gebhart/patrepeval huggingface dataset:
Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1 (1997)

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple mutant virus strains that gradually became resistant to the quinoxaline and other nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs). A novel mutation, Pro225His, consistently appeared in a Val106Ala RT-mutated genetic background. The contribution of this mutation to the resistance of the mutant HIV-1 RT to NNRTIs was additive to the resistance caused by the Val106Ala mutation. Interestingly, site-directed mutagenesis studies revealed that the Pro225His-mutated RT had acquired markedly greater sensitivity to bis(heteroaryl)piperazine (BHAP U-90152) (delavirdine) but not to any of the other NNRTIs. The kinetics of inhibition of the Pro225His mutant RT by the NNRTIs (including BHAP U-90152) was not substantially different from that observed for the wild-type RT. The hypersensitivity of the mutant enzyme and virus to BHAP U-90152 could be rationally explained by the molecular-structural determinants of the RT-BHAP complex, which has recently been resolved by X-ray crystallography.
Persistence of Low HDL-C Levels After Weight Reduction in Older Men With Small LDL Particles (1995)

LDL subclass pattern B is characterized by a predominance of small LDL particles (LDL peak particle size < or = 255 A) and is associated with increased plasma triglyceride (TG) and reduced HDL cholesterol (HDL-C) concentrations. This study compared the effect of weight loss on lipoprotein and glucose metabolism in 15 healthy, obese (body mass index [BMI], 30.9 +/- 2.4 kg/m2), older (60 +/- 9 years) men with LDL pattern B and in 25 men of comparable age and BMI with LDL pattern A (LDL peak particle size > or = 260 A). At baseline, men with LDL pattern B had higher TG and lower apolipoprotein (apo) A-I, HDL-C, and HDL2-C levels (P < .001) than men with LDL pattern A, while the total cholesterol and LDL cholesterol levels and fasting and 2-hour postprandial glucose and insulin levels did not differ between groups. With weight loss (10.1 +/- 3.6 kg) there were significant decreases in 2-hour postprandial glucose and insulin levels in men with LDL patterns B and A (P < .05). However, the change in plasma TG, HDL-C, HDL2-C, and apoA-I levels with weight loss differed between groups. In men with LDL pattern A, plasma TG levels decreased by 15% (P < .001) compared with a 34% (P < .001) decrease in LDL pattern B (two-factor ANOVA, P < .01). Plasma HDL-C concentrations increased by 0.16 mmol/L (P < .001) in the men with LDL pattern A but by only 0.07 mmol/L in the men with LDL pattern B (two-factor ANOVA, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
An inverted-growth approach to development of an IR-transparent, high-efficiency AlGaAs/GaAs cascade solar cell (2002)

An approach for inverted-grown AlGaAs/GaAs cascade cells, where the AlGaAs top cell is grown first at high temperatures, placing the surface to be illuminated nearest to the substrate, is presented. Following the growth of the top cell, the GaAs tunnel interconnect and the bottom cell are grown at lower temperatures. After the inverted growth, the AlGaAs/GaAs cascade structure is selectively removed from the parent substrate, Ge in this case. Advantages of the inverted-growth approach are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dynamic impact analysis of DFIG‐based wind turbine generators on low‐frequency oscillations in power system (2017)

The increasing integration of wind turbines mainly doubly fed induction generators (DFIGs) introduces dynamic interaction with the conventional synchronous generators (SGs) affecting the damping of low‐frequency electromechanical oscillations (LFEOs) in the system. This study presents a complete impact analysis of DFIG integration on system damping. The damping ratio sensitivity to inertia is used to evaluate the impact of DFIG integration on the critical modes. This study identifies that the impact could be positive or negative based on the location of DFIG. The results obtained are verified by detailed eigenvalue analysis and time‐domain simulations for different operating conditions with three‐phase fault. The negative impact on damping is improved by optimally tuned power oscillation dampers (PODs) with input signals obtained from the phasor measurement units. The impact on dynamic performance of the system due to removal of SGs and addition of DFIGs is investigated. The DFIG penetration is increased on the basis of participation of SGs in critical modes and the results of sensitivity analysis. The proposed approach is tested on standard IEEE 39‐bus test system. The investigations carried out in this work can be employed for planning studies of power system integrated with DFIG for identifying their suitable locations and improving LFEO damping with their high penetration.
Detection of Range-Based Rail Gage and Missing Rail Fasteners (2014)

Defects in railroad tracks are responsible for several incidents every year. Rail gage is one of the most important measurements for track maintenance because deviations in gage indicate where potential defects may exist. In addition, missing rail fasteners can be considered a critical defect that should be detected and repaired because missing fasteners are a common cause of gage misalignment issues. An improvement or enhancement to the currently available automatic inspection system specifically devised to estimate rail gage and detect missing rail fasteners is presented. A three-dimensional (3-D) imaging sensor, which produces high-resolution two-dimensional images and 3-D profiles, is used to capture the data. Then a range-based approach is used to inspect the railroad track. The 3-D structure of the rail components (rail heads and rail fasteners) is relied on instead of a vision-based approach, which suffers from illumination changes. The system is evaluated with data recorded from real scenarios in two cities (Metro Madrid in Spain and the London Underground) with different nominal gage values and fastening elements. The system is described, and results are presented, evaluated, and discussed.
Variational Inference for the Indian Buffet Process (2009)

The Indian Buet Process (IBP) is a nonparametric prior for latent feature models in which observations are influenced by a combination of hidden features. For example, images may be composed of several objects and sounds may consist of several notes. Latent feature models seek to infer these unobserved features from a set of observations; the IBP provides a principled prior in situations where the number of hidden features is unknown. Current inference methods for the IBP have all relied on sampling. While these methods are guaranteed to be accurate in the limit, samplers for the IBP tend to mix slowly in practice. We develop a deterministic variational method for inference in the IBP based on a truncated stick-breaking approximation, provide theoretical bounds on the truncation error, and evaluate our method in several data regimes.
Studies on antihyperlipidemic agents. I. Synthesis and hypolipidemic activities of phenoxyphenyl alkanoic acid derivatives. (1980)

The alkanoic acids containing phenoxyphenyl moiety at omega-position were prepared and tested for hypolipidemic property. Some of the compounds showed hypoglycemic activity besides hypolipidemic one. Further study on the selected compound, 3-[4-(4-chlorophenoxy)benzoyl] propionic acid (8) revealed that it increased insulin sensitivity of adipose tissue of obese and diabetic mice (KKAY). The structure-activity relationship was discussed briefly.
Classification using functional data analysis for temporal gene expression data (2005)

MATLAB programs are available upon request.
Mass Spectrometric Analysis of a Native Zinc-Finger Structure: The Glucocorticoid Receptor DNA Binding Domain (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMass Spectrometric Analysis of a Native Zinc-Finger Structure: The Glucocorticoid Receptor DNA Binding DomainH. Ewa Witkowska, Cedric H. L. Shackleton, Karin Dahlman-Wright, John Y. Kim, and Jan-Aake GustafssonCite this: J. Am. Chem. Soc. 1995, 117, 12, 3319–3324Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ja00117a001https://doi.org/10.1021/ja00117a001research-articleACS PublicationsRequest reuse permissionsArticle Views166Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Detection of Nonthermal Melting by Ultrafast X-ray Diffraction (1999)

Using ultrafast, time-resolved, 1.54 angstrom x-ray diffraction, thermal and ultrafast nonthermal melting of germanium, involving passage through nonequilibrium extreme states of matter, was observed. Such ultrafast, optical-pump, x-ray diffraction probe measurements provide a way to study many other transient processes in physics, chemistry, and biology, including direct observation of the atomic motion by which many solid-state processes and chemical and biochemical reactions take place.
Flexible carbon nanotube papers with improved thermoelectric properties (2011)

Although theoretical calculations indicate that the thermoelectric figure of merit, ZT, of carbon nanotubes (CNTs) could reach >2, the experimentally reported ZT values of CNTs are typically in the range of 10−3–10−2, which is not attractive for thermal energy conversion applications. In this work, we report the preparation of flexible CNT bulky paper for thermoelectric applications. The ZT values of the CNT bulky papers could be significantly enhanced by Ar plasma treatment, i.e. increasing it from 0.01 for pristine CNTs to 0.4 for Ar-plasma treated CNTs. The improved thermoelectric properties were mainly due to the greatly increased Seebeck coefficients and a reduction in the thermal conductivities, although the electrical conductivities also decreased. Such an improvement makes the plasma treated CNT bulky papers promising as a new type of thermoelectric material for certain niche applications as they are easily processed, mechanically flexible and durable, and chemically stable.
Structure of Stem Cell Growth Factor R-spondin 1 in Complex with the Ectodomain of Its Receptor LGR5 (2013)

Leucine-rich repeat-containing G protein-coupled receptors 4-6 (LGR4-LGR6) are receptors for R-spondins, potent Wnt agonists that exert profound trophic effects on Wnt-driven stem cells compartments. We present crystal structures of a signaling-competent fragment of R-spondin 1 (Rspo1) at a resolution of 2.0 Å and its complex with the LGR5 ectodomain at a resolution of 3.2 Å. Ecto-LGR5 binds Rspo1 at its concave leucine-rich-repeat (LRR) surface, forming a dimeric 2:2 complex. Fully conserved residues on LGR4-LGR6 explain promiscuous binding of R-spondins. A phenylalanine clamp formed by Rspo1 Phe106 and Phe110 pinches Ala190 of LGR5 and is critical for binding. Mutations related to congenital anonychia reduce signaling, but not binding of Rspo1 to LGR5. Furthermore, antibody binding to the extended loop of the C-terminal LRR cap of LGR5 activates signaling in a ligand-independent manner. Thus, our data reveal binding of R-spondins to conserved sites on LGR4-LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR4-LGR6 in addition to its formation of Wnt receptor and coreceptor complexes.
Novel Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains (2006)

A novel series of benzofuran derivatives as potential positron emission tomography (PET) tracers targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of benzofurans were successfully achieved by an intramolecular Wittig reaction between triphenylphosphonium salt and 4-nitrobenzoyl chloride. When in vitro binding studies using AD brain gray matter homogenates were carried out with a series of benzofuran derivatives, all the derivatives examined displayed high binding affinities with K(i) values in the subnanomolar range. Among these benzofuran derivatives, compound 8, 5-hydroxy-2-(4-methyaminophenyl)benzofuran, showed the lowest K(i) value (0.7 nM). In vitro fluorescent labeling of AD sections with compound 8 intensely stained not only amyloid plaques, but also neurofibrillary tangles. The (11)C labeled compound 8, [(11)C]8, was prepared by reacting the normethyl precursor, 5-hydroxy-2-(4-aminophenyl)benzofuran, with [(11)C]methyl triflate. The [(11)C]8 displayed moderate lipophilicity (log P = 2.36), very good brain penetration (4.8%ID/g at 2 min after iv injection in mice), and rapid washout from normal brains (0.4 and 0.2%ID/g at 30 and 60 min, respectively). In addition, this PET tracer showed in vivo amyloid plaque labeling in APP transgenic mice. Taken together, the data suggest that a relatively simple benzofuran derivative, [(11)C]8, may be a useful candidate PET tracer for detecting amyloid plaques in the brains of patients with Alzheimer's disease.
From Mott insulator to ferromagnetic metal: A pressure study ofCa2RuO4 (2002)

We show that the pressure-temperature phase diagram of the Mott insulator ${\mathrm{Ca}}_{2}{\mathrm{RuO}}_{4}$ features a metal-insulator transition at 0.5 GPa: at 300 K from paramagnetic insulator to paramagnetic quasi-two-dimensional metal, and at $T&lt;~12 \mathrm{K}$ from antiferromagnetic insulator to ferromagnetic, highly anisotropic, three-dimensional metal. We compare the metallic state to that of the structurally related p-wave superconductor ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4},$ and discuss the importance of structural distortions, which are expected to couple strongly to pressure.
Flat volume control (2004)

The hardware-inspired volume user interface model that is in use across all of today's operating systems is the source of several usability issues. One of them is that restoring the volume of a muted application can require an inappropriately long troubleshooting process: in addition to manipulating the application's volume and mute controls, users may also have to visit the system's volume control panel to find and adjust additional controls there. The "flat" volume control model presented in this paper eliminates this and other problems by hiding the hardware-oriented volume model from the user. Using the flat model, users use one slider per application to indicate how loud they want the respective applications to play; the slider then internally adjusts all hardware volume variables necessary to obtain the requested output. By offering a single point of control for each application, the flat model simplifies controlling application volume and restoring muted applications. In our studies, participants completed all four volume control and mixing tasks faster and with less error when using the flat model than when using the existing hardware-oriented volume control model. Participants also indicated a subjective preference for the flat model over the existing model.
Efficacy and safety of 5‐hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding (2020)

This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD. Larger studies with a longer treatment duration are needed to corroborate these early findings.
Tunable Degradation of Maleimide–Thiol Adducts in Reducing Environments (2011)

Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here, we show that the resulting succinimide thioether formed by the Michael-type addition of thiols to N-ethylmaleimide (NEM), generally accepted as stable, undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature, offering a novel strategy for controlled release. Model studies ((1)H NMR, HPLC) of NEM conjugated to 4-mercaptophenylacetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP) incubated with glutathione showed half-lives of conversion from 20 to 80 h, with extents of conversion from 20% to 90% for MPA and N-acetylcysteine conjugates. After ring-opening, the resultant succinimide thioether did not show retro and exchange reactions. The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore, the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at time scales different than those currently possible via disulfide-mediated release. Such approaches may find a new niche for controlled release in reducing environments relevant in chemotherapy and subcellular trafficking.
Hairpin-Line and Hybrid Hairpin-Line/Half-Wave Parallel-Coupled-Line Filters (1972)

A new class of microwave filters, hairpin-line and hybrid hairpin-line/half-wave parallel-coupled-line filters, is reported. This class of filters is particularly well suited for microstrip and TEM printed-circuit realizations because grounding of the filter resonators is generally not required. Hairpin-line filters have been divided into two types. The first (Type A) is characterized by having its input and output lines open-circuited at their ends. The Type A filter has been found to yield practical impedance levels for narrow to approximately 25-percent bandwidths. The second (Type B) is characterized by having its input and output lines short-circuited at their ends. However, because of space limitations, details of the Type B filter are not presented in this paper. Theoretical background and design equations for Type A bandpass filters are presented. Experimental data for several stripline filters of 5- and 20-percent bandwidths are given. Experimental results for two microwave-integrated-circuit (MIC) filters are discussed.
Bipolar Electrode Focusing: Simultaneous Concentration Enrichment and Separation in a Microfluidic Channel Containing a Bipolar Electrode (2009)

A method for simultaneously concentrating and separating analytes in a buffer-filled microfluidic channel is reported. The approach is based on modulation of the local electric field within the channel and the corresponding opposition of electrophoretic and electroosmotic flow (EOF) velocities. Dye molecules having different electrophoretic mobilities are focused at different locations within the channel where concentration takes place. At least three species, all small dye molecules, can be simultaneously concentrated and separated, with localized enrichment factors up to approximately 600 achieved within 400 s. The enrichment zones affect the electric field profile, as evidenced by significant differences in focusing of single versus multiple analytes. The EOF could be modulated by modifying the channel walls with an appropriate polymer, and this had the effect of increasing both the enrichment factors and resolution of the separation. Numerical simulations provide insights into the underlying fundamental principles for the experimental findings.
Dendritic Cells, Interleukin 12, and CD4+ Lymphocytes in the Initiation of Class l-restricted Reactivity to a Tumor/Self Peptide (1998)

Cell-mediated immunity involving CD8+ lymphocytes is effective in mediating rejection of murine mastocytoma cells bearing P815AB, a tumor-associated and self antigen showing similarity to tumor-specific shared antigens in humans. Although this antigen may act as an efficient target for class I-restricted responses in immunized mice, neither P815AB expressed on tumor cells nor a related synthetic nonapeptide will activate unprimed CD8+ cells for in vivo reactivity, measured by skin test assay. We review evidence showing that the failure of P815AB to initiate CD8+ cell reactivity may be due to defective recruitment of accessory and Th1-like cells to the afferent phase of the response initiated by transfer of mice with dendritic cells pulsed in vitro with the P815AB peptide. Although the copresence of a T helper peptide in dendritic cell priming in vitro with P815AB may compensate for the poor generation of accessory and Thl cells in the adoptively transferred mice, recombinant IL-12 can replace the helper peptide in both effects. Effective priming to P815AB in vivo is achieved by either exposing dendritic cells to IL-12 prior to P815AB priming or administering the recombinant cytokine in vivo. Different approaches suggest that IL-12 may act both on accessory cells to improve presentation of previously undescribed class II-restricted epitopes of P815AB and on CD4+ cells to improve recognition of such epitopes. In particular, at the CD4+ cell level, IL-12 apparently acts as an adjuvant and an inhibitor of anergy induction. These data offer useful information for developing vaccination strategies using dendritic cells and class I-restricted tumor peptides in humans.
Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation (2003)

The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment of human diseases. However, many of these proteins are from functional classes that have never been validated as viable candidates for the development of small molecule inhibitors. Thus, to exploit fully the potential of the Human Genome Project to advance human medicine, there is a need to develop generic methods of inhibiting protein activity that do not rely on the target protein's function. We previously demonstrated that a normally stable protein, methionine aminopeptidase-2 or MetAP-2, could be artificially targeted to an Skp1-Cullin-F-box (SCF) ubiquitin ligase complex for ubiquitination and degradation through a chimeric bridging molecule or Protac (proteolysis targeting chimeric molecule). This Protac consisted of an SCF(beta-TRCP)-binding phosphopeptide derived from IkappaBalpha linked to ovalicin, which covalently binds MetAP-2. In this study, we employed this approach to target two different proteins, the estrogen (ER) and androgen (AR) receptors, which have been implicated in the progression of breast and prostate cancer, respectively. We show here that an estradiol-based Protac can enforce the ubiquitination and degradation of the alpha isoform of ER in vitro, and a dihydroxytestosterone-based Protac introduced into cells promotes the rapid disappearance of AR in a proteasome-dependent manner. Future improvements to this technology may yield a general approach to treat a number of human diseases, including cancer.