gebhart/patrepeval huggingface dataset:
Effect of Biodiesel Composition on Engine Emissions from a DDC Series 60 Diesel Engine: Final Report; Report 2 in a Series of 6 (2003)

NREL conducted an investigation of various biodiesel fuels produced from waste oils in order to determine the effect of biodiesel source material and ester molecular structure, nitrogen oxides, and certain unregulated pollutants.
Accelerated structure-based design of chemically diverse allosteric modulators of a muscarinic G protein-coupled receptor (2016)

Design of ligands that provide receptor selectivity has emerged as a new paradigm for drug discovery of G protein-coupled receptors, and may, for certain families of receptors, only be achieved via identification of chemically diverse allosteric modulators. Here, the extracellular vestibule of the M2 muscarinic acetylcholine receptor (mAChR) is targeted for structure-based design of allosteric modulators. Accelerated molecular dynamics (aMD) simulations were performed to construct structural ensembles that account for the receptor flexibility. Compounds obtained from the National Cancer Institute (NCI) were docked to the receptor ensembles. Retrospective docking of known ligands showed that combining aMD simulations with Glide induced fit docking (IFD) provided much-improved enrichment factors, compared with the Glide virtual screening workflow. Glide IFD was thus applied in receptor ensemble docking, and 38 top-ranked NCI compounds were selected for experimental testing. In [(3)H]N-methylscopolamine radioligand dissociation assays, approximately half of the 38 lead compounds altered the radioligand dissociation rate, a hallmark of allosteric behavior. In further competition binding experiments, we identified 12 compounds with affinity of ≤30 μM. With final functional experiments on six selected compounds, we confirmed four of them as new negative allosteric modulators (NAMs) and one as positive allosteric modulator of agonist-mediated response at the M2 mAChR. Two of the NAMs showed subtype selectivity without significant effect at the M1 and M3 mAChRs. This study demonstrates an unprecedented successful structure-based approach to identify chemically diverse and selective GPCR allosteric modulators with outstanding potential for further structure-activity relationship studies.
Modular and Tunable Chemosensor Scaffold for Divalent Zinc (2003)

A modular peptide scaffold has been developed for fluorescent sensing of divalent zinc. The signaling component of the chemosensor is the chelation-sensitive fluorophore 8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline, which is prepared as the protected amino acid derivative Fmoc-Sox-OH and integrated into peptide sequences. Nineteen synthetic peptides incorporating the signaling element exhibit a range of affinities for Zn(2+) through variation of the type and number of Zn(2+) ligands, ligand arrangement and the beta-turn sequence that acts as a preorganization element between the ligands. The stoichiometry of the peptide-Zn(2+) complexes is evaluated by several criteria. The fluorescence response of these peptides to pH and various important metal ions is reported. Eleven of these sequences form only 1:1 complexes with Zn(2+) and their affinities range from 10 nM to nearly 1 microM. When used in concert, these sensors can provide Zn(2+) concentration information in a valuable range.
Evidence of Increased Glyceraldehyde-3-phosphate Dehydrogenase and Fatty Acid Synthetase Promoter Activities in Transiently Transfected Adipocytes from Genetically Obese Rats (1995)

Previous studies have shown that the adipose tissue of young genetically obese Zucker rats was characterized by a coordinate overtranscription of lipogenic genes, suggesting that the fa mutation triggers transcription factor(s) acting in common on the promoters of these genes. To test this hypothesis, we developed a system of transient transfection of rat adipocytes with constructs containing glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthetase (FAS) promoters fused to gene reporter CAT. Those transfected cells expressed high levels of promoter-driven chloramphenicol acetyltransferase (CAT) activity through correctly initiated transcription as shown by primer extension analysis. Using this system we found a direct effect of insulin on GAPDH and FAS gene expression in rat adipocytes. In transfected adipocytes from obese compared to lean rats, activity of GAPDH and FAS promoters fused to CAT, was 2.6- and 8-fold increased, respectively. In contrast when reporter gene activity was driven by either phosphoenolpyruvate carboxykinase or beta-actin promoter, no difference could be observed between lean and obese, pointing out the promoter specificity of genotype effect. 5' deletion analysis of GAPDH promoter allowed us to narrow down the fa responsive region to nucleotide -488-329. As assessed by gel retardation and DNase I footprinting analysis, adipocyte nuclear protein interactions to this 159-bp fragment were found to be identical and to footprint the same 20-bp sequence. This study pointed out that overexpression of GAPDH and FAS genes in adipose tissue of genetically obese rats relies on promoter activation, through a 159-bp cis-acting region within the GAPDH promoter. The effects of the fa mutation on trans-acting factors binding to this region remain to be identified.
A peptidoglycan recognition protein in innate immunity conserved from insects to humans (1998)

Innate nonself recognition must rely on common structures of invading microbes. In a differential display screen for up-regulated immune genes in the moth Trichoplusia ni we have found mechanisms for recognition of bacterial cell wall fragments. One bacteria-induced gene encodes a protein that, after expression in the baculovirus system, was shown to be a peptidoglycan recognition protein (PGRP). It binds strongly to Gram-positive bacteria. We have also cloned the corresponding cDNA from mouse and human and shown this gene to be expressed in a variety of organs, notably organs of the immune system-i.e., bone marrow and spleen. In addition, purified recombinant murine PGRP was shown to possess peptidoglycan affinity. From our results and the sequence homology, we conclude that PGRP is a ubiquitous protein involved in innate immunity, conserved from insects to humans.
Increased Water Retention in Polymer Electrolyte Membranes at Elevated Temperatures Assisted by Capillary Condensation (2007)

We establish a new systematic methodology for controlling the water retention of polymer electrolyte membranes. Block copolymer membranes comprising hydrophilic phases with widths ranging from 2 to 5 nm become wetter as the temperature of the surrounding air is increased at constant relative humidity. The widths of the moist hydrophilic phases were measured by cryogenic electron microscopy experiments performed on humid membranes. Simple calculations suggest that capillary condensation is important at these length scales. The correlation between moisture content and proton conductivity of the membranes is demonstrated.
Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions (2008)

Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis.
Calcium/Calmodulin-Dependent Protein Kinase II Contributes to Cardiac Arrhythmogenesis in Heart Failure (2009)

We conclude that CaMKII contributes to cardiac arrhythmogenesis in TG CaMKIIdelta(C) mice having heart failure and suggest the increased SR Ca leak as an important mechanism. Moreover, CaMKII inhibition reduces cardiac arrhythmias in vitro and in vivo and may therefore indicate a potential role for future antiarrhythmic therapies warranting further studies.
Design and Synthesis of Phosphotyrosine Peptidomimetic Prodrugs (2006)

A novel approach to the intracellular delivery of aryl phosphates has been developed that utilizes a phosphoramidate-based prodrug approach. The prodrugs contain an ester group that undergoes reductive activation intracellularly with concomitant expulsion of a phosphoramidate anion. This anion undergoes intramolecular cyclization and hydrolysis to generate aryl phosphate exclusively with a t(1/2) = approximately 20 min. Phosphoramidate prodrugs (8-10) of phosphate-containing peptidomimetics that target the SH2 domain were synthesized. Evaluation of these peptidomimetic prodrugs in a growth inhibition assay and in a cell-based transcriptional assay demonstrated that the prodrugs had IC50 values in the low micromolar range. Synthesis of phosphorodiamidate analogues containing a P-NH-Ar linker (16-18) was also carried out in the hope that the phosphoramidates released might be phosphatase-resistant. Comparable activation rates and cell-based activities were observed for these prodrugs, but the intermediate phosphoramidate dianion underwent spontaneous hydrolysis with a t(1/2) = approximately 30 min.
Clinical implications of determination of plasma haloperidol levels (1989)

The aim of this study was to analyze the clinical utility of monitoring plasma levels, since the utility of monitoring is not yet well established. After a washout period, 30 schizophrenic patients were given fixed doses of haloperidol for 3 weeks. A U-shaped second-grade polynomic relationship (R = 0.69) was found between steady state of haloperidol and percentage improvement in total score on the Brief Psychiatric Rating Scale. The interval of effective concentrations was between 12 and 59 ng/ml. Fourteen of the 15 patients who had a steady state of haloperidol within that therapeutic interval were responders: only 5 out of the 15 patients below the therapeutic interval were responders. None of the 5 patients who had concentrations below 8 ng/ml was a responder. Furthermore, responder patients showed a steady-state level of haloperidol significantly higher than that of nonresponders. These data suggest that plasma levels of haloperidol are predictors of therapeutic response in schizophrenic disorders.
Applications of silicon-germanium-carbon in MOS and bipolar transistors (1997)

This paper will review growth of Si-Ge and Si-Ge-C alloys using various low thermal budget epitaxial schemes such as UHVCVD, RTPCVD and MBE. The growth issues, materials aspects and bandgap and strain engineering in these alloys will be discussed. The prospective of using these alloys in strained-channel Si-Ge MOSFETs and MODFETs in order to enhance CMOS in the giga-scale era will be discussed. We will also describe the use of these films in Si-Ge HBTs for high speed r-f type applications.
Blood-Brain Barrier Disruption and Intra-Arterial Methotrexate-Based Therapy for Newly Diagnosed Primary CNS Lymphoma: A Multi-Institutional Experience (2009)

PURPOSE Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. PATIENTS AND METHODS This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age > or = 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS > or = 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. CONCLUSION This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.
Interfacially Active SWNT/Silica Nanohybrid Used In Enhanced Oil Recovery (2010)

Abstract Single-Walled-Carbon-Nanotube (SWNT)-Silica nanohybrid particles are a very promising material that could be used in a near future for enhanced oil recovery because of their interfacial activity. The mechanism used to recover additional oil in this case would be to deliver catalytically active nanohybrid particles to the O/W interface, where they would react with and modify the oil properties to mobilize the oil in the reservoir. To demonstrate the basic principle, aqueous nanohybrid particle dispersions were evaluated by looking at the effect of pH, salt, surfactant and polymer. The results showed that pH and salt did not have significant effect on the dispersion stability of nanohybrid particles. Although surfactant could improve the dispersion stability, it reduced the interfacial activity of the nanohybrid particles, causing them to stay in the aqueous phase. The best nanohybrid particle dispersion stability was found upon polymer addition, where the dispersions were stable for more than a week even at low polymer concentration (50 ppm). After the best conditions for dispersions stability were determined, one-dimensional-sand-pack studies were performed to evaluate the flow of the nanohybrid particles through porous media. The results showed that the most of the nanohybrid particles could pass through a column packed with glass beads while a measurable fraction of the particles were retained in the column packed with crushed Berea. When the columns contained a residual saturation of decane, additional nanohybrid particles were retained at the oil/water interface in both media (glass bead and crushed Berea sand packs). The sand pack studies showed that not only can the nanohybrid particles flow through porous media, but also about half of the particles injected will go the O/W interface when the porous medium contains a residual saturation of hydrocarbon, where they could be used to support a catalytic conversion of components of the oil.
Macrophage treatment of pressure sores in paraplegia (1998)

This report describes two cases where wound healing was achieved by local injection of a macrophage suspension after conventional treatments had failed for many years
The Groove between the α- and β-Subunits of Hormones with Lutropin (LH) Activity Appears to Contact the LH Receptor, and Its Conformation Is Changed during Hormone Binding (1995)

Gonadotropins are heterodimeric glycoprotein hormones that control vertebrate fertility through their actions on gonadal lutropin (luteinizing hormone, LH) and follitropin (follicle-stimulating hormone, FSH) receptors. The beta-subunits of these hormones control receptor binding specificity; however, the region of the beta-subunit that contacts the receptor has not been identified. By a process of elimination we show this contact to be the portions of beta-subunit loops one and three found in a hormone groove created by the juxtaposition of the alpha- and beta-subunits. Most other regions of the beta-subunit can be recognized by antibodies that bind to human chorionic hormone (hCG)-receptor complexes or replaced without disrupting hormone function. Using a series of bovine LH/hCG and human FSH/hCG beta-subunit chimeras we identified key hCG beta-subunit residues in the epitopes of two antibodies that bind to hCG-receptor complexes. These epitopes include the surfaces of beta-subunit loops one and three near residue 74 on the outside of the hormone groove and parts of the C-terminal end of the "seat belt" that holds the two subunits together. The antibody that recognized residue 74 bound to receptor complexes containing most mammalian lutropins better than to the free hormones, an indication that the outside surface of the beta-subunit groove is altered during hormone binding. This region of the beta-subunit is furthest from the alpha-subunit and is recognized equally well in the free beta-subunit and in the heterodimer. Thus, the receptor associated increase in antibody binding appears due to an interaction of this portion of the beta-subunit with the receptor and not to an effect of the receptor on the relative positions of the alpha- and beta-subunits. Unlike most previous studies designed to identify portions of the beta-subunit likely to contact the LH receptor, this indirect approach provides data that are more easily interpreted because it does not rely on the use of mutations that disrupt hormone function. The approach described here should be valuable for studying the receptor interactions of other complex ligands.
Hypothermia and Electrical Activity of Cerebral Cortex (1961)

Changes in cortical excitability incident to brain cooling have been examined on several occasions, utilizing spontaneous ECG,<sup>1-3</sup>evoked response<sup>4-6</sup>or cortical threshold for seizure discharge.<sup>7-9</sup>However, the effects of cold upon slower components of cortical potentials have not been studied, owing largely, we believe, to the general use of capacity coupled amplifiers which attenuate slow frequencies. In earlier studies from this laboratory direct current (d.c.) recording has been utilized, permitting accurate recording of slow changes in cortical potential. Evoked potentials studied in this fashion have been (1) the direct cortical response recorded from a cortical site immediately adjoining a surface-stimulating electrode; (2) recruiting response to repetitive stimulation of the midline thalamus; (3) evoked response of visual cortex activated by brief shocks to optic nerve or light flashes to retina.<sup>10-13</sup>Graphically, the usual short-latency, fast component of evoked response is followed by a slower component of longer
Capacity comparison of an OFDM based multiple access system using different dynamic resource allocation (2002)

A future mobile communication system must support not only the traditional speech service but also other services such as multimedia, circuit switched and packet based data. Though no "killer application" is known today the system design must be flexible enough to simultaneously handle different types of services (circuit switched and packet based), with different demands on quality of service (blocking, delay and throughput). Efficient handling of different mixtures of services must be a key issue, for a high capacity system. This work has been done in connection with the evaluation of candidates for the European, Universal Mobile Telecommunication System (UMTS). The paper studies what effects a mixed service scenario would give on the capacity of the cellular system, using different types of resource allocation. The different profiles of the services, in combination with the large amount of freedom regarding user behaviour, motivates scenario simulations. Two scenarios (speech and circuit switched data dominated) are studied. The performance is compared for different types of resource allocation schemes, in an OFDM based multiple access system. In OFDM, all resources are available in all cells as the FFT works on the total available bandwidth. This makes a multiple access system based on OFDM suitable for using together with dynamic resource allocation.
Isolation and properties of two actin-binding domains in gelsolin. (1985)

Gelsolin is a Ca2+-sensitive 90-kDa protein which regulates actin filament length. A molecular variant of gelsolin is present in plasma as a 93-kDa protein. Functional studies have shown that gelsolin contains two actin-binding sites which are distinct in that after Ca2+-mediated binding, removal of free Ca2+ releases actin from one site but not from the other. We have partially cleaved human plasma gelsolin with alpha-chymotrypsin and identified two distinct actin-binding domains. Peptides CT17 and CT15, which contain one of the actin-binding domains, bind to actin independently of Ca2+; peptides CT54 and CT47, which contain the other domain, bind to actin reversibly in response to changes in Ca2+ concentration. These peptides sequester actin monomers inhibiting polymerization. Unlike intact gelsolin, neither group of peptides nucleates actin assembly or forms stable filament end caps. CT17 and CT15 can however sever actin filaments. Amino acid sequence analyses place CT17 at the NH2 terminus of gelsolin and CT47 at the carboxyl-terminal two-thirds of gelsolin. Circular dichroism measurements show that Ca2+ induces an increase in the alpha-helical content of CT47. These studies provide a structural basis for understanding the interaction of gelsolin with actin and allow comparison with other Ca2+-dependent actin filament severing proteins.
Cold Start Improvement by use of Latent Heat Stores (1992)

&lt;div class="htmlview paragraph"&gt;Engine and cabin heating problems associated with cold starts at subzero conditions are greatly reduced by use of a Heat Battery. This is a latent heat store, collecting waste heat from the engine and storing it by use of efficient heat insulation. On the next cold start the heat is released with high initial power. The performance increases with colder environment conditions. Startability of the engine and the warm-up performance are improved. Emissions of hydrocarbons and carbonmonoxide are reduced up to 80 % in the CVS test at -7°C (20°F) and Diesel noise is lowered.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The windshield is cleared of ice and frost and kept free of mist. Passenger comfort improves since hot air flows into the cabin within seconds after the Heat Battery is engaged.&lt;/div&gt;