gebhart/patrepeval huggingface dataset:
A Rapid Electrochemical Method for Determining Rate Coefficients for Copper-Catalyzed Polymerizations (2011)

Copper(I) polyamine complexes have emerged as excellent atom-transfer radical polymerization catalysts. The rate of their reaction with organic halide initiators (the so-called activation step) varies across a broad range, depending on both the structure of the copper complex and the initiator. Herein, we report a new technique for determining the rate of copper-catalyzed activation (k(act)) using cyclic voltammetry coupled with electrochemical simulation. This method is applied to measuring k(act) for one of the most active catalysts, [Cu(I)(Me(6)tren)](+) (Me(6)tren = N,N,N-tris-(2-(dimethylamino)ethyl)amine), in reaction with ethyl bromoisobutyrate.
Differential expression of arachidonate 5-lipoxygenase transcripts in human brain tumors: evidence for the expression of a multitranscript family. (1992)

In addition to the important role of leukotrienes as mediators in allergy and inflammation, these compounds are also linked to pathophysiological events in the brain including cerebral ischemia, brain edema, and increased permeability of the blood-brain barrier in brain tumors. Although brain tumors have been shown to secrete leukotrienes, no studies to date have provided evidence for the tumor expression of genes encoding enzymes involved in leukotriene production. Therefore, the present study determined the abundance of the mRNA for arachidonate 5-lipoxygenase (5-LO; arachidonate:oxygen 5-oxidoreductase, EC 1.13.11.34), which is the rate-limiting enzyme in leukotriene synthesis, in a series of human brain tumors. Macrophage/monocyte infiltration of the tumor was estimated by measuring the abundance of the transcript for the 91-kDa glycoprotein phagocyte-specific oxidase (gp91-phox), which is the phagocyte-specific cytochrome b heavy chain. The present study shows that (i) the 5-LO transcript is expressed in normal bovine brain and in human brain tumors; (ii) the 5-LO gene in human brain tumors and in the dimethyl sulfoxide-induced promyelocytic human leukemic HL-60 cells is expressed as a multitranscript family (2.7, 3.1, 4.8, 6.4, 8.6 kilobases); and (iii) the abundance of 5-LO transcripts, the expression of the larger transcripts, and the 5-LO/gp91-phox ratio correlate with the tumor malignancy. Overall, the present study supports the hypothesis that the 5-LO gene product may play a role in human tumor-induced brain edemas and provides evidence for tumor-associated expression of high molecular weight 5-LO transcripts in human brain tumors.
Curious model-building control systems (1991)

A novel curious model-building control system is described which actively tries to provoke situations for which it learned to expect to learn something about the environment. Such a system has been implemented as a four-network system based on Watkins' Q-learning algorithm which can be used to maximize the expectation of the temporal derivative of the adaptive assumed reliability of future predictions. An experiment with an artificial nondeterministic environment demonstrates that the system can be superior to previous model-building control systems, which do not address the problem of modeling the reliability of the world model's predictions in uncertain environments and use ad-hoc methods (like random search) to train the world model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Advanced Groupband Data Modem Using Orthogonally Multiplexed QAM Technique (1986)

An advanced groupband data modem based on the orthogonally multiplexed QAM technique is proposed. Its performance is evaluated through experiments. In the proposed modem, data are transmitted by a number of orthogonally multiplexed parallel subchannels. Because of this orthogonally multiplexing parallelism, the proposed modem becomes more immune to Gaussian noises, impulsive noises, and channel distortions, compared to the conventional Class IV partial response VSB modem. Furthermore, the orthogonally multiplexed QAM modem retains high flexibility in multiplexing a variety of data terminals and in carrying out fallback operation to a wide range of data rates. Experimental results demonstrate the robustness of the proposed groupband data modem.
Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli–Induced Acute Respiratory Distress Syndrome (2016)

Our results demonstrate that freshly thawed cryopreserved xeno-free human umbilical cord-mesenchymal stem/stromal cells reduce the severity of rodent E. coli-induced acute respiratory distress syndrome. Umbilical cord-mesenchymal stem/stromal cells, therefore, represent an attractive option for future clinical trials in acute respiratory distress syndrome.
Microarray based analysis of an inherited terminal 3p26.3 deletion, containing only the CHL1 gene, from a normal father to his two affected children (2011)

a terminal 3p26.3 deletion including only the CHL1 gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.
Enzymatic labeling of a single chain variable fragment of an antibody with alkaline phosphatase by microbial transglutaminase (2004)

Functional cross-linking of a single chain Fv fragment of anti-hen egg-white lysozyme antibody (scFv) and alkaline phosphatase (AP) was explored using microbial transglutaminase (MTG) from Streptomyces mobaraensis. A specific peptidyl linker for MTG was genetically fused to the N-terminus of each protein and the resultant proteins were obtained separately by bacterial expression. The recombinant peptide-tagged scFv and AP were site-specifically cross-linked by MTG through the extra peptidyl linkers in vitro, which mainly yielded the heterodimer (i.e., scFv-AP conjugate). The enzymatic cross-linking reaction had little influence on either the antigen-binding ability of the scFv moiety or the enzymatic activity of the AP moiety of the conjugate, allowing use within an enzyme-linked immunosorbent assay. The results obtained suggest that the enzymatic approach with MTG facilitates the posttranslational construction of functional fusion proteins.
High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria (1997)

Formation of H2O2 has been studied in rat heart mitochondria, pretreated with H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the delta psi decrease by these compounds. A threshold delta psi value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 delta psi level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169-2021 that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.
Role of gamma-carboxyglutamic acid. Cation specificity of prothrombin and factor X-phospholipid binding. (1976)

Divalent cations are required for two roles in prothrombin-phospholipid interaction.The first role, catalysis of a prothrombin protein transition has a reaction half-life of 100 min at 0" and is a prerequisite to phospholipid binding.The binding sites required for the transition have a very low cation specificity.All di-and trivalent cations tested were effective in this role with the exception of beryllium.Barium catalyzed the transition but only at high concentrations (6.6 mM was required for half-reaction).Bloodclotting Factor X, another y-carboxyglutamic acid-containing protein, also undergoes a cation-catalyzed protein transition which is a prerequisite to Factor X-phospholipid binding.In both proteins, the transition can be monitored by a decrease in the protein's intrinsic fluorescence.Compared to prothrombin, the Factor X transition occurs much more rapidly, has a somewhat greater specificity for cations, and requires higher concentrations of cations.This indicates that the cation binding sites provided by ycarboxyglutamic acid are not completely uniform in all proteins.The second role of divalent cations in prothrombin-phospholipid interaction is in the actual protein-phospholipid binding.This interaction was studied by protein fluorescence quenching resulting from excitation energy transfer to a chromophore attached to the phospholipid membrane.Only strontium and barium satisfactorily replaced calcium in this role.A number of other cations form protein.phospholipid complexes but of the wrong structure.These cations inhibit the prothrombinase complex (Factor X,, calcium, phospholipid, Factor V).The cation specificity for Factor X-phospholipid binding is the same as for prothrombin except that higher concentrations of cations are required.Factor X, (generated by action of Russell's viper venom on Factor X) displayed the same calcium requirements for the protein transition and phospholipid interaction as Factor X.The cation requirements of the prothrombinase complex correlate with the cation requirements of prothrombin and Factor X-phospholipid binding.Strontium is the only cation that will singly replace calcium.Barium is ineffective alone because the concentrations required to catalyze the protein transitions cause precipitation of the phospholipid.Combination of certain other cations with barium will, however, substitute for calcium.The other cations (specifically magnesium or manganous ion) catalyze the protein transitions and barium forms the correct protein.phospholipidcomplexes.
Fast Automatic Passage Ranking (MultiText Experiments for TREC-8). (1999)

this article may be sent to mt@plg.uwaterloo.ca. The MultiText project is funded by Communications and Information Technology Ontario.
MUC18/MCAM (CD146), an activation antigen of human T lymphocytes (1997)

Extravasation and tissue infiltration of leukocytes and metastatic tumor cells require the regulated expression and function of adhesive and pro-proteolytic surface molecules. We demonstrate here that human T cells, upon activation, neo-express the melanoma metastasis-associated surface molecule MUC18/melanoma cell adhesion molecule (MCAM). Expression of MUC18/MCAM (CD146) on T cells could be identified with two mAbs (541-10B2 and 541-2E5) obtained after immunization with HUT102 T cells and found to react with activated T cells. The specificity of our mAbs for MUC18/MCAM (CD146) was revealed by 1) definition of the appropriate molecular mass of approximately 110 kDa unreduced and 120 kDa reduced, 2) reactivity of mAbs with MUC18/MCAM (CD146) cDNA-transfected mouse L cells, 3) conclusive crosswise immunoblotting experiments with MUC18/MCAM (CD146)-specific mAbs, and 4) N-terminal amino acid sequencing of precipitated protein. In vitro activation by PHA caused neo-expression of MUC18/MCAM (CD146) on peripheral blood T cells within 1 day of stimulation, reaching a maximum on day 3. In vivo expression of MUC18/MCAM (CD146) was confirmed on CD3+ T cells infiltrating delayed-type hypersensitivity lesions of the skin, on synovial fluid T cells of rheumatoid arthritis patients, and on distinct T leukemia cells. MUC18/MCAM (CD146) cell surface expression on activated T cells is mirrored by the presence of specific mRNA. Leukocytes of healthy donors do not show significant MUC18/MCAM (CD146) expression. The finding that MUC18/MCAM (CD146) is also expressed on activated T cells might suggest that this adhesion molecule is involved in the extravasation and/or homing of activated T cells.
Children with Respiratory Disease Associated with Metapneumovirus in Hong Kong (2003)

Human metapneumovirus (HMPV) is a newly discovered pathogen thought to be associated with respiratory disease. We report the results of a study of 587 children hospitalized with respiratory infection over a 13-month period. HMPV was detected in the nasopharyngeal aspirates from 32 (5.5%) children by reverse transcription-polymerase chain reaction. HMPV infection was associated with clinical diagnoses of pneumonia (36%), asthma exacerbation (23%), or acute bronchiolitis (10%). When compared to those with respiratory syncytial virus infection, children with HMPV infection were older, and wheezing was more likely to represent asthma exacerbation rather than acute bronchiolitis. HMPV viral activity peaked during the spring-summer period in Hong Kong. Phylogenetically, all HMPV virus strains from Hong Kong belonged to one of the two genetic lineages previously described. HMPV contributed to 441.6 hospital admissions per 100,000 population <6 years of age.
Siglecs as sensors of self in innate and adaptive immune responses (2012)

Siglecs are expressed on most white blood cells of the immune system and are known to modulate the activity of cell signaling receptors via regulatory motifs in their cytoplasmic domains. This immunoglobulin subfamily of coreceptors recognize sialic acid containing glycans as ligands, which are found on glycoproteins and glycolipids of all mammalian cells. By virtue of their ability to recognize this common structural element, siglecs are increasingly recognized for their ability to help immune cells distinguish between self and nonself, and dampen autoimmune responses.
Complete amino acid sequence of cyanobacterial gas-vesicle protein indicates a 70-residue molecule that corresponds in size to the crystallographic unit cell (1986)

Gas vesicles of cyanobacteria are formed by a protein called 'gas-vesicle protein' (GVP). The complete amino acid sequence has been determined of GVP from Anabaena flos-aquae. It is 70 residues long and has an Mr of 7388. This corresponds to the size of the repeating unit cell demonstrated by X-ray crystallography of intact gas vesicles. Details of the sequence are related to the secondary beta-sheet structure of the protein and its contrasting hydrophilic and hydrophobic surfaces. Extensive amino acid sequences have also been determined for GVPs from two other cyanobacteria, species of Calothrix and Microcystis; they are highly homologous with that of Anabaena GVP. Electrophoretic analysis indicates that GVPs of different cyanobacteria form a variety of stable oligomers.
HMS Beagle: the story of Darwin's ship (1996)

After having twice been driven back by heavy south-west gales, His Majesty's Ship Beagle, a ten-gun under the command of Captain Fitzroy, sailed from Devonport on the 27th of December, 1813. These words open Darwin's story of his historical in the Beagle. Darwin's views and his books are well known but very little is known of the ship that circumnavigated the world. The Beagle was not a dashing frigate of the time but was known in its day as a coffin brig, more likely to founder than to sail twice round the world. While the voyage has been celebrated in the history of exploration, her other two voyages - a prior survey of South America, including Tierra del Fuego and Cape Horn, and the first complete exploration of the coasts of Australia - are less well known. This work provides a biography of the Beagle and her crew whose voyages figured so prominently in the natural science of the 1830s and 1840s. Commencing with the discovery of plans that show how she was laid down, the book describes her three major rebuildings, the reconstruction of the cabin in which Darwin lived and worked, and her last days as Watch Vessel 7, in 1870.
Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics (1976)

Lasers play an increasingly important role in a variety of detection techniques, making inelastic light scattering a tool of growing value in the investigation of dynamic and structural problems in chemistry, biology, and physics. Until the initial publication of this work, however, no monograph treated the principles behind current developments in the field.This volume presents a comprehensive introduction to the principles underlying laser light scattering, focusing on the time dependence of fluctuations in fluid systems; it also serves as an introduction to the theory of time correlation f
Irreversible Inhibition of Lysyl Oxidase by Homocysteine Thiolactone and Its Selenium and Oxygen Analogues (1997)

Homocysteine thiolactone, selenohomocysteine lactone, and homoserine lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with KI values of 21 +/- 3 microM, 8.3 +/- 2.2 microM, and 420 +/- 56 microM, respectively. The first order rate constants for inactivation (k2) of the enzyme varied over a much smaller range, ranging from 0.12 to 0.18 to 0.28 min-1 for the Se-, thio-, and O-lactones, respectively. Mutually exclusive labeling of the enzyme by [1-14C]beta-aminopropionitrile, [U-14C]phenylhydrazine, or [35S]homocysteine thiolactone was observed. These labeling results, together with the closely similar perturbations of the near UV-visible spectra of lysyl oxidase and of a model of its lysine tyrosylquinone cofactor by the thiolactone, indicate that the lactones likely derivatize and reduce the active site carbonyl cofactor. Substitution with deuterium at the alpha-carbon of the thiolactone caused a deuterium kinetic isotope effect on k2 of 3.2 +/- 0.2, consistent with the involvement of rate-limiting alpha-proton abstraction during lactone-induced inactivation of the enzyme. The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium lactones that fully inhibited lysyl oxidase. Thus, these lactones constitute a new category of mechanism-based inactivators selective for lysyl oxidase. Further, these results may relate to the development of connective tissue defects seen in homocystinuria.
Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity (2020)

Coronaviruses cause severe human viral diseases including SARS, MERS and COVID-19. Most recently SARS-CoV-2 virus (causing COVID-19) has led to a pandemic with no successful therapeutics. The SARS-CoV-2 infection relies on trimeric spike (S) proteins to facilitate virus entry into host cells by binding to ACE2 receptor on host cell membranes. Therefore, blocking this interaction with antibodies are promising agents against SARS-CoV-2. Here we describe using humanized llama antibody VHHs against SARS-CoV-2 that would overcome the limitations associated with polyclonal and monoclonal combination therapies. From two llama VHH libraries, unique humanized VHHs that bind to S protein and block the S/ACE2 interaction were identified. Furthermore, pairwise combination of VHHs showed synergistic blocking. Multi-specific antibodies with enhanced affinity and avidity, and improved S/ACE2 blocking are currently being developed using an <i>in-silico</i> approach that also fuses VHHs to Fc domains. Importantly, our current bi-specific antibody shows potent S/ACE2 blocking (KD - 0.25 nM, IC100 ∼ 36.7 nM, IC95 ∼ 12.2 nM, IC50 ∼ 1 nM) which is significantly better than individual monoclonal VHH-Fcs. Overall, this design would equip the VHH-Fcs multiple mechanisms of actions against SARS-CoV-2. Thus, we aim to contribute to the battle against COVID-19 by developing therapeutic antibodies as well as diagnostics.
HIV Type 1 Protease Cleavage Site Mutations and Viral Fitness: Implications for Drug Susceptibility Phenotyping Assays (2000)

The recombinant virus assay (RVA) is a method for assessing the susceptibility of human immunodeficiency virus type 1 (HIV-1) plasma isolates to antiretroviral drugs. The RVA involves the production of viable virus in vitro by homologous recombination of RT-PCR products from plasma virus with a noninfectious reverse transcriptase (RT) or protease (PR)-deleted cloned HIV-1 provirus. In this study, we have constructed RVA plasmids with contiguous deletions in RT, PR, and the p7/p1 and p1/6 gag protease cleavage sites (CS). The deletions in these plasmids allow generation of recombinant viruses with all loci currently identified as important for resistance to anti-HIV-1 drugs being derived from the clinical isolate, including CS mutations that compensate for the reduced fitness of viruses resistant to protease inhibitors (Doyon et al., J Virol 1996:70:3763-3769). We have also used these new constructs to generate viruses with or without compensatory CS mutations, and examined the effects on fitness. In the case of an indinavir-selected virus, fitness was restored close to that of a wild type virus when a vector deleted in the CS and PR was used. With an amprenavir-selected isolate, virus fitness was incompletely restored by including the CS, and this defect appeared to be partially due to reduced infectivity of the virions. We conclude that the CS mutations were required for optimum detection of resistance in the RVA, but that virus fitness can remain compromised even in the presence of compensatory CS mutations.
17-β Estradiol Can Reduce Secondary Ischemic Damage and Mortality of Subarachnoid Hemorrhage (2001)

Subarachnoid hemorrhage (SAH) is a unique disorder commonly occurring when an aneurysm ruptures, leading to bleeding and clot formation, with a higher incidence in females. To evaluate the influence of 17-beta estradiol (E2) in the outcome of subarachnoid hemorrhage, SAH was induced by endovascular puncture of the intracranial segment of internal carotid artery in 15 intact females (INT), 19 ovariectomized females (OVX), and 13 ovariectomized female rats with E2 replacement (OVX + E2). Cerebral blood flow was recorded before and after SAH. All animals were decapitated immediately after death or 24 hours after SAH for clot area analysis. Brains were sliced and stained with 2,3,5-triphenyltetrazolium chloride (TTC) for secondary ischemic lesion analysis. The cortical cerebral blood flow (CBF), which was measured by a laser-Doppler flowmeter, decreased to 29.6%+/-17.7%, 22.8%+/-8.3%, and 43.5%+/-22.9% on the ipsilateral side (P = 0.01), and decreased to 63.4%+/-14.1%, 57.4%+/-11.0%, and 66.6%+/-17.9% on the contralateral side (P = 0.26) in INT, OVX, and OVX + E2, respectively. The subcortical CBF, which were measured by the H2 clearance method, were 7.77+/-12.03, 7.80+/-8.65, and 20.58+/-8.96 mL 100 g(-1) min(-1) on the ipsilateral side (P < 0.01), and 21.53+/-2.94, 25.13+/-3.01, and 25.30+/-3.23 mL 100 g(-1) min(-1) on the contralateral side in INT, OVX, and OVX + E2, respectively. The mortality was 53.3%, 68.4%, and 15.4% in INT, OVX, and OVX + E2, respectively (P = 0.01), whereas no significant difference in clot area was noted among the groups. The secondary ischemic lesion volume was 9.3%+/-8.4%, 24.3%+/-16.3%. and 7.0%+/-6.4% in INT, OVX, and OVX + E2, respectively (P < 0.01). This study demonstrated that E2 can reduce the mortality and secondary ischemic damage in a SAH model without affecting the clot volume.
Fluorescence Activated Cell Sorting (1972)

An instrument has been developed for sorting biological cells. The cells are rendered differentially fluorescent and incorporated into a small liquid stream illuminated by a laser beam. The cells pass sequentially through the beam, and fluorescent light from the cells gives rise to electrical signals. The stream is broken into a series of uniform size drops downstream of the laser. The cell signals are used to give appropriate electrostatic charges to drops containing the cells. The drops then pass between two charged plates and are deflected to appropriate containers. The system has proved capable of providing fractions containing large numbers of viable cells highly enriched in a particular functional type.