gebhart/patrepeval huggingface dataset:
Superantigen-Induced T Cell:B Cell Conjugation Is Mediated by LFA-1 and Requires Signaling Through Lck, But Not ZAP-70 (2001)

The formation of a conjugate between a T cell and an APC requires the activation of integrins on the T cell surface and remodeling of cytoskeletal elements at the cell-cell contact site via inside-out signaling. The early events in this signaling pathway are not well understood, and may differ from the events involved in adhesion to immobilized ligands. We find that conjugate formation between Jurkat T cells and EBV-B cells presenting superantigen is mediated by LFA-1 and absolutely requires Lck. Mutations in the Lck kinase, Src homology 2 or 3 domains, or the myristoylation site all inhibit conjugation to background levels, and adhesion cannot be restored by the expression of Fyn. However, ZAP-70-deficient cells conjugate normally, indicating that Lck is required for LFA-1-dependent adhesion via other downstream pathways. Several drugs that inhibit T cell adhesion to ICAM-1 immobilized on plastic, including inhibitors of mitogen-activated protein/extracellular signal-related kinase kinase, phosphatidylinositol-3 kinase, and calpain, do not inhibit conjugation. Inhibitors of phospholipase C and protein kinase C block conjugation of both wild-type and ZAP-70-deficient cells, suggesting that a phospholipase C that does not depend on ZAP-70 for its activation is involved. These results are not restricted to Jurkat T cells; Ag-specific primary T cell blasts behave similarly. Although the way in which Lck signals to enhance LFA-1-dependent adhesion is not clear, we find that cells lacking functional Lck fail to recruit F-actin and LFA-1 to the T cell:APC contact site, whereas ZAP-70-deficient cells show a milder phenotype characterized by disorganized actin and LFA-1 at the contact site.
Identification of a Sequence of Apolipoprotein A-I Associated with the Activation of Lecithin:Cholesterol Acyltransferase (2000)

We aimed to distinguish between the effects of mutations in apoA-I on the requirements for the secondary structure and a specific amino acid sequence for lecithin:cholesterol acyltransferase (LCAT) activation. Several mutants were constructed targeting region 140-150: (i) two mutations affecting alpha-helical structure, deletion of amino acids 140-150 and substitution of Ala(143) for proline; (ii) two mutations not affecting alpha-helical structure, substitution of Val(149) for arginine and substitution of amino acids 63-73 for sequence 140-150; and (iii) a mutation in a similar region away from the target area, deletion of amino acids 63-73. All mutations affecting region 140-150 resulted in a 4-42-fold reduction in LCAT activation. Three mutations, apoA-I(Delta140-150), apoA-I(P143A), and apoA-I(140-150 --> 63-73), affected both the apparent V(max) and K(m), whereas the mutation apoA-I(R149V) affected only the V(max). The mutation apoA-I(Delta63-73) caused only a 5-fold increase in the K(m). All mutants, except apoA-I(P143A) and apoA-I(Delta63-73), were active in phospholipid binding assay. All mutants, except apoA-I(P143A), formed normal discoidal complexes with phospholipid. The mutation apoA-I(Delta63-73) caused a significant reduction in the stability of apoA-I.phospholipid complexes in denaturation experiments. Combined, our results strongly suggest that although the correct conformation and orientation of apoA-I in the complex with lipids are crucial for activation of LCAT, when these conditions are fulfilled, activation also strongly depends on the sequence that includes amino acids 140-150.
PAI-1 donor polymorphism influences long-term kidney graft survival (2008)

Our study suggests that donor PAI-1 polymorphism influences kidney graft survival and that the donor 4G/4G genotype is an independent risk factor for graft loss. Prospective studies are needed to confirm these results.
Disulfide bond effects on protein stability: Designed variants of Cucurbita maxima trypsin inhibitor‐V (2001)

Attempts to increase protein stability by insertion of novel disulfide bonds have not always been successful. According to the two current models, cross-links enhance stability mainly through denatured state effects. We have investigated the effects of removal and addition of disulfide cross-links, protein flexibility in the vicinity of a cross-link, and disulfide loop size on the stability of Cucurbita maxima trypsin inhibitor-V (CMTI-V; 7 kD) by differential scanning calorimetry. CMTI-V offers the advantage of a large, flexible, and solvent-exposed loop not involved in extensive intra-molecular interactions. We have uncovered a negative correlation between retention time in hydrophobic column chromatography, a measure of protein hydrophobicity, and melting temperature (T(m)), an indicator of native state stabilization, for CMTI-V and its variants. In conjunction with the complete set of thermodynamic parameters of denaturation, this has led to the following deductions: (1) In the less stable, disulfide-removed C3S/C48S (Delta Delta G(d)(50 degrees C) = -4 kcal/mole; Delta T(m) = -22 degrees C), the native state is destabilized more than the denatured state; this also applies to the less-stable CMTI-V* (Delta Delta G(d)(50 degrees C) = -3 kcal/mole; Delta T(m) = -11 degrees C), in which the disulfide-containing loop is opened by specific hydrolysis of the Lys(44)-Asp(45) peptide bond; (2) In the less stable, disulfide-inserted E38C/W54C (Delta Delta G(d)(50 degrees C) = -1 kcal/mole; Delta T(m) = +2 degrees C), the denatured state is more stabilized than the native state; and (3) In the more stable, disulfide-engineered V42C/R52C (Delta Delta G(d)(50 degrees C) = +1 kcal/mole; Delta T(m) = +17 degrees C), the native state is more stabilized than the denatured state. These results show that a cross-link stabilizes both native and denatured states, and differential stabilization of the two states causes either loss or gain in protein stability. Removal of hydrogen bonds in the same flexible region of CMTI-V resulted in less destabilization despite larger changes in the enthalpy and entropy of denaturation. The effect of a cross-link on the denatured state of CMTI-V was estimated directly by means of a four-state thermodynamic cycle consisting of native and denatured states of CMTI-V and CMTI-V*. Overall, the results show that an enthalpy-entropy compensation accompanies disulfide bond effects and protein stabilization is profoundly modulated by altered hydrophobicity of both native and denatured states, altered flexibility near the cross-link, and residual structure in the denatured state.
Threats to military transport aircraft: A technical review (2003)

Without assuming any particular operational scenario, possible threats to military transport aircraft include hits from small arms, high explosive incendiary projectiles with impact or proximity fuzes, frangible armour piercing discarding sabot (APDS) rounds, and small warheads from man-portable anti-aircraft missiles or medium-to-large anti-aircraft warheads. This paper briefly describes each of these threats and their potential effect on aircraft. The hit density as a function of distance is schematically presented whereby high hit densities lead to different synergistic effects. The principal function of radar proximity sensors is briefly described, as well as the prediction of the initial velocities of fragments and their decrease in the ambient atmosphere. Some tests are proposed to define quantitatively the blast/fragmenting loads on aircraft skins with cost-effective individual fragment tests and with fragment generators for high hit densities.
Mobile positioning in CDMA cellular networks (2005)

Mobile positioning in cellular networks will provide several services such as, locating stolen mobiles, emergency calls, network self optimisation, different billing tariffs depending on where the call is originated and many more. The IS-95 2/sup nd/ generation digital code division multiple access (CDMA) cellular standard has potential to accommodate mobile positioning in its architecture. Moreover, on the eve of the 3/sup rd/ generation (3G) wireless network standardization, required steps must be taken for the implementation of mobile positioning. In this paper, mobile positioning in CDMA cellular networks has been discussed, the simulation and the measurement results using standard CDMA mobile phones, are presented. The purpose of this study is to analyse the accuracy of mobile positioning using standard CDMA mobile phones. Positioning calculations were performed in the mobile station using the CDMA forward link channels in order to provide total privacy. This technique can also be incorporated in the 3G WCDMA networks.
Aggregation of complement receptors on human neutrophils in the absence of ligand. (1987)

C3bi receptors (CR3) on human polymorphonuclear leukocytes (PMN) bind ligand-coated particles and promote their ingestion. The binding activity of CR3 is not constitutive but is transiently enabled by phorbol esters (Wright, S. D., and B. D. Meyer, 1986, J. Immunol. 136:1759-1764). Our observations indicate that the capacity of CR3 to bind ligand is tightly correlated with the degree of ligand-independent aggregation of the receptor in the plane of the membrane. Fixed PMN were labeled with anti-CR3 monoclonal antibodies and streptavidin colloidal gold before viewing in the electron microscope either en face or in thin section. On unstimulated PMN, gold particles marking CR3 were dispersed randomly. Stimulation of PMN for 25 min with phorbol myristate acetate (PMA) dramatically enhances binding of C3bi-coated particles, and the CR3 on such stimulated cells was observed in clusters containing more than six gold particles. CR3 was not aggregated over coated pits. After 50 min in PMA, the binding activity of CR3 falls, and the distribution of CR3 was again observed to be disperse. If a hydrophilic phorbol ester was washed away after a 20-min stimulation, binding activity remains elevated for at least 50 min, and CR3 remained aggregated. Thus, clustering of CR3 was temporally correlated with its ability to bind ligand and initiate phagocytosis. Unlike CR3, Fc receptors and HLA did not exhibit changes in their aggregation state in response to PMA. Treating PMN with formyl-methionyl-leucyl-phenylalanine, which enhances expression of CR3 but not its function, did not lead to aggregation of CR3. These observations suggest that a clustered configuration is a precondition necessary for binding ligand and signaling phagocytosis.
HER-2 Is an Independent Prognostic Factor in Endometrial Cancer: Association With Outcome in a Large Cohort of Surgically Staged Patients (2006)

Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.
Synergy of water soluble prodrug triptolide (minnelide) with gemcitabine and nab-paclitaxel in pancreatic cancer. (2016)

259 Background: Gemcitabine with nab-paclitaxel is the standard of care for metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Addition of nab-paclitaxel to gemcitabine improves the survival of patients with metastatic pancreatic cancer by only 6 weeks while increasing toxicity. Meaningful combinations that reduce the doses while improving efficacy are required. Water soluble prodrug of triptolide (Minnelide) is effective against PDAC in preclinical studies and has demonstrated activity in the ongoing phase I trial. We have evaluated the combination of low dose triptolide prodrug with lowered doses of Abraxane and gemcitabine in PDAC. Methods: Pancreatic cancer cell lines S2-013 and S2-VP10 were xenografted both subcutaneously as well as orthotopically in athymic nude mice. Efficacy of a combination of triptolide prodrug (Minnelide: 0.21mg/kg) with reduced dose of gemcitabine 100mg/kg + Abraxane 10mg/kg (~40% of the clinically effective dose) was evaluated and compared with both standard of care gemcitabine 250mg/kg + Abraxane 25mg/kg as well as reduced dose of gemcitabine + Abraxane in animal models. We also used the immunocompetent model where murine PDAC cell line KPC001 implanted subcutaneously in C57/bl6 mice. Results: In subcutaneous syngeneic model, combination of triptolide prodrug and paclitaxel significantly inhibited tumor growth (tumor volumes expressed as % of Control, Mean±SEM: triptolide prodrug : 75.4±25, paclitaxel: 50.0 ±3, triptolide prodrug + paclitaxel: 11.0 ±1). In metastasis model combination therapy markedly improved survival (median survival in days: Vehicle-13, triptolide prodrug -20, standard of care -45, reduced dose standard of care-30, and Minnelide + reduced dose standard of care (all mice alive at 90 days). Combination of triptolide prodrug and low dose gemcitabine + nab-paclitaxel decreased tumor size, increased survival, reduced metastases and malignant ascites in orthotopic model of PDAC. Conclusions: Triptolide prodrug synergizes with reduced dose standard of care (gemcitabine and nab-paclitaxel) and helps in reducing the doses of these toxic drugs all the while achieving same or better efficacy in animal models of PDAC.
An Online Simplified Rotor Resistance Estimator for Induction Motors (2009)

This brief presents an adaptive variable structure identifier that provides finite time convergent estimate of the induction motor rotor resistance under feasible persistent of excitation condition. The proposed rotor resistance scheme is based on the standard dynamic model of induction motor expressed in a fixed reference frame attached to the stator. The available variables are the rotor speed, the stator currents and voltages. Experiments show that the proposed method achieved very good estimation of the rotor resistance which is subjected to online large variation during operation of the induction motor. Also, the proposed online simplified rotor resistance estimator is robust with respect to the variation of the stator resistance, measurement noise, modeling errors, discretization effects and parameter uncertainties. Important advantages of the proposed algorithm include that it is an online method (the value of R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> can be continuously updated) and it is very simple to implement in real-time (this feature distinguishes the proposed identifier from the known ones).
Effect of Serotonin-Releasing Drugs on Serum Corticosterone Concentration in Rats (1980)

(+/-)p-Chloroamphetamine hydrochloride, at doses of 1-8 mg/kg i.p. in rats, caused a dose-related increase in serum corticosterone concentration. The increase occurred rapidly, within 30 min, and was over within 4 h. Evidence that the increase was mediated by serotonin release consisted of the following findings: (1) a similar increase did not occur with (+/-)o-chloroamphetamine or (+/-)p-chloro-alpha-methylbenzylamine, analogs of p-chloroamphetamine lacking its ability to deplete serotonin; (2) the increase was prevented by prior treatment with p-chlorophenylalanine, which reduced the brain stores of serotonin available for release by p-chloroamphetamine; (3) the increase was prevented by prior treatment with fluoxetine, an inhibitor of the uptake pump on serotonin neurons, which blocks serotonin release by p-chloroamphetamine, and (4) the increase was mimicked by fenfluramine and norfenfluramine, agents known to release brain serotonin in a manner similar to the action of p-chloroamphetamine. These findings strengthen earlier evidence that brain serotonin neurons have a stimulatory influence on pituitary-adrenocortical function in rats.
Steroid hormones—agonists and antagonists (1981)

Steroid hormones are frequently classified into broad categories such as ‘progestins’, ‘androgens’ and ‘glucocorticoids’, but this classification is often misleading or just incomplete since it only accounts for their known primary biological activity and does not adequately describe the multiplicity of actions that many of them display. In view of the ubiquity of the receptors of different classes of steroid hormone (for instance, each of the oestrogen, progestin, androgen and glucocorticoid receptors has been identified in peripheral target tissues such as the uterus and pituitary and in central tissues such as the hypothalamus), it is of interest to be able to define the receptor binding profile of a new substance and thus extrapolate, by comparison with the natural hormones and well-established steroid drugs, the possible actions of this new compound in different organs. Furthermore, since interdependent regulatory mechanisms seem to condition many hormonal responses (for example, both progestin and androgen binding sites can be induced by oestrogens), it is useful to know whether certain potent drugs classified as agonists of one natural hormone are antagonists of another.
A second functional Δ5 fatty acid desaturase in the cellular slime mould Dictyostelium discoideum (2000)

A cDNA with homology to fatty acid desaturases was selected by searching the cDNA data bank of Dictyostelium discoideum (http://www. csm.biol.tsukuba.ac.jp/cDNAproject.html) with conserved histidine box motifs. Using this sequence, genomic DNA encoding the Delta5 desaturase was amplified from the genomic DNA of D. discoideum, and its desaturase activity was confirmed by the overexpression mutation in D. discoideum and the gain-of-function mutation in yeast. The cloned cDNA is 1565 nucleotides in length, and the deduced amino-acid sequence comprised 467 amino-acid residues containing an N-terminal cytochrome b5 domain that shared 43% identity with cytochrome b5 of Oryza sativa. The whole sequence was 42% identical to the Delta5 desaturase of Mortierella alpina. This desaturase is a novel member of the cytochrome b5-containing Delta5 fatty acid desaturase. As we have already reported one other Delta5 desaturase in Dictyostelium, this organism is the first to be confirmed as having two functional Delta5 fatty acid desaturase genes. The substrate specificities of the two functional Delta5 desaturases of D. discoideum were also examined.
Enhanced Release of Amyloid -Protein from Codon 670/671 Swedish Mutant -Amyloid Precursor Protein Occurs in Both Secretory and Endocytic Pathways (1996)

The mutation at codons 670/671 of beta-amyloid precursor protein (betaPP) dramatically elevates amyloid beta-protein (Abeta) production. Since increased Abeta may be responsible for the disease phenotype identified from a Swedish kindred with familial Alzheimer's disease, evaluation of the cellular mechanism(s) responsible for the enhanced Abeta release may suggest potential therapies for Alzheimer's disease. In this study, we analyzed Chinese hamster ovary cells stably transfected with either wild type betaPP (betaPP-wt) or "Swedish" mutant betaPP (betaPP-sw) for potential differences in betaPP processing. We confirmed that increased amounts of Abeta and a beta-secretase-cleaved COOH-terminally truncated soluble betaPP (betaPPs) were secreted from betaPP-sw cells. As shown previously for betaPP-wt cells, Abeta was released more slowly than the secretion of betaPPs from surface-labeled betaPP-sw cells, indicating that endocytosis of cell surface betaPP is one source of Abeta production. In contrast, by [35S]methionine metabolic labeling, the rates of Abeta and betaPPs release were virtually identical for both cell lines. In addition, the identification of intracellular betaPPs and Abeta shortly after pulse labeling suggests that Abeta is produced in the secretory pathway. Interestingly, more Abeta was present in medium from betaPP-sw cells than betaPP-wt cells after either cell surface iodination or [35S]methionine labeling, indicating that betaPP-sw cells have enhanced Abeta release in both the endocytic and secretory pathways. Furthermore, a variety of drug treatments known to affect protein processing similarly reduced Abeta release from both betaPP-wt and betaPP-sw cells. Taken together, the data suggest that the processing pathway for betaPP is similar for both betaPP-wt and betaPP-sw cells and that increased Abeta production by betaPP-sw cells arises from enhanced cleavage of mutant betaPP by beta-secretase, the as-yet unidentified enzyme(s) that cleaves at the NH2 terminus of Abeta.
Reduction in threading dislocation densities in AlN epilayer by introducing a pulsed atomic-layer epitaxial buffer layer (2008)

A method of reducing threading dislocation (TD) density in AlN epilayers grown on sapphire substrate is reported. By introducing an AlN buffer layer grown by a pulsed atomic-layer epitaxy method, TDs in epitaxial AlN films were greatly decreased. From transmission electron microscopic images, a clear subinterface was observed between the buffer layer and the subsequently continuous grown AlN epilayer. In the vicinity of the subinterface, the redirection, annihilation, and termination of TDs were observed. The increase in lateral growth rate accounted for TD redirection and annihilation in the AlN epilayer. Strain variation between the two regions resulted in the termination of TDs owing to the dislocation line energy minimization.
Rescue of Targeted Regions of Mammalian Chromosomes by in Vivo Recombination in Yeast (1998)

In contrast to other animal cell lines, the chicken pre-B cell lymphoma line, DT40, exhibits a high level of homologous recombination, which can be exploited to generate site-specific alterations in defined target genes or regions. In addition, the ability to generate human/chicken monochromosomal hybrids in the DT40 cell line opens a way for specific targeting of human genes. Here we describe a new strategy for direct isolation of a human chromosomal region that is based on targeting of the chromosome with a vector containing a yeast selectable marker, centromere, and an ARS element. This procedure allows rescue of the targeted region by transfection of total genomic DNA into yeast spheroplasts. Selection for the yeast marker results in isolation of chromosome sequences in the form of large circular yeast artificial chromosomes (YACs) up to 170 kb in size containing the targeted region. These YACs are generated by homologous recombination in yeast between common repeated sequences in the targeted chromosomal fragment. Alternatively, the targeted region can be rescued as a linear YACs when a YAC fragmentation vector is included in the yeast transformation mixture. Because the entire isolation procedure of the chromosomal region, once a target insertion is obtained, can be accomplished in approximately 1 week, the new method greatly expands the utility of the homologous recombinationproficient DT40 chicken cell system.
The Fecal Viral Flora of California Sea Lions (2011)

California sea lions are one of the major marine mammal species along the Pacific coast of North America. Sea lions are susceptible to a wide variety of viruses, some of which can be transmitted to or from terrestrial mammals. Using an unbiased viral metagenomic approach, we surveyed the fecal virome in California sea lions of different ages and health statuses. Averages of 1.6 and 2.5 distinct mammalian viral species were shed by pups and juvenile sea lions, respectively. Previously undescribed mammalian viruses from four RNA virus families (Astroviridae, Picornaviridae, Caliciviridae, and Reoviridae) and one DNA virus family (Parvoviridae) were characterized. The first complete or partial genomes of sapeloviruses, sapoviruses, noroviruses, and bocavirus in marine mammals are reported. Astroviruses and bocaviruses showed the highest prevalence and abundance in California sea lion feces. The diversity of bacteriophages was higher in unweaned sea lion pups than in juveniles and animals in rehabilitation, where the phage community consisted largely of phages related to the family Microviridae. This study increases our understanding of the viral diversity in marine mammals, highlights the high rate of enteric viral infections in these highly social carnivores, and may be used as a baseline viral survey for comparison with samples from California sea lions during unexplained disease outbreaks.