gebhart/patrepeval huggingface dataset:
Interaction between endogenously produced carbon monoxide and nitric oxide in regulation of renal afferent arterioles (2006)

Heme oxygenases (HO-1 and HO-2) catalyze the conversion of heme to carbon monoxide (CO), iron, and biliverdin. CO causes vasorelaxation via stimulation of soluble guanylate cyclase (sGC) and/or activation of calcium-activated potassium channels. Because nitric oxide (NO) exerts effects via the same pathways, we tested the interaction between CO and NO on rat afferent arterioles (AAs) using the blood-perfused juxtamedullary nephron preparation. AAs were superfused with either tricarbonyldichlororuthenium (II) dimer, known as CO releasing molecule (CORM-2), 10 micromol/l CO solution, or 15 micromol/l chromium mesoporphyrin (CrMP, HO inhibitor). AAs were also superfused with 1 mmol/l N(omega)-nitro-L-arginine (L-NNA) to inhibit NO synthase (NOS) or 10 micromol/l 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one to inhibit sGC, and then CrMP was superfused during NOS inhibition or sGC inhibition. Treatment with 150 and 300 micromol/l CORM-2 or with CO (10 micromol/l) significantly dilated AAs (22.0 +/- 0.9 and 22.8 +/- 0.9 vs. 18.3 +/- 0.9 microm, n = 5, P < 0.05; and 26.0 +/- 1.4 vs. 18.8 +/- 0.7 microm, n = 5, P < 0.05). In untreated vessels, HO inhibition did not alter AA diameter (17.5 +/- 0.7 vs. 17.2 +/- 0.6 microm, n = 7, P > 0.05); however, during inhibition of NO production, which constricted arterioles to 14.6 +/- 1.2 microm, n = 6, P < 0.05, concurrent HO inhibition led to further vasoconstriction (11.7 +/- 1.6 microm, n = 6, P < 0.05). CORM-2 attenuated the L-NNA-induced vasoconstriction. Inhibition of sGC caused significant constriction (15.7 +/- 0.4 vs. 18.8 +/- 0.4 microm, n = 6, P < 0.05). HO inhibition during sGC inhibition did not cause further change in AAs (15.5 +/- 0.7 microm, n = 6). We conclude that endogenously produced CO does not exert a perceptible influence on AA diameter in the presence of intact NO system; however, when NO production is inhibited, CO serves as an important renoprotective reserve mechanism to prevent excess afferent arteriolar constriction.
Engineering of a functional human NADH-dependent cytochrome P450 system (2001)

A functional human NADH-dependent cytochrome P450 system has been developed by altering the cofactor preference of human NADPH cytochrome P450 reductase (CPR), the redox partner for P450s. This has been achieved by a single amino acid change of the conserved aromatic amino acid Trp-676, which covers the re-side of the FAD isoalloxazine ring in the nicotinamide-binding site. Of the mutations made, the substitution of Trp-676 with alanine (W676A) resulted in a functional NADH-dependent enzyme, which catalyzed the reduction of cytochrome c and ferricyanide as well as facilitated the metabolism of 7-ethoxyresorufin by CYP1A2. Kinetic analysis measuring cytochrome c activity revealed that the NADH-dependent k(cat) of W676A is equivalent (90%) to the NADPH-dependent k(cat) of the wild-type enzyme, with W676A having an approximately 1,000-fold higher specificity for NADH. The apparent K(M)(NADPH) and K(M)(NADH) values of W676A are 80- and 150-fold decreased, respectively. In accordance with structural data, which show a bipartite binding mode of NADPH, substitution of Trp-676 does not affect 2'-AMP binding as seen by the inhibition of both wild-type CPR and the W676A mutant. Furthermore, NADPH was a potent inhibitor of the W676A NADH-dependent cytochrome c reduction and CYP1A2 activity. Overall, the results show that Trp-676 of human CPR plays a major role in cofactor discrimination, and substitution of this conserved aromatic residue with alanine results in an efficient NADH-dependent cytochrome P450 system.
Theoretical and experimental study of the fundamental mode propagation phase temperature sensitivity in air-core photonic-bandgap fibers (2005)

We measured the dependence on temperature of the phase of the fundamental mode of air-core photonic-bandgap fibers. The expected weaker dependence (factor of 3.6-5.2) compared to conventional fibers is quantitatively well explained by a simple model.
Time Delay Estimation in Room Acoustic Environments: An Overview (2006)

Time delay estimation has been a research topic of significant practical importance in many fields (radar, sonar, seismology, geophysics, ultrasonics, hands-free communications, etc.). It is a first stage that feeds into subsequent processing blocks for identifying, localizing, and tracking radiating sources. This area has made remarkable advances in the past few decades, and is continuing to progress, with an aim to create processors that are tolerant to both noise and reverberation. This paper presents a systematic overview of the state-of-the-art of time-delay-estimation algorithms ranging from the simple cross-correlation method to the advanced blind channel identification based techniques. We discuss the pros and cons of each individual algorithm, and outline their inherent relationships. We also provide experimental results to illustrate their performance differences in room acoustic environments where reverberation and noise are commonly encountered.
Study on Dual-Tutor System of Postgraduates (2015)

Due to the expansion of postgraduate enrollment scale in recent years, the traditional single-tutor system has been unable to meet the needs of higher education and social development. In order to ensure the quality of graduate education and cultivate high-tech talents with innovation ability, dual-tutor system of postgraduates arises at the critical moment. This article mainly introduces the connotation of dual-tutor system, its practical significance and value, and the important principles to be obeyed in the process of implementation.
Liquid-vapor equilibria and interfacial properties of n-alkanes and perfluoroalkanes by molecular simulation (2010)

A molecular dynamics study is presented to assess the performance of a united-atom model in the prediction of liquid-vapor interfacial properties for short-chain perfluoroalkanes and their alkane counterparts. In particular, the ability of this model to discriminate between the surface-energy values of these two types of compounds was investigated over a wide temperature range corresponding to the liquid-vapor region. Comparisons with available experimental data and surface-tension predictions given by other force-field parameterizations, including those based on the more computationally demanding all-atom method, were performed to gauge the viability of this model. It was found that the model used in this study captures qualitatively the expected behavior of surface energy between alkanes and perfluoroalkanes and yields values that are in excellent agreement with experimental data, especially in the high-temperature limit as the critical temperature is approached.
Using GUI Run-Time State as Feedback to Generate Test Cases (2007)

This paper presents a new automated model-driven technique to generate test cases by using feedback from the execution of a "seed test suite" on an application under test (AUT). The test cases in the seed suite are designed to be generated automatically and executed very quickly. During their execution, feedback obtained from the AUT's run-time state is used to generate new, "improved" test cases. The new test cases subsequently become part of the seed suite. This "anytime technique" continues iteratively, generating and executing additional test cases until resources are exhausted or testing goals have been met. The feedback-based technique is demonstrated for automated testing of graphical user interfaces (GUIs). An existing abstract model of the GUI is used to automatically generate the seed test suite. It is executed; during its execution, state changes in the GUI pinpoint important relationships between GUI events, which evolve the model and help to generate new test cases. Together with a reverse- engineering algorithm used to obtain the initial model and seed suite, the feedback-based technique yields a fully automatic, end-to-end GUI testing process. A feasibility study on four large fielded open-source software (OSS) applications demonstrates that this process is able to significantly improve existing techniques and help identify/report serious problems in the OSS. In response, these problems have been fixed by the developers of the OSS in subsequent versions.
Importance of Conformational Variability in Protein Engineering of Subtilisin (1987)

Enzymes are highly specific catalysts. The nature of this specificity is believed to result from structural and electrostatic complementarity between the enzyme and its substrate. The serine protease, subtilisin, is being extensively studied as a model system to explore the effects of single amino acid substitutions on its structure and function (1). The gene for Bacillus amyloliquefaciens subtilisin has been expressed and secreted in B. subtilis (2). A site-directed mutagenesis scheme, cassette mutagenesis (3), has been used to produce a series of subtilisin variants that are more resistant to oxidants (4), and have altered stability (5), specificity, and specific activity. Here we report the analysis of the functional and structural effects of single amino acid substitutions at position 166 where a glycine is found in all the sequences of naturally occurring subtilisins from a number of Bacillus species. All substitutions have measurable activity. Substitutions of asparagine or lysine for glycine
Studies on tertiary amine oxides. LXXV. Reactions of aromatic N-oxides with Meldrum's acid in the presence of acetic anhydride. (1982)

Reactions of quinoline, lepidine, 4-chloro-, 4-methoxy- and 4-morpholino-quinoline 1-oxides (1a-e) with Meldrum's acid (2) in acetic anhydride smoothly occurred at room temperature to afford the corresponding 5-(2-quinolyl)-Meldrum's aoids (3a-e) in good yields. On the other hand, when the reactions were carried out in dimethylformamide containing 1.2 eq acetic anhydride the N-ylides (4a-e) were produced ; while the reactions of 1a, d, e yielded only N-ylides 4a, d, e, 4b, c were formed along with smaller amounts of 3b, c in the reactions of 1b, c. 3-Bromoquinoline 1-oxide (1f) gave only the N-ylide (4f) and isoquinoline 2-oxide (6) gave the 1-substituted isoquinoline (7) independently of the reaction conditions. Further, 5-alkyl-Meldrum's acids (8a-c) also reacted readily with 1a in acetic anhydride to give the corresponding 2-substituted quinolines (9a-c) in good yields. Heating of 3a, b with conc. hydrochloric acid, 10% hydrochloric acid or methanol containing 10% hydrogen chloride gave 2-methylquinolines (10a, b), 2-quinolineacetic acids (11a, b) or their methyl esters (12a, b), respectively. Similarly, 9a-c afforded 2-alkylquinolines (14a-c) in good yields upon being refluxed with conc. hydrochloric acid.
Uptake of cell‐penetrating peptides in yeasts (2005)

The uptake of different cell-penetrating peptides (CPPs) in two yeast species, Saccharomyces cerevisiae and Candida albicans, was studied using fluorescence HPLC-analyses of cell content. Comparison of the ability of penetratin, pVEC and (KFF)(3)K to traverse the yeast cell envelope shows that the cellular uptake of the peptides varies widely. Moreover, the intracellular degradation of the CPPs studied varies from complete stability to complete degradation. We show that intracellular degradation into membrane impermeable products can significantly contribute to the fluorescence signal. pVEC displayed highest internalizing capacity, and considering its stability in both yeast species, it is an attractive candidate for further studies.
Can Accurate Predictions Improve Video Streaming in Cellular Networks? (2015)

Existing video streaming algorithms use various estimation approaches to infer the inherently variable bandwidth in cellular networks, which often leads to reduced quality of experience (QoE). We ask the question: "If accurate bandwidth prediction were possible in a cellular network, how much can we improve video QoE?". Assuming we know the bandwidth for the entire video session, we show that existing streaming algorithms only achieve between 69%-86% of optimal quality. Since such knowledge may be impractical, we study algorithms that know the available bandwidth for a few seconds into the future. We observe that prediction alone is not sufficient and can in fact lead to degraded QoE. However, when combined with rate stabilization functions, prediction outperforms existing algorithms and reduces the gap with optimal to 4%. Our results lead us to believe that cellular operators and content providers can tremendously improve video QoE by predicting available bandwidth and sharing it through APIs.
Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics (2007)

Autoimmune diseases are often marked by autoantibodies binding to self antigens. However, many healthy persons also manifest autoantibodies that bind to self antigens, known as natural autoantibodies. In order to characterize natural autoantibodies present at birth, we used an antigen microarray (antigen chip) to analyze informatically (with clustering algorithms and correlation mapping) the natural IgM, IgA, and IgG autoantibody repertoires present in 10 pairs of sera from healthy mothers and the cords of their newborn babies. These autoantibodies were found to bind to 305 different, mostly self, molecules. We report that in utero, humans develop IgM and IgA autoantibodies to relatively uniform sets of self molecules. The global patterns of maternal IgM autoantibodies significantly diverged from those at birth, although certain reactivities remained common to both maternal and cord samples. Because maternal IgG antibodies (unlike IgM and IgA) cross the placenta, maternal and cord IgG autoantibodies showed essentially identical reactivities. We found that some self antigens that bind cord autoantibodies were among the target self antigens associated with autoimmune diseases later in life. Thus, the obviously benign autoimmunity prevalent at birth may provide the basis for the emergence of some autoimmune diseases relatively prevalent later in life.
Synthetic sites for transcription termination and a functional comparison with tryptophan operon termination sites in vitro. (1981)

Termination of transcription by Escherichia coli RNA polymerase in vitro appears to depend primarily on two structural features of the termination site--a G+C-rich region of dyad symmetry and a series of terminal uridine residues in the transcript. To determine whether these two features are sufficient to specify rho-independent termination in vitro, we have introduced new sequences within a tryptophan (trp) operon structural gene to create two sites with these characteristics. Transcription with wild-type RNA polymerase in vitro demonstrates that discrete termination occurs at one of these new sites, although at a low level. Use of the mutant RNA polymerase rpo203, which is more sensitive to certain weak terminators than is the wild-type enzyme, increases termination at both sites. We have compared the activity of our synthetic terminators with those of several termination sites in the E. coli trp operon. Under normal conditions of transcription in vitro, termination becomes more efficient with an increase in the length of the stem in the RNA hairpin or an increase in the number of consecutive uridine residues. Transcription with the rpo203 polymerase and with ribonucleotide analogs gives changes consistent with these general trends. These results support a model for termination involving separate but essential roles for the RNA hairpin and the stretch of uridines in the transcript.
Impaired Bottom-Up Effective Connectivity Between Amygdala and Subgenual Anterior Cingulate Cortex in Unmedicated Adolescents with Major Depression: Results from a Dynamic Causal Modeling Analysis (2015)

Major depressive disorder (MDD) is a significant contributor to lifetime disability and frequently emerges in adolescence, yet little is known about the neural mechanisms of MDD in adolescents. Dynamic causal modeling (DCM) analysis is an innovative tool that can shed light on neural network abnormalities. A DCM analysis was conducted to test several frontolimbic effective connectivity models in 27 adolescents with MDD and 21 healthy adolescents. The best neural model for each person was identified using Bayesian model selection. The findings revealed that the two adolescent groups fit similar optimal neural models. The best across-groups model was then used to infer upon both within-group and between-group tests of intrinsic and modulation parameters of the network connections. First, for model validation, within-group tests revealed robust evidence for bottom-up connectivity, but less evidence for strong top-down connectivity in both groups. Second, we tested for differences between groups on the validated parameters of the best model. This revealed that adolescents with MDD had significantly weaker bottom-up connectivity in one pathway, from amygdala to sgACC (p=0.008), than healthy controls. This study provides the first examination of effective connectivity using DCM within neural circuitry implicated in emotion processing in adolescents with MDD. These findings aid in advancing understanding the neurobiology of early-onset MDD during adolescence and have implications for future research investigating how effective connectivity changes across contexts, with development, over the course of the disease, and after intervention.
Molecular genetics of yeast :a practical approach (1994)

1: Procedures for isolating yeast DNA for different purposes. 2: Construction of cloning and expression vectors. 3: Cosmid cloning of yeast DNA. 4: The construction and use of cDNA libraries for genetic selections. 5: Pulsed field gel electrophoresis. 6: Plasmid shuffling and mutant isolation. 7: Ty insertional mutagenesis. 8: High efficiency transformation with lithium acetate. 9: Measurement of transcription. 10: Measurement of mRNA stability. 11: Production of foreign proteins at high level. 12: Cell-free translation of natural and synthetic mRNAs. 13: Virus-like particles: Ty retrotransposons. 14: The K1 killer toxin: molecular and genetic applications to secretion and cell surface assembly. 15: Immuno-electron microscopy. 16: Industrial Saccharomyces yeasts
Dual Fatty Acid Elongase Complex Interactions in Arabidopsis (2016)

Very long chain fatty acids (VLCFAs) are involved in plant development and particularly in several cellular processes such as membrane trafficking, cell division and cell differentiation. However, the precise role of VLCFAs in these different cellular processes is still poorly understood in plants. In order to identify new factors associated with the biosynthesis or function of VLCFAs, a yeast multicopy suppressor screen was carried out in a yeast mutant strain defective for fatty acid elongation. Loss of function of the elongase 3 hydroxyacyl-CoA dehydratase PHS1 in yeast and PASTICCINO2 in plants prevents growth and induces cytokinesis defects. PROTEIN TYROSIN PHOSPHATASE-LIKE (PTPLA) previously characterized as an inactive dehydratase was able to restore yeast phs1 growth and VLCFAs elongation but not the plant pas2-1 defects. PTPLA interacted with elongase subunits in the Endoplasmic Reticulum (ER) and its absence induced the accumulation of 3-hydroxyacyl-CoA as expected from a dehydratase involved in fatty acid (FA) elongation. However, loss of PTPLA function increased VLCFA levels, an effect that was dependent on the presence of PAS2 indicating that PTPLA activity repressed FA elongation. The two dehydratases have specific expression profiles in the root with PAS2, mostly restricted to the endodermis, while PTPLA was confined in the vascular tissue and pericycle cells. Comparative ectopic expression of PTPLA and PAS2 in their respective domains confirmed the existence of two independent elongase complexes based on PAS2 or PTPLA dehydratase that are functionally interacting.
RING1 Is Associated with the Polycomb Group Protein Complex and Acts as a Transcriptional Repressor (1997)

The Polycomb (Pc) protein is a component of a multimeric, chromatin-associated Polycomb group (PcG) protein complex, which is involved in stable repression of gene activity. The identities of components of the PcG protein complex are largely unknown. In a two-hybrid screen with a vertebrate Pc homolog as a target, we identify the human RING1 protein as interacting with Pc. RING1 is a protein that contains the RING finger motif, a specific zinc-binding domain, which is found in many regulatory proteins. So far, the function of the RING1 protein has remained enigmatic. Here, we show that RING1 coimmunoprecipitates with a human Pc homolog, the vertebrate PcG protein BMI1, and HPH1, a human homolog of the PcG protein Polyhomeotic (Ph). Also, RING1 colocalizes with these vertebrate PcG proteins in nuclear domains of SW480 human colorectal adenocarcinoma and Saos-2 human osteosarcoma cells. Finally, we show that RING1, like Pc, is able to repress gene activity when targeted to a reporter gene. Our findings indicate that RING1 is associated with the human PcG protein complex and that RING1, like PcG proteins, can act as a transcriptional repressor.
Stability indicating HPTLC method for determination of Metopimazine in pharmaceutical formulation and human plasma (2014)

Accurate, selective and sensitive stability indicating high performance thin layer chromatographic (HPTLC) method was developed and validated for determination of Metopimazine (MPZ) in presence of its degradation products; including the oxidative degradation product (Deg I) and the alkaline hydrolysis degradation product (Deg II; formerly reported as acid metabolite). The proposed method was applied for analysis of MPZ in pure form, pharmaceutical formulation (tablets) and human plasma over the concentration range of 0.4–1.4 μg band−1 with accuracy of mean percentage recovery 100.10 ± 0.941. The method depends on separation of MPZ from its degradation products on HPTLC silica gel 60 F254 plates using chloroform–methanol–ammonia (12:2:0.1, by volume) as developing system followed by densitometric measurement of bands at 254 nm. The method was validated according to ICH guidelines. The degradation products were well resolved from the pure drug with significantly different Rf values (MPZ, Rf = 0.58, Deg I, Rf = 0.35 and Deg II, Rf = 0.03). The results obtained by the proposed method were statistically compared to the reported HPTLC method, and there was no significant difference between them regarding both accuracy and precision; indicating the ability of the proposed method to be used for routine analysis of drug product.
Inhibition of bladder carcinoma angiogenesis, stromal support, and tumor growth by halofuginone. (1999)

We have previously demonstrated that halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. We investigated the effect of halofuginone on transplantable and chemically induced mouse bladder carcinoma. In both systems, oral administration of halofuginone resulted in a profound anticancerous effect, even when the treatment was initiated at advanced stages of tumor development. Although halofuginone failed to prevent proliferative preneoplastic alterations in the bladder epithelium, it inhibited further progression of the chemically induced tumor into a malignant invasive stage. Histological examination and in situ analysis of the tumor tissue revealed a marked decrease in blood vessel density and in both collagen alpha1(I) and H19 gene expression. H19 is regarded as an early marker of bladder carcinoma. The antiangiogenic effect of halofuginone was also demonstrated by inhibition of microvessel formation in vitro. We attribute the profound antitumoral effect of halofuginone to its combined inhibition of the tumor stromal support, vascularization, invasiveness, and cell proliferation.