gebhart/patrepeval huggingface dataset:
A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity (2009)

Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers. However, all currently available antibodies against mesothelin are either murine or chimeric, which could limit their use because of increased likelihood of immunogenicity compared with fully human antibodies. Here, we report the identification and characterization of a novel fully human monoclonal antibody, m912, which was isolated from a human Fab library by panning against recombinant mesothelin. This antibody in scFv, Fab, and IgG1 formats bound specifically and with high affinity (equilibrium dissociation constant in the nmol/L range) to cell surface-associated human mesothelin and to recombinant mesothelin. It specifically lysed cancer cells engineered to express mesothelin in the presence of peripheral blood mononuclear cells isolated from healthy donors most likely by antibody-dependent cellular cytotoxicity. M912 is the first reported fully human monoclonal antibody to mesothelin, which has potential for cancer treatment and diagnosis.
Outer membrane proteins of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus studied by SDS‐PAGE and immunoblotting (1990)

This investigation characterized and compared outer membrane proteins (OMP) of the closely related Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus by means of SDS-PAGE patterns and reactions on immunoblots with rabbit antiserum against A. actinomycetemcomitans FDC Y4. Reactions with serum from a patient with Papillon Lefévre syndrome (PLS), from whom periodontal wild strains of A. actinomycetemcomitans had been isolated, were also studied. OMP were purified with selective solubilization from lyophilized cells of 10 wild and 4 reference strains of A. actinomycetemcomitans and 4 reference strains of H. aphrophilus. OMP profiles from wild and reference strains of A. actinomycetemcomitans were similar while those from A. actinomycetemcomitans and H. aphrophilus differed. The most prominent difference was absence of a heat modifiable protein in H. aphrophilus strains. Immunoblotting revealed strong common antigens in most strains, including a heat modifiable protein with mol wt 34 kDa, as well as a 29 kDa and a 16.5 kDa protein. Treatment with pronase and sodium periodate confirmed the protein nature of the major OMP antigens.
A comparison of the effects of tramadol and morphine on gastric emptying in man (1997)

In a previous study using an electrical bioimpedance technique and the paracetamol absorption test, we demonstrated that 0.09 mg.kg-1 of morphine delayed gastric emptying in healthy human volunteers. The aim of this study was to investigate whether analgesic doses of tramadol would cause a delay in gastric emptying similar to conventional opioids. Using the same volunteers and techniques as in our previous study, placebo or tramadol (1 mg.kg-1) was given in a randomised, double-blinded, cross-over placebo-controlled study. Gastric emptying was measured concurrently by a noninvasive epigastric bioimpedance technique and by the paracetamol absorption test. After the ingestion of 500 ml of deionised water plus paracetamol 1.5 g, the mean (SEM) time taken for gastric volume to decrease to 50% (t0.5) was recorded. No difference in gastric emptying rates (t0.5) between placebo, 7.7 (1 min), and tramadol, 9.5 (2 min), was noted. In our previous study, morphine prolonged t0.5 to 21 (3) min (p < 0.03). The maximum concentration and area under the curve of serum paracetamol concentrations following morphine were significantly different from placebo (p < 0.05) and tramadol (p < 0.05). We conclude that tramadol at a dose of 1 mg.kg-1 does not delay gastric emptying in humans.
Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus (2000)

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.
Surface Interaction Forces of Well-Defined, High-Density Polymer Brushes Studied by Atomic Force Microscopy. 1. Effect of Chain Length (2000)

We made direct force measurements by atomic force microscopy (AFM) at surfaces of polymer brushes comprised of low-polydispersity poly(methyl methacrylate) (PMMA) chains densely end-grafted on a silicon substrate by living radical polymerization. These brushes are characterized by an exceptionally high, nearly constant graft density (approximately 0.4 chains/nm2) and a wide range of molecular weights of the graft chains. This graft density is at least 10 times larger than those of the previously studied polymer brushes prepared by the adsorption of block copolymers. Force measurements were made in toluene with a silica particle-attached cantilever. The hysteresis behavior of a piezo actuator used in the AFM was corrected by simultaneously measuring its piezo current. The true distance D between the substrate surface and the silica probe, which usually is difficult to define in AFM experiments, was successfully determined by AFM imaging across the boundary of a scratched and an unscratched region on the sample surface. In this way, we could obtain quantitative force−distance profiles. The repulsive force was observed to rapidly increase with decreasing separation. The equilibrium thickness Le of the brushes, i.e., the critical distance at which a repulsive force was detectable, was found to be proportional to the weight-average chain contour length Lc,w, giving Le/Lc,w = 0.6. This indicates formation of a homogeneous polymer layer with highly stretched graft chains. Unlike the previously reported results for lower density polymer brushes, the force−distance profiles for different graft chain lengths were not scaled by the reduced distance D/Le. Longer brushes were more resistant to compression: for example, the longest studied brush was compressible only to D/Le = 0.8, which was about 3 times as large as the scaled dry thickness Ld/Le.
Transcriptional effects of CRP* expression in Escherichia coli (2009)

While the simplest model of CRP*-mediated gene expression assumes insensitivity to glucose (or cAMP), our results show that gene expression in the context of CRP* is very different from that of wild-type in the absence of glucose, and is influenced by the presence of glucose. Most of the transcription changes in response to CRP* expression are difficult to interpret in terms of possible systematic effects on metabolism. Elevated NADPH availability resulting from CRP* expression suggests potential biocatalytic applications of crp* strains that extend beyond relief of catabolite repression.
Various glucocorticoids differ in their ability to induce gene expression, apoptosis and to repress NF‐κB‐dependent transcription (1998)

Glucocorticoids (GCs) influence a great variety of cellular functions by at least three important modes of action: the activation (or repression) of genes controlled by binding sites for the glucocorticoid receptor (GR), the induction of apoptosis in lymphocytes and the recently discovered cross-talk to other transcription factors such as NF-kappaB. In this study we systematically compared various natural and synthetic steroid hormones frequently used as therapeutic agents on their ability to mediate these three modes of action. Betamethasone, triamcinolone, dexamethasone and clobetasol turned out to be the best inducers of gene expression and apoptosis. All GCs including the antagonistic compound RU486 efficiently reduced NF-kappaB-mediated transactivation to comparable extents, suggesting that ligand-induced nuclear localization of the GR is sufficient for transrepression. Glucocorticoid treatment of cells did not result in elevated IkappaB-alpha expression, but impaired the tumor necrosis factor (TNF)-alpha-induced degradation of IkappaB-alpha without affecting DNA binding of NF-kappaB. The structural requirements for the various functions of glucocorticoids are discussed.
Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets (1998)

Circulating human platelets lack nuclei, cannot synthesize mRNA, and are considered incapable of regulated protein synthesis. We found that thrombin-activated, but not resting, platelets synthesize Bcl-3, a member of the IkappaB-alpha family of regulatory proteins. The time- and concentration-dependent generation of Bcl-3 in platelets signaled by thrombin was blocked by translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol-3-kinase, indicating that it occurs via a specialized translational control pathway that involves phosphorylation of the inhibitory protein 4E-BP1. After its synthesis in activated platelets Bcl-3 binds to the SH3 domain of Fyn (p59(fyn)), a Src-related tyrosine kinase. This, along with its expression in anucleate cells, suggests that Bcl-3 has previously unrecognized functions aside from modulation of transcription. We also demonstrate that platelets synthesize and secrete numerous proteins besides Bcl-3 after they adhere to fibrinogen, which mediates adhesion and outside-in signaling of these cells by engagement of alphaIIb/beta3 integrin. Taken together, these data demonstrate that regulated synthesis of proteins is a signal-dependent activation response of human platelets.
INCREASED EXPRESSION OF THE LYMPHOCYTE EARLY ACTIVATION MARKER CD69 IN PERIPHERAL BLOOD CORRELATES WITH HISTOLOGIC EVIDENCE OF CARDIAC ALLOGRAFT REJECTION1 (2000)

Measurement of the expression of the early activation marker CD69 in peripheral blood lymphocytes by flow cytometry may provide a noninvasive means of assessing immune activation and possible rejection in cardiac transplant recipients.
Characterization and Thermal Conversion of Charcoal Derived from Fluidized-Bed Fast Pyrolysis Oil Production of Switchgrass (2007)

The charcoal coproduct associated with pyrolysis oil (bio-oil) production can add economic value to the process operation if it can be successfully employed as an activated biochar for soil amendment applications or can be used as a combustion fuel to power the pyrolysis process or as a gasifier feedstock. Although proposed, none of these have been extensively studied. In this submission, the surfaces and interfaces of the charcoal produced from making pyrolysis oil from switchgrass in a fluidized bed were characterized to establish its usefulness as an adsorbent material. Its reactivity in air and in CO2 were also determined to establish its potential as combustion fuel or gasification feedstock. It was found that the surface areas were low, typically 7.7 and 7.9 m2/g, 2 orders of magnitude of the areas encountered in activated charcoal. Compounding this was high surface crystallinity of the structure as measured by X-ray diffraction, thereby suggesting poor characteristics as a sorption agent without further activation. However, this does not preclude its use for other soil applications including carbon storage and as a nutrient delivery substrate. Upon further pyrolysis in helium, the charcoal yielded equal amounts of CO and CO2, exhibiting reaction kinetics similar to that of coal pyrolysis. Furthermore, reactivity in CO2 and in air atmosphere resulted in activation energies of 8 411 and 11 487 J/mol, respectively. It appears that the charcoal could be better used as combustion fuel or gasification feedstock than as an activated charcoal applied for metal sorption for the fact that the latter application will require higher surface and interfacial areas than measured.
Role of the essential thiol group in the thiol‐activated cytolysin from Clostridium perfringens (1987)

A hemolysin, 0-toxin, produced by Clostridium perfringens has one cysteinyl residue in the free thiol form which is essential for its hemolytic activity. The cysteinyl residue was shown to be located at a position about 5 kDa from the C terminus of the molecule by the method of cysteine-specific chemical cleavage. Modification of the residue with a thiol-blocking agent, 5,5'-dithiobis(2-nitrobenzoic acid), reduced the binding affinity of the toxin to sheep erythrocytes to 1/100 that of intact toxin, resulting in a failure of binding at low cell concentrations (0.5%). Thus the failure of hemolysis at low cell concentrations is primarily ascribed to a decreased affinity of the toxin for erythrocytes. Effects of the modification on the lytic processes were examined using high cell concentrations where considerable amounts of modified toxin bound to the cells. The modified toxin hemolyzes erythrocytes once it binds to them; however, the efficiency of hemolysis is reduced by the modification. These, and additional results indicating that modification alters the sensitivity of toxin molecules to protease digestion, show that thiol-modification inactivates the toxin by affecting both binding and the subsequent lytic processes, probably through a conformational change introduced in the toxin molecules.
Interscience Conference on Antimicrobial Agents and Chemotherapy - 50th Annual Meeting - Research on Promising New Agents: Part 1. (2010)

The 50th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held in Boston, included topics covering new therapeutic developments in the field of infectious disease. This conference report highlights selected presentations on research with novel antimicrobial agents. Investigational drugs discussed include the dicationic porphyrin derivative XF-73 (Destiny Pharma), the tetracycline analog TP-434 (Tetraphase Pharmaceuticals), an elongation factor Tu inhibitor (Novartis Institutes for BioMedical Research), the dihydrofolate reductase inhibitor Rx-101005 (Trius Therapeutics), SII RMab, a fully human mAb to rabies glycoprotein (Massachusetts Biologic Laboratories/Serum Institute of India), the oral lipopeptide CB-183315 (Cubist Pharmaceuticals) for the treatment of Clostridium difficile-associated diarrhea, the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor LMV-601 (Lumavita), and DS-003 (International Partnership for Microbicides), a small-molecule Gp120 inhibitor.
Lysosomal Phospholipase A2 and Phospholipidosis (2006)

A lysosomal phospholipase A2, LPLA2, was recently characterized and shown to have substrate specificity for phosphatidylcholine and phosphatidylethanolamine. LPLA2 is ubiquitously expressed but is most highly expressed in alveolar macrophages. Double conditional gene targeting was employed to elucidate the function of LPLA2. LPLA2-deficient mice (Lpla2-/-) were generated by the systemic deletion of exon 5 of the Lpla2 gene, which encodes the lipase motif essential for the phospholipase A2 activity. The survival of the Lpla2-/- mice was normal. Lpla2-/- mouse mating pairs yielded normal litter sizes, indicating that the gene deficiency did not impair fertility or fecundity. Alveolar macrophages from wild-type but not Lpla2-/- mice readily degraded radiolabeled phosphatidylcholine. A marked accumulation of phospholipids, in particular phosphatidylethanolamine and phosphatidylcholine, was found in the alveolar macrophages, the peritoneal macrophages, and the spleens of Lpla2-/- mice. By 1 year of age, Lpla2-/- mice demonstrated marked splenomegaly and increased lung surfactant phospholipid levels. Ultrastructural examination of Lpla2-/- mouse alveolar and peritoneal macrophages revealed the appearance of foam cells with lamellar inclusion bodies, a hallmark of cellular phospholipidosis. Thus, a deficiency of lysosomal phospholipase A2 results in foam cell formation, surfactant lipid accumulation, splenomegaly, and phospholipidosis in mice.
Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension (2017)

The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays. 5c had an excellent PK profile across species. Enterohepatic recirculation most probably contributes to a concentration-time profile after oral administration in the cynomolgus monkey that showed a very low peak-to-trough ratio. Following the identification of an acceptable solid form, 5c was selected for further development for the treatment of PAH.
Motion Artifact Reduction in Photoplethysmographic Signals using Singular Value Decomposition (2007)

Artifact free photoplethysmographic (PPG) signals, obtained with red and infrared (IR) optical sources and detectors are necessary for non-invasive estimation of oxygen saturation (SpO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) in arterial blood. Movement of a patient corrupts the PPGs with motion artifacts, resulting in large errors in the computation of SpO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . This paper presents a novel singular value decomposition (SVD) based method to reduce motion artifacts from corrupted PPG signals. Test results on a prototype incorporating the proposed SVD technique show that stable and reliable SpO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> measurement is achieved even when PPGs are distorted by motion artifacts, thus establishing the efficacy of the proposed method.
Transcranial Magnetic Stimulation for Tinnitus: Influence of Tinnitus Duration on Stimulation Parameter Choice and Maximal Tinnitus Suppression (2005)

TMS of the auditory cortex is capable of modifying tinnitus perception for a very short time. The maximal amount of suppression and best stimulation frequency depends on the tinnitus duration.
Evidence for Distinct Cation and Calcimimetic Compound (NPS 568) Recognition Domains in the Transmembrane Regions of the Human Ca2+ Receptor (2002)

The Ca(2+) receptor, a member of the family 3 of G protein-coupled receptors (GPCR), responds not only to its primary physiological ligand Ca(2+) but also to other di- and trivalent metals (Mg(2+), Gd(3+)) and the organic polycations spermine and poly-l-Arginine. As has been found for other family 3 GPCRs, the large amino-terminal extracellular domain (ECD) of the Ca(2+) receptor is the primary Ca(2+) binding domain. To examine how the signal is propagated from the ECD to the seven-transmembrane core domain (7TM) we constructed a Ca(2+) receptor mutant (T903-Rhoc) lacking the entire ECD but containing the 7TM. We have found that this structure initiates signaling in human embryonic kidney (HEK) 293 cells stably expressing the construct. One or more cation recognition sites are also located within the 7TM. Not only Ca(2+), but also several other Ca(2+) receptor-specific agonists, Mg(2+), Gd(3+), spermine, and poly-l-Arginine, can activate T903-Rhoc truncated receptor-initiated phosphoinositide hydrolysis in HEK 293 cells. The phenylalkylamine compound, NPS 568, identified as a positive allosteric modulator of the Ca(2+) receptor can selectively potentiate the actions of Ca(2+) and other polycationic agonists on the T903-Rhoc receptor. Similarly, organic polycations synergistically activate T903-Rhoc with di- and trivalent metals. Alanine substitution of all the acidic residues in the second extracellular loop of the T903-Rhoc receptor significantly impairs activation by metal ions and organic polycations in the presence of NPS 568 but not the synergistic activation of Ca(2+) with poly-l-Arginine. These data indicate that although the ECD has been thought to be the main determinant for Ca(2+) recognition, the 7TM core of the Ca(2+) receptor contains activating site(s) recognizing Ca(2+) and Gd(3+) as well as the allosteric modulators NPS 568 and organic polycations that may play important roles in the regulation of receptor activation.
Ovarian Cancer Risk After Salpingectomy: A Nationwide Population-Based Study (2015)

Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population.
Peptide Antimicrobial Agents (2006)

Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.
High-spectral-resolution coherent anti-Stokes Raman scattering with interferometrically detected broadband chirped pulses (2006)

To achieve high-spectral-resolution multiplex coherent anti-Stokes Raman scattering (CARS), one typically uses a narrowband pump pulse and a broadband Stokes pulse. This is to ensure a correspondence between anti-Stokes and vibrational frequencies. We obtain high-resolution CARS spectra of isopropanol, using a broadband chirped pump pulse and a broadband Stokes pulse, by detecting the anti-Stokes pulse with spectral interferometry. With the temporally resolved anti-Stokes signal, we can remove the chirp of the anti-Stokes pulse and restore high spectral resolution while also rejecting nonresonant scattering.