gebhart/patrepeval huggingface dataset:
Covariance analysis of protein families: The case of the variable domains of antibodies (2000)

A nonrestrictive method for identifying covariance in protein families is described and applied to human and mouse germline Vkappa and VH sequence alignments. Amino acids that occur at each position in a sequence alignment are divided into two sets, called a word, by generating all possible combinations of alternative amino acids. Each word is associated with a pattern of changes. Words with identical patterns identify covariant positions. In antibody variable domains, the number of words generated ranged between 1103 and 2195 depending on the alignment, of which 4 to 12 % occurred in covariant pairs. Despite the nonrestrictive character of pattern generation, covariant residues did not reflect a random selection with respect to the nature of amino acid changes and/or their spatial proximity in a reference crystallographic structure. This approach allowed the identification of a covariance signal for positions with high variability, mostly located in the outer part of the common structural framework of antibody variable domains. Covariance in these regions may reflect the existence of alternative and mutually exclusive atomic arrangements that are compatible with antibody function. The method may be of general applicability to rationalize residue variability in protein families.
Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. (2001)

These results suggest that VEGF level is related to RA disease activity, suggesting that VEGF may play some role in the pathogenesis of RA.
The Adjudication of Labor Relations Disputes in Canada (1991)

Canada is a federal state consisting of ten provinces and two territories.Canada's Constitution' divides the powers of government between the federal government and the provinces in a manner that is similar to the division of powers between the federal government and the states in the United States.However, legislative jurisdiction over labor relations in Canada is vested primarily in the provinces.The "labor relations" jurisdiction of the federal government is restricted to employees of the federal government, inter-provincial transportation, and other institutions regulated by the federal government.Canadian industry is concentrated in Ontario, the largest Canadian province in terms of population, and Quebec.Seventy-five percent of Canada's industrial activity takes place in these two provinces.Herein will be discussed the dispute settlement mechanisms in Ontario and some that pertain to federal law.In so doing, virtually all types of Canadian labor and employment dispute resolution will be covered as most other provinces have similar labor relations regulatory systems. 2 II. THE REGULATION OF INDUSTRIAL RELATIONSIn Ontario, labor relations in the private sector are regulated by the Labour Relations Act.'The public sector is governed by two basic pieces of legislation: the Crown Employees Collective Bargaining Act, 4 which deals with public servants in Ontario, and the School Boards and Teachers' Collective Negotiations Act, 5 which regulates labor relations between public school teachers and school boards within the province of Ontario.There also exists special legislation which provides for interest arbitration including arbitration of disputes involving hospital employees, 6 police, 7 and firefighters.'
Remote Ischemic Preconditioning Protects against Liver Ischemia-Reperfusion Injury via Heme Oxygenase-1-Induced Autophagy (2014)

RIPC may protect the liver from IRI by induction of HO-1/p38-MAPK-dependent autophagy.
ANTIHISTAMINES IN TOPICAL PREPARATIONS (1973)

Antihistamines were introduced in France by Halpern in 1942 and in the United States at the end of World War II; they had been investigated extensively during the war for therapy of motion sickness. By the late 1940s, a mass of information on the structure activity relationship had accumulated and most major drug manufacturens had introduced antihistamines into the market for oral, parenteral, and topical administration. Topical use was efficacious in acute dermatitis because the local anesthetic activity of the drugs diminished pruritus. The first reports of sensitization to the topical antihistamines, which began to appear in 1947, incriminated tnipelennamine (Pyribenzamine), diphenhydramine (Benadryl), antazoline (Antistine), and pheniramine (Trimeton).1-4 In the ensuing 25 years, though thousands of instances of antihistamine contact dermatitis have occurred, many topical antihistamines remain on the market. The Committee is concerned about the use of topical antihistamines which are sold over the counter for use in such conditions as chickenpox and poison ivy. Table I lists most of the preparations currently available for topical use. CLASSES OF ANTIHISTAMINES The antihistamines are classified according to their chemical structure into five primary groups as shown in Table II. Each drug carries its own index of sensitization and other adverse effects when employed topically. The ethylenediamine derivatives include the following: antazoline phosphate (Antistine), promethazine hydrochloride (Phenergan*), and tripelennamine (Pyribenzamine). They are particularly active in inducing contact dermatitis and were responsible for the cases first reported.5,6 Ethylenediamine, because of its dibasic structure, is widely used in various organic syntheses for the preparation of dyes, inhibitors, rubber accelerators, fungicides, synthetic waxes, resins, insecticides, and asphalt-wetting agents.
Structure-activity relationships of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine antagonists for .mu.- and .kappa.-opioid receptors (1993)

A series of racemic N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines were evaluated for opioid agonist and antagonist activity at mu and kappa receptors. Several highly potent mu and kappa antagonists were discovered; however, no compounds with high selectivity for either the mu or kappa receptor were identified. Importantly, no derivative was found to have significant opioid agonist activity. Two derivatives were resolved, and the activities of the enantiomers were investigated. Only a limited stereochemical effect on opioid receptor selectivities was observed. The structure-activity relationships described establish the existence of an important lipophilic binding site distal to the nitrogen for both mu and kappa receptors and confirm the pure opioid antagonist pharmacophore nature of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine structure.
Preparation, Use, and Safety of O-Mesitylenesulfonylhydroxylamine (2009)

The aminating reagent O-mesitylsulfonylhydroxylamine (MSH) has a known potential hazard since it contains high-energy functional groups in its structure. There are references in the literature that report several incidents involving the use of pure and crystalline MSH. The preparation and safe use of this reagent at kilo scale are described herein.
High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations (2009)

Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies. For the top-ranking 1,000 compounds obtained by docking to a target protein, approximately 6,000 molecular dynamics simulations were performed using multiple docking poses in about a week. As a result, the enrichment performance of the top 100 compounds by our approach was improved by 1.6-4.0 times that of the enrichment performance of molecular dockings. This result indicates that the application of molecular dynamics simulations to virtual screening for lead discovery is both effective and practical. However, further optimization of the computational protocols is required for screening various target proteins.
TNF‐α induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3‐L1 adipocytes (2003)

Tumor necrosis factor-alpha (TNF-alpha) increases adipocyte lipolysis after 6-12 h of incubation. TNF-alpha has been demonstrated to activate mitogen-activated protein (MAP) kinases including extracellular signal-related kinase (ERK) and N-terminal-c-Jun-kinase (JNK) in different cell types. To determine if the MAP kinases have a role in TNF-alpha-induced lipolysis, 3T3-L1 adipocytes were treated with the cytokine (10 ng/ml), in the presence or absence of PD98059 or U0126 (100 micromoles), specific inhibitors of ERK activity. We demonstrated that U0126 or PD98059 blocked TNF-alpha-induced ERK activity and decreased TNF-alpha-induced lipolysis by 65 or 76% respectively. The peroxisome-proliferator-activated receptor gamma (PPARgamma) agonists, rosiglitazone (ros), and 15-deoxy-Delta-(12,14)- prostaglandin J(2) (PGJ2) have been demonstrated to block TNF-alpha-induced lipolysis. Pretreatment of adipocytes with these agents almost totally blocked TNF-alpha-induced ERK activation and reduced lipolysis by greater than 90%. TNF-alpha also stimulated JNK activity, which was not affected by PD98059 or PPARgamma agonist treatment. The expression of perilipin, previously proposed to contribute to the mechanism of lipolysis, is diminished in response to TNF-alpha treatment. Pretreatment of adipocytes with PD98059 or ros significantly blocked the TNF-alpha-induced reduction of perilipin A protein level as determined by Western analysis. These data suggest that activation of the ERK pathway is an early event in the mechanism of TNF-alpha-induced lipolysis.
Multi-User MIMO with flexible numerology for 5G (2016)

Flexible numerologies are being considered as part of designs for 5G systems to support vertical services with diverse requirements such as enhanced mobile broadband, ultra-reliable low-latency communications, and massive machine type communication. Different vertical services can be multiplexed in either frequency domain, time domain, or both. In this paper, we investigate the use of spatial multiplexing of services using MU-MIMO where the numerologies for different users may be different. The users are grouped according to the chosen numerology and a separate pre-coder and FFT size is used per numerology at the transmitter. The pre-coded signals for the multiple numerologies are added in the time domain before transmission. We analyze the performance gains of this approach using capacity analysis and link level simulations using conjugate beamforming and signal-to-leakage noise ratio maximization techniques. We show that the MU interference between users with different numerologies can be suppressed efficiently with reasonable number of antennas at the base-station. This feature enables MU-MIMO techniques to be applied for 5G across different numerologies.
Wnt Signaling Enhances Neurogenesis and Improves Neurological Function after Focal Ischemic Injury (2012)

Stroke potently stimulates cell proliferation in the subventricular zone of the lateral ventricles with subsequent neuroblast migration to the injured striatum and cortex. However, most of the cells do not survive and mature. Extracellular Wnt proteins promote adult neurogenesis in the neurogenic niches. The aim of the study was to examine the efficacy of Wnt signaling on neurogenesis and functional outcome after focal ischemic injury. Lentivirus expressing Wnt3a-HA (LV-Wnt3a-HA) or GFP (LV-GFP) was injected into the striatum or subventricular zone of mice. Five days later, focal ischemic injury was induced by injection of the vasoconstrictor endothelin-1 into the striatum of the same hemisphere. Treatment with LV-Wnt3a-HA into the striatum significantly enhanced functional recovery after ischemic injury and increased the number of BrdU-positive cells that differentiated into mature neurons in the ischemic striatum by day 28. Treatment with LV-Wnt3a-HA into the subventricular zone significantly enhanced functional recovery from the second day after injury and increased the number of immature neurons in the striatum and subventricular zone. This was accompanied by reduced dissemination of the neuronal injury. Our data indicate that Wnt signaling appears to contribute to functional recovery after ischemic injury by increasing neurogenesis or neuronal survival in the striatum.
Suppression of reverse short channel effect by nitrogen implantation and its implications on nitrogen as a dopant species for applications in 0.25 μm technology (2002)

Nitrogen implantation into the channel region was used for the reduction of the Reverse Short Channel Effect(RSCE). This approach was found to be very effective in reducing the RSCE without adverse effects on the short channel behavior. The reduction of the RSCE is believed to be due to the implanted nitrogen ions. These implanted nitrogen ions retards the redistribution of the channel boron concentration, which is believed to be the cause of the RSCE. Threshold voltage shifts were observed in both n- and p-ch MOSFETs. We propose that these threshold voltage shifts are due to the partial activation of the nitrogen atoms that have taken up substitutional sites in the silicon lattice and thus behave as a dopant species for silicon.
Perspectives on lymphangiogenesis and angiogenesis in cancer (2011)

Tumor-associated neovascularization allows tumor cells to express their critical growth advantage, whereas lymphatic invasion is crucial for the metastatic process. Various growth factors stimulate blood and lymphatic neovascularization and modulate vessel permeability in tumors. The first anti-angiogenic drugs are already in routine use, and new anti-vascular therapeutics are evaluated in clinical trials. Conversely, pro-lymphangiogenic therapy could be implemented to treat cancer survivors suffering from secondary lymphedema.
Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β (1997)

The rat estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand binding domain and in the N-terminal transactivation domain. In this study we investigated the messenger RNA expression of both ER subtypes in rat tissues by RT-PCR and compared the ligand binding specificity of the ER subtypes. Saturation ligand binding analysis of in vitro synthesized human ER alpha and rat ER beta protein revealed a single binding component for 16 alpha-iodo-17 beta-estradiol with high affinity [dissociation constant (Kd) = 0.1 nM for ER alpha protein and 0.4 nM for ER beta protein]. Most estrogenic substances or estrogenic antagonists compete with 16 alpha-[125I]iodo-17 beta-estradiol for binding to both ER subtypes in a very similar preference and degree; that is, diethylstilbestrol > hexestrol > dienestrol > 4-OH-tamoxifen > 17 beta-estradiol > coumestrol, ICI-164384 > estrone, 17 alpha-estradiol > nafoxidine, moxestrol > clomifene > estriol, 4-OH-estradiol > tamoxifen, 2-OH-estradiol, 5-androstene-3 beta, 17 beta-diol, genistein for the ER alpha protein and dienestrol > 4-OH-tamoxifen > diethylstilbestrol > hexestrol > coumestrol, ICI-164384 > 17 beta-estradiol > estrone, genistein > estriol > nafoxidine, 5-androstene-3 beta, 17 beta-diol > 17 alpha-estradiol, clomifene, 2-OH-estradiol > 4-OH-estradiol, tamoxifen, moxestrol for the ER beta protein. The rat tissue distribution and/or the relative level of ER alpha and ER beta expression seems to be quite different, i.e. moderate to high expression in uterus, testis, pituitary, ovary, kidney, epididymis, and adrenal for ER alpha and prostate, ovary, lung, bladder, brain, uterus, and testis for ER beta. The described differences between the ER subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER agonists and antagonists in different tissues.
A Highly Active Zinc Catalyst for the Controlled Polymerization of Lactide (2003)

We report the preparation, structural characterization, and detailed lactide polymerization behavior of a new Zn(II) alkoxide complex, (L(1)ZnOEt)(2) (L(1) = 2,4-di-tert-butyl-6-{[(2'-dimethylaminoethyl)methylamino]methyl}phenolate). While an X-ray crystal structure revealed the complex to be dimeric in the solid state, nuclear magnetic resonance and mass spectrometric analyses showed that the monomeric form L(1)ZnOEt predominates in solution. The polymerization of lactide using this complex proceeded with good molecular weight control and gave relatively narrow molecular weight distribution polylactide, even at catalyst loadings of <0.1% that yielded M(n) as high as 130 kg mol(-)(1). The effect of impurities on the molecular weight of the product polymers was accounted for using a simple model. Detailed kinetic studies of the polymerization reaction enabled integral and nonintegral orders in L(1)ZnOEt to be distinguished and the empirical rate law to be elucidated, -d[LA]/dt = k(p)[L(1)ZnOEt][LA]. These studies also showed that L(1)ZnOEt polymerizes lactide at a rate faster than any other Zn-containing system reported previously. This work provides important mechanistic information pertaining to the polymerization of lactide and other cyclic esters by discrete metal alkoxide complexes.
Current status of radionuclide tracer imaging of thrombi and atheroma (1999)

The imaging of thrombi and atherosclerotic plaques has great potential for decision making in the management of patients with all types of disease within the circulatory system. This importance is owing to the developments showing that areas of moderate stenosis with underlying atheroma are physiologically reactive and capable of causing reversible clinical symptoms that can progress to irreversible end-organ damage if not effectively treated. Identifying and quantifying areas of smaller vulnerable plaque and areas of acute thrombosis will assist in identification of patients at risk and help determine when and how to treat these patients. Initial efforts in this area used nonspecific constituents of thrombi and atheroma that were radiolabeled using long-lived isotopes, which had high background activity that required imaging over 48 to 72 hours. Newer approaches have focused on the use of small antibody fragments or small peptides, so-called molecular recognition units, that specifically target antigens present only in areas of thrombosis or active atherogenesis. These compounds are labeled Technetium-99 m (99mTc) and provide excellent images. Efforts to image thrombi have been directed at the IIB/IIIA receptor, which is present in low concentration on the cell membrane of circulating quiescent platelets, but on stimulation and active thrombosis, more than 80,000 potential binding sites per platelet appear. One such peptide has been clinically approved for imaging of deep vein thrombophlebitis. Parallel efforts are being made for imaging areas of active atherogenesis by targeting smooth muscle cells and other constituents unique for vulnerable plaques. Efforts in developing these modalities are important to expand the applications to new areas in nuclear cardiology.
Outer Membrane Permeability Barrier in Escherichia coli Mutants That Are Defective in the Late Acyltransferases of Lipid A Biosynthesis (1999)

The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that the Escherichia coli msbB mutant, which elaborates defective, penta-acylated lipid A, is practically as resistant to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control strain. The susceptibility index, i.e., the approximate ratio between the MIC for the msbB mutant and that for the parent-type control, was maximally 2.7-fold. In comparison, the rfa mutant defective in the deep core oligosaccharide part of LPS displayed indices ranging from 20 to 64. The lpxA and lpxD lipid A mutants had indices higher than 512. Furthermore, the msbB mutant was resistant to glycopeptides (vancomycin, teicoplanin), whereas the rfa, lpxA, and lpxD mutants were susceptible. The msbB htrB double mutant, which elaborates even-more-defective, partially tetra-acylated lipid A, was still less susceptible than the rfa mutant. These findings indicate that hexa-acylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.
Assessing White Wine Viscosity Variation Using Polarized Laser Speckle: A Promising Alternative to Wine Sensory Analysis (2017)

In this paper, we report measurements of wine viscosity, correlated to polarized laser speckle results. Experiments were performed on white wine samples produced with a single grape variety. Effects of the wine making cellar, the grape variety, and the vintage on wine Brix degree, alcohol content, viscosity, and speckle parameters are considered. We show that speckle parameters, namely, spatial contrast and speckle decorrelation time, as well as the inertia moment extracted from the temporal history speckle pattern, are mainly affected by the alcohol and sugar content and hence the wine viscosity. Principal component analysis revealed a high correlation between laser speckle results on the one hand and viscosity and Brix degree values on the other. As speckle analysis proved to be an efficient method of measuring the variation of the viscosity of white mono-variety wine, one can therefore consider it as an alternative method to wine sensory analysis.
Dietary Fat Intake and the Risk of Coronary Heart Disease in Women (1997)

Our findings suggest that replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.
Low-complexity algorithms for large-MIMO detection (2010)

Low-complexity near-optimal detection of large multiple-input multiple-output (MIMO) signals has attracted recent research attention. Recently, it has been shown that certain algorithms rooted in machine learning/artificial intelligence are well suited to achieve near-optimal detection performance in MIMO systems with large number (tens) of antennas at practically affordable complexities. In this paper, we present three such low-complexity algorithms that we have proposed recently, and compare their bit error rate performance and complexities in large-MIMO detection. These algorithms include two local neighborhood search based algorithms, namely, likelihood ascent search (LAS) and reactive tabu search (RTS) algorithms, and a message passing algorithm based on and belief propagation (BP). Feasibility of such low-complexity algorithms for large-MIMO detection can enable practical implementation of high-spectral efficiency (tens to hundreds of bps/Hz) large-MIMO systems.