gebhart/patrepeval huggingface dataset:
Delineation of three pharmacological subtypes of α2‐adrenoceptor in the rat kidney (1991)

1. Simultaneous computer modelling of plain and ARC 239- and guanoxabenz-masked [3H]-RX821002 saturation curves, plain ARC 239 and guanoxabenz competition curves as well as ARC 239-masked guanoxabenz competition curves revealed that the drugs bound to three alpha 2-adrenoceptor subtypes in the rat kidney with grossly differing selectivities. These alpha 2-adrenoceptor subtypes were termed alpha 2 A, alpha 2B1 and alpha 2B2. The order of affinities for [3H]-RX821002 for the adrenoceptor sites was alpha 2A greater than alpha 2B1 greater than alpha 2B2, the KdS being 0.62 +/- 0.05, 2.52 +/- 0.11 and 6.74 +/- 1.21 nM, respectively. The order of affinities for ARC 239 was alpha 2B1 greater than alpha 2B2 much greater than alpha 2A with KdS 4.78 +/- 1.04, 28.8 +/- 4.1 and 1460 +/- 270 nM, respectively. For guanoxabenz the order of affinities was alpha 2A greater than alpha 2B1 much greater than alpha 2B2 with KdS 99.7 +/- 15.1, 508 +/- 135 and 25,400 +/- 2400 nM, respectively. 2. Binding constants for 14 compounds for the three rat kidney alpha 2-adrenoceptor subtypes were determined by the simultaneous computer modelling of plain and ARC 239- and guanoxabenz-masked drug competition curves, plain ARC 239 and guanoxabenz competition curves as well as ARC 239-masked guanoxabenz competition curves. Of the 14 compounds tested, oxymetazoline and guanfacine were found to bind with low affinities to both of the alpha 2B1- and alpha 2B2-adrenoceptor but with high affinity to the alpha 2A-adrenoceptor. 3. (-)-Adrenaline and (-)-noradrenaline showed dissimilar order of affinities for the three alpha2-adrenoceptors. For (-)-adrenaline the order of affinities was alpha2Bl >- alpha2A> alpha2B2 and for (-)-noradrenaline alpha2B2 > alpha2Bl > alpha2A. All three alpha2-adrenoceptors showed the expected stereoselective binding for adrenaline enantiomers, the (+)-form being 7-10 fold less potent than the (-)form. 4. [3H]-yohimbine was also used as radioligand. The data with this ligand were fully compatible with the [3H]-RX821002 data. However, [3H]-yohimbine appeared to label only alpha2Bl- and alpha2B2-adrenoceptors presumably because it had too low an affinity for alpha2A-adrenoceptors. 5. We conclude that three pharmacological subtypes of alpha2-adrenoceptors are labelled by [3H]-RX821002 in the rat kidney. Guanoxabenz and ARC 239 may be used in competition studies to delineate between these three alpha2-adrenoceptor subtypes. Moreoever, we here present a method allowing the determination of binding constants for an arbitrary drug to the three alpha2-adrenoceptor subtypes.
Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals (2022)

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
A comparison of methionine, histidine and cysteine in copper(i)-binding peptides reveals differences relevant to copper uptake by organisms in diverse environments (2010)

The N-terminal, extracellular regions of eukaryotic high affinity copper transport (Ctr) proteins vary in composition of the Cu(i) binding amino acids: methionine, histidine, and cysteine. To examine why certain amino acids are exploited over others in Ctrs from different organisms, the relative Cu(i) binding affinity and the dependence of binding on pH were examined for 3 peptides of the sequence MG(2)XG(2)MK, where X is either Met, His, or Cys. Cu(i) affinity was examined using an ascorbic acid oxidation assay, an electrospray ionization mass spectrometry technique, and spectrophotometric titration with a competitive Cu(i) chelator. The relative affinities of the peptides with Cu(i) reveal a trend whereby Cys > His > Met at pH 7.4 and Cys > Met > His at pH 4.5. Ligand geometry and metric parameters were determined with X-ray absorption spectroscopy. Susceptibility of the peptides to oxidation by hydrogen peroxide and copper-catalyzed oxidative conditions was evaluated by mass spectrometry. These results support hypotheses as to why certain Cu(i) binding amino acids are preferred over others in proteins expressed at different pH and exposed to oxidative environments. The results also have implications for interpreting site-directed mutagenesis studies aimed at identifying copper binding amino acids in copper trafficking proteins.
Search for pair production of second-generation leptoquarks at s=13  TeV (2019)

A search for pair production of second-generation leptoquarks is performed using proton-proton collision data collected at $\sqrt{s}=13\text{ }\text{ }\mathrm{TeV}$ in 2016 with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of $35.9\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$. Final states with two muons and two jets, or with one muon, two jets, and missing transverse momentum are considered. Second-generation scalar leptoquarks with masses less than 1530(1285) GeV are excluded for $\ensuremath{\beta}=1.0(0.5)$, where $\ensuremath{\beta}$ is the branching fraction for the decay of a leptoquark to a charged lepton and a quark. The results of the search are also interpreted as limits on the pair production of long-lived top squarks in an $R$-parity violating supersymmetry model that has a final state with two muons and two jets. These limits represent the most stringent limits to date on these models.
A 2.8GHz 128-entry &#x00D7; 152b 3-read/2-write multi-precision floating-point register file and shuffler in 32nm CMOS (2012)

A 128-entry × 152b 3-read/2-write ported multi-precision floating-point register file/shuffler with measured 2.8GHz operation is fabricated in 1.05V, 32nm CMOS. Single-precision (24b-mantissa), 2-way 12b or 4-way 6b reduced mantissa precision modes, certainty tracking bits, mode-dependent gating, area-efficient windowing using 1R/1W cells, and ultra-low-voltage read/write circuits enable 350mV-1.2V wide dynamic voltage range with measured peak energy-efficiency of 751GOPS/W at 400mV, 4-way 6b-mode (22.3× higher than 1.05V single-precision mode) and 19% area reduction over single-precision 3R/2W implementations.
Wafer scale oblique angle plasma etching (2023)

Wafer scale oblique angle etching of a semiconductor substrate is performed in a conventional plasma etch chamber by using a fixture that supports a multiple number of separate Faraday cages. Each cage is formed to include an angled grid surface and is positioned such that it will be positioned over a separate one of the die locations on the wafer surface when the fixture is placed over the wafer. The presence of the Faraday cages influences the local electric field surrounding each wafer die, re-shaping the local field to be disposed in alignment with the angled grid surface. The re-shaped plasma causes the reactive ions to follow a linear trajectory through the plasma sheath and angled grid surface, ultimately impinging the wafer surface at an angle. The selected geometry of the Faraday cage angled grid surface thus determines the angle at with the reactive ions will impinge the wafer.
A Novel System for Expressing Toxic Actin Mutants in Dictyostelium and Purification and Characterization of a Dominant Lethal Yeast Actin Mutant (2007)

We have developed a novel system for expressing recombinant actin in Dictyostelium. In this system, the C terminus of actin is fused to thymosin beta via a glycine-based linker. The fusion protein is purified using a His tag attached to the thymosin beta moiety and then cleaved by chymotrypsin immediately after the native final residue of actin to yield intact actin. Wild-type actin prepared in this way was functionally normal in terms of its polymerization kinetics and muscle myosin-mediated motility. We expected that this system would be particularly useful for expressing toxic actin mutants, because the actin moiety of the fusion protein is unlikely to interact with the actin cytoskeleton of the host cells. We therefore chose to express the E206A/R207A/E208A mutant, which appears to be dominant lethal in yeast, as a model case of a toxic actin mutant that is difficult to express. We found that the E206A/R207A/E208A mutant could be expressed and purified with a yield comparable to the wild-type molecule (3-4 mg/20 g cells), even though green fluorescent protein-fused actin carrying the E206A/R207A/E208A mutation was expressed at a much lower level than wild-type actin. Purified E206A/R207A/E208A actin did not polymerize, even in the presence of muscle actin; however, it accelerated polymerization of muscle actin and inhibited the nucleating and severing activities of gelsolin. Given that the location of the substituted residues is near the pointed end face of the mutant, we suggest that E206A/R207A/E208A actin behaves like a weak pointed end-capping protein that perturbs the actin cytoskeleton of the host cells.
ADVANCED HYDROGEN TRANSPORT MEMBRANES FOR VISION 21 FOSSIL FUELS PLANTS (2003)

Eltron Research Inc. and team members CoorsTek, Sued Chemie, and Argonne National Laboratory are developing an environmentally benign, inexpensive, and efficient method for separating hydrogen from gas mixtures produced during industrial processes, such as coal gasification. This project was motivated by the National Energy Technology Laboratory (NETL) Vision 21 initiative, which seeks to economically eliminate environmental concerns associated with the use of fossil fuels. Currently, this project is focusing on four basic categories of dense membranes: (1) mixed conducting ceramic/ceramic composites, (2) mixed conducting ceramic/metal (cermet) composites, (3) cermets with hydrogen permeable metals, and (4) layered composites containing hydrogen permeable alloys. Ultimately, these materials must enable hydrogen separation at practical rates under ambient and high-pressure conditions, without deactivation in the presence of feedstream components such as carbon dioxide, water, and sulfur. This report presents hydrogen permeation data during long term tests and tests at high pressure in addition to progress with cermet, ceramic/ceramic, and thin film membranes.
Measurements of3Hespin-exchange rates (2002)

Spin-exchange rate coefficients for Rb-${}^{3}\mathrm{He}$ are measured using three different methods. Two methods, using Rb repolarization and rate balance, require no assumption about the nature of the ${}^{3}\mathrm{He}$ wall relaxation and agree well; we find spin-exchange rate coefficients of $6.7\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}20}{\mathrm{cm}}^{3}/\mathrm{s}$ and $6.8\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}20}{\mathrm{cm}}^{3}/\mathrm{s}.$ These results agree with a recent repolarization measurement of Baranga and co-workers [Phys. Rev. Lett. 80, 2801 (1998)]. The third method uses the temperature dependence of the ${}^{3}\mathrm{He}$ relaxation and is 30% larger than the other two, implying a temperature-dependent wall or an unreasonably large value of the anisotropic spin-exchange interaction for $\mathrm{Rb}{\ensuremath{-}}^{3}\mathrm{He}.$ In the course of these measurements we developed and tested a new method for Rb density measurements under high power pumping conditions, and a new variant of Rb EPR polarimetry, both of which are described here.
ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling (2003)

Dendritic cells (DCs) are specialized antigen-presenting cells residing in tissues, from which they take up antigen. Activated DCs migrate through chemokine gradients from sites of inflammation to lymph nodes to stimulate T cells. At sites of inflammation, nucleotides, such as adenosine triphosphate (ATP), are released by activated or dying cells and can function as signaling molecules through P2 receptors (P2Rs). We investigated P2R expression in different DC populations and the effect of nucleotides on chemokine-directed migration. Exposure of monocyte-derived DCs (MoDCs) and CD1a+ dermal DCs to gradients of ATP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y11R. On maturation, MoDCs down-regulated P2Y11R expression and were less sensitive to ATP-mediated inhibition of migration. In contrast, ATP did not inhibit the migration of CD1c+ peripheral blood (PB) DCs or interleukin-3 receptor-positive (IL-3R+) plasmacytoid DCs. Although all 4 DC populations expressed mRNA for P2Y11R, calcium-flux studies showed that blood DC types were unresponsive to P2Y11R agonists. In conclusion, DCs use distinct subtypes of P2R. The formation of ATP gradients at sites of inflammation may transiently inhibit the migration of local DCs, thus prolonging the time of antigen encounter. P2R inhibition may represent a new strategy to improve the migration of antigen-loaded DCs from the vaccination site to lymph nodes.
Increased length of DNA made by virions of murine leukemia virus at limiting magnesium ion concentration (1977)

Conditions have been developed for reverse transcription by detergent-disrupted virions of Moloney murine leukemia virus which permit synthesis of molecules that appear to be complete transcripts of the 35S RNA subunits. At limiting Mg2+ concentration, DNA is synthesized in good yield, up to a maximum size of about 2.4 X 10(6) daltons. DNA larger than 2 X 10(6) daltons, taken from alkaline sucrose gradients, has no detectable self-complementarity and was protected from digestion by S1 nuclease to an extent of 90% by annealing to 70S RNA. All size classes of DNA made in these reactions are primed with RNA, because all are initiated with a pApdAjunction. To produce such long molecules, it is necessary to keep the concentration of Mg2+ in the reaction mixture below the total concentration of deoxyribonucleoside triphosphates. Under these conditions, degradation of the RNA template is minimized. The rate of DNA synthesis is also slowed by 30 to 50%, but products longer than 5,000 nucleotides, which are not found otherwise, are completed between 3 and 6h of reaction.
The Mycobacterial Transcriptional Regulator whiB7 Gene Links Redox Homeostasis and Intrinsic Antibiotic Resistance (2011)

Intrinsic drug resistance in Mycobacterium tuberculosis limits therapeutic options for treating tuberculosis. The mycobacterial transcriptional regulator whiB7 contributes to intrinsic resistance by activating its own expression and many drug resistance genes in response to antibiotics. To investigate whiB7 activation, we constructed a GFP reporter to monitor its expression, and we used it to investigate the whiB7 promoter and to screen our custom library of almost 600 bioactive compounds, including the majority of clinical antibiotics. Results showed whiB7 was transcribed from a promoter that was conserved across mycobacteria and other actinomycetes, including an AT-rich sequence that was likely targeted by WhiB7. Expression was induced by compounds having diverse structures and targets, independent of the ability of whiB7 to mediate resistance, and was dependent on media composition. Pretreatment with whiB7 activators resulted in clinically relevant increases in intrinsic drug resistance. Antibiotic-induced transcription was synergistically increased by the reductant dithiothreitol, an effect mirrored by a whiB7-dependent shift to a highly reduced cytoplasm reflected by the ratio of reduced/oxidized mycothiol. These data provided evidence that intrinsic resistance resulting from whiB7 activation is linked to fundamental changes in cell metabolism.
ChemInform Abstract: REDUCTIVE AMINATION OF ETHYL 2‐OXO‐4‐PHENYLBUTANOATE WITH L‐ALANYL‐L‐PROLINE. SYNTHESIS OF ENALAPRIL MALEATE (1984)

Abstract Phenethyl‐keto‐carbonsäureester (I) kondensiert mit L‐Alanyl‐L‐proIin (II) zum Imin (III), das zu (IV) hydriert, über das Maleat getrennt und in Enalaprilat (Vb) übergeführt wird.
An Evaluation of a Composite Model for Predicting Drop-Drop Collision Outcomes in Multidimensional Spray Computations (2002)

&lt;div class="htmlview paragraph"&gt;The standard model for predicting the outcome of drop-drop collisions in sprays is one developed based on measurements in rain drops under atmospheric pressure conditions. This model includes the possible outcomes of grazing collisions and coalescence. Recent measurements with hydrocarbon drops and at higher pressure (up to 12 bar) indicate the possibility of additional outcomes: bounce, reflexive separation and drop shattering. The measurements also indicate that the Weber number range over which bounce occurs is dependent on the gas pressure. The probability of a drop-drop collision resulting in bounce increases with gas pressure. A composite model that includes all these outcomes as possibilities is employed to carry out computations in a constant volume chamber and in a Diesel engine. A sub-model for bounce that includes the pressure effects is also part of the composite model. Comparisons of results obtained with the composite model are compared with those obtained with the standard model. Sauter-mean-diameter variations and mixing characteristics are studied under non-vaporizing, vaporizing and combustion conditions. It is shown that the probability of coalescence is noticeably reduced with the new model compared to the model based on the work of Brazier-Smith et al.&lt;/div&gt;
Limit results for Markovian models of TCP (2002)

We study in this paper the throughput of a TCP connection performing ideal congestion avoidance. With respect to existing studies published on the same topic, we determine upper and lower bounds for the throughput of a TCP connection experiencing an arbitrary constant loss. We then derive exact convergence results when the loss probability becomes arbitrarily small. A remarkable property of the results obtained in this paper is that they justify a posteriori constants, which appear in the approximation of the throughput and which has been observed earlier via simulation or experiments. The analysis is performed by assuming a finite and infinite maximum congestion window size.
Electromagnetics made easy: differential forms as a teaching tool (2002)

The calculus of differential forms clarifies the relationship between field intensity and flux density and provides intuitive pictures of Ampere's and Faraday's laws, the curl operation, the Poynting vector, and boundary conditions. These and other advantages over vector analysis make differential forms an optimal tool for teaching electromagnetics.
Induced density changes in 193-nm excimer-laser-damaged silica glass: a kinetic model (2004)

Silica glass exposed to pulsed UV excimer laser irradiation undergoes optical changes that can include either an optical path increase or a decrease. During a given exposure the sign of the induced optical path change can reverse as a function of pulse count. The reduced optical path and sign reversal are only observed in H<sub>2</sub>-containing glasses, and at high exposure fluence only optical path increase is observed. In past work we proposed an induced density change model invoking a dynamic equilibrium density to explain the high fluence experiments. Here we present a model that extends the density model to the low fluence regime by allowing the equilibrium density to be a function of the time-dependent break-up of the silica network during exposure. The network break-up is tracked by calculation of the induced SiH concentration in the glass. The agreement of optical path change obtained from experimental data with that deduced from the kinetic approach covers a wide range of exposure fluence and molecular hydrogen concentration. Using the model one can predict the change in optical path that arises from the excimer laser exposure.
Development and first results of the width-tapered beam method for adhesion testing of photovoltaic material systems (2016)

A fracture mechanics based approach for quantifying adhesion at every interface within the PV module laminate is presented. The common requirements of monitoring crack length and specimen compliance are circumvented through development of a width-tapered cantilever beam method. This technique may be applied at both the module and coupon level to yield a similar, quantitative, measurement. Details of module and sample preparation are described and first results on field-exposed modules deployed for over 27 years presented.
Probing the Structural Requirements of Peptoids That Inhibit HDM2−p53 Interactions (2006)

Many cellular processes are controlled by protein-protein interactions, and selective inhibition of these interactions could lead to the development of new therapies for several diseases. In the area of cancer, overexpression of the protein, human double minute 2 (HDM2), which binds to and inactivates the protein p53, has been linked to tumor aggressiveness and drug resistance. In general, inhibition of protein-protein interactions with synthetic molecules is challenging and currently remains a largely uncharted area for drug development. One strategy to create inhibitors of protein-protein interactions is to recreate the three-dimensional arrangement of side chains that are involved in the binding of one protein to another, using a nonnatural scaffold as the attachment point for the side chains. In this study, we used oligomeric peptoids as the scaffold to begin to develop a general strategy in which we could rationally design synthetic molecules that can be optimized for inhibition of protein-protein interactions. Structural information on the HDM2-p53 complex was used to design our first class of peptoid inhibitors, and we provide here, in detail, the strategy to modify peptoids with the appropriate side chains that are effective inhibitors of HDM2-p53 binding. While we initially tried to develop rigid, helical peptoids as HDM2 binders, the best inhibitors were surprisingly peptoids that lacked any helix-promoting groups. These results indicate that starting with rigid peptoid scaffolds may not always be optimal to develop new inhibitors.
A Novel Ground Faults Detection Method for Variable Speed Drives (2020)

The necessity of improving the efficiency and adapt the machines' conditions to the processes made essential the power electronic presence in electric systems. The AC to DC and DC to AC conversions thanks rectifiers and inverters provoked difficulties in the ground fault detection. In this paper a new method to detect ground faults in variable speed drives is presented. It is based on the analysis of the voltage signal of a grounding resistor connected between the neutral of the secondary main power transformer and ground. Attending to the waveform, the ground fault could be detected in the AC grid side, DC positive or negative terminals or AC variable frequency side. To corroborate the method numerous simulations were carried out achieving satisfactory results.