gebhart/patrepeval huggingface dataset:
Fibrinogen Milano V: a congenital dysfibrinogenaemia with a gamma 275 Arg-->Cys substitution. (1994)

An abnormal fibrinogen was discovered in a clinically asymptomatic woman from Italy. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times and a discrepancy between the plasma fibrinogen levels determined by the clotting assay and electroimmunoassay. Release of fibrinopeptides A and B from fibrinogen Milano V by thrombin was normal. Fibrin polymerization was strongly delayed in the presence of EDTA and was partially corrected at physiological calcium concentration. Normal migration of mercaptolysed polypeptide chains was observed in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Moreover, there was no apparent abnormality in the charge of the reduced chains of the variant fibrinogen, as judged by two-dimensional gel electrophoresis. A fragment of the gamma-chain gene coding for the amino acids 259-350 was amplified and cloned. The amino acid gamma 275 arginine was found to be substituted by cysteine. Immunoblotting analysis with a rabbit antiserum against human serum albumin indicated that albumin was not linked to the odd sulphydryl group of fibrinogen Milano V. Treatment of fibrinogen Milano V with cysteamine, that is surmised to convert the mutant cysteine to a positively charged lysine analogue, did not improve the clotting properties of fibrinogen Milano V.
Alkylation of H-Phosphinate Esters under Basic Conditions (2007)

An efficient and general procedure was developed for the direct alkylation of H-phosphinate esters with LHMDS at low temperature. The simplicity of the reaction allows the use of various H-phosphinate esters and takes place with a wide range of electrophiles. The approach can be employed to access some GABA analogues or precursors to GABA analogues. The isolated yields are moderate to good. This is the first report of an alkylation with a secondary iodide or a primary chloride.
Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. (1990)

Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation (since proalbumin contains adjacent Arg residues at -1 and -2) or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala----Thr. This introduces an Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg----Cys. This introduces a prepro sequence, Met-Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr- Ser-Arg-Gly-Val-Phe-Cys-Arg (cf.-Tyr-Ser-Arg-Gly-Val-Phe-Arg-Arg- in normal human pre-proalbumin). We propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase.
A Putative Catenin–Cadherin System Mediates Morphogenesis of the Caenorhabditis elegans Embryo (1998)

During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or epidermal) cells migrate to enclose the embryo in an epithelium and, subsequently, change shape coordinately to elongate the body (Priess, J.R., and D.I. Hirsh. 1986. Dev. Biol. 117:156- 173; Williams-Masson, E.M., A.N. Malik, and J. Hardin. 1997. Development [Camb.]. 124:2889-2901). We have isolated mutants defective in morphogenesis that identify three genes required for both cell migration during body enclosure and cell shape change during body elongation. Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes anchor contractile actin filament bundles at the adherens junctions between hypodermal cells and, thereby, transmit the force of bundle contraction into cell shape change. The protein products of all three genes localize to hypodermal adherens junctions in embryos. The sequences of the predicted HMP-1, HMP-2, and HMR-1 proteins are related to the cell adhesion proteins alpha-catenin, beta-catenin/Armadillo, and classical cadherin, respectively. This putative catenin-cadherin system is not essential for general cell adhesion in the C. elegans embryo, but rather mediates specific aspects of morphogenetic cell shape change and cytoskeletal organization.
Sixteen–Kinase Gene Expression Identifies Luminal Breast Cancers with Poor Prognosis (2008)

Breast cancer is a heterogeneous disease made of various molecular subtypes with different prognosis. However, evolution remains difficult to predict within some subtypes, such as luminal A, and treatment is not as adapted as it should be. Refinement of prognostic classification and identification of new therapeutic targets are needed. Using oligonucleotide microarrays, we profiled 227 breast cancers. We focused our analysis on two major breast cancer subtypes with opposite prognosis, luminal A (n = 80) and basal (n = 58), and on genes encoding protein kinases. Whole-kinome expression separated luminal A and basal tumors. The expression (measured by a kinase score) of 16 genes encoding serine/threonine kinases involved in mitosis distinguished two subgroups of luminal A tumors: Aa, of good prognosis and Ab, of poor prognosis. This classification and its prognostic effect were validated in 276 luminal A cases from three independent series profiled across different microarray platforms. The classification outperformed the current prognostic factors in univariate and multivariate analyses in both training and validation sets. The luminal Ab subgroup, characterized by high mitotic activity compared with luminal Aa tumors, displayed clinical characteristics and a kinase score intermediate between the luminal Aa subgroup and the luminal B subtype, suggesting a continuum in luminal tumors. Some of the mitotic kinases of the signature represent therapeutic targets under investigation. The identification of luminal A cases of poor prognosis should help select appropriate treatment, whereas the identification of a relevant kinase set provides potential targets.
Characterization of an anti-p185HER2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. (1991)

The HER2 protooncogene encodes a growth factor receptor-like transmembrane protein tyrosine kinase (p185HER2) whose ligand remains to be fully characterized. The overexpression of p185HER2 is implicated in aggressive forms of breast and ovarian cancers. The role of p185HER2 in aggressive malignancy, as well as its cell surface localization, makes it an attractive target for therapeutic monoclonal antibodies. In this report we have studied the modulation of p185HER2 function with 2 monoclonal antibodies, termed 4D5 and 6E9, which bind the extracellular domain of p185HER2. 4D5 inhibited proliferation of p185HER2 overexpressing SK-BR-3 human breast carcinoma cells (ED50 of approximately 1 nM) but did not inhibit proliferation of cultured human breast carcinoma MCF7 cells, low expressors of p185HER2. Monoclonal antibody 6E9 does not inhibit the growth of either cell line. Antibody binding studies revealed 2 populations of p185HER2 molecules on SK-BR-3 cells: one of high abundance (approximately 2 x 10(6) sites/cell) recognized by 4D5 (Kd approximately 6 nM) and the other of low abundance (2 x 10(4) sites/cell) recognized by 6E9 (Kd approximately 0.1 nM). 4D5, in an agonistic manner, downregulated SK-BR-3 cell surface p185HER2, was internalized, and stimulated p185HER2 phosphorylation in intact cells. Phosphoamino acid analysis of p185HER2 derived from SK-BR-3 cells incubated with the 4D5 monoclonal antibody demonstrated increased tyrosine, serine and threonine phosphorylation. 4D5, on short term (5 min) exposure to SK-BR-3 cells, stimulated inositol lipid hydrolysis as evidenced by increased intracellular levels of inositol polyphosphates (InsP) and sn-1,2-diacylglycerol (sn-1,2-DAG). On longer (24 h) exposure to the cells, the antibody appeared to downregulate this signalling pathway since the intracellular levels of InsP and sn-1,2-DAG decreased by 30 to 40%. 6E9 did not inhibit SK-BR-3 cell proliferation, downregulate surface p185HER2, stimulate receptor phosphorylation, or stimulate the second messenger pathway. Despite these agonistic properties, 4D5 was an inhibitor of SK-BR-3 cell proliferation at all concentrations tested (0.7 to 70 pM). The data suggest that 4D5 is a partial or weak agonist and thus may inhibit cell proliferation by mimicking ligand-like receptor downregulation.
The action of selected isothiocyanates on bacterial biofilm prevention and control (2013)

The activity of two selected isothiocyanates (ITCs), allylisothiocyanate (AITC) and 2-phenylethy-lisothiocyanate (PEITC) was evaluated on the prevention and control of biofilms formed by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. In addition, the effect of ITCs was also tested on planktonic cell susceptibility, bacterial motility and adhesion. Biofilm prevention and control were tested using a microtiter plate assay and the effect of ITCs was assessed on biofilm mass and metabolic activity. The minimum bactericidal concentration for E. coli and P. aeruginosa was 1000 μg mL−1 (AITC) and >1000 μg mL−1 (PEITC), for S. aureus and L. monocytogenes was >1000 μg mL−1 (for both ITCs). AITC caused total inhibition of swimming (P. aeruginosa) and swarming (E. coli) motilities. PEITC caused total inhibition of swimming (E. coli, P. aeruginosa and L. monocytogenes) and swarming (E. coli and P. aeruginosa) motilities. Colony spreading of S. aureus was completely inhibited with PEITC. Adhesion assessed in terms of free energy was less favorable when bacteria were exposed to AITC for E. coli and P. aeruginosa and PEITC for P. aeruginosa. Both ITCs had preventive action on biofilm formation and showed a higher potential to reduce the mass of biofilms formed by the Gram-negative bacteria. AITC and PEITC promoted reductions in biofilm activity higher than 60% for all the biofilms tested. The overall study emphasizes the potential of ITCs as emergent products to inhibit bacterial motility and prevent/control biofilms of important human pathogenic bacteria.
Adaptive optics for structured illumination microscopy (2008)

We implement wave front sensor-less adaptive optics in a structured illumination microscope. We investigate how the image formation process in this type of microscope is affected by aberrations. It is found that aberrations can be classified into two groups, those that affect imaging of the illumination pattern and those that have no influence on this pattern. We derive a set of aberration modes ideally suited to this application and use these modes as the basis for an efficient aberration correction scheme. Each mode is corrected independently through the sequential optimisation of an image quality metric. Aberration corrected imaging is demonstrated using fixed fluorescent specimens. Images are further improved using differential aberration imaging for reduction of background fluorescence.
Initial Access in 5G mmWave Cellular Networks (2016)

The massive amounts of bandwidth available at millimeter-wave frequencies (above 10 GHz) have the potential to greatly increase the capacity of fifth generation cellular wireless systems. However, to overcome the high isotropic propagation loss experienced at these frequencies, highly directional antennas will be required at both the base station and the mobile terminal to achieve sufficient link budget in wide area networks. This reliance on directionality has important implications for control layer procedures. In particular, initial access can be significantly delayed due to the need for the base station and the user to find the proper alignment for directional transmission and reception. This article provides a survey of several recently proposed techniques for this purpose. A coverage and delay analysis is performed to compare various techniques including exhaustive and iterative search, and context-information-based algorithms. We show that the best strategy depends on the target SNR regime, and provide guidelines to characterize the optimal choice as a function of the system parameters.
Effects of Continuous Positive Airway Pressure on Cardiac Output in Experimental Heart Failure (1996)

Continuous positive airway pressure (CPAP) is used to treat congestive heart failure (CHF). Mechanisms for improved cardiac output (CO) include increased left ventricular (LV) surface pressure, changes in sympathoadrenal tone, nonadrenergic vasodilation, or shifting blood volume from intra- to extrathoracic compartments. At CPAP = 0 and CPAP = 5 cm H2O we measured CO, LV surface pressure, plasma norepinephrine (PNE), and systemic vascular resistance (SVR) in normal and hypervolemic pigs and pigs with CHF (rapid ventricular pacing). In normovolemia CPAP led to no change in CO. With both hypervolemia and CHF. CPAP led to increased CO (10-20%). With CPAP, LV surface pressure increased slightly in normovolemia, but did not increase, or even decreased, in hypervolemia. With CPAP, PNE did not change in normovolemia, increased in hypervolemia, and decreased in CHF, SVR always decreased when cardiac output increased with CPAP. We conclude that changes in cardiac surface pressure and overall sympathoadrenal tone cannot explain changes in CO with CPAP. Non-adrenergic mediated vasodilation could lead to unloading the LV. Alternatively, volume shift from intra- to extrathoracic compartments could lead to greater decreases in systolic than diastolic volume, thus increasing stroke volume. CPAP increases CO in the presence of cardiac distension whether or not myocardial function is impaired.
A Second, Lower Affinity Growth Hormone-Binding Protein in Human Plasma* (1990)

In our previous description of the circulating GH-binding protein (GH-BP) we observed, in addition to the main GH-BP complex, a second macromolecular component designated peak I during gel filtration of [125I]GH-plasma mixtures. This component was not further characterized because of its small magnitude, seeming nonsaturability, and suspected artifactual nature. We have now characterized peak I as the complex of a low affinity BP with GH. To gain a better knowledge of the nature of peak I, whole plasma or plasma fractions containing isolated peak I-BP (ammonium sulfate precipitated or prepared by gel filtration of plasma) were incubated with monomeric [125I]GH and varying concentrations of unlabeled GH. The mixtures were then analyzed by Sephadex G-100 chromatography to separate free from protein-bound GH. Peak I-associated radioactivity was saturable at high concentrations of human GH, but not with animal GHs. Saturation/Scatchard analysis yielded an association constant of 10(5) M-1 and a maximum binding capacity of 15 mg/L plasma. Chemically cross-linked complexes of [125I]GH with isolated peak I BP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and two-dimensional electrophoresis. These experiments yielded a mol wt of 124 kD and a pI of 7 for the cross-linked complex. This is in contradistinction to the previously reported high affinity GH-BP complex, which when cross-linked has a mol wt of 76 kD and a pI of 5.(ABSTRACT TRUNCATED AT 250 WORDS)
A Regulatory Gene of Phenylalanine Biosynthesis ( pheR ) in Salmonella typhimurium (1973)

4-Fluorophenylalanine-resistant mutants of Salmonella typhimurium were isolated in which synthesis of chorismate mutase P-prephenate dehydratase (specified by pheA) was highly elevated. Transduction analysis showed that the mutation affecting pheA activity was not linked to pheA, and conjugation and merodiploid analysis indicated that it was in the 95- to 100-min region of the Salmonella chromosome. Evidence is presented for the hypothesis that the mutation responsible for constitutivity of chorismate mutase P-prephenate dehydratase occurred in pheR, a gene specifying a cytoplasmic product that affected pheA. pheR mutants were found to carry a second mutation, tyrO. The tyrO mutation acts cis to cause increased levels of the tyrosine biosynthetic enzymes 3-deoxy-d-arabinoheptulosonate 7-phosphate synthetase (tyr) and prephenate dehydrogenase, but it has no effect on regulation of pheA.
Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity. (1986)

Previous studies have shown that heteroconjugates of monoclonal antibodies in which one of the component antibodies is directed at the T-cell receptor and the other is directed against any chosen site can focus effector T cells to function at the targeted site. We report here the production of a hybrid hybridoma cell line, H1.10.1.6, which secretes large amounts of a bispecific hybrid antibody of the IgG2a class, that can focus T-cell activity. The parental hybridoma lines for the secondary fusion were F23.1, which secretes an antibody specific for an allotypic determinant on the T-cell receptor of most mouse strains, and 19E12, secreting an anti-Thy-1.1 antibody. The bispecific hybrid antibody was partially purified by hydroxylapatite chromatography and characterized by isoelectric focusing. It efficiently targets Thy-1.1-expressing tumor cells for lysis by F23.1 receptor-positive cytotoxic T-cell clones in vitro. Such hybrid antibodies produced by hybrid hybridoma cell lines may have application in the therapeutic targeting of tumors or sites of viral infections for attack by T cells.
Efficacy and current limitations of intravascular stents for intracranial internal carotid, vertebral, and basilar artery aneurysms (1999)

A new generation of flexible stents can be used to treat complex aneurysms in difficult-to-access areas such as the proximal intracranial segments of the ICA, the VA, or the BA trunk. The stent allows tight coil packing even in the presence of a wide-necked, irregularly shaped aneurysm and may provide an endoluminal matrix for endothelial growth. Although convincing experimental evidence suggests that stent placement across the aneurysm neck may by itself promote intraluminal thrombosis, the role of this phenomenon in clinical practice may be limited at present by the high porosity of currently available stents.
Critical Analysis of Antibody Catalysis (2000)

Antibody molecules elicited with rationally designed transition-state analogs catalyze numerous reactions, including many that cannot be achieved by standard chemical methods. Although relatively primitive when compared with natural enzymes, these catalysts are valuable tools for probing the origins and evolution of biological catalysis. Mechanistic and structural analyses of representative antibody catalysts, generated with a variety of strategies for several different reaction types, suggest that their modest efficiency is a consequence of imperfect hapten design and indirect selection. Development of improved transition-state analogs, refinements in immunization and screening protocols, and elaboration of general strategies for augmenting the efficiency of first-generation catalytic antibodies are identified as evident, but difficult, challenges for this field. Rising to these challenges and more successfully integrating programmable design with the selective forces of biology will enhance our understanding of enzymatic catalysis. Further, it should yield useful protein catalysts for an enhanced range of practical applications in chemistry and biology.
Gelsolin Inhibits the Inflammatory Process Induced by LPS (2017)

GSN exhibited a protective role in endotoxemia.
Heterogeneity of binding sites for tamoxifen and tamoxifen derivatives in estrogen target and nontarget fetal organs of guinea pig. (1982)

The present paper shows that the antiestrogen tamoxifen and different tamoxifen derivatives bind to two distinct cytoplasmic binding sites in the fetal uterus of guinea pig. The first one (Site A) corresponds to the estrogen receptor and binds tamoxifen with a dissociation constant (Kd) of 1.8 +/- 0.4 nM. The dissociation rate constant (k-1) of th Site A:tamoxifen complex at 4 degrees is 8.3 +/- 2 x 10(-4) sec-1 and at 26 degrees is 123 +/- 26 x 10(-4) sec-1. The binding ability of Site A appears to be thermolabile, being destroyed by heating at 37 degrees. The hydroxylated derivatives of tamoxifen (Metabolites B and D) have a higher affinity for Site A as compared to tamoxifen. The second binding site for tamoxifen (Site B) appears to be specific for the triphenylethylene class of antiestrogens (nafoxidine and several tamoxifen metabolites), the hydroxylation of tamoxifen decreasing the affinity for Site B. In contrast, natural and synthetic estrogens as well as cortisol, testosterone, and progesterone do not compete for Site B. Site B shows a higher affinity for tamoxifen (Kd 0.39 +/- 0.01 nM) as compared to Site A and a higher stability of the complex at both 4 and 26 degrees (k-1 0.81 +/- 0.14 and 3.0 +/- 0.4 x 10(-4) sec-1, respectively). The binding ability of Site B appears to be resistant to heating at 37 degrees. Both Sites A and B are destroyed by proteolytic treatment and are precipitated by 36% saturated ammonium sulfate. The tamoxifen:Site A complex translocates into the uterine nuclei in a "cell free" system by a temperature-dependent process, but the tamoxifen:Site B complex does not. Nevertheless, a site with a Kd similar to cytoplasmic Site B (0.47 +/- 0.1 nM) is spontaneously present in untreated fetal uterine nuclei. In other fetal organs which contain no estrogen receptor (heart) or very low levels (lung), the concentration of Site B is found to be significantly lower than in the fetal uterus (5 to 6 times). Furthermore, progressively lower levels of Site B are found in neonatal, immature, and mature uteri (as compared to fetal uterus) which contain also decreasing amounts of estrogen receptors. It is concluded that, besides binding to the estrogen receptor, the triphenylethylene antiestrogens bind to a specific site distinct from the estrogen receptor, that appears to be localized mainly in estrogen target cells.
Modeling of the Melt Blowing Performance of Slot Dies (2004)

The dual-jet slot die is the most common device used for producing melt-blown fibers. In this die, high-velocity air impinges upon a polymer stream. A comprehensive model was applied to predict the performance of these slot dies. This model involves the simultaneous solution of the momentum, energy, and continuity equations that are applied to the fiber threadline. Predicted parameters include fiber attenuation, vibration frequency, vibration amplitude, temperature, and stress. Experimental measurements were taken during melt blowing with an actual slot die. These measurements compared very well with the simulated results.