gebhart/patrepeval huggingface dataset:
Initiation of the extrinsic pathway of coagulation. Association of factor VIIa with a cell line expressing tissue factor. (1987)

We have examined initial assembly of the extrinsic pathway of blood coagulation on cell surfaces with radiolabeled human factor VIIa and a human fetal lung cell line possessing abundant functional tissue factor activity. Binding of factor VIIa to these cells was observed and was time- and temperature-dependent. Binding of factor VIIa was quantitatively equivalent at 37 and 6 degrees C, although the kinetics of binding differed. The radiolabeled ligand bound by the cell was indistinguishable by sodium dodecyl sulfate-polyacrylamide gel analysis from the factor VIIa offered. Factor VIIa binding was influenced by calcium ions. The binding appears to involve at least two classes of calcium-dependent binding sites. Optimal binding occurred at 2 mM calcium for both classes of sites, and there was inhibition of binding to the high affinity sites at higher calcium. Association of factor VIIa was specific, saturable, had a Kd of 123 +/- 37 pm, and factor VIIa interacted with about 100,000 binding sites per cell. Once established, specific binding was rapidly reversible. Direct cellular binding of human factor X also was observed and was calcium, time- and temperature-dependent. Factor X binding was specific and saturable with half-maximal binding at 87.6 +/- 27.4 nM to 6.03 +/- 1.03 X 10(6) sites per cell. Specific high affinity binding of factor VIIa correlated with generation of factor Xa. A direct linear relationship was observed at low factor VIIa binding; however, at higher bound factor VIIa, the relationship was nonstoichiometric, i.e. less factor Xa was formed per mole of factor VIIa. Expression of specific binding sites for factors VIIa and X provides further substantiation for the molecular assembly hypothesized to initiate the extrinsic coagulation protease cascade on cells.
Hidden Dynamics of Vesicle Adhesion Induced by Specific Stickers (2004)

We experimentally studied the adhesion dynamics of vesicles decorated with specific stickers onto bioactive surfaces. The growth laws were found to strongly depend upon the chemical preparation of the substrate and were rationalized with theoretical descriptions based on scaling law arguments. By using a micropipette-free approach, we demonstrate that two-dimensional binding rates between receptor and ligand can be lower than three dimensional on rates by orders of magnitude due to reduced accessibility of the immobilized protein.
The Renin-Angiotensin System (1974)

Plasma Renin Activity as a Screening Procedure in HypertensionTwo approaches to the use of peripheral plasma renin activity as a screening test for hypertensive disease have been taken: to hospitalize the patient and impose strict control of dietary sodium in an effort to be able to relate his response to a rigidly defined set of normal criteria; and to allow the patient to remain ambulatory and on an ad lib sodium intake and rely on his 24-hour urinary sodium excretion to normalize his response. Stimulation or suppression tests give more information about the patient's renin reserve and the responsiveness . . .
Cascaded silicon Raman lasers as mid-infrared sources (2006)

It is shown by numerical simulations that cascaded silicon Raman lasers, in which the pump light undergoes multiple Stokes shifts in a silicon waveguide, can efficiently convert near-IR to mid-IR radiation. For pump wavelengths significantly below 2 µm, two-photon-absorption-induced free-carrier absorption degrades conversion efficiency, and the effective carrier lifetime determines the shortest possible pump wavelength.
Linear sensing of speckle-pattern displacements using a photorefractive GaP crystal (1999)

Linear transformation of lateral speckle-pattern displacements into the transmitted intensity modulation is achieved in a photorefractive GaP crystal using the polarization self-modulation effect. The optical system is very simple, self-referenced, and as sensitive as an interferometer.
Fast and robust hydrogen sensors based on discontinuous palladium films on polyimide, fabricated on a wafer scale (2010)

Fast hydrogen sensors based on discontinuous palladium (Pd) films on supporting polyimide layers, fabricated by a cost-efficient and full-wafer compatible process, are presented. The films, deposited by electron-beam evaporation with a nominal thickness of 1.5 nm, consist of isolated Pd islands that are separated by nanoscopic gaps. On hydrogenation, the volume expansion of Pd brings initially separated islands into contact which leads to the creation of new electrical pathways through the film. The supporting polyimide layer provides both sufficient elasticity for the Pd nanoclusters to expand on hydrogenation and a sufficiently high surface energy for good adhesion of both film and contacting electrodes. The novel order of the fabrication processes involves a dicing step prior to the Pd deposition and stencil lithography for the patterning of microelectrodes. This allows us to preserve the as-deposited film properties. The devices work at room temperature, show response times of a few seconds and have a low power consumption of some tens of nW.
Identity of High Molecular Weight Gliadin and Ethanol-Soluble Glutenin Subunits of Wheat: Relation to Gluten Structure! (1980)

The exact relationship, origin and function of high MW gliadin (HMWG) and ethanol-soluble reduced glutenin (ESRG), 2 heterogeneous wheat protein fractions, are not known. HMWG occurs as small oligomers, soluble in 70% ethanol, whereas ESRG is a disulfide-bonded fraction of glutenin, wheat's highest MW protein class. Upon reduction and alkylation, both fractions are alcohol-soluble, consist of subunits having MW near 44,000 and 36,000, and have similar electrophoretic and chromatographic properties and amino acid compositions. Amino-terminal sequence analyses now prove that many of the same polypeptides comprise HMWG and ESRG. Their N-terminal sequence distribution is H2N-(Val+Asn+Gln+Met)-(His+Gln+Met)-(Ile+Val)-(Pro+Val+Gln)-(Gly+Val+Gln+Asn)-(Leu+Pro)-Gln-(Leu+Gly)-(Pro+Gln+Leu)-(Gln+Pro+Val)-Gln-(Gln+Pro)-(Gln+Pro)-Pro-(Gln+Leu-)Pro-Gln-Gln-. These data imply that many of these polypeptides are homologous and that the heterogeneity of HMWG and ESRG results from duplication and mutation of a common ancestral gene. During biosynthesis, kernel maturation or drying, these polypeptides can combine either with each other to form HMWG or with higher MW ethanol-insoluble polypeptides and with highly aggregating polypeptides to form glutenin. A hypothesis explains how the ethanol-soluble nongliadin polypeptides with 44,000 and 36,000 MW contribute to gluten's structure and to dough's unique viscoelastic properties.
Combined Tumor Therapy by Using Radiofrequency Ablation and 5-FU–Laden Polymer Implants: Evaluation in Rats and Rabbits (2005)

PURPOSE: To evaluate the use of 5-fluorouracil (5-FU)-laden polymer implants as an adjunct to radiofrequency (RF) ablation for tumor treatment. MATERIALS AND METHODS: All animal studies were performed in compliance with the Case Western Reserve University Institutional Animal Care and Use Committee guidelines. Three studies were performed to investigate (a) in vitro dissolution of 5-FU–laden polymer implants in saline and bovine serum, (b) tissue distribution of 5-FU and its metabolite, 5-fluorouridine (5-FUrd), in the ablated liver tissue of rats (n = 4), and (c) efficacy of combined approach (n = 4) compared with that of ablation alone (n = 6) for VX2 liver tumor model in rabbits. Characterization of 5-FU release in vitro and distribution of 5-FU in rat liver tissue were analyzed by using high performance liquid chromatography; in vivo efficacy was assessed by using computed tomography and pathologic examination. RESULTS: Results of the in vitro dissolution study showed that a 75% release of 5-FU occurred in 2 days when exposed to bovine serum and in 9 days when exposed to phosphate-buffered saline. In the ablated rat liver, the 5-FU level was higher at the center and lower at the periphery of the tissue both at 24 hours (41.0 mg per kilogram tissue vs 15.0 mg per kilogram tissue, respectively) and at 48 hours (8.0 mg per kilogram tissue vs 2.0 mg per kilogram tissue, respectively). The 5-FUrd concentration was twofold higher peripherally than centrally and was higher at 48 hours than at 24 hours. In rabbits, local delivery of 5-FU immediately after RF ablation provided a significant (P < .05) reduction in tumor size compared with ablation alone (1.80 cm3 ± 0.28 [standard error] vs 3.53 cm3 ± 0.52, respectively; P = .034) and a more than 20-fold reduction in tumor size compared with the control (1.80 cm3 ± 0.28 vs 41.95 cm3 ± 11.58, respectively; P = .018). CONCLUSION: Combined treatment by using 5-FU polymer implants and RF ablation shows uniform sustained release of 5-FU for 48 hours at least 8 mm from the edge of the ablation zone and appears to be successful at controlling the growth of an experimental tumor in rabbits appreciably better than does ablation alone. © RSNA, 2005
Mechanistic aspects the dioxin (aryl hydrocarbon) receptor (2000)

The Ah receptor mediates the toxicological responses of 2,3,7,8-TCDD and related compounds. Receptor-deficient animals were shown to be resistant to the toxic effects of dioxin, although there is also evidence for the existence of a receptor-independent pathway for dioxin-induced toxicity. In the cytosol the receptor is present in a non-activated ligand binding conformation. Association with Arnt in the nucleus turns the receptor complex into a ligand activated form. The physiological role of the receptor is not yet understood; however, the conservation of the receptor in a wide range of animal species (including humans) suggests a fundamental role in cellular physiology.
Direct database searching with MALDI‐PSD spectra of peptides (1995)

The analysis of matrix-assisted laser desorption ionization post-source decay (MALDI-PSD) mass spectra of peptides by using the cross-correlation method for database searching is illustrated. MALDI-PSD mass spectra are shown to contain sufficient fragmentation information to uniquely identify the correct amino acid sequence from large protein databases (approximately 160,000 entries). A search employing the MALDI-PSD mass spectrum of a phosphorylated peptide that correctly identifies the amino acid sequence and the site of phosphorylation is also illustrated.
Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents (2010)

The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies by exposure to noxious heat. 9- and 13-HODE and their metabolites, 9- and 13-oxoODE, activated TRPV1 and therefore constitute a family of endogenous TRPV1 agonists. Moreover, blocking these substances substantially decreased the heat sensitivity of TRPV1 in rats and mice and reduced nociception. Collectively, our results indicate that HODEs contribute to the heat sensitivity of TRPV1 in rodents. Because oxidized linoleic acid metabolites are released during cell injury, these findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs.
Uniquely Hominid Features of Adult Human Astrocytes (2009)

Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells (2006)

Metastasis-supporting physiological alterations are regulated by cell signaling molecules, which target signal transduction pathways and gene expression. Osteopontin (OPN) overexpression may represent a key molecular event in cancer metastasis. In this study, using metastatic 4T1 and non-metastatic 4T07 murine mammary cancer cell lines, we demonstrate that 4T1 cells exhibit significantly increased OPN, integrin-linked kinase (ILK), matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (uPA) expression in contrast to 4T07 cells. Blockade of OPN binding to 4T1 cell-surface integrins by the competitive ligand inhibitor, RGD, or a blocking antibody to alphavbeta3 integrin decreases OPN, ILK, MMP-2 and uPA expression. Conversely, exposure of 4T07 cells to exogenous OPN increases ILK, MMP-2 and uPA levels. Further experiments demonstrate that OPN-alphavbeta3 integrin binding in 4T1 with subsequent activation of ILK results in binding of AP-1 to MMP-2 and uPA promoter and increased in vitro promoter activation, as measured by transient transfection assays using MMP-2 and uPA promoter-reporter constructs. AP-1 activity is ablated by co-transfection of DN-ILK or exposure to RGD. Finally, functional correlative assays demonstrate that inhibition of ILK activity or RGD-mediated blockade of alphavbeta3 integrin binding significantly inhibits in vitro invasion, migration and invasion properties of 4T1 cells. In addition, uPA and MMP-2 have overlapping contributions to 4T1 migration and invasion characteristics. However, OPN and ILK activities contribute to 4T1 adhesion activities via mechanisms that are independent of uPA and MMP-2. Our results indicate that binding of an RGD-bearing ligand, such as OPN, to integrin receptors in metastatic 4T1 cells transcriptionally mediates MMP-2, uPA and OPN expression through ILK-dependent AP-1 activity and significantly increases in vitro functional correlates of metastasis. In 4T1 murine mammary cancer cells, we conclude that OPN mediates metastatic behavior, in part, through upregulation of MMP-2 and uPA protein expression.
Maternal Periodontitis and Prematurity. Part II: Maternal Infection and Fetal Exposure (2001)

Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.
Control of Axonal Growth and Regeneration of Sensory Neurons by the p110δ PI 3-Kinase (2007)

The expression and function of the 8 distinct catalytic isoforms of PI 3-kinase (PI3K) in the nervous system are unknown. Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110delta isoform has previously been shown to be enriched in leukocytes. Here we report that p110delta is also highly expressed in the nervous system. Inactivation of p110delta in mice did not affect gross neuronal development but led to an increased vulnerability of dorsal root ganglia neurons to exhibit growth cone collapse and decreases in axonal extension. Loss of p110delta activity also dampened axonal regeneration following peripheral nerve injury in adult mice and impaired functional recovery of locomotion. p110delta inactivation resulted in reduced neuronal signaling through the Akt protein kinase, and increased activity of the small GTPase RhoA. Pharmacological inhibition of ROCK, a downstream effector of RhoA, restored axonal extension defects in neurons with inactive p110delta, suggesting a key role of RhoA in p110delta signaling in neurons. Our data identify p110delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system.
Efficacy of a Second Line Luteinizing Hormone-Releasing Hormone Agonist After Advanced Prostate Cancer Biochemical Recurrence (2011)

Prostate specific antigen decreased after switching luteinizing hormone-releasing hormone therapies. This decrease appeared most significant in the group that switched from leuprolide acetate to goserelin. The duration of response after switching was approximately 5 months. The study is limited by its retrospective nature but should encourage prospective evaluation of this observation.
A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independently of age, transplant dose and granulocyte colony-stimulating factor support (2018)

Hematopoietic stem cell transplantation following myeloablative chemotherapy is a curative treatment for many hematopoietic malignancies. However, profound granulocytopenia during the interval between transplantation and marrow recovery exposes recipients to risks of fatal infection, a significant source of transplant-associated morbidity and mortality. We have previously described the discovery of a small molecule, SW033291, that potently inhibits the prostaglandin degrading enzyme 15-PGDH, increases bone marrow prostaglandin E2, and accelerates hematopoietic recovery following murine transplant. Here we describe the efficacy of (+)-SW209415, a second-generation 15-PGDH inhibitor, in an expanded range of models relevant to human transplantation. (+)-SW209415 is 10,000-fold more soluble, providing the potential for intravenous delivery, while maintaining potency in inhibiting 15-PGDH, increasing <i>in vivo</i> prostaglandin E2, and accelerating hematopoietic regeneration following transplantation. In additional models, (+)-SW209415: (i) demonstrated synergy with granulocyte colony-stimulating factor, the current standard of care; (ii) maintained efficacy as transplant cell dose was escalated; (iii) maintained efficacy when transplant donors and recipients were aged; and (iv) potentiated homing in xenotransplants using human hematopoietic stem cells. (+)-SW209415 showed no adverse effects, no potentiation of <i>in vivo</i> growth of human myeloma and leukemia xenografts, and, on chronic high-dose administration, no toxicity as assessed by weight, blood counts and serum chemistry. These studies provide independent chemical confirmation of the activity of 15-PGDH inhibitors in potentiating hematopoietic recovery, extend the range of models in which inhibiting 15-PGDH demonstrates activity, allay concerns regarding potential for adverse effects from increasing prostaglandin E2, and thereby, advance 15-PGDH as a therapeutic target for potentiating hematopoietic stem cell transplantation.
Remodeling of Capillary Network in Left Ventricular Subendocardial Tissues Induced by Intravenous Vasopressin Administration (1997)

A remodeling of capillary network which would increase the oxygen transport capacity to cardiac tissues was produced in left ventricular tissues by intravenous injection of vasopressin. bFGF located around capillaries and in the interstitial space may have been involved in the capillary remodeling.