gebhart/patrepeval huggingface dataset:
Plasma concentrations of sodium cromoglycate given by nebulisation and metered dose inhalers in patients with exercise‐induced asthma: relationship to protective effect. (1986)

Plasma sodium cromoglycate (SCG) concentrations were measured in 11 patients at regular intervals before and after exercise in a double-blind study to assess the protective effect in exercise-induced asthma (EIA) of 2, 10 and 20 mg SCG aerosol and placebo, and (on an open basis) nebulised SCG (10 g l-1). There was a dose related increase in plasma concentration and AUC (0-1 h) with the aerosol formulations; values with nebulised SCG were significantly higher than with any aerosol dose. Protection from EIA increased to a maximum of 66% at plasma concentrations of 4 ng ml-1 and above. Thus measurement of plasma concentration can allow a comparison to be made between the protective effects of SCG following different methods of inhalation. It is important to note, however, that plasma concentration per se is almost certainly not related directly to protective effect.
Demonstration of chlamydial RNA and DNA during a culture-negative state (1992)

Trachoma is a common blinding disease of humans caused by ocular infections with Chlamydia trachomatis. The cynomolgus monkey is a valuable primate model for the detection, pathobiology, and treatment of this infection. We have used this model system to compare the relative ability of tissue culture, direct fluorescence cytology, a modified polymerase chain reaction, and RNA blotting to detect C. trachomatis following primary infection and reinfection over 34 weeks. Six cynomolgus monkeys were given a primary ocular chlamydia infection, and 20 weeks later they were reinoculated with the same organism. All animals showed brisk inflammatory responses to the primary infection and milder inflammatory reactions to reinfection. All four diagnostic techniques detected chlamydia at 1 week after primary infection, but both nucleic acid detection methods suggested that organisms were present longer after primary infection than did either tissue culture or direct fluorescence cytology (16 weeks for RNA blotting versus 12 weeks for tissue culture). Following reinoculation at 20 weeks, the period of C. trachomatis detection by tissue culture or direct fluorescence cytology (4 weeks) was much shorter than after primary infection. In contrast, nucleic acid detection was positive for up to 5 weeks longer than tissue culture or direct fluorescence cytology. Both polymerase chain reaction and RNA blotting, which involved no amplification step, indicated the presence of organisms during the culture-negative period. These data suggest that live chlamydiae may remain at a site of infection and produce inflammation beyond the time at which standard microbiological techniques are able to detect them.
Spray damage and residue levels in tobacco treated with various concentrations of 2,4-D at different stages of growth (1973)

The effects of 2,4-D on tobacco at various stages of growth were investigated. Symptoms of damage were recorded and illustrated. The herbicide had no obvious effect on mature plants at any concentration used, but it caused considerable damage to plants at other phases of growth at moderate and high concentrations. A chemical method was developed for accurate determination of 2,4-D residues in tobacco. Investigation of the herbicide residues in irrigation water was necessary following the discovery of 2,4-D residues in control plants.
Protein footprinting at cysteines: Probing ATP-modulated contacts in cysteine-substitution mutants of yeast DNA topoisomerase II (1999)

Cysteine-substitution mutants of yeast DNA topoisomerase II were used to test footprinting of the enzyme by 2-nitro-5-thiocyanobenzoate, which cyanylates exposed cysteines in a native protein for peptide cleavage at the cyanylated sites upon unfolding and incubating the protein at pH 9. For a mutant enzyme containing a single cysteine, the extent of peptide cleavage was found to reflect the accessibility of the residue in the native protein. For proteins with multiple cysteines, however, such a correlation was obscured by the transfer of cyano groups from modified to unmodified cysteines during incubation of the unfolded protein at pH 9; accessibilities of the cysteinyl residues in a native protein could be assessed only if cyano shuffling was prevented by blocking uncyanylated sulfhydryls with a second thiol reagent. The successive use of two reagents in cysteine footprinting was applied in probing the ATP-modulated formation of contacts in yeast DNA topoisomerase II.
Distinct Reactivities of Four Monoclonal Antibodies with Human Interleukin 2 Receptor (1985)

Two new murine monoclonal IgG1 antibodies, H-31 and H-A26, were characterized in comparison with two previously obtained monoclonal antibodies against human interleukin 2 (IL-2) receptor (IL-2 R), anti-Tac and HIEI. In immunofluorescence assays with various human hematopoietic cells, H-31 and H-A26 antibodies both reacted with only IL-2 R-positive cells, and they precipitated IL-2 R molecules, glycoproteins with molecular weights of 60K and 53K daltons (gp60/gp53), from human T-cell leukemia virus type I (HTLV-I)-carrying MT-2 cells, as demonstrated by sequential immunoprecipitation after absorption of IL-2 R with anti-Tac. Antibody-binding competition assays showed that H-31 and anti-Tac, and H-A26 and HIEI, respectively, competed reciprocally in binding to the cells, and that anti-Tac also inhibited the binding of HIEI but not vice versa. H-31, like anti-Tac, strongly inhibited the IL-2-dependent proliferation of normal activated T-cells, absorption of IL-2 and direct binding of IL-2 to the cells, while H-A26, like HIEI, inhibited those processes only weakly. The spectra of reactivities of these antibodies with various simian cell lines derived by HTLV-I infection were different, as revealed by immunofluorescence studies. Human IL-2 R was shown to express a unique antigenic determinant, detected with HIEI, that was not detectable in IL-2 R molecules of Old and New World monkeys, and also to express determinants common to simian IL-2 R molecules. These observations indicate that H-31 and H-A26 recognize human IL-2 R molecules and that the antigenic sites on the IL-2 R molecule defined by H-31, H-A26, anti-Tac, and HIEI are different.
Enhanced Downregulation of the p75 Nerve Growth Factor Receptor by Cholesteryl and Bis-Cholesteryl Antisense Oligonucleotides (1998)

The effects of conjugating cholesterol to either or both ends of a phosphorothioate (PS) oligonucleotide were analyzed in terms of cellular uptake and antisense efficacy. The oligo sequence was directed against the p75 nerve growth factor receptor (p75), and was tested in differentiated PC12 cells, which express high levels of this protein. The addition of a single cholesteryl group to the 5'-end significantly increased cellular uptake and improved p75 mRNA downregulation compared with the unmodified PS oligo. However, only a minor degree of downregulation of p75 protein was obtained with 5' cholesteryl oligos. Three different linkers was used to attach the 5' cholesteryl group but were found not to have any impact on efficacy. Addition of a single cholesteryl group to the 3'-end led to greater p75 mRNA downregulation (31%) and p75 protein downregulation (28%) than occurred with the 5' cholesteryl oligos. The biggest improvement in antisense efficacy, both at the mRNA and protein levels, was obtained from the conjugation of cholesterol to both ends of the oligo. One of the bischolesteryl oligos was nearly as effective as cycloheximide at decreasing synthesis of p75. The bis-cholesteryl oligos also displayed significant efficacy at 1 microM, whereas the other oligos required 5 microM to be effective. The enhanced efficacy of bis-cholesteryl oligos is likely to be due to a combination of enhanced cellular uptake and resistance to both 5' and 3' exonucleases.
Cost of Self-Monitoring of Blood Glucose in Canada among Patients on an Insulin Regimen for Diabetes (2012)

This study shows that SMBG accounts for approximately 40% of the total diabetes-related pharmacy costs for insulin users.
Redox 반응을 이용한 해수 살균에 대한 연구 (2011)

The sterilization of strain and algae in sea water was studied to see the possibility to apply the redox reaction of metal alloy to meet the international marine organization(IMO) regulation, which was to regulate deballasting concentration of strain and algae above 99% of sterilization. Two different kinds of brass were heat treated at different temperature and cooled rapidly to conserve the specific character of β brass. Untreated Muntz metal showed the best result of antimicrobial rate in sea water, and 7:3 brass showed similar result to Muntz metal. Heavy metal elution rate was inversely proportional to the sterilization capability.
A databank (3D-ali) collecting related protein sepquences and structures (1996)

An updated version of the 3D_ali databank (Pascarella and\nArgos, 1992) was constructed to incorporate new protein\nstructural and sequence data acquired since the original release\nin 1992. The databank has proved useful in many research\nfields, such as protein sequence and structure analysis and\ncomparison, protein folding, engineering and design, evolution,\nand the like. The collection enhances present protein structural\nknowledge by merging information from proteins having a\nsimilar main-chain fold with homologous primary structures\ntaken from large databases of known sequences. However, the\nconstruction philosophy of the databank has been modified.\nOriginally, the Protein Data Bank (PDB; Bernstein et al,\n1977) of known 3-D structures was exhaustively scanned for\nfold redundancy, and all the possible unique structures were\nincorporated either in multiple structural alignment files or in\nthose containing only one structure where no relatives could\nbe detected. The tertiary structural superpositioning of the\nbackbones, which yielded spatial and topological Co atom\nequivalencing and thus corresponding sequence alignments,\nwas mostly taken from the literature, but was sometimes\ndetermined by the authors using the Rossman-Argos superposition\ntechnique (Argos and Rossmann, 1979). In the updated\n3D_ali databank, only published alignments based on superpositioning\nby the authors of the tertiary structures were\ncollected and only folds with more than one sample structure\nwere considered. Different literature alignments were also\nmerged if they included common folds. As in the former\nrelease, only full coordinate sets with assigned side chains\nwere included, while NMR structures, excluded in the 1992\nrelease, are now incorporated.
Transplant-related Immunosuppression: A Review of Immunosuppression and Pulmonary Infections (2005)

Solid organ and hematopoietic stem cell transplantation are definitive therapies for a variety of end-stage diseases. Immunosuppression has improved graft survival but leaves the patient susceptible to infectious complications. Of these, pulmonary infections are the leading cause of morbidity and mortality in the transplant recipient. Allograft rejection is mediated primarily by T cells, with B cells playing a role via antibody production. Depending on the transplant type, rejection can be hyperacute, acute, or chronic. Hyperacute rejection occurs as an immediate response to preformed antibodies to donor human leukocyte antigens. Acute cellular rejection involves recipient T-cell recognition of human leukocyte antigen molecules expressed on donor-derived, antigen-presenting cells (direct allorecognition) or presentation of donor-derived peptides by recipient antigen-presenting cells to recipient T cells (indirect allorecognition). Once the alloantigens are recognized as foreign, the activation, proliferation, and production of cytokines by T lymphocytes and other immune cells lead to the amplification of the alloimmune response. This complex process involves the generation of effector T cells, antibody production by activated B cells, and macrophage activation. Alloimmunity is facilitated by the production of many cytokines, chemokines, and other effector molecules, such as complement. The immunosuppressants involve many classes of drugs, including antibody therapies that eliminate specific groups of cells or alter signaling pathways used by effector cells. The article reviews the agents and associated infections.
Zinc-dependent dimers observed in crystals of human endostatin (1998)

The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent of both human and murine endostatin in solution. The human endostatin zinc site is formed by three histidines at the N terminus, residues 1, 3, and, 11, and an aspartic acid at residue 76. The N-terminal loop ordered around the zinc makes a dimeric contact in human endostatin crystals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility that the zinc may be involved in activation of the antiangiogenic activity following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.
Expression Level of the Canonical Transient Receptor Potential 3 (TRPC3) Channel Determines Its Mechanism of Activation (2003)

Studies on the mechanism of activation of canonical transient receptor potential (TRPC) channels have often yielded conflicting results. In the current study, we have investigated the influence of expression level on the mode of regulation of TRPC3 channels. At relatively low levels of expression in DT40 chicken B-lymphocytes, TRPC3 was activated by the depletion of Ca2+ stores. Expression was increased by either transfecting with a 10-fold greater concentration of plasmid or transfecting with TRPC3 under control of a more efficient avian beta-actin promoter. At higher levels of expression, TRPC3 was no longer store-operated but could be activated through receptor-coupled phospholipase C. Under these expression conditions, TRPC3 was efficiently activated in DT40 cells lacking inositol 1,4,5-trisphosphate receptors. The Ca2+ store-operated channels formed upon expression of TRPC3 at limited levels were blocked by gadolinium; the receptor-activated channels formed upon expression of higher levels of TRPC3 were insensitive to gadolinium. These findings indicate that a single ion channel protein can form or contribute to the formation of channels regulated in two very distinct ways, i.e. either by phospholipase C-derived messengers or Ca2+ store-depletion. The mechanism of regulation of the channels depends on their level of expression.
Assessing Immunogenicity in the Presence of Excess Protein Therapeutic Using Immunoprecipitation and Quantitative Mass Spectrometry (2008)

The administration of biological protein therapeutics can lead to an unwanted immune response resulting in the generation of anti-drug antibodies (ADA) with potentially harmful clinical consequences. Hence, to develop safe and efficacious biotherapeutics, the immunogenic potential needs to be examined during the development phase. Current assay technologies measuring ADAs are subject to interference by high circulating concentrations of the protein therapeutic, raising concerns about data reliability since protein therapeutic-free washout samples are not always available. Herein, we report the development and characterization of a magnetic bead based immunoprecipitation method followed by quantitative LC/MS to determine ADA in human and cynomolgus serum in the presence of high circulating concentrations of the protein therapeutic. Available ADA binding sites are saturated by the addition of excess therapeutic followed by magnetic bead based protein G isolation of IgG antibodies and their bound antigens before elution and digestion. Peptides of the target therapeutic proteins are then quantified by LC/MS using stable isotope labeled standards inferring the presence of total ADA. This approach complements established methodologies for the assessment of immunogenicity responses and currently supports clinical programs addressing the safety and tolerability of human growth hormone analogues.
Genetic and biochemical analysis of gonococcal IgA1 protease: cloning in Escherichia coli and construction of mutants of gonococci that fail to produce the activity. (1982)

The biological significance of bacterial extracellular proteases that specifically cleave human IgA1 is unknown. We have prepared a gene bank of gonococcal chromosomal DNA in Escherichia coli K-12 using a cosmid cloning system. Among these clones, we have identified and characterized an E. coli strain that elaborates an extracellular endopeptidase that is indistinguishable from gonococcal IgA1 protease in its substrate specificity and action on human IgA1. Analysis of recombinant plasmids and examination of plasmid-specific peptides in minicells have shown that the IgA1 protease activity in E. coli is associated with expression of a Mr 140,000 peptide. We have isolated IgA1 protease-deficient mutants of Neisseria gonorrhoeae by reintroduction of physically defined deletions of the cloned gene into the gonococcal chromosome by transformation.
Atherosclerotic Lesions and Mitochondria DNA Deletions in Brain Microvessels as a Central Target for the Development of Human AD and AD‐Like Pathology in Aged Transgenic Mice (2002)

We have studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD brain biopsy, human short postmortem brain tissues, and yeast artificial chromosome (YAC) and C57B6/SJL transgenic positive (Tg+) mice overexpressing amyloid beta precursor protein (AbetaPP). In situ hybridization using mitochondrial DNA (mtDNA) probes for human wild type, 5 kb deleted, and mouse mtDNA was performed, along with immunocytochemistry using antibodies against amyloid precursor protein (APP), 8-hydroxy-2'-guanosine (8-OHG), and cytochrome c oxidase (COX). There was a higher degree of amyloid deposition in the vascular walls of the human AD, YAC, and C57B6/SJL Tg (+) mice compared to age-matched controls. In addition, vessels with more severe lesions showed immunopositive staining for APP and possessed large, lipid-laden vacuoles in the cytoplasm of endothelial cells (EC). Significantly more mitochondrial abnormalities were seen in human AD, YAC, and C57B6/SJL Tg (+) mouse microvessels where lesions occurred. In situ hybridization using wild and chimera (5 kb) mtDNA probes revealed positive signals in damaged mitochondria from the vascular endothelium and in perivascular cells of lesioned microvessels close to regions of large amyloid deposition. These features were absent in undamaged regions of human AD tissues, YAC and C57B6/SJL Tg (+) mouse tissues, and in age-matched control subjects. In addition, vessels with atherosclerotic lesions revealed endothelium and perivascular cells possessing clusters of wild and deleted mtDNA positive probes. These mtDNA deletions were accompanied by increased amounts of immunoreactive APP, 8-OHG, and COX in the same cellular compartment. Our observations demonstrate that vascular wall cells, especially their mitochondria, appear to be a central target for oxidative stress-induced damage.
Controlled Drug Delivery by Biodegradable Poly(Ester) Devices: Different Preparative Approaches (1998)

There has been extensive research on drug delivery by biodegradable polymeric devices since bioresorbable surgical sutures entered the market two decades ago. Among the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) such as poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide referred to as poly(lactide-co-glycolide) (PLGA) have generated tremendous interest because of their excellent biocompatibility, biodegradability, and mechanical strength. They are easy to formulate into various devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Most importantly, they have been approved by the United States Food and Drug Administration (FDA) for drug delivery. This review presents different preparation techniques of various drug-loaded PLGA devices, with special emphasis on preparing microparticles. Certain issues about other related biodegradable polyesters are discussed.
Social force model for pedestrian dynamics (1995)

It is suggested that the motion of pedestrians can be described as if they would be subject to ``social forces.'' These ``forces'' are not directly exerted by the pedestrians' personal environment, but they are a measure for the internal motivations of the individuals to perform certain actions (movements). The corresponding force concept is discussed in more detail and can also be applied to the description of other behaviors. In the presented model of pedestrian behavior several force terms are essential: first, a term describing the acceleration towards the desired velocity of motion; second, terms reflecting that a pedestrian keeps a certain distance from other pedestrians and borders; and third, a term modeling attractive effects. The resulting equations of motion of nonlinearly coupled Langevin equations. Computer simulations of crowds of interacting pedestrians show that the social force model is capable of describing the self-organization of several observed collective effects of pedestrian behavior very realistically.
The action of magnesium and of Grignard reagents on certain benzyl ethers. Part II. The action of Grignard reagents on o-, m-, and p-methoxy- and -phenoxy-methylanilines (1954)

F. G. Mann and F. H. C. Stewart, J. Chem. Soc., 1954, 4127 DOI: 10.1039/JR9540004127
ChemInform Abstract: POTENTIAL DIURETIC‐β‐ADRENERGIC BLOCKING AGENTS: SYNTHESIS OF 3‐(2‐((1,1‐DIMETHYLETHYL)AMINO)‐1‐HYDROXYETHYL)‐1,4‐DIOXINO(2,3‐G)QUINOLINES (1982)

Abstract Die Herstellung verschiedener pharmakologisch interessanter Dioxinochinoline wird beschrieben.
Scaled p-channel Ge FinFET with optimized gate stack and record performance integrated on 300mm Si wafers (2013)

We demonstrate scaled, replacement gate high-k/metal gate p-channel Ge FinFETs integrated onto 300mm Si wafers for which the best device shows record peak g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m, ext</inf> =2.7mS/μm (g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m, int</inf> =3.3mS/μm), Q (≡g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m, ext</inf> /SS <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sat</inf> ) = 32.4 and I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</inf> = 497μA/μm at I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</inf> = 100nA/μm, all at V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ds</inf> = −0.5V. The high performance is a result of successful integration of <110> oriented, highly scaled Ge fins on silicon substrates and of a low D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">it</inf> gate stack with capacitance equivalent thickness=8Å. This optimized gate stack supports the highest hole mobility ever reported at sub-10Å CET. Furthermore, Ge FinFETs in the present work outperform any other reported Ge devices by more than ∼2.5× (g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</inf> /SS metric) and ∼2× (I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</inf> /I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</inf> metric) at shortest gate lengths (down to 20nm) to the best of our knowledge.