gebhart/patrepeval huggingface dataset:
Structure and Dynamics of a DNA.cntdot.RNA Hybrid Duplex with a Chiral Phosphorothioate Moiety: NMR and Molecular Dynamics with Conventional and Time-Averaged Restraints (1995)

The three-dimensional structure of two thiophosphate-modified DNA.RNA hybrid duplexes d(GCTATAApsTGG).r(CCAUUAUAGC), one with R-thiophosphate chirality and one with S-thiophosphate chirality, have been determined by restrained molecular dynamics simulations (rMD). As the two yielded almost identical results, a description of results can be presented in the singular. The conformational flexibility of this hybrid has been investigated by employing time-averaged constraints during the molecular dynamics simulations (MD-tar). A set of structural restraints, comprising 322 precise interproton distance constraints obtained by a complete relaxation matrix analysis of the 2D NOE intensities as well as J coupling constants obtained from quantitative simulations of DQF-COSY cross-peaks in deoxyriboses, was reported in our previous paper [González, C., Stec, W., Kobylanska, A., Hogrefe, R. I., Reynolds, M., & James, T. L. (1994) Biochemistry 33, 11062-11072]. Multiple conformations of the deoxyribose moieties were evident from the scalar coupling constant analysis. Accurate distance constraints, obtained from complete relaxation matrix analysis, yielded a time-averaged solution structure via conventional restrained molecular dynamics which is not compatible with the experimental J coupling constants (root-mean-square deviation in J value approximately 2 Hz). However, vicinal coupling constant information can be reproduced when time-averaged constraints are used during the molecular dynamics calculations instead of the conventional restraints (Jrms approximately 0.6 Hz). MD-tar simulations also improve the NMR R factors. This improvement is more evident in the DNA than in the RNA strand, where no indication of conformational flexibility had been obtained. Analysis of the MD-tar trajectories confirms that deoxyriboses undergo pucker transitions between the S and N domain, with the major conformer in the S domain. The ribose moieties in the RNA strand, however, remain in the N domain during the entire simulation. Conformations of deoxyriboses in the intermediate domain near O4'-endo are obtained when the average structure is calculated with conventional NMR restraints. Since these conformations cannot account for the experimental J coupling information, and they only appear in a very low population in the MD-tar ensemble, we conclude that intermediate E sugar puckers are artifacts produced by the attempt to fit all the structural constraints simultaneously when in reality more than one conformer is present. Most structural features of the duplex remain the same in the average structure and in the MD-tar ensemble, e.g., the minor groove width, exhibiting an intermediate value compared with those of canonical A- and B-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct genomic fluorescent on-line sequencing and analysis usingin vitroamplification of DNA (1989)

In vitro amplification of genomic DNA and total RNA, as well as recombinant DNA, using one fluorescently labelled and one unlabelled primer during amplification, together with on-line analysis of the products on the EMBL fluorescent DNA sequencer, is described. Further is reported direct sequencing of fluorescently labelled amplified probes by solid-phase chemical degradation, without subcloning and purification steps involved. At present up to 350 bases in 4 hours are determined with this technique. The fluorescent dye and its bond to the oligonucleotide are stable during the amplification cycles, and do not interfere with the enzymatic polymerization. High sensitivity of the detection device, down to 10(-18) moles, corresponding to less than 10(6) molecules makes possible analyses of the non-radioactive amplified probes after only 10 amplification cycles, starting with about 5 x 10(4) copies of recombinant DNA.
A high-performance end system architecture for real-time CORBA (1997)

Many application domains (e.g., avionics, telecommunications, and multimedia) require real-time guarantees from the underlying networks, operating systems, and middleware components to achieve their quality of service (QoS) requirements. In addition to providing end-to-end QoS guarantees, applications in these domains must be flexible and reusable. Requirements for flexibility and reusability motivate the use of object-oriented middleware like the Common Object Request Broker Architecture (CORBA). However, the performance of current CORBA implementations is not yet suited for hard real-time systems (e.g., avionics) and constrained latency systems (e.g., teleconferencing). This article describes the architectural features and optimizations required to develop real-time ORB end systems that can deliver end-to-end QoS guarantees to applications. While some operating systems, networks, and protocols now support real-time scheduling, they do not provide integrated solutions. The main thrust of this article is that advances in real-time distributed object computing can be achieved only by systematically pinpointing performance bottlenecks; optimizing the performance of networks, ORB end systems, common services, and applications; and simultaneously integrating techniques and tools that simplify application development.
Performance Test Results of an Integrated GPS/MEMS Inertial Navigation Package (2004)

This paper describes the design, operation and performance test results of a miniature, low cost integrated GPS/inertial navigation system (INS) designed for use in UAV or UGV guidance systems. The system integrates a miniaturized commercial GPS with a low grade Micro-Electro-Mechanical (MEMS) inertial measurement unit (IMU). The MEMS IMU is a small self-contained package (< 1 cu inch) and includes a triad of accelerometers and gyroscopes with additional sensors integrated for temperature compensation and baro pressure altitude aiding. The raw IMU data is provided through a serial interface to a processor board where the inertial navigation solution and integrated GPS/inertial Kalman filter is generated. The GPS/Inertial software integration is performed using NAVSYS’ modular InterNav software product. This allows integration with different low cost GPS chips sets or receivers and also allows the integrated GPS/inertial navigation solution to be embedded as an application on a customer’s host computer. This modular, object oriented architecture facilitates integration of the miniature MEMS GPS/INS navigation system for embedded navigation applications. Test results are presented in this paper showing the performance of the integrated MEMS GPS/INS navigation system when used to perform guidance for a small Unmanned Ground Vehicle (UGV). Data is provided showing the position, velocity and attitude accuracy when operating with GPS aiding and also for periods where GPS dropouts occur and alternative navigation update sources are used to bound the MEMS inertial navigation error growth.
An Efficient Three‐Step Synthesis of Cyclopenta[b]pyrans via 2‐Donor‐Substituted Fischer Ethenylcarbenechromium Complexes (2005)

A wide range of cyclopenta[b]pyrans 4 has been synthesized in a one-pot reaction by treatment of different 2-donorsubstituted ethenylcarbenechromium complexes 2 with alkynes in THF in moderate to excellent yields (41-90 % for 14 out of 25 examples). The starting materials 2 are readily available in good to excellent yields (76-99 % for 25 out of 36 examples) by Michael addition of amines, alcohols and thiols, respectively, to the corresponding alkynylcarbenechromium complexes 1. Due to their 10 pi-electrons in a cross-conjugated bicyclic system, cyclopenta[b]pyrans have been termed pseudoazulenes, as they indeed have similar UV/Vis-spectroscopic properties.
A benchmark for Affymetrix GeneChip expression measures (2004)

We have developed a graphical tool to evaluate summaries of Affymetrix probe level data. Plots and summary statistics offer a picture of how an expression measure performs in several important areas. This picture facilitates the comparison of competing expression measures and the selection of methods suitable for a specific investigation. The key is a benchmark data set consisting of a dilution study and a spike-in study. Because the truth is known for these data, we can identify statistical features of the data for which the expected outcome is known in advance. Those features highlighted in our suite of graphs are justified by questions of biological interest and motivated by the presence of appropriate data.
Photooxidation of Methane over TiO2 (2004)

Abstract Fourier‐transform infrared spectroscopy has been employed to investigate the adsorption and photo‐oxidation of CH 4 over powdered TiO 2 . The interaction between the CH 4 and TiO 2 surface is weak. It is found that no CH 4 molecules are adsorbed on the surface at 35 °C in a vacuum. Under UV irradiation, CH 4 decomposes to form CO (a) , CO 2(g) , H20 (a) , and HCOO (a) in the presence of O 2 . The photoreaction rate is retarded and only small amounts of CO (a) and HCOO (a) are formed in the absence of O 2 . It is observed that the oxygen atoms of O 2 are incorporated into these photoproducts as 18 O 2 is used. The major 18 O‐containing products are C 18 O (a) , C 18 O 2(g) , H 2 18 O (a) , HC 16 O 18 O (a) , and HC 18 O 18 O (a) after 180 min UV irradiation. However, the extent of 18 O incorporating into the adsorbed formate is dependent on UV irradiation time. In the early stage of UV irradiation HC 16 O 16 O (a) is the major formate form indicating the involvement of TiO 2 lattice oxygens for its formation, but HC 18 O 18 O (a) becomes the major one after 180 min indicating the involvement of 18 O 2 . Formate on TiO 2 further photodecomposes to CO 2(g) , but not to CO (a) . CO (a) formation is directly from CH 4 photodecomposition with the participation of TiO 2 lattice oxygens and O 2 .
Human mast cell tryptase activates single-chain urinary-type plasminogen activator (pro-urokinase) (1994)

Human lung mast cell tryptase is a trypsin-like serine proteinase that is stored in mast cell granules and released by activated mast cells. Here we report that mast cell tryptase is a potent activator of single-chain urinary-type plasminogen activator (scu-PA, or prourokinase), the zymogen form of urinary-type plasminogen activator (u-PA). Activation was complete within 75 min using an enzyme:substrate molar ratio of 1:50 and was accompanied by cleavage of scu-PA at Lys158-Ile159, generating active two-chain u-PA. The reaction was dependent on enzyme concentration and obeyed Michaelis-Menten kinetics. Kinetic constants calculated for scu-PA activation by mast cell tryptase are Km = 34 microM, Vmax = 3.6 pmol of u-PA/min, and kcat = 0.08 s-1. These data suggest that tryptase from tumor-associated mast cells may participate in the activation of scu-PA.
Expert Systems for AT&T Switched Network Maintenance (1988)

As AT&T's telecommunications network becomes increasingly sophisticated and complex, advanced operations systems capabilities are needed to provision, manage, and maintain the network. To meet this need, artificial intelligence concepts are being incorporated into operations systems. This paper focuses on an expert system for switched circuit operations that builds on AT&T's Testing Operations Provisioning Administration System (TOPAS). The TOPAS Expert System (TOPAS-ES) is a real-time, distributed, multitasking expert system for switched circuit network maintenance that uses the diagnostic knowledge of experts in network maintenance to analyze network problems and locate faults.
Cancer Pharmacogenomics: Powerful Tools in Cancer Chemotherapy and Drug Development (2005)

Interindividual differences in tumor response and normal tissue toxicities are consistently observed with most chemotherapeutic agents or regimens. While many clinical variables have been associated with drug responses (e.g., age, gender, diet, drug-drug interactions), inherited variations in drug disposition (metabolism and transport) genes and drug target genes also likely contribute to the observed variability in cancer treatment outcome. Pharmacogenomic studies aim to elucidate the genetic bases for interindividual differences and to use such genetic information to predict the safety, toxicity, and/or efficacy of drugs. There exist several clinically relevant examples of the utility of pharmacogenomics that associate specific genetic polymorphisms in drug metabolizing enzymes (e.g., TPMT, UGT1A1, DPD), drug transporters (MDR1), and drug target enzymes (TS) with clinical outcomes in patients treated with commonly prescribed chemotherapy drugs, such as 5-fluorouracil and irinotecan (Camptosar; Pfizer Pharmaceuticals; New York, NY http://www.pfizer.com). Techniques to discover and evaluate the functional significance of these polymorphisms have evolved in recent years and may soon be applied to clinical practice and clinical trials of currently prescribed anticancer drugs as well as new therapeutic agents. This review discusses the current and future applications of pharmacogenomics in clinical cancer therapy and cancer drug development.
20 Splicing of Precursors to mRNAs by the Spliceosomes (1999)

The splicing of precursors to mRNAs occurs in two steps, both involving single transesterification reactions (Fig. 1). The first step generates a 2′ – 5′ bond at the branch site upstream of the 3′ splice site and a free 3′ hydroxyl group on the 5′ exon. The resulting lariat RNA intermediate, with its slow migration in gels, is the most common assay for splicing in vitro. In the second step, attack of the 3′ hydroxyl on the phosphodiester bond at the 3′ splice site displaces the lariat intron with a 3′ hydroxyl group and results in joining of the two exons. The bimolecular nature of the intermediate in splicing indicated that the reaction must occur within a stable splicing body or spliceosome. Surprisingly, assembly and functioning of the spliceosome requires approximately 100 polypeptides and five small nuclear RNAs (snRNAs), not considering gene-specific RNA-binding factors. There are two distinct types of spliceosomes in most cells. The major class or U2-type spliceosome is universal in eukaryotes, whereas the minor class or U12-type spliceosome may not be present in some organisms. The evolutionary relationship of these two spliceosomes is uncertain. The sequence specificity for the splicing of introns must be encoded within the gene. In vertebrate genes, particularly for U2-type introns, the sequence specificity for splicing is not determined solely by the consensus sequences at the intron boundaries but is more broadly distributed within the gene. In contrast, the consensus sequences of the introns in the yeast Saccharomyces cerevisiae are generally adequate to specify...
Effect of Pyocyanin on a Crude-Oil-Degrading Microbial Community (2004)

Pseudomonas aeruginosa is an n-alkane degrader that is frequently isolated from petroleum-contaminated sites and produces factors that enhance its competitiveness and survival in many environments. In this study, one such factor, pyocyanin, has been detected in an oil-degrading culture containing P. aeruginosa and is a redox-active compound capable of inhibiting microbial growth. To examine the effects of pyocyanin further, an oil-degrading culture was grown with and without 9.5 microM pyocyanin and microbial community structure and oil degradation were monitored for 50 days. Denaturing gradient gel electrophoresis (DGGE) analysis of cultures revealed a decrease in the microbial community diversity in the pyocyanin-amended cultures compared to that of the unamended cultures. Two members of the microbial community in pure culture exhibited intermediate and high sensitivities to pyocyanin corresponding to intermediate and low levels of activity for the antioxidant enzymes catalase and superoxide dismutase, respectively. Another member of the community that remained constant in the DGGE gels over the 50-day culture incubation period exhibited no sensitivity to pyocyanin, corresponding to a high level of catalase and superoxide dismutase when examined in pure culture. Pyocyanin also affected the overall degradation of the crude oil. At 50 days, the culture without pyocyanin had decreased polycyclic aromatic hydrocarbons compared to the pyocyanin-amended culture, with a specific reduction in the degradation of dibenzothiophenes, naphthalenes, and C(29) and C(30) hopanes. This study demonstrated that pyocyanin influenced the diversity of the microbial community and suggests the importance of understanding how interspecies interactions influence the degradation capability of a microbial community.
Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock (2004)

In the present study, we used glucocorticoid-induced tumor necrosis factor (TNF) receptor family gene knockout (GITR-KO) mice to evaluate a possible role of GITR on the pathogenesis of splanchnic artery occlusion (SAO) shock, which was induced in mice by clamping the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the lipid peroxidation in the ileum of the SAO-shocked, GITR wild-type (WT) mice after reperfusion. The absence of GITR significantly reduced the lipid peroxidation in the intestine. SAO-shocked WT mice developed a significant increase of ileum tissue, TNF-alpha, and myeloperoxidase activity and marked histological injury. SAO shock was also associated with a significant mortality (5% survival at 24 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin, intercellular adhesion molecule 1 (ICAM-1), and E-selectin. The intensity and degree of P-selectin, E-selectin, and ICAM-1 were markedly reduced in tissue section from SAO-shocked, GITR-KO mice. SAO-shocked, GITR-KO mice also showed a significant reduction of the TNF-alpha production and neutrophil infiltration into the reperfused intestine, an improved histological status of the reperfused tissues, and an improved survival. Taken together, our results clearly demonstrate that GITR plays an important role in the ischemia and reperfusion injury and put forward the hypothesis that modulation of GITR expression may represent a novel and possible strategy.
One strategy for cell and gene therapy: Harnessing the power of adult stem cells to repair tissues (2003)

Most recent evidence suggests that the process of tissue repair is driven by stem-like cells that reside in multiple tissues but are replenished by precursor cells from bone marrow. Among the candidates for the reparative cells are the adult stem cells from bone marrow referred to as either mesenchymal stem cells or marrow stromal cells (MSCs). We recently found that after MSCs were replated at very low densities to generate single-cell-derived colonies, they did not exit a prolonged lag period until they synthesized and secreted considerable quantities of Dickkopf-1, an inhibitor of the canonical Wnt signaling pathway. We also found that when the cells were cocultured with heat-shocked pulmonary epithelial cells, they differentiated into epithelial cells. Most of the MSCs differentiated without evidence of cell fusion but up to one-quarter underwent cell fusion with the epithelial cells. A few also underwent nuclear fusion. The results are consistent with the interesting possibility that MSCs and similar cells repair tissue injury by three different mechanisms: creation of a milieu that enhances regeneration of endogenous cells, transdifferentiation, and perhaps cell fusion.
Overcharge protection of lithium-ion batteries with phenothiazine redox shuttles (2021)

Overcharge protection of Li-ion batteries with a variety of phenothiazine derivatives.
The effect of atenolol, a p!‐adrenergic antagonist, on nocturnal plasma melatonin secretion: Evidence for a dose‐response relationship in humans (1997)

Nathan PJ, Maguire KP, Burrows GD, Norman T.R. The effect of atenolol, a β 1 ‐adrenergic antagonist, on nocturnal plasma melatonin secretion: Evidence for a dose‐response relationship in humans. J. Pineal Res. 1997; 23:131–135. © Munksgaard, Copenhagen Abstract Pineal β 1 ‐adrenergic receptors are involved in the regulation of melatonin secretion. The involvement of β 1 adrenergic receptors has been demonstrated by the ability of acute administration ofβ‐antagonists to suppress the nocturnal rise of circulating melatonin and its urinary metabolite 6‐sulphatoxymelatonin (aMT6s). The present study was undertaken to examine the relationship between increasing doses of atenolol and nocturnal plasma melatonin concentrations. Six healthy subjects participated in the study for a period of 5 weeks. Subjects were administered placebo, 12.5, 25, 37.5, and 50 mg doses of atenolol in a randomized single blind design. Each dose was separated by a 1 week washout period. Blood samples were collected at regular intervals from 19.00 hr to 06.00 hr. Repeated measures analysis of variance showed a dose‐dependent decrease in plasma melatonin concentrations ( P &lt; 0.01). A Student Newman‐Keuls post hoc test indicated significant differences between placebo and all doses of atenolol ( P &lt; 0.05). The results demonstrate a dose‐dependent relationship between β 1 ‐receptor blockade and suppression of nocturnal plasma melatonin in humans.
Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations (2016)

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*). In vitro functional studies further supported the putative role of these novel T-ALL genes in driving transformation. U2AF1 p.R35L was shown to induce aberrant splicing of downstream target genes, and shRNA knockdown of MED12 and USP9X was shown to confer resistance to apoptosis following T-ALL relevant chemotherapy drug treatment in Jurkat leukemia cells. Interestingly, nearly 60% of novel candidate driver events were identified among immature T-ALL cases, highlighting the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment.