gebhart/patrepeval huggingface dataset:
Molecular Dynamics Simulation of Cocaine Binding with Human Butyrylcholinesterase and Its Mutants (2005)

Molecular dynamics (MD) simulations were carried out to study cocaine binding with wild-type human butyrylcholinesterase (BChE) and its mutants based on a recently reported X-ray crystal structure of human BChE. For each BChE-cocaine system, we simulated both the nonprereactive and prereactive complexes in water. Despite the significant difference found at the acyl binding pocket, the simulated structures confirm the fundamental structural and mechanistic insights obtained from earlier computational studies of wild-type BChE with cocaine based on a homology model, e.g. the rate-determining step for BChE-catalyzed hydrolysis of biologically active (-)-cocaine is the (-)-cocaine rotation in the active site from the nonprereactive BChE-(-)-cocaine complex to the prereactive complex. It has been demonstrated that the MD simulations on both the nonprereactive and prereactive BChE-cocaine complexes can clearly reveal whether specific mutations produce the desired BChE-(-)-cocaine binding structures in which the (-)-cocaine rotation is less hindered while the required prereactive BChE-(-)-cocaine binding is maintained. Based on the MD simulations, both A328W/Y332A and A328W/Y332G BChE's are expected to have catalytic activity for (-)-cocaine hydrolysis higher than that of wild-type BChE and the activity of A328W/Y332G BChE should be slightly higher than that of A328W/Y332A BChE due to the less-hindered (-)-cocaine rotation in the mutant BChE's. However, the less-hindered (-)-cocaine rotation is only a necessary condition for a higher activity mutant BChE. The (-)-cocaine rotation is also less hindered in A328W/Y332A/Y419S BChE, but (-)-cocaine binds with A328W/Y332A/Y419S BChE in a way that is not suitable for the catalysis. Thus, A328W/Y332A/Y419S BChE is expected to lose the catalytic activity. The computational predictions were confirmed by our experimental kinetic data, demonstrating that the MD simulation-based computational protocol used in this study is reliable in prediction of the catalytic activity of BChE mutants for (-)-cocaine hydrolysis.
Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain (2009)

Given the advantages of being stable in the ambient environment, being permeable to the blood-brain and/or blood-eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague-Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer's disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, preclinical data to justify bringing such therapeutic compounds to clinical trials in humans is feasible.[This corrects the article on p. in vol. .].
Research on Speech Enhancement Based on Wiener Filtering (2014)

eech enhancement based on Wiener filtering has good noise robustness, and it is efficient and easy-to-implement. In this paper, Wiener filtering and its modified form, Iterative Wiener Filtering are demonstrated. Then, their respective advantages and disadvantages are outlined. Finally, the application field and location of each method are also pointed out.
Design, Synthesis, and Enzymatic Evaluation of N-Acyloxyalkyl- and N1-Oxazolidin-2,4-dion-5-yl-Substituted β-lactams as Novel Inhibitors of Human Leukocyte Elastase (2005)

Human leukocyte elastase (HLE) is a serine protease that very efficiently degrades various tissue matrix proteins such as elastin. The imbalance between HLE and its endogenous inhibitors leads to excessive elastin proteolysis and is considered to be responsible for the onset of chronic obstructive pulmonary disease (COPD). A novel series of C-3-, C-4-, and N-1-substituted azetidin-2-ones were prepared as potential mechanism-based inhibitors of HLE to restore the protease/antiprotease imbalance. N-Acyloxyalkylazetidin-2-ones, 4, and their carbamate counterparts, 5, are weak HLE inhibitors, being 5 times less active than their bicyclic oxazolidin-2,4-dione-substituted analogues, 6, containing an electron-withdrawing substituent at C-4. Compounds 6 containing a C-4 substituent exist as two diastereomeric pairs of enantiomers, each pair presenting similar inhibitory activity against HLE. Comparative docking experiments with the C-4-substituted oxazolidin-2,4-dione inhibitors 6 suggest that only the 4R,5'S and 4S,5'S diastereomers consistently interact with the beta-lactam carbonyl carbon atom accessible to the serine hydroxyl oxygen.
Primary structure of lymphocyte function-associated antigen 3 (LFA-3). The ligand of the T lymphocyte CD2 glycoprotein. (1987)

We have isolated the cDNA for human lymphocyte function-associated antigen 3 (LFA-3), the ligand of the T lymphocyte CD2 molecule. The identity of the clones was established by comparison of the deduced amino acid sequence to the LFA-3 NH2-terminal and tryptic peptide sequences. The cDNA defines a mature protein of 222 amino acids that structurally resembles typical membrane-anchored proteins. An extracellular domain with six N-linked glycosylation sites is followed by a hydrophobic putative transmembrane region and a short cytoplasmic domain. The mature glycoprotein is estimated to be 44-68% carbohydrate. Southern blots of human genomic DNA indicate that only one gene codes for human LFA-3. Northern blot analysis demonstrates that the LFA-3 mRNA of 1.3 kb is widely distributed in human tissues and cell lines.
Detection of circulating tumor cells in carcinoma patients by a novel epidermal growth factor receptor reverse transcription-PCR assay. (2000)

The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells. We developed a novel reverse transcription-PCR (RT-PCR)-Southern blot assay for the detection of circulating, EGFR mRNA-expressing tumor cells in carcinoma patients. The assay was set up by increasing the amount of cDNA step by step in the PCR reaction. The highest sensitivity and specificity were found when using 800 ng of cDNA in the PCR reaction. Peripheral blood samples from 91 patients with either colon (38), lung (30), or breast (23) carcinomas and from 38 healthy volunteers were analyzed. EGFR transcripts were found in 44 of 75 (59%) patients with metastatic carcinoma and in 4 of 38 (10.5%) healthy donors (P < 0.001; chi2 test). The expression of EGFR, cytokeratin 19, and carcinoembryonic antigen mRNA in blood samples from patients with metastatic colon carcinoma was compared. EGFR, cytokeratin 19, and carcinoembryonic antigen transcripts were found in 8 of 11 (73%), 3 of 11 (27%), and 5 of 11 (45%) patients, respectively. Furthermore, two of seven (29%) Dukes' B and five of nine (55%) Dukes' C colon carcinoma patients were found to express EGFR mRNA in the peripheral blood. All patients that expressed EGFR transcripts in the peripheral blood were found to express the EGFR protein in the corresponding primary carcinoma, as assessed by immunohistochemistry. These data suggest that the EGFR assay that we developed is a highly specific and sensitive technique to detect circulating tumor cells in patients affected by different carcinoma types.
Demonstration of subthrehold swing smaller than 60mV/decade in Fe-FET with P(VDF-TrFE)/SiO<inf>2</inf> gate stack (2008)

This work experimentally demonstrates, for the first time, that by integrating a thin ferroelectric layer into a gate stack of a standard MOS transistor one, it is possible to overcome the 60 mV/decade subthreshold swing limit at room temperature of MOSFET. We find sub-threshold swings as low as 13 mV/decade in Fe-FETs with 40 nm P(VDF-TrFE)/SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> gate stack. The mechanism governing the low subthreshold swing in Fe-FET transistors is the negative capacitance of the ferroelectric layer that provides voltage amplification; with our particular ferroelectric gate stack we report for the first time negative capacitance at room temperature.
Isolation of species-specific protein antigens of Rickettsia typhi and Rickettsia prowazekii for immunodiagnosis and immunoprophylaxis (1981)

A simple procedure for the selective isolation of the protective species-specific protein antigens (SPAs) of Rickettsia typhi and Rickettsia prowazekii was developed to permit use of the SPAs in the immunodiagnosis and immunoprophylaxis of typhus infections. Although the SPAs were readily extracted from lysozyme- or detergent-treated rickettsiae, as measured by rocket immunoelectrophoresis, other polypeptides were also present, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast, both water and seven buffers, each at a 10 mM concentration and pH 7.6, were nearly equally effective in the selective release of the SPAs from whole cells by extraction for 30 min at 45 degrees C. High-ionic-strength buffers and MgCl2 abolished this SPA release, thus suggesting that divalent cations were important in the binding of the SPAs to the cell envelope. The efficacy of the dilute buffer extraction procedure for isolation of large amounts of SPAs was tested by further characterization of the supernatants obtained by centrifugation (200,000 x g) of two successive tris-(hydroxymethyl)aminomethane-hydrochloride buffer (Tris) extracts. With this procedure, between 10 and 15 mg of SPA was obtained from 100 mg of purified rickettsiae. Although low-molecular-weight ribonucleic acid fragments were released into the Tris extracts in significant amounts, only the SPAs were detected, in significant quantities, as measured by polyacrylamide gel electrophoresis and rocket immunoelectrophoresis. The Tris extracts contained the same major and minor SPA polypeptides as those observed previously in SPA preparations obtained by extensive diethylaminoethyl-cellulose column chromatography, but the Tris SPAs were more satisfactory antigens in an enzyme-linked immunosorbent assay.
Binding of Heparin Fractions to von Willebrand Factor: Effect of Molecular Weight and Affinity for Antithrombin III (1994)

To investigate the influence of the structure of heparin on its binding to vWF, we compared heparin fractions of different molecular weight (MW) or affinity for antithrombin III (ATIII). We studied the interaction of purified 125I-vWF or plasma vWF, labeled with a pool of 125I-monoclonal antibodies to vWF, with unfractionated heparin immobilized on agarose beads. Fractions were compared as competitors of these interactions and their effect was quantitated by their half-maximal inhibition (IC50). When the MW of the fractions decreased, especially below 7500, their IC50 increased, indicating that the affinity of the fractions for vWF decreased with their MW. Using heparin-derived oligosaccharides, we also demonstrated that a minimal chain length of 18 monosaccharides was required for heparin binding to vWF. In addition, different fractions with low affinity for ATIII were compared as competitors of 125I-vWF binding to heparin-agarose. Despite a very low content of ATIII binding sites, some fractions retained a low IC50. Thus, heparin interaction with vWF is independent of the presence of the ATIII binding site and is mostly dependent on the length of the heparin chain. These data suggest that unfractionated heparin is a more potent inhibitor of vWF-dependent functions than low MW heparin fractions.
Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model (2001)

Local delivery provides high levels of Lu-Tex selectively within atheroma. Photoactivation results in a significant decrease in macrophage and a small decrease in atheroma burden without damage to the normal vessel wall.
Sex Ratio after Insemination of Bovine Spermatozoa Isolated using a Bovine Serum Albumin Gradient (1984)

This experiment was undertaken to determine if a method reported to successfully enrich the proportion of Y-chromosome-bearing spermatozoa in human semen could be adapted for separation of bovine spermatozoa. Semen was collected from four Angus bulls and aliquots were either separated on discontinuous gradients of bovine serum albumin (BSA) or untreated before processing for cryopreservation. Two hundred seventy-one cows or heifers were assigned randomly to be artificially inseminated (20 X 10(6) sperm/insemination) with separated or unseparated spermatozoa. The proportions of male offspring were 45 and 54% after inseminations with separated or unseparated spermatozoa, respectively. In a second phase of the experiment, pooled semen from three Holstein bulls was either extended and frozen without separation or frozen after separation using the discontinuous BSA gradient. Separated and unseparated spermatozoa were analyzed by flow cytometry to determine the ratio of X- and Y-chromosome-bearing spermatozoa based on differences in DNA content. The ratios of X- and Y-bearing spermatozoa in separated or unseparated samples were indistinguishable. We concluded that the separation method did not enrich the proportion of Y-bearing bovine spermatozoa.
Least Squares Generative Adversarial Networks (2016)

Unsupervised learning with generative adversarial networks (GANs) has proven hugely successful. Regular GANs hypothesize the discriminator as a classifier with the sigmoid cross entropy loss function. However, we found that this loss function may lead to the vanishing gradients problem during the learning process. To overcome such a problem, we propose in this paper the Least Squares Generative Adversarial Networks (LSGANs) which adopt the least squares loss function for the discriminator. We show that minimizing the objective function of LSGAN yields minimizing the Pearson $χ^2$ divergence. There are two benefits of LSGANs over regular GANs. First, LSGANs are able to generate higher quality images than regular GANs. Second, LSGANs perform more stable during the learning process. We evaluate LSGANs on five scene datasets and the experimental results show that the images generated by LSGANs are of better quality than the ones generated by regular GANs. We also conduct two comparison experiments between LSGANs and regular GANs to illustrate the stability of LSGANs.
Variable-focus microlenses: Issues for confocal imaging (2005)

We present the investigation of integration of Variable Focal Length (VFL) microlenses into the confocal system. VFL microlenses acting as an array of objective lenses is examined with a novel method for scanning in the axial direction presented. By variation of the focal length of the lenses the focal plane can be scanned through the sample without the mechanical movement of the sample or the objective lens, we have named this 'focal scanning'. Some of the issues related to this experiment are noted and discussed, in particular with reference to the low Numerical Aperture (NA) of the VFL microlenses available. Proposed solutions to these issues deal with the design of higher NA microlenses.
<title>Design of a waveguide refractive index profile to obtain a flat modal field</title> (1999)

We present here a refractive index profile design which can enable us to obtain a flat modal field (FMF) around the center. The design can be used to obtain FMF both for planar waveguides as well as for fibers. The design can be useful in reducing non-linear effects in fibers.
Phage-Derived Fully Human Monoclonal Antibody Fragments to Human Vascular Endothelial Growth Factor-C Block Its Interaction with VEGF Receptor-2 and 3 (2010)

Vascular endothelial growth factor C (VEGF-C) is a key mediator of lymphangiogenesis, acting via its receptors VEGF-R2 and VEGF-R3. High expression of VEGF-C in tumors correlates with increased lymphatic vessel density, lymphatic vessel invasion, sentinel lymph node metastasis and poor prognosis. Recently, we found that in a chemically induced skin carcinoma model, increased VEGF-C drainage from the tumor enhanced lymphangiogenesis in the sentinel lymph node and facilitated metastatic spread of cancer cells via the lymphatics. Hence, interference with the VEGF-C/VEGF-R3 axis holds promise to block metastatic spread, as recently shown by use of a neutralizing anti-VEGF-R3 antibody and a soluble VEGF-R3 (VEGF-C/D trap). By antibody phage-display, we have developed a human monoclonal antibody fragment (single-chain Fragment variable, scFv) that binds with high specificity and affinity to the fully processed mature form of human VEGF-C. The scFv binds to an epitope on VEGF-C that is important for receptor binding, since binding of the scFv to VEGF-C dose-dependently inhibits the binding of VEGF-C to VEGF-R2 and VEGF-R3 as shown by BIAcore and ELISA analyses. Interestingly, the variable heavy domain (V(H)) of the anti-VEGF-C scFv, which contains a mutation typical for camelid heavy chain-only antibodies, is sufficient for binding VEGF-C. This reduced the size of the potentially VEGF-C-blocking antibody fragment to only 14.6 kDa. Anti-VEGF-C V(H)-based immunoproteins hold promise to block the lymphangiogenic activity of VEGF-C, which would present a significant advance in inhibiting lymphatic-based metastatic spread of certain cancer types.
Synthesis of tetanus toxin fragment C in insect cells by use of a baculovirus expression system (1991)

The baculovirus expression vector p36C was used to express in cells of the insect Spodoptera frugiperda fragment C of tetanus toxin under the control of the strong polyhedrin promoter. Fragment C was expressed intracellularly at a high level and was soluble, allowing it to be purified by affinity chromatography with monoclonal antibody TT08. Purified fragment C from baculovirus was used to immunize mice and was shown to successfully prevent the symptoms of tetanus following a toxin challenge. The ganglioside-binding properties of baculovirus-derived fragment C were compared with those of intact tetanus toxin and native fragment C and were found to be dissimilar.
Differential and pass-transistor CMOS logic for high-performance systems (2002)

This paper presents a review of differential and pass-transistor logic used in today's high-performance systems. Various circuit and logic design styles used in contemporary high-performance processors have been reviewed. The new logic is advantageous over standard CMOS in terms of performance and very often in terms of: area, speed and power as well. Evolution of various high-performance latches has been presented.
Condensation coefficients of noble metals on polymers: a novel method of determination by x-ray photoelectron spectroscopy (2000)

We developed a method to determine condensation coefficients, C, of noble metals on polymer surfaces and to determine cluster sizes by means of XPS only, or in combination with transmission electron microscopy (TEM). The surface concentration of the adatoms was determined using a mathematical correction of the XPS intensity that takes into account cluster growth of the noble metals on the polymer surfaces. We establish our method with experimental results of C for Cu and Ag on pyromellitic dianhydride (PMDA)–4,4′-oxydianiline (ODA) polyimide, bisphenol-A polycarbonate, trimethylcyclohexane bisphenol-A polycarbonate, polystyrene and Teflon AF 1601. Values of C for Ag determined with the XPS method agree well with those of radiotracer measurements. The condensation coefficient varies by three orders of magnitude from 1 to 0.002, depending on the deposition parameters and properties of the adsorbents. The method can be applied in general to investigate the deposition of non-wetting metals on solid surfaces. Copyright © 2000 John Wiley & Sons, Ltd.
Desorption of CO from Ru(001) induced by near-infrared femtosecond laser pulses (2000)

Irradiation of a Ru(001) surface covered with CO using intense femtosecond laser pulses (800 nm, 130 fs) leads to desorption of CO with a nonlinear dependence of the yield on the absorbed fluence (100–380 J/m2). Two-pulse correlation measurements reveal a response time of 20 ps (FWHM). The lack of an isotope effect together with the strong rise of the phonon temperature (2500 K) and the specific electronic structure of the adsorbate–substrate system strongly indicate that coupling to phonons is dominant. The experimental findings can be well reproduced within a friction-coupled heat bath model. Yet, pronounced dynamical cooling in desorption, found in the fluence-dependence of the translational energy, and in a non-Arrhenius behavior of the desorption probability reflect pronounced deviations from thermal equilibrium during desorption taking place on such a short time scale.
The PR Domain of the Rb-binding Zinc Finger Protein RIZ1 Is a Protein Binding Interface and Is Related to the SET Domain Functioning in Chromatin-mediated Gene Expression (1998)

The PR domain, first noted as the PRDI-BF1-RIZ1 homologous region, defines a sub-class of zinc finger genes that appear to function as negative regulators of tumorigenesis. This family includes the MDS1-EVI1 gene inactivated in myeloid leukemia, the PRDI-BF1/BLIMP1 transcription repressor of c-myc involved in driving B-cell differentiation, and the RIZ gene, which encodes proteins capable of binding to the retinoblastoma tumor suppressor protein (Rb). The PR domain of MDS1-EVI1 is disrupted by translocations linked to myeloid leukemia, resulting in the activation of the PR-minus oncogenic product EVI1. Remarkably similar to MDS1-EVI1, RIZ gene also normally produces two protein products of different length, and the smaller protein RIZ2 lacks the PR domain of RIZ1 but is otherwise identical to RIZ1. These observations raise considerable interest to determine the function of PR. We show here that RIZ1 PR domain mediates protein-protein interaction. Recombinant fusion proteins of PR can bind to in vitro translated RIZ1 and RIZ2 proteins. The binding can be disrupted by amino acid substitutions at conserved residues of PR, suggesting that binding is specific. Of the three conserved exons of PR, the first two appear dispensable for binding, whereas the third exon is required. A region in the carboxyl terminus of RIZ proteins was mapped to be necessary and sufficient for PR binding. We also found that the PR domain shares significant sequence identity to the SET domain present in chromosomal proteins that function in modulating gene expression from yeast to mammals. Our data suggest that the PR domain is a derivative of SET domain and may function as protein binding interface in the regulation of chromatin-mediated gene expression.