gebhart/patrepeval huggingface dataset:
Characterization of human anti-cytomegalovirus monoclonal antibody as biologics. (1990)

Human anti-cytomegalovirus (CMV) monoclonal antibody designated C23 was purified from the culture fluid of hybridoma cells which were generated by cell fusion of human lymphocytes and mouse myeloma cells. The purified C23 was found to be identical to human gammaglobulin (HGG) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and non-reducing conditions and in gel filtration chromatography. C23 was not contaminated with either aggregated IgG molecules or mouse immunoglobulin chains. In addition, the formulated C23 preparation showed an anti-complement activity low enough to permit its use as a biologic. A virus neutralization titer of C23 was about 1,000 times higher than the titers of HGG preparations. All the tested CMV strains were susceptible to neutralization by C23 and this neutralization was not affected by addition of either beta 2 microglobulin or fresh human serum. These results suggest that human monoclonal antibody C23 is as safe as conventional HGG preparations which have been used in humans, and much more effective in providing host protection against CMV infection.
Lysine-156 and serine-119 are required for LexA repressor cleavage: a possible mechanism. (1987)

LexA repressor of Escherichia coli is inactivated in vivo by a specific cleavage reaction requiring activated RecA protein. In vitro, cleavage requires activated RecA at neutral pH and proceeds spontaneously at alkaline pH. These two cleavage reactions have similar specificities, suggesting that RecA acts indirectly to stimulate self-cleavage, rather than directly as a protease. We have studied the chemical mechanism of cleavage by using site-directed mutagenesis to change selected amino acid residues in LexA, chosen on the basis of kinetic data, homology to other cleavable repressors, and potential similarity of the mechanism to that of proteases. Serine-119 and lysine-156 were changed to alanine, a residue with an unreactive side chain, resulting in two mutant proteins that had normal repressor function and apparently normal structure, but were completely deficient in both types of cleavage reaction. Serine-119 was also changed to cysteine, another residue with a nucleophilic side chain, resulting in a protein that was cleaved at a significant rate. These and other observations suggest that hydrolysis of the scissile peptide bond proceeds by a mechanism similar to that of serine proteases, with serine-119 being a nucleophile and lysine-156 being an activator. Possible roles for RecA are discussed.
Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart. (1984)

Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.
Compatible phase co-scheduling on a CMP of multi-threaded processors (2006)

The industry is rapidly moving towards the adoption of chip multi-processors (CMPs) of simultaneous multi-threaded (SMT) cores for general purpose systems. The most prominent use of such processors, at least in the near term, is as job servers running multiple independent threads on the different contexts of the various SMT cores. In such an environment, the co-scheduling of phases from different threads plays a significant role in the overall throughput. Less throughput is achieved when phases from different threads that conflict for particular hardware resources are scheduled together, compared with the situation where compatible phases are co-scheduled on the same SMT core. Achieving the latter requires precise per-phase hardware statistics that the scheduler can use to rapidly identify possible incompatibilities among phases of different threads, thereby avoiding the potentially high performance cost of inter-thread contention. In this paper, we devise phase co-scheduling policies for a dual-core CMP of dual-threaded SMT processors. We explore a number of approaches and find that the use of ready and in-flight instruction metrics permits effective co-scheduling of compatible phases among the four contexts. This approach significantly outperforms the worst static grouping of threads, and very closely matches the best static grouping, even outperforming it by as much as 7%.
Characterization of transgenic mice—a comparison of protocols for welfare evaluation and phenotype characterization of mice with a suggestion on a future certificate of instruction (2003)

A thorough welfare evaluation performed as part of a general phenotype characterization for both transgenic and traditional mouse strains could not only contribute to the improvement of the welfare of laboratory animals, but could also be of benefit to scientists, laboratory veterinarians and the inspecting authorities. A literature review has been performed to identify and critically evaluate already existing protocols for phenotype and welfare characterization. There are several relevant schemes available, among others the SHIRPA method, the modified score sheet of Morton and Griffiths, the FRIMORFO phenotype characterization scheme and the behavioural phenotype schemes as described by Crawley. These protocols have been evaluated according to four goals: Their ability (1) to reveal any special needs or problems with a transgenic strain, (2) to cover the informational needs of the purchaser/user of the strain, (3) to refine the welfare of the transgenic animal model by identifying relevant humane endpoints, (4) to prevent the duplication of animal models that have already been developed. The protocols described are useful for characterizing the phenotype and judging welfare disturbances, however the total amount of information and the degree of detail varies considerably from one scheme to another. We present a proposal regarding the practical application of the various schemes that will secure proper treatment and the identification of humane endpoints. It is advocated that with every purchase of a particular strain, an instruction document should accompany the strain. This document needs to give detailed descriptions of the typical characteristics of the strain, as well as necessary actions concerning relevant treatment and humane endpoints. At the moment no such documents are required. The introduction of these types of documents will contribute to improvements in animal welfare as well as experimental results in laboratory animal experimentation.
Hypoxanthine in deoxyribonucleic acid: generation by heat-induced hydrolysis of adenine residues and release in free form by a deoxyribonucleic acid glycosylase from calf thymus (1980)

A slow conversion of adenine residues to hypoxanthine occurs in single-stranded DNA when heated in neutral aqueous buffers. The rate of this reaction at pH 7.6 and 110 degrees C is k = 4 x 10(-8) s-1, as determined by base analysis of heat-treated DNA that contains radioactively labeled adenine residues. It is proposed that adenine deamination is one of several forms of hydrolytic damage that may occur as spontaneous premutagenic lesions in DNA in vivo. Cell extracts from calf thymus and human fibroblasts contain a DNA glycosylase activity with specifically catalyzes the release of free hypoxanthine from DNA or polydeoxyribonucleotides that contain dIMP residues. Several properties of the purified enzyme from calf thymus are described: It has an approximate molecular weight of 31 000. No cofactors are required for activity. The enzymatic release of hypoxanthine occurs readily from double-stranded polydeoxyribonucleotides that have either thymine or cytosine residues in the complementary strand. Single-stranded polymers are 10-20-fold more slowly attacked, and there is no detectable cleavage of monomeric dIMP. Hypoxanthine is liberated from DNA directly as a free base. Thus, when poly(dI) x poly(dC) containing both [3H]-dIMP and [32P]dIMP residues was employed as the substrate, 3H-labeled hypoxanthine but no 32P-labeled material was released in ethanol-soluble form. The hypoxanthine-DNA glycosylase presumably acts in DNA repair by preventing deaminated adenine residues from being expressed as mu.
Laboratory and Field Evaluations of German Cockroach (Orthoptera: Blattellidae) Traps (1984)

In laboratory and field studies, traps were evaluated to determine effectiveness in the capture of the German cockroach, Blattella germanica (L.). Traps tested included: modified sticky (“Kuru Kuru”; Mr. Sticky), electrified cans, and bottles. Unbaited sticky traps caught significantly more cockroaches than other unbaited designs. There was no significant difference in cockroach catch between bottles or can traps or between petroleum jelly or cans fitted with 18-volt electric barriers. Increased cockroach catch in traps with roughened exterior (paper or sand) was noted. A flat sticky surface was as efficacious as other sticky trap designs tested. In field trials, electrified cans caught significantly more cockroaches than bottle traps. Although large numbers of cockroaches were caught and removed, we conclude that cockroach traps are most effective as monitoring devices, rather than providing acceptable control.
Nanoparticles for Multiplex Diagnostics and Imaging (2006)

The drive to understand biology and medicine at the molecular level with accurate quantitation demands much of current high-throughput analysis systems. Nanomaterials and nanotechnology combined with modern instrumentation have the potential to address this emerging challenge. Using a variety of nanomaterials for multiplex diagnostics and imaging applications will offer sensitive, rapid and cost-effective solutions for the modern clinical laboratory. New nanomaterials have been developed with optical-encoding capabilities for selective tagging of a wide range of medically important targets, including bacteria, cancer cells and individual molecules, such as proteins and DNA, in a single assay. We envision further development in this field will provide numerous advanced tools with increased sensitivity and improved multiplexing capability, for unique applications in molecular biology, genomics and drug discovery.
Isolation and identification of two CD34+cell subpopulations from normal human peripheral blood (1994)

Circulating CD34+ progenitors were separated from normal human peripheral blood on the basis of size and density by counterflow centrifugal elutriation (CCE). The CD34+ cells, 0.15% of peripheral blood mononuclear cells, were heterogeneous with respect to their elutriation characteristics, mainly size and density. The least mature CD34+ cells, characterized by lack of CD38 antigen, were predominantly found in the small lymphoid cell fraction. In fractions containing larger and denser cells (large lymphocytes, monocytes, and granulocytes), CD38 was increasingly expressed on the CD34+ cells, as were lineage commitment markers CD10 (B lymphoid), CD33 (myeloid), CD13 (myelomonocytic) and CD71 (erythroid) antigens. The smaller and less dense CD34+ cells expressed CD34 antigen brightly while the larger and denser CD34+ cells expressed it dimly. The smaller and less dense CD34+ high cells failed to establish colony growth in short-term culture while the larger and denser CD34+low cells gave rise to high counts of colony forming units-granulocyte macrophage (CFU-GM). Physical separation on the basis of size and density by CCE differentiates between two main classes of steady-state CD34+ cells from normal human peripheral blood. The smaller and less dense CD34+high cells correspond to the earliest progenitors that express differentiation markers poorly but CD34 antigen brightly, do not give rise to short-term colony growth in vitro, and thus represent indirect evidence for pluripotent hematopoietic stem cells (PHSC). The larger and denser CD34+low cells are the more mature progenitor cells, already committed to myeloid, lymphoid or erythroid differentiation but only dimly expressing CD34 antigen, and these cells were responsible for short-term colony growth in vitro.
Presynaptic Ca2+Channels and Neurotransmitter Release at the Terminal of a Mouse Cortical Neuron (2001)

Regional variation in synaptic efficacy is an important determinant of associative processing as information flows through major circuits of the brain. The perforant path is the principal route of entry from cortex to the hippocampus and contains the first synapse in the cortical-hippocampal projection pathway. We used optical imaging techniques to analyze presynaptic Ca(2+) entry and neurotransmitter release at synapses in the medial perforant path linking stellate neurons located in layer II of the entorhinal cortex to granule cells in the dentate gyrus. Similar to other excitatory central synapses, the relationship between neurotransmitter release and the amount of Ca(2+) influx can be best described by a Hill equation with a Hill coefficient of 3.5. Our Ca(2+) channel toxin studies indicate that P/Q-type channels are the predominant Ca(2+) source triggering neurotransmitter release in this pathway, as shown by a potent inhibition of Ca(2+) entry and synaptic transmission by the P/Q-type channel blocker omega-agatoxin IVA. However, compared with the downstream hippocampal pyramidal neuron CA3-CA1 synapse, neurotransmitter release was less sensitive to the N-type Ca(2+) channel blocker omega-conotoxin GVIA, although the amount of N-type Ca(2+) current is comparable. The contribution of N-type channels to neurotransmitter release approximates that found at the CA3-CA1 synapse when tested under lower [Ca(2+)](o), which effectively reduces the size of the Ca(2+) microdomain surrounding each channel. These results suggest that P/Q-type channels are more closely associated with release machinery then N-type channels at this synapse and that cooperativity differences for each channel subtype may characterize variations in signaling at central synapses.
Surface contact requirements for activation of cytotoxic T lymphocytes (1992)

Cell activation resulting from binding of receptors on one cell to ligands on another is governed by receptor affinities and by ligand concentrations. Effective ligand concentration is determined by its density on the cell surface, but receptor occupancy level will also be influenced by the area of surface contact between the cells. The present study demonstrates the critical importance of a large, continuous surface contact area for effective CTL activation. Using class I alloantigen immobilized on latex microspheres, particle sizes of 4 to 5 microns were found to provide an optimum stimulus. Below 4 microns, responses decreased rapidly with decreasing particle size, and large numbers of small particles could not compensate for suboptimal size. Comparable size dependence was found for activation of degranulation by cloned CTL and for stimulation of in vitro generation of CTL responses by spleen cells from in vivo primed mice. In the presence of fluid-phase anti-TCR antibody, CD8-dependent binding to non-Ag class I (i.e., class I that is not recognized by the TCR) can provide a costimulatory signal to activate degranulation. This response is also critically dependent upon the class I being presented on a particle of 4 or 5 microns diameter. The results suggest that sufficient receptor occupancy (both TCR and CD8) over a contiguous region of the cell surface, as opposed to total interactions over the entire cell surface, is a critical determinant for activation. The ability of CTL to distinguish between Ag on cell-size vs subcellular fragments is probably necessary for their effective functioning, and may also explain the inability to significantly influence CTL activation in vivo with subcellular or soluble forms of Ag.
Determination and quantitative analysis of designer drugs in human urine by liquid chromatography-mass spectrometry (2014)

A robust liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC-ESI-ITMS) method was developed and utilized for the determination and quantitative analysis of four designer drugs in human urine.
Regioselective and Non-reductive C3-Debromination of Indole Nucleus1 (1996)

A method of debromination of 3-bromoindole derivatives was developed. Various ethyl 3-bromoindole-2-carboxylates were treated with H2SO4 and LiBr in acetic acid to give corresponding C3-debrominated indoles in excellent yields. The same reaction of 3-bromo-N-tosylindoles gave lower yields. The present reaction shows the possibility of indolic C3-protection by bromine atom.
The atp operon: nucleotide sequence of the genes for the γ, β, and ε subunits of Escherichia coli ATP synthase (1981)

The nucleotide sequence of the promoter distal region of the atp (or unc) operon of Escherichia coli has been determined. It encodes the gamma, beta and epsilon subunits of the ATP-synthase complex and includes a noncoding sequence in which transcription of the operon probably terminates. This work completes the nucleotide sequence of the operon which contains nine genes: eight encode structural proteins of the ATP-synthase complex; a ninth, the first in the operon, may be a pilot for assembly. The genes for the alpha and beta subunits have evolved from a common ancestor.
Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1 (1997)

We have studied the antibody responses to Env and Gag antigens of human immunodeficiency virus type 1 (HIV-1) in several cohorts of HIV-1-infected individuals: long-term nonprogressors, progressors to disease, acute seroconvertors, and recipients of HIV-1 protease inhibitors. We conclude that the antibody responses to Env and Gag antigens are differentially regulated and that changes in the plasma viral load in the measurable range (500 to 10(8) RNA copies per ml) do not directly affect the antibody responses to these HIV-1 proteins. We provide quantitative estimates of HIV-1-specific immunoglobulin G concentrations in plasma, which can be in excess of 1 mg/ml for both anti-gp120 and anti-p24 once the immune response to HIV-1 has stabilized after seroconversion. We discuss the apparent paradox that the absence of anti-Gag antibodies (which have, at best, limited antiviral activity) is indicative of disease progression, while the retention of anti-Env antibodies (which do have antiviral activity) is of limited (or no) prognostic value. We show that the disappearance of anti-Gag antibodies during disease progression is highly unlikely to be due to immune complexing; instead, we believe that it reflects the loss of T-cell help that is more necessary for the anti-Gag than the anti-Env response.
Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice (2010)

This study suggests that LcS has the potential to prevent obesity-associated metabolic abnormalities by improving insulin resistance.
New method of three‐dimensional analysis of bipedal locomotion for the study of displacements of the body and body‐parts centers of mass in man and non‐human primates: Evolutionary framework (1993)

The current biomechanical interpretation of the chimpanzee's bipedal walking argues that larger lateral and vertical displacements of the body center of mass occur in the chimpanzee's "side-to-side" gait than in the human striding gait. The evolutionary hypothesis underlying this study is the following: during the evolution of human bipedalism one of the necessary changes could have been the progressive reduction of these displacements of the body center of mass. In order to quantitatively test this hypothesis, it is necessary to obtain simultaneously the trajectories of the centers of mass of the whole body and of the different body parts. To solve this problem, a new method of three-dimensional analysis of walking, associated with a volumetric modelling of the body, has been developed based on finite-element modeling. An orthogonal synchrophotographic device yielding four synchronous pictures of the walking subject allows a qualitative analysis of the photographic sequences together with the results of their quantitative analysis. This method was applied to an adult man, a 3-year-old girl and a 9-year-old male chimpanzee. Our results suggest that the trajectory of the body center of mass of the human is distinguished from that of the chimpanzee not by a lower movement amplitude but by the synchronization of the transverse and vertical displacements into two periodic curves in phase with one another. The non-human primate uses its repertoire of arboreal movements in its bipedal terrestrial gait, provisionally referred to as a "rope-walker" gait. We show that the interpretation of a "side-to-side" gait is not applicable to the chimpanzee. We argue that similarly this interpretation and the initial hypothesis presuppose a basic symmetric structure of the gait, in relation to the sagittal plane of progression, similar to the human one. This lateral symmetry of the right and left displacements of the center of gravity, in phase with the right and left single supports of walking, is probably a very derived feature of the human gait. We suggest that low lateral and vertical displacements of the body center of mass are not indicative of a progressive bipedal gait and we discuss the new evolutionary implications of our results.
A 10‐year serogroup B meningococcal disease epidemic in New Zealand: Descriptive epidemiology, 1991–2000 (2001)

Meningococcal disease rates are likely to remain elevated in New Zealand for at least several more years. A vaccine which could induce immunity to the P1.7b,4 PorA subtype may have a role in controlling this epidemic. Efforts are underway to obtain and trial such a vaccine. Measures are also underway to reduce overcrowded living conditions which are contributing to the epidemic. Early recognition and antibiotic treatment of cases improves outcomes and should continue to be promoted. Integrated notification and laboratory-based surveillance of meningococcal disease provides relatively complete surveillance of this disease in New Zealand and has supported the development of public health interventions.