gebhart/patrepeval huggingface dataset:
Comparison of the platelet pro‐aggregatory effect of conventional unfractionated heparins and a low molecular weight heparin fraction (CY 222) (1987)

Two unfractionated heparins (UH), a porcine intestinal mucosal heparin (PIM), a bovine lung heparin (BLH) and a low molecular weight heparin (LMWH), CY 222, were assessed for their capacity to enhance platelet aggregation in vitro. Their potential proaggregatory effect was investigated in four systems: (a) enhancement of submaximal platelet aggregation induced by conventional agonists in platelet rich plasma and (b) in whole blood; (c) reversal of inhibition of platelet aggregation induced by iloprost, a stable analogue of prostacyclin; (d) the direct aggregatory effect of these anticoagulants on hyperactive platelets prepared from patients with severe peripheral vascular disease or anorexia nervosa. Whereas BLH and PIM, at therapeutic concentrations, had a proaggregatory effect in all four systems, CY 222 had no significant effect when compared with the controls. BLH was more potent than PIM in three of the four systems studied. These observations confirm that conventional UH are more proaggregatory than LMWH, and thus the latter may be potentially safer. These observations are also consistent with the fact that BLH administration causes thrombocytopenia more frequently than PIM. The direct activation by UH of platelets from patients not previously exposed to heparin also challenges the hypothesis that heparin-induced platelet activation and thrombocytopenia is solely mediated by classical heparin-dependent immune mechanisms.
Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma (2007)

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens. EGFRvIII is a truncated extracellular mutant of the EGF receptor (EGFR) commonly found in GBMs that confers enhanced tumorigenic behavior. To gain a molecular understanding of the mechanisms by which EGFRvIII acts, we have performed a large-scale analysis of EGFRvIII-activated phosphotyrosine-mediated signaling pathways and thereby have identified and quantified 99 phosphorylation sites on 69 proteins. Distinct signaling responses were observed as a function of titrated EGFRvIII receptor levels with the phosphatidylinositol 3-kinase pathway being dominant over the MAPK and STAT3 pathways at a high level of EGFRvIII expression. Within this data set, the activating phosphorylation site on the c-Met receptor was found to be highly responsive to EGFRvIII levels, indicating cross-activation of the c-Met receptor tyrosine kinase by EGFRvIII. To determine the significance of this finding, we devised a combined treatment regimen that used a c-Met kinase inhibitor and either an EGFR kinase inhibitor or cisplatin. This regimen resulted in enhanced cytotoxicity of EGFRvIII-expressing cells compared with treatment with either compound alone. These results suggest that the clinical use of c-Met kinase inhibitors in combination with either EGFR inhibitors or standard chemotherapeutics might represent a previously undescribed therapeutic approach to overcome the observed chemoresistance in patients with GBMs expressing EGFRvIII.
Proteomic analysis of the proliferative and secretory phases of the human endometrium: Protein identification and differential protein expression (2004)

Proteomic analyses of the proliferative and secretory phases of the human endometrium were carried out to identify proteins and discover differentially expressed proteins using isotope-coded affinity tags, three stages of chromatographic separation and online tandem mass spectrometry (MS/MS). From an initial list of 346 proteins identified by ProICAT, manual inspection of MS/MS spectra and confirmatory searches pared the list down to 119 positively identified proteins. Only five of the proteins showed consistent differential expression. The utility of some of these proteins as indicators of true differential expression in the endometrium is open to discussion. The two proteins with unquestionable differential expressions in the secretory endometrium are: glutamate NMDA receptor subunit zeta 1 precursor and FRAT1. Some of the proteins that show no differential expression have previously been examined in gene-expression studies with similar conclusions.
Convolution algebras arising from Sturm‐Liouville transforms and applications (2001)

A regular Sturm‐Liouville eigenvalue problem gives rise to a related linear integral transform. Churchill has shown how such an integral transform yields, under certain circumstances, a generalized convolution operation. In this paper, we study the properties of convolution algebras arising in this fashion from a regular Sturm‐Liouville problem. We give applications of these convolution algebras for solving certain differential and integral equations, and we outline an operational calculus for classes of such equations.
Role of the Y1 Receptor in the Regulation of Neuropeptide Y-Mediated Feeding: Comparison of Wild-Type, Y1 Receptor-Deficient, and Y5 Receptor-Deficient Mice (2000)

Neuropeptide Y (NPY) increases food intake through the action of hypothalamic NPY receptors. At least six subtypes of NPY, peptide YY (PYY), and pancreatic polypeptide (PP) receptors have been identified in mice. Although the involvement of Y1 and Y5 receptors in feeding regulation has been suggested, the relative importance of each of these NPY receptors and the participation of a novel feeding receptor are still unclear. To address this issue, we generated a Y1 receptor-deficient (Y1-/-) and a Y5 receptor-deficient (Y5-/-) mouse line in which we directly compared the orexigenic effects of NPY and its analogs after intracerebroventricular (icv) administration. The icv NPY-induced food intake was remarkably reduced in Y1-/- mice, but was not significantly altered by inactivation of the Y5 receptor. The Y1 receptor therefore plays a dominant role in NPY-induced feeding. Stimulation of feeding by moderately selective Y5 agonists [PYY-(3-36), human PP, and bovine PP] was reduced in Y5-/- mice, although food intake did not decrease to vehicle control levels. These results indicate that the Y5 receptor functions as one of the feeding receptors. In addition, the finding that Y5-preferring agonists still induce food intake in Y5-/- mice suggests a role for another NPY receptor(s), including the possibility of novel NPY receptors. Surprisingly, despite the limited efficacy of PYY-(3-36) and PPs at the Y1 receptor, food consumption induced by these agonists was significantly diminished in Y1-/- mice compared with that in wild-type controls. These observations suggest that the feeding stimulation induced by NPY and its analogs may be directly or indirectly modulated by the action of the Y1 receptor. We conclude that multiple NPY receptors, possibly including the novel feeding receptor, are involved in the feeding response evoked by NPY and its analogs. Among them, the Y1 receptor plays a key role in NPY-induced feeding in mice.
A prism combination for near isotropic fluorescence excitation by total internal reflection (2003)

Total internal reflection fluorescence (TIRF) microscopy is finding increasing application for selectively detecting molecules at or near a glass-water surface. As with all fluorescence methods, the efficiency of excitation of a fluorophore is potentially sensitive to the polarization state of the source. In TIRF, s-polarized excitation produces an evanescent field that is perpendicular to the incident plane (y direction), whereas p-polarized light generates a more complex pattern but one dominated by a field that is vertical to the surface (z direction). Thus, fluorophores whose absorption dipoles are fixed in the x direction are not favourably aligned for excitation. Here we describe a beam-splitting prism arrangement that allows excitation by two orthogonal beams, thus giving isotropic excitation in the x-y plane with s-polarized light. With linearly polarized light at the magic angle, near isotropic excitation in three dimensions should be achieved. This prism design should find application in polarized fluorescence microscopy to investigate the rotational motions of macromolecules or to minimize flickering of fluorescence emission arising from molecular rotations in single molecule studies.
De novo design of the hydrophobic cores of proteins (1995)

We have developed and experimentally tested a novel computational approach for the de novo design of hydrophobic cores. A pair of computer programs has been written, the first of which creates a "custom" rotamer library for potential hydrophobic residues, based on the backbone structure of the protein of interest. The second program uses a genetic algorithm to globally optimize for a low energy core sequence and structure, using the custom rotamer library as input. Success of the programs in predicting the sequences of native proteins indicates that they should be effective tools for protein design. Using these programs, we have designed and engineered several variants of the phage 434 cro protein, containing five, seven, or eight sequence changes in the hydrophobic core. As controls, we have produced a variant consisting of a randomly generated core with six sequence changes but equal volume relative to the native core and a variant with a "minimalist" core containing predominantly leucine residues. Two of the designs, including one with eight core sequence changes, have thermal stabilities comparable to the native protein, whereas the third design and the minimalist protein are significantly destabilized. The randomly designed control is completely unfolded under equivalent conditions. These results suggest that rational de novo design of hydrophobic cores is feasible, and stress the importance of specific packing interactions for the stability of proteins. A surprising aspect of the results is that all of the variants display highly cooperative thermal denaturation curves and reasonably dispersed NMR spectra. This suggests that the non-core residues of a protein play a significant role in determining the uniqueness of the folded structure.
Demand Response Scheduling by Stochastic SCUC (2010)

Considerable developments in the real-time telemetry of demand-side systems allow independent system operators (ISOs) to use reserves provided by demand response (DR) in ancillary service markets. Currently, many ISOs have designed programs to utilize the reserve provided by DR in electricity markets. This paper presents a stochastic model to schedule reserves provided by DR in the wholesale electricity markets. Demand-side reserve is supplied by demand response providers (DRPs), which have the responsibility of aggregating and managing customer responses. A mixed-integer representation of reserve provided by DRPs and its associated cost function are used in the proposed stochastic model. The proposed stochastic model is formulated as a two-stage stochastic mixed-integer programming (SMIP) problem. The first-stage involves network-constrained unit commitment in the base case and the second-stage investigates security assurance in system scenarios. The proposed model would schedule reserves provided by DRPs and determine commitment states of generating units and their scheduled energy and spinning reserves in the scheduling horizon. The proposed approach is applied to two test systems to illustrate the benefits of implementing demand-side reserve in electricity markets.
Vγ2Vδ2 T Cell Receptor Recognition of Prenyl Pyrophosphates Is Dependent on All CDRs (2010)

gammadelta T cells differ from alphabeta T cells in the Ags they recognize and their functions in immunity. Although most alphabeta TCRs recognize peptides presented by MHC class I or II, human gammadelta T cells expressing Vgamma2Vdelta2 TCRs recognize nonpeptide prenyl pyrophosphates. To define the molecular basis for this recognition, the effect of mutations in the TCR CDR was assessed. Mutations in all CDR loops altered recognition and cover a large footprint. Unlike murine gammadelta TCR recognition of the MHC class Ib T22 protein, there was no CDR3delta motif required for recognition because only one residue is required. Instead, the length and sequence of CDR3gamma was key. Although a prenyl pyrophosphate-binding site was defined by Lys109 in Jgamma1.2 and Arg51 in CDR2delta, the area outlined by critical mutations is much larger. These results show that prenyl pyrophosphate recognition is primarily by germline-encoded regions of the gammadelta TCR, allowing a high proportion of Vgamma2Vdelta2 TCRs to respond. This underscores its parallels to innate immune receptors. Our results also provide strong evidence for the existence of an Ag-presenting molecule for prenyl pyrophosphates.
Fast Isolation of Recombinant Baculovirus by Antibody Screening (2003)

The use of a rapid and efficient scheme for the detection and purification of recombinant baculoviruses is described. The method is based on the detection of foreign proteins in cellular lysates of baculovirus-infected insect cells by antibody screening. The recombinant virus is purified by repeated serial dilutions. The method allows the identification and purification of recombinant viruses within two to three weeks.
Pasteurella and Pasteurellosis (1989)

This book brings together for the first time current knowledge about the organism and the disease. The first part of the work covers the taxonomy, structure, growth characteristics, immunogenic properties, and virulence attributes of pasteurella species. The second part reviews the diseases themselves, including discussion of their diagnosis, pathology, treatment and prevention, and their distribution and economic importance.
Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. (1983)

We report here that FcR for human monomeric IgG1 can be induced on cells of myeloid origin cultured in the presence of IFN gamma for 8 h. Supernatant fluids from cultures of lymphocytes infected with a variety of viruses or cocultured with cell lines have the same FcR enhancing effect as IFN gamma. We identify the factor in the supernatant fluid responsible for the induction as immune interferon. Among the different types of IFN, only the gamma type (both purified and recombinant) specifically induces the appearance of FcR for monomeric IgG1 on normal and leukemic myeloid cells but not on cells of lymphoid origin. This effect is also evident on mature PMN. We show that the specificity and the affinity of the receptor induced on HL-60 promyelocytic cells, peripheral blood monocytes, and PMN are identical to those of the receptor spontaneously present on the same cells, except for PMN, which do not spontaneously express this type of receptor. The results of inhibition experiments performed with mouse IgG of and IgG3. These results suggest that the receptor present on human monocytes different isotypes indicate that the receptor can be inhibited by murine IgG2a or immature myeloid cells, selectively inducible by IFN gamma, has a specificity similar to the FcR1 described on mouse macrophages.
Isolation of Cell-Free DNA from Maternal Plasma Using Manual and Automated Systems (2008)

Cell-free fetal DNA present in the maternal circulation holds great potential for noninvasive prenatal diagnosis and analysis of fetal genetic traits. However, only approximately 3-6% of total DNA in the maternal plasma is of fetal origin. Because of its scarcity in the maternal circulation, various methods have been developed and tested to optimize the extraction of this rare material from plasma. Here, we first describe the commonly used protocol for separating plasma from whole blood samples. We also describe two commercially available methods for the extraction of cell-free DNA from maternal plasma, which we have found particularly straightforward and easy to use: a manual method using the High Pure PCR Template Preparation kit (Roche Diagnostics) and an automated system using the MagNA Pure LC instrument (Roche Diagnostics). Use of the methods described here will help to ensure maximum yield and purity of cell-free fetal DNA extracted from maternal plasma samples for downstream analyses.
Determination of the refractive index of highly scattering human tissue by optical coherence tomography (1995)

We describe two new techniques, based on optical coherence tomography (OCT), for determining the refractive index of highly scattering human tissue. We obtained refractive indices of in vitro human tissue, using OCT to measure the physical and optical path lengths of the sample. We obtained measurements of the refractive index of in vitro and in vivo human tissue, using OCT to track the focal length shift that results from translating the focus along the optic axis within the tissue. The refractive indices of human skin, adipose, and muscle were measured and compared with previously published estimates.
Understanding the Fundamentals of Aqueous ATRP and Defining Conditions for Better Control (2015)

Conducting an atom transfer radical polymerization (ATRP) in water provides several intriguing challenges. In order to attain a deeper understanding of the mechanism of aqueous ATRP, with particular attention to the reasons for the potential loss of control, a systematic investigation was carried out with three copper-amine catalysts ([CuIIL]2+, L = PMDETA, TPMA and Me6TREN). The association constants (KX) of [CuIIL]2+ and [CuIL]+ with X– and OH–, as well as the relative stabilities and redox properties of the complexes, were determined as a function of both [X–] and pH. In addition, rate constants and equilibrium constants of disproportionation for all three [CuIL]+ complexes were measured. Finally, ATRP equilibrium constants (KATRP) were estimated for all complexes, using 2-hydroxyethyl 2-bromoisobutyrate (HEBiB) as initiator. The primary factors affecting control in aqueous ATRP were identified as catalyst instability at both low and high pH, easy dissociation of deactivator (KX < 15), very high KATRP and fast disproportionation of [CuIL]+. Overall, the results obtained in this study provide a set of guidelines for a well-controlled aqueous ATRP. The guidelines were used to conduct several efficient electrochemically mediated aqueous ATRP experiments with oligo(ethylene oxide) methyl ether methacrylate as monomer, HEBiB as initiator and copper complexes with three different ligands. A successful ATRP in a strongly acidic environment (pH 1.5) is reported for the first time, contrary to what was believed until now, indicating that ATRPs can be easily controlled in acidic conditions, while high pH should be avoided.
Immunomodulatory Effects of theLutzomyia longipalpisSalivary Gland Protein Maxadilan on Mouse Macrophages (2007)

Infection with Leishmania major is enhanced when the sand fly Lutzomyia longipalpis salivary peptide maxadilan (MAX) is injected along with the parasite. Here we determined the effect that MAX has on the secretion of cytokines and nitric oxide (NO) and on parasite survival in macrophages (MPhis). The cytokines produced by MPhis can enhance a type 1 response, which will increase NO and the killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody production that is ineffective against intracellular pathogens such as L. major. A mouse macrophage cell line (RAW 264.7) was stimulated with various concentrations of MAX and lipopolysaccharide (LPS), and the supernatants were collected after 1, 2, and 3 days. Supernatants were assayed for interleukin-12p70 (IL-12p70), IL-10, IL-6, transforming growth factor beta (TGF-beta), NO, and tumor necrosis factor alpha (TNF-alpha). Our results indicate that the addition of MAX upregulates the cytokines associated with a type 2 response (IL-10, IL-6, and TGF-beta) but downregulates type 1 cytokines (IL-12p70 and TNF-alpha) and NO. MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs), and the parasite load increased significantly. The enhanced parasite load correlated with decreased NO production by PECs that were stimulated with LPS and gamma interferon in the presence of MAX. The ability of MAX to foster a type 2 response, to enhance parasite survival, and to decrease NO argues that MAX may be crucial for the early survival of Leishmania in the vertebrate host, and therefore, MAX holds considerable promise as an antigenic component for a vaccine against Leishmania.
Fast and Easy Multiresidue Method Employing Acetonitrile Extraction/Partitioning and “Dispersive Solid-Phase Extraction” for the Determination of Pesticide Residues in Produce (2003)

A simple, fast, and inexpensive method for the determination of pesticide residues in fruits and vegetables is introduced. The procedure involves initial single-phase extraction of 10 g sample with 10 mL acetonitrile, followed by liquid-liquid partitioning formed by addition of 4 g anhydrous MgSO4 plus 1 g NaCl. Removal of residual water and cleanup are performed simultaneously by using a rapid procedure called dispersive solid-phase extraction (dispersive-SPE), in which 150 mg anhydrous MgSO4 and 25 mg primary secondary amine (PSA) sorbent are simply mixed with 1 mL acetonitrile extract. The dispersive-SPE with PSA effectively removes many polar matrix components, such as organic acids, certain polar pigments, and sugars, to some extent from the food extracts. Gas chromatography/mass spectrometry (GC/MS) is then used for quantitative and confirmatory analysis of GC-amenable pesticides. Recoveries between 85 and 101% (mostly > 95%) and repeatabilities typically < 5% have been achieved for a wide range of fortified pesticides, including very polar and basic compounds such as methamidophos, acephate, omethoate, imazalil, and thiabendazole. Using this method, a single chemist can prepare a batch of 6 previously chopped samples in < 30 min with approximately 1 dollar (U.S.) of materials per sample.
Decreased T-Cell Receptor Excision Circles in Cutaneous T-Cell Lymphoma (2005)

We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.
Gastrointestinal adaptation to diets of differing fat composition in human volunteers. (1991)

The effect of a low fat diet (9 MJ) v a high fat diet (19.26 MJ), each consumed separately for four and 14 days, on gastric emptying and mouth to caecum transit time of a high fat test meal and body weight and satiety were examined in groups of 10 and six normal male volunteers. The half time for gastric emptying (t1/2) and the mouth to caecum transit time of a high fat test meal was significantly faster after the high fat diet than the low fat diet when consumed for 14 days (t1/2=98 (80-116) v 147 (88-206) minutes (median (range)), p less than 0.05; mouth to caecum transit time 240 (130-350) v 360 (200-520) minutes, p less than 0.05), but not when consumed for only four days. The mean (SEM) body weight of all subjects significantly increased during the 14 day high fat diet (74.7 (1.3) v 72.7 (1.6) kg, p less than 0.05) but was not influenced during the consumption of the low fat diet. When subjects were given an appetising meal to consume on the day that they had consumed the transit test meal, they ate similar amounts irrespective of their recent dietary history, though the eating rate was significantly slower after the high fat diet (mean (SEM)) 46.7 (1.9) v 71.3 (14.8)/min, p less than 0.05). Maintaining normal subjects on a high or low fat diet for two weeks resulted in a desensitisation or sensitisation respectively of the mechanisms by which nutrients regulate gastrointestinal transit. These findings emphasise the importance of the recent dietary history in the interpretation of gastric emptying and small bowel transit time data.