gebhart/patrepeval huggingface dataset:
1,8-Diazabicyclo[5.4.0]undecene Mediated Transesterification ofp-Nitrophenyl Phosphonates: A Novel Route to Phosphono Esters (1993)

DBU (1,8-diazabicyclo[5.4.0]undecene) was found to efficiently mediate the transesterification of p-nitrophenyl (PNP) phosphonates by various alcohols. The reactions of bis-PNP phosphonates in the presence of DBU, using both primary and secondary alcohols, phenols and amines, proceed rapidly and with high yield to afford the corresponding monoalkyl/aryl mono-PNP phosphonates as sole products (1, Scheme 2). The resulting monoalkyl/aryl mono-PNP phosphonates can be further reacted with a second alcohol to give the corresponding differently disubstituted phosphonates 3, or selectively hydrolysed to yield the monoalkyl/aryl phosphonic acids 2. We have applied this chemistry to the preparation of a series of phosphono ester transition state analogues 11a-e (Scheme 3) that were used as haptens for raising catalytic antibodies.
Tumor Marker Protocols (1998)

This much-needed collection of Tumor Marker Protocols presents cutting-edge methods for the detection and discovery of new cancer markers, particularly molecular tumor markers. Each method is fully described by a hands-on expert who uses it regularly in the laboratory and has perfected it to a high degree of ready reproducibility. The book also places special emphasis on statistical considerations in the analysis of tumor markers, recent discoveries in the field of serum and tissue marker proteins, cytogenetic markers, molecular markers, and markers for the early detection of cancer. Tumor Marker Protocols offers many promising opportunities for transferring new technologies from the realm of basic science to that of clinical practice. The well-honed procedures detailed here will enable cancer researchers and clinical oncologists alike to realize the promise of these powerful new diagnostic strategies for the detection, therapy, and successful prevention of cancer
Priority rendering with a virtual reality address recalculation pipeline (1994)

Virtual reality systems are placing never before seen demands on computer graphics hardware, yet few graphics systems are designed specifically for virtural reality. An address recalculation pipeline is a graphics display controller specifically designed for use with head mounted virtual reality systems, it performs orientation viewport mapping after rendering which means the users head orientation does not need to be known accurately until less than a microsecond before the first pixel of an update frame is actually sent to the head mounted display device. As a result the user perceived latency to head rotations is minimal.
RNA Interference Reveals a Requirement for Myocyte Enhancer Factor 2A in Activity-dependent Neuronal Survival (2002)

RNA interference (RNAi) provides a powerful method of gene silencing in eukaryotic cells, including proliferating mammalian cells. However, the utility of RNAi as a method of gene knock-down in primary postmitotic mammalian neurons remained unknown. Here, we asked if RNAi might be utilized to allow the assessment of the biological function of a specific gene in the nervous system. We employed a U6 promoter-driven DNA template approach to induce hairpin RNA-triggered RNAi to characterize the role of the transcription factor myocyte enhancer factor 2A (MEF2A) in the neuronal activity-dependent survival of granule neurons of the developing rat cerebellum. We found that the expression of MEF2A hairpin RNAs leads to the efficient and specific inhibition of endogenous MEF2A protein expression in primary cerebellar granule neurons. We also found that RNAi of MEF2A reduces significantly MEF2 response element-mediated transcription in granule neurons and inhibits activity-dependent granule neuron survival. Taken together, our RNAi experiments have revealed that MEF2A plays a critical role in activity-dependent neuronal survival. In addition, our findings indicate that RNAi does operate in postmitotic mammalian neurons and thus offers a rapid genetic method of studying gene function in the development and function of the mammalian nervous system.
In vivo gene electroinjection and expression in rat liver (1996)

In vivo targeted gene transfer by non-viral vectors is subjected to anatomical constraints depending on the route of administration. Transfection efficiency and gene expression in vivo using non-viral vectors is also relatively low. We report that in vivo electropermeabilization of the liver tissue of rats in the presence of genes encoding luciferase or beta-galactosidase resulted in the strong expression of these genetic markers in rat liver cells. About 30-40% of the rat liver cells electroporated expressed the beta-galactosidase genetic marker 48 h after electroporation. The marker expression was also detected at least 21 days after transfection at about 5% of the level 48 h after electroporation. The results indicate that gene transfer by electroporation in vivo may avoid anatomical constraints and low transfection efficiency.
Probing the Structure of Single-Molecule Surface-Enhanced Raman Scattering Hot Spots (2008)

We present here a detailed study of the specific nanoparticle structures that give rise to single-molecule surface-enhanced Raman scattering (SMSERS). A variety of structures are observed, but the simplest are dimers of Ag nanocrystals. We chose one of these structures for detailed study using electrodynamics calculations and found that the electromagnetic SERS enhancement factors of 10(9) are easily obtained and are consistent with single-molecule SERS activity.
Agglomeration of oppositely charged particles in nonpolar liquids (2006)

We study the aggregation of insulating electrically charged spheres suspended in a nonpolar liquid. Regarding the van der Waals interaction as an irreversible sticking force, we are especially interested in the charge distribution after aggregation. Solving the special case of two oppositely charged particles exactly, it is shown that the surface charges either recombine or form a residual dipole, depending on the initial condition. The theoretical findings are compared to numerical results from Monte Carlo simulations.
Harness Oil and Gas Big Data with Analytics: Optimize Exploration and Production with Data-Driven Models (2014)

Use big data analytics to efficiently drive oil and gas exploration and production Harness Oil and Gas Big Data with Analytics provides a complete view of big data and analytics techniques as they are applied to the oil and gas industry. Including a compendium of specific case studies, the book underscores the acute need for optimization in the oil and gas exploration and production stages and shows how data analytics can provide such optimization. This spans exploration, development, production and rejuvenation of oil and gas assets. The book serves as a guide for fully leveraging data, statistical, and quantitative analysis, exploratory and predictive modeling, and fact-based management to drive decision making in oil and gas operations. This comprehensive resource delves into the three major issues that face the oil and gas industry during the exploration and production stages: * Data management, including storing massive quantities of data in a manner conducive to analysis and effectively retrieving, backing up, and purging data * Quantification of uncertainty, including a look at the statistical and data analytics methods for making predictions and determining the certainty of those predictions * Risk assessment, including predictive analysis of the likelihood that known risks are realized and how to properly deal with unknown risks Covering the major issues facing the oil and gas industry in the exploration and production stages, Harness Big Data with Analytics reveals how to model big data to realize efficiencies and business benefits.
Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. (1998)

The results of this study indicate that the combination of cisplatin and vinorelbine is a superior treatment when compared with single-agent cisplatin in the treatment of advanced NSCLC. Cisplatin and vinorelbine is the new standard for SWOG against which new therapies will be evaluated.
Oxazole-Based Peptide Macrocycles:  A New Class of G-Quadruplex Binding Ligands (2006)

Herein we report on the synthesis and DNA binding properties of a new class of water soluble oxazole-based peptide macrocycles that bind selectively to quadruplex DNA, with no detectable binding to duplex DNA. We have recently identified one quadruplex in the proto-oncogene c-kit that is suspected to act as a regulatory element for the expression of the c-kit gene. Here we provide the first example of a ligand binding to and stabilizing the c-kit quadruplex. Moreover, we show that these macrocycles show a preference for the c-kit quadruplex as compared to the human telomeric quadruplex.
siRNA directed against c-Src enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity1 (2004)

c-Src is a determinant of pancreatic adenocarcinoma chemoresistance and represents a potential target for therapeutic intervention.
Restoration of Wild-Type Infectivity to Human Immunodeficiency Virus Type 1 Strains Lacking nef by Intravirion Reverse Transcription (2001)

Human immunodeficiency virus type 1 (HIV-1) Nef protein exerts several effects, both on infected cells and as a virion protein, which work together to enhance viral replication. One of these activities is the ability to enhance infectivity and the formation of proviral DNA. The mechanism of this enhancement remains incompletely understood. We show that virions with nef deleted can be restored to wild-type infectivity by stimulating intravirion reverse transcription. Particle composition and measures of reverse transcriptase activity remain the same for Nef(+) and Nef(-) virions both before and after natural endogenous reverse transcription (NERT) treatment. The effect of NERT treatment on virions pseudotyped with murine leukemia virus envelope protein was similar to that on particles pseudotyped with HIV-1 envelope protein. However, virions pseudotyped with vesicular stomatitis virus G envelope protein showed no influence of Nef on NERT enhancement of infectivity. These observations suggest that Nef may function at a level prior to reverse transcription. Since NERT treatment results in partial disassembly of the viral core, we speculate that Nef may function at the level of core particle disassembly.
Injectable Polypeptide Thermogel as a Tissue Engineering System for Hepatogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells (2017)

A poly(ethylene glycol)-b-poly(l-alanine) (PEG-l-PA) hydrogel incorporating tonsil-derived mesenchymal stem cells (TMSCs), tauroursodeoxycholic acid (TUDCA), hepatocyte growth factor (HGF), and fibroblast growth factor 4 (FGF4) was prepared through thermal gelation of an aqueous polymer solution for an injectable tissue engineering application. The thermal gelation accompanied conformational changes of both PA and PEG blocks. The gel modulus at 37 °C was controlled to be 1000 Pa by using a 14.0 wt % aqueous polymer solution. The gel preserved its physical integrity during the 3D culture of the cells. TUDCA, HGF, and FGF4 were released from the PEG-l-PA hydrogel over 21 days of the 3D cell culture period. TMSCs initially exhibited a spherical shape, whereas some fibers protruded from the cells on days 14-21 of 3D culture. The injectable system exhibited pronounced expressions of the hepatic biomarkers at both mRNA and protein levels, which are significantly better than the commercially available hyaluronic acid gel. In particular, the hepatogenically differentiated cells from the TMSCs in the injectable system demonstrated hepatic biofunctions comparable to HepG2 cells for the uptakes of low density lipoproteins (52%) and indocyanine green (76%), and the production of albumin (40%) and urea (52%), which are also significantly better than the 3D-cultured cells in the commercially available hyaluronic acid gel. Our studies suggest that the PEG-l-PA thermogel incorporating TMSCs, TUDCA, and growth factors is highly promising as an in situ forming tissue engineering system.
A family of Acrp30/adiponectin structural and functional paralogs (2004)

Biochemical, genetic, and animal studies in recent years have established a critical role for the adipokine Acrp30/adiponectin in controlling whole-body metabolism, particularly by enhancing insulin sensitivity in muscle and liver, and by increasing fatty acid oxidation in muscle. We describe a widely expressed and highly conserved family of adiponectin paralogs designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs) 1-7. In the present study, we focus on mCTRP2, the mouse paralog most similar to adiponectin. At nanomolar concentrations, bacterially produced mCTRP2 rapidly induced phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, and mitogen-activated protein kinase in C2C12 myotubes, which resulted in increased glycogen accumulation and fatty acid oxidation. The discovery of a family of adiponectin paralogs has implications for understanding the control of energy homeostasis and could provide new targets for pharmacologic intervention in metabolic diseases such as diabetes and obesity.
Isolation of a specific chromosomic DNA sequence ofBacillus anthracisand its possible use in diagnosis (1996)

A 277-bp long DNA fragment, Ba813, was isolated from an avirulent Bacillus anthracis strain 7700 genomic library. Two oligonucleotides derived from the Ba813 sequence were used as primers in polymerase chain reaction tests on genomic DNA from 28 Bacillus anthracis and from 33 heterologous bacteria strains. A specific, 152-bp long DNA fragment was amplified only when Bacillus anthracis DNA was used as the target. The amplified product was analysed by non-radioactive sandwich hybridisation in microtiter plates using two oligonucleotides. The capture oligonucleotide C1 was covalently linked onto aminated wells of microtiter plates. The detection oligonucleotide D3 was labelled with biotine. The hybrid molecules were detected by avidine conjugated with alkaline phosphatase and chromogenic substrate. Amplification of Ba813 sequence may provide the basis for rapid and reliable assay for the detection and identification of Bacillus anthracis.
Both Microtubule-Stabilizing and Microtubule-Destabilizing Drugs Inhibit Hypoxia-Inducible Factor-1α Accumulation and Activity by Disrupting Microtubule Function (2005)

We have recently identified a mechanistic link between disruption of the microtubule cytoskeleton and inhibition of tumor angiogenesis via the hypoxia-inducible factor-1 (HIF-1) pathway. Based on this model, we hypothesized that other microtubule-targeting drugs may have a similar effect on HIF-1alpha. To test that hypothesis, we studied the effects of different clinically relevant microtubule-disrupting agents, including taxotere, epothilone B, discodermolide, vincristine, 2-methoxyestradiol, and colchicine. In all cases, HIF-1alpha protein, but not mRNA, was down-regulated in a drug dose-dependent manner. In addition, HIF-1alpha transcriptional activity was also inhibited by all drugs tested. To further examine whether these effects were dependent on microtubule network disruption, we tested the ability of epothilone B to inhibit HIF-1alpha protein in the human ovarian cancer cell line 1A9 and its beta-tubulin mutant epothilone-resistant subclone 1A9/A8. Our data showed that epothilone B treatment down-regulated HIF-1alpha protein in the parental 1A9 cells but had no effect in the resistant 1A9/A8 cells. These observations were confirmed by confocal microscopy, which showed impaired nuclear accumulation of HIF-1alpha in parental 1A9 cells at epothilone B concentrations that induced extensive microtubule stabilization. In contrast, epothilone B treatment had no effect on either microtubules or HIF-1alpha nuclear accumulation in the resistant 1A9/A8 cells. Furthermore, epothilone B inhibited HIF-1 transcriptional activity in 1A9 cells, as evidenced by a hypoxia response element-luciferase reporter assay, but had no effect on HIF-1 activity in the resistant 1A9/A8 cells. These data directly link beta-tubulin drug binding with HIF-1alpha protein inhibition. Our results further provide a strong rationale for testing taxanes and epothilones in clinical trials targeting HIF-1 in cancer patients.
Genetic Basis of Susceptibility to Drug-induced Liver Injury: What Have we Learned and where do we go from here? (2012)

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction that represents a major problem in pharmacotherapy, both clinically and economically. A considerable effort has been made over the past several decades to identify genetic factors that predispose to risk for DILI, and the pace of discovery has vastly increased over just the past several years. Here, we describe the major findings in DILI pharmacogenetics with an emphasis on the recent results of unbiased genome-wide association studies, and suggest some directions for future research in this area.
Multiframe deep neural networks for acoustic modeling (2013)

Deep neural networks have been shown to perform very well as acoustic models for automatic speech recognition. Compared to Gaussian mixtures however, they tend to be very expensive computationally, making them challenging to use in real-time applications. One key advantage of such neural networks is their ability to learn from very long observation windows going up to 400 ms. Given this very long temporal context, it is tempting to wonder whether one can run neural networks at a lower frame rate than the typical 10 ms, and whether there might be computational benefits to doing so. This paper describes a method of tying the neural network parameters over time which achieves comparable performance to the typical frame-synchronous model, while achieving up to a 4X reduction in the computational cost of the neural network activations.
Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia (2003)

Mandibuloacral dysplasia (MAD; OMIM 248370) is a rare, genetically and phenotypically heterogeneous, autosomal recessive disorder characterized by skeletal abnormalities including hypoplasia of the mandible and clavicles, acro-osteolysis, cutaneous atrophy and lipodystrophy. A homozygous missense mutation, Arg527His, in the LMNA gene which encodes nuclear lamina proteins lamins A and C has been reported in patients with MAD and partial lipodystrophy. We studied four patients with MAD who had no mutations in the LMNA gene. We now show compound heterozygous mutations, Phe361fsX379 and Trp340Arg, in the zinc metalloproteinase (ZMPSTE24) gene in one of the four patients who had severe MAD associated with progeroid appearance and generalized lipodystrophy. ZMPSTE24 is involved in post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A in two steps to form mature lamin A. Deficiency of Zmpste24 in mice causes accumulation of prelamin A and phenotypic features similar to MAD. The yeast homolog, Ste24, has a parallel role in processing of prenylated mating pheromone a-factor. Since human ZMPSTE24 can also process a-factor when expressed in yeast, we assessed the functional significance of the two ZMPSTE24 mutations in the yeast to complement the mating defect of the haploid MATa yeast lacking STE24 and Ras-converting enzyme 1 (RCE1; another prenylprotein-specific endoprotease) genes. The ZMPSTE24 mutant construct, Phe361fsX379, was inactive in complementing the yeast a-factor but the mutant, Trp340Arg, was partially active compared to the wild type ZMPSTE24 construct. We conclude that mutations in ZMPSTE24 may cause MAD by affecting prelamin A processing.
Intelligent document information retrieval system for determinants of medication research literature collection (1988)

The subject domain “determinants of medication” is an interesting one for information retrieval system development. Literature concerning the selling, advertising, marketing, prescribing, purchasing, and taking of medications forms a well-defined and rather small subject domain, but is scattered over a broad range of publication sources with widely varying publication practices. Furthermore, this subject domain is not well covered by any single existing medical database. An established collection of documents concerning determinants of medication forms the basis for an intelligent document retrieval system, the prototype implementation of which is underway at the University of Mississippi Department of Computer and Information Science, working in cooperation with the Department of Health Care Administration in the UM School of Pharmacy.
Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity (2002)

A novel approach for the identification of tumor antigen-derived sequences recognized by CD8(+) cytolytic T lymphocytes (CTL) consists in using synthetic combinatorial peptide libraries. Here we have screened a library composed of 3.1 x 10(11) nonapeptides arranged in a positional scanning format, in a cytotoxicity assay, to search the antigen recognized by melanoma-reactive CTL of unknown specificity. The results of this analysis enabled the identification of several optimal peptide ligands, as most of the individual nonapeptides deduced from the primary screening were efficiently recognized by the CTL. The results of the library screening were also analyzed with a mathematical approach based on a model of independent and additive contribution of individual amino acids to antigen recognition. This biometrical data analysis enabled the retrieval, in public databases, of the native antigenic peptide SSX-2(41-49), whose sequence is highly homologous to the ones deduced from the library screening, among the ones with the highest stimulatory score. These results underline the high predictive value of positional scanning synthetic combinatorial peptide library analysis and encourage its use for the identification of CTL ligands.
Super-High-Frequency SAW Resonators on AlN/Diamond (2012)

This letter describes the procedure to manufacture high-performance surface acoustic wave (SAW) resonators on AlN/diamond heterostructures working at frequencies beyond 10 GHz. In the design of SAW devices on AlN/diamond systems, the thickness of the piezoelectric layer is a key parameter. The influence of the film thickness on the SAW device response has been studied. Optimized thin films combined with advanced e-beam lithographic techniques have allowed the fabrication of one-port SAW resonators with finger width and pitch of 200 nm operating in the 10-14 GHz range with up to 36 dB out-of-band rejection.