-cycle cultures. The PKC activator, TPA (12-O-tetradecanoyl-phorbol-13-acetate; 10 ng/ml), inhibited (approximately 20%; p < 0.01) basal and LDL-supported steroidogenesis, but did not suppress 22(OH)-C-stimulated P secretion. (ABSTRACT TRUNCATED AT 250 WORDS)
Assessing the Value of Social-Cognitive Constructs in Career Development.

This study assessed the relative value of Bandura's (1977, 1982, 1986) self-efficacy theory and Rotter's (1966) locus of control model in predicting the career maturity of college students. A sample of 113 undergraduates (83 women and 30 men) completed a demographics questionnaire and measures of career decision-making (CDM) self-efficacy (Taylor & Betz, 1983), career locus of control (Trice, Haire, & Elliott, 1989), CDM attitudes (Crites, 1978a), and CDM skills (Super, Thompson, Lindeman, Jordaan, & Myers, 1981). Results reveal that self-efficacy theory is superior to the locus of control model in predicting the CDM attitudes of college students. Results also showed that the most powerful predictor of CDM skills among college students was their CDM attitudes. Locus of control accounted for additional variance in the CDM attitudes of the participants. Age did not enter either of the regression equations despite its significant correlation with CDM attitudes and CDM skills. (Contains 43 references and 3 data tables.) (Author/YLB) *********************************************************************** * Reproductions supplied by EDRS are the best that can be made from the original document. * ***********************************************************************
The stimulation of antral motility by erythromycin is attenuated by hyperglycemia

OBJECTIVE:Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia.METHODS:A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min.RESULTS:Intravenous erythromycin increased the amplitude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and amplitude of duodenal waves did not differ between the two blood glucose concentrations.CONCLUSIONS:Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.