gebhart/patrepeval huggingface dataset:
Human Corneal Cells and Other Fibroblasts Can Stimulate the Appearance of Herpes Simplex Virus from Quiescently Infected PC12 Cells (1999)

A two-cell system for the stimulation of herpes simplex virus type 1 (HSV-1) from an in vitro model of long-term (quiescent) infection is described. Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were infected with HSV-1 strain 17. Little, if any, cytotoxicity was observed, and a quiescent infection was established. The long-term infection was characterized by the absence of all detectable virus in the culture medium and little, if any, detectable early or late viral-gene expression as determined by reverse transcriptase PCR analysis. The presence of HSV-1 DNA was determined by PCR analysis. This showed that approximately 180 viral genomes were present in limiting dilutions where as few as 16 cells were examined. The viral DNA was infectious, since cocultivation with human corneal fibroblasts (HCF) or human corneal epithelial cells (HCE) resulted in recovery of virus from most, if not all, clusters of PC12 cells. Following cocultivation, viral antigens appeared first on PC12 cells and then on neighboring inducing cells, as determined by immunofluorescent staining, demonstrating that de novo viral protein synthesis first occurred in the long-term-infected PC12 cells. Interestingly, the ability to induce HSV varied among the cell lines tested. For example, monkey kidney CV-1 cells and human hepatoblastoma HepG2 cells, but not mouse neuroblastoma cells or undifferentiated PC12 cells, mediated stimulation. This work thus shows that (i) quiescent HSV infections can be maintained in PC12 cells in vitro, (ii) HSV can be induced from cells which do not accumulate significant levels of latency-associated transcripts, and (iii) the activation of HSV gene expression can be induced via neighboring cells. The ability of adjacent cells to stimulate HSV gene expression in neuron-like cells represents a novel area of study. The mechanism(s) whereby HCF, HCE, and HepG2 and CV-1 cells communicate with PC12 cells and stimulate viral replication, as well as how this system compares with other in vitro models of long-term infection, is discussed.
Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors (2006)

Glutamate acts at central synapses via ionotropic (iGluR--NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed.
Voltage-clamp analysis of the effects of classical conditioning on the hippocampus (1991)

1. Effects of nictitating membrane conditioning on K+ currents of CA1 pyramidal cells of rabbit hippocampus were studied by the use of the single-electrode voltage-clamp (SEVC) technique. 2. IQ, IM, IC, and IAHP were recorded in slices from control animals, showing behavior similar to that previously described for other preparations. IQ developed as an inward current during hyperpolarizing steps to potentials more negative than the K+ equilibrium potential. IM appeared as an inward inactivating relaxation during hyperpolarizing pulses, from potentials slightly more positive than the resting potential (approximately -40 mV). Such depolarization is thought to activate the IM, IC was recorded during long depolarizing pulses as a slow outward current. IAHP appeared during short depolarizing pulses as an outward current peaking at approximately 200 ms after the pulse. Progressively more positive pulses were accompanied by a linear increase of the peak IAHP value. The slope of the IAHP-voltage relation was used for comparison of cells between groups of animals that had different training experience. 3. Responses of control cells to cholinergic agents were similar to those previously characterized in other preparations. Specifically, cholinergic agonists blocked IM and IAHP, partially reduced IC, and did not affect IQ. 4. Conditioning did not affect IQ, IM, and IC but reduced the slope values of the IAHP-voltage relation. This change is consistent with the conditioning-specific afterhyperpolarization (AHP) reduction previously reported. 5. The effect of conditioning on the IAHP but not on the IC, both Ca(2+)-dependent K+ currents, suggests a direct effect on the former, rather than a reduction of ICa2+ or a change in the levels of Cai2+.
Medical and Nutritional Aspects of Citrus Bioflavonoids (1980)

In 1936 the discovery that the flavonone fraction of lemons exerted therapeutic effects on abnormal capillary permeability and fragility ushered in the era of research on role of flavonoids in the mammalian body (1). Flavonoids were proposed to be vitamins (Vitamin P) necessary to maintain the capillaries, but the vitamin concept was never substantiated and in 1950 Vickery et al. (2) recommended the term Vitamin P be discontinued (term Vitamin P was replaced by bioflavonoid). Subsequent research had failed to confirm early indications that abnormal capillary permeability and fragility were due to a bioflavonoid deficiency but showed these capillary defects accompanied many diseases and stresses (3,4). In 1954 Martin (4) stated "There is no disease state in which the capillaries are not detrimentally modified and conversely there are no disease states that will not benefit by assuring proper capillary strength and integrity." In 1955 Hendrickson and Kesterson (5) listed more
Characterization of the Time Scales of Molecular Motion in Pharmaceutically Important Glasses (1999)

Increased interest in molecular time scales below the glass transition temperature, Tg, has arisen from the desire to identify the conditions (e.g., temperature) where the molecular processes which lead to unwanted changes in amorphous systems (e.g., chemical reactivity, crystallization, structural collapse) are improbable. The purpose of this study was to characterize the molecular mobility of selected amorphous systems (i.e., indomethacin, sorbitol, sucrose, and trehalose) below Tg using a combined experimental and theoretical approach. Of particular interest was the temperature where the time scales for molecular motion (i.e., relaxation time) exceed expected lifetimes or storage times. As a first approximation of this temperature, the temperature where the thermodynamic properties of the crystal and the equilibrium supercooled liquid converge (i.e., the Kauzmann temperature, TK) was determined. TK values derived from heat capacity and enthalpy of fusion data ranged from 40 to 190 K below the calorimetric Tg. A more refined approach, using a form of the Vogel−Tamman−Fulcher (VTF) equation derived from the Adam−Gibbs formulation for nonequilibrium systems below Tg, was used to predict the temperatures where the relaxation times of real glasses exceed practical storage times. Relaxation times in glasses were characterized in terms of their fictive temperature, as determined from heat capacity data measured using modulated differential scanning calorimetry. The calculated relaxation times were in good agreement with measured relaxation times for at least two materials. Relaxation times in real glasses were on the order of three years at temperatures near TK, indicating low (but not zero) mobility under conditions where the equilibrium supercooled liquid experiences total loss of structural mobility. The results of this study demonstrate the importance of excess configurational entropy formed during vitrification in determining structural relaxation dynamics in real glasses.
Algorithms for Using B-Type Natriuretic Peptide Levels in the Diagnosis and Management of Congestive Heart Failure (2002)

From the Division of Cardiology and Department of Medicine, San Diego VA Healthcare System and University of California, San Diego, California. Address for correspondence: Dr. Alan Maisel, VAMC Cardiology 111-A, 3350 La Jolla Village Drive, San Diego, CA 921161, E-mail: [email protected]
Kunitz domain inhibitors of tissue factor-factor VIIa. I. Potent inhibitors selected from libraries by phage display. (1994)

Potent active-site inhibitors of human tissue factor-Factor VIIa (TF.FVIIa) have been selected from Alzheimer's amyloid beta-protein precursor inhibitor (APPI) Kunitz domain libraries displayed on phage. Eight randomized positions on the extended primary binding loop (P5 through P4') and positions 34 and 39 were examined in three separate libraries. Libraries contained from 3.2 x 10(5) to 3.2 x 10(6) potential variants resulting from replacing up to 5 positions with all 20 amino acids. Following 4 rounds of selection against FVIIa associated with immobilized tissue factor (TF), 12 clones from each library were sequenced. Variants were purified by trypsin affinity chromatography and reverse-phase high performance liquid chromatography, and characterized for their ability to inhibit TF.FVIIa chromogenic activity. Measured apparent equilibrium dissociation constants (Ki*) ranged from about 10 to 500 nM. From sequence and activity data, an overall consensus sequence, TF7I-C, was constructed by site-directed mutagenesis. TF7I-C differed from APPI at 4 key residues, T11P, M17L, S19L, and G39Y, and inhibited TF.FVIIa with a Ki* = 1.9 +/- 0.4 nM, which represented an increase in binding affinity of more than 150-fold compared to APPI. At 40 microM, TF7I-C prolonged the clotting times 3.5-fold in a prothrombin time assay and > 10-fold at 7 microM in an activated partial thromboplastin time assay. Prolongation of the activated partial thromboplastin time correlates with potent inhibition of FXIa (Ki* = 0.8 nM) and plasma kallikrein (Ki* = 1.2 nM). TF7I-C also inhibited plasmin (Ki* = 40 nM) and FXa (Ki* = 55 nM), but not activated protein C, thrombin, or FXIIa (Ki* > 10 microM each).
Diagnosis of Cerebral Neoplasms Using Monoclonal Antibodies (2015)

Methode immunohistologique appliquee a la biopsie tumorale et aux preparations cytologiques de LCR. Radioimmunolocalisation in vivo (scintigraphie par anticorps monoclonal marque)
Speech enhancement using a minimum mean-square error log-spectral amplitude estimator (1985)

In this correspondence we derive a short-time spectral amplitude (STSA) estimator for speech signals which minimizes the mean-square error of the log-spectra (i.e., the original STSA and its estimator) and examine it in enhancing noisy speech. This estimator is also compared with the corresponding minimum mean-square error STSA estimator derived previously. It was found that the new estimator is very effective in enhancing the noisy speech, and it significantly improves its quality.
Similar organization of the sigB and spoIIA operons encoding alternate sigma factors of Bacillus subtilis RNA polymerase (1990)

Bacillus subtilis sigma-B is an alternate sigma factor implicated in controlling stationary-phase gene expression. We characterized the genetic organization and regulation of the region containing the sigma-B structural gene (sigB) to learn which metabolic signals and protein factors govern sigma-B function. sigB lay in an operon with four open reading frames (orfs) in the order orfV-orfW-sigB-orfX, and lacZ gene fusions showed that all four frames were translated in vivo. Experiments with primer extension, S1 nuclease mapping, and lacZ transcriptional fusions found that sigB operon transcription initiated early in stationary phase from a site 32 nucleotides upstream of orfV and terminated 34 nucleotides downstream of orfX. Fusion expression was abolished in a strain carrying an in-frame deletion in sigB, suggesting that sigma-B positively regulated its own synthesis, and deletions in the sigB promoter region showed that sequences identical to the sigma-B-dependent ctc promoter were essential for promoter activity. Fusion expression was greatly enhanced in a strain carrying an insertion mutation in orfX, suggesting that the 22-kilodalton (kDa) orfX product was a negative effector of sigma-B expression or activity. Notably, the genetic organization of the sigB operon was strikingly similar to that of the B. subtilis spoIIA operon, which has the gene order spoIIAA-spoIIAB-spoIIAC, with spoIIAC encoding the sporulation-essential sigma-F. The predicted sequence of the 12-kDa orfV product was 32% identical to that of the 13-kDa SpoIIAA protein, and the 18-kDa orfW product was 27% identical to the 16-kDa SpoIIAB protein. On the basis of this clear evolutionary conservation, we speculate these protein pairs regulate their respective sigma factors by a similar molecular mechanism and that the spoIIA and sigB operons might control divergent branches of stationary-phase gene expression.
Phenotype changes resulting in high-affinity binding of von Willebrand factor to recombinant glycoprotein Ib-IX: analysis of the platelet-type von Willebrand disease mutations (2001)

To maintain hemostasis under shear conditions, there must be an interaction between the platelet glycoprotein (GP) Ib-IX receptor and the plasma ligand von Willebrand factor (vWf). In platelet-type von Willebrand disease (Pt-vWD), hemostasis is compromised. Two mutations in the GPIbalpha polypeptide chain have been identified in these patients-a glycine-233 to valine change and a methionine-239 to valine change. For this investigation, these mutant proteins have been expressed in a Chinese hamster ovary cell model system. Ligand-binding studies were performed at various concentrations of ristocetin, and adhesion assays were performed under flow conditions. The Pt-vWD mutations resulted in a gain-of-function receptor. vWf binding was increased at all concentrations of ristocetin examined, and adhesion on a vWf matrix was enhanced in terms of cell tethering, slower rolling velocity, and decreased detachment with increasing shear rate. Two other mutations were also introduced into the GPIbalpha chain. One mutation, encompassing both the Pt-vWD mutations, created an increase in the hydrophobicity of this region. The second mutation, involving a valine-234 to glycine change, decreased the hydrophobicity of this region. Both mutations also resulted in a gain-of-function receptor, with the double mutation producing a hyperreactive receptor for vWf. These data further support the hypothesis that ligand binding is regulated by conformational changes in the amino-terminal region of GPIbalpha, thereby influencing the stability of the GPIbalpha-vWf interaction.
Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. (1989)

We identified by a monoclonal antibody-based immunoradiometric assay high concentrations of an exocrine pancreatic protein called pancreatic thread protein (PTP) in several areas of Alzheimer disease (AD) brain. The saline-extractable soluble immunoreactivity shares at least three epitopes in common with the native pancreatic form of the protein; the Mr varies from approximately 17,000 to 20,000. Quantitative measurements of PTP immunoreactivity in various regions of several AD brains revealed levels varying from 12 to 295 ng/g of tissue (mean, 116 ng/g) compared with 1-11 ng/g of tissue (mean, 5 ng/g) found in comparable areas of control brains. Immunocytochemistry performed with the anti-PTP monoclonal antibodies demonstrate PTP immunoreactivity within large pyramidal neurons--many of which contain neurofibrillary tangles in both AD and Down syndrome. Less accumulation was observed in astrocytes, and some PTP immunoreactivity was found extracellularly. The highest number of labeled cells in AD and Down syndrome was seen in the hippocampal formation. Fewer positive-staining cells were noted in normal and disease control brains. We conclude, therefore, that an exocrine pancreatic protein is present in the central nervous system of normal individuals at low levels; in AD brain concentrations of this protein are much higher.
AT1receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats (2005)

Angiotensin II (ANG II)-infused rats exhibit increases in distal nephron renin expressed in principal cells of connecting tubules and collecting ducts. This study was performed to determine whether the augmentation of distal nephron renin involves ANG II type 1 (AT1) receptor activation. Male Sprague-Dawley rats (200-220 g) were divided into three groups: 1) sham operated (n = 8); 2) ANG II infused (80 ng/min, 13 days, n = 8); and 3) ANG II infused plus AT1 receptor blocker (ARB), olmesartan (5 mg/days, n = 8). ANG II infusion increased systolic blood pressure (BP; 178 +/- 4 vs. 122 +/- 1 mmHg; P < 0.001) and suppressed plasma renin activity (PRA; 0.08 +/- 0.1 vs. 5.3 +/- 0.8 ng ANG I x ml(-1) x h(-1)). ARB treatment prevented the increase in BP (113 +/- 6 mmHg) and led to increases in PRA (15.8 +/- 1.5 ng ANG I x ml(-1) x h(-1)). Renin protein levels measured in the kidney medulla, to avoid contribution from juxtaglomerular apparatus cells, were higher in ANG II-infused rats [1.64 +/- 0.3 vs. 1.00 +/- 0.1 densitometric units (DU) compared with sham-operated rats; P < 0.05], and ARB treatment prevented this increase (1.01 +/- 0.1). Similarly, renin immunoreactivity increased in medullary collecting ducts of ANG II-infused compared with sham-operated rats (2.5 +/- 0.3 vs. 1.0 +/- 0.2 DU; P < 0.001), which was also prevented by ARB (1.01 +/- 0.06). Renin qRTPCR in ANG II-infused rats showed higher mRNA levels in the kidney medulla compared with sham-operated rats (5.5 +/- 2.3 vs. 0.04 +/- 0.02 ratio to GAPDH mRNA levels; P < 0.001); however, renin transcript levels were normalized in the ARB-treated rats. These data demonstrate that the augmentation of distal nephron renin in ANG II-infused hypertensive rats is AT1 receptor mediated. The augmented distal tubular renin may contribute to increased intratubular ANG II levels and distal nephron sodium reabsorption in ANG II-dependent hypertension.
Synthesis and Structural Characterization of Monomeric Selenolato Complexes of Zinc, Cadmium, and Mercury (1998)

The synthesis and characterization of homoleptic zinc(II), cadmium(II), and mercury(II) selenolates incorporating the intramolecularly chelating oxazoline ligand are described. The derivatives, M[Se(Ox)](2) [M = Zn (1), Cd (2), Hg (3); Ox = 2-(4,4-dimethyl-2-oxazolinyl)benzene], were prepared in good yield via the metathesis reactions of MCl(2) with a lithium areneselenolate, OxSe(-)Li(+). The mercury complex 3 was also synthesized by treating the corresponding diselenide with elemental mercury. The complexes are quite stable and highly soluble in common nonpolar organic solvents. X-ray diffraction results show that the complexes are monomeric in the solid state. The geometry around the metal ion in all complexes is found to be distorted tetrahedral. The crystal structure of Zn[Se(Ox)](2) (1) shows that the complex is "helically" chiral and enantiomerically pure. The spontaneous splitting of the racemates indicates the solubility differences between the racemates and pure enantiomers. (1)H, (13)C, and (77)Se NMR measurements indicate that complex 1 retains its "helical" structure in solution. Crystal data (Mo Kalpha; 293(2) K) are as follows: 1, monoclinic space group P2(1), a = 9.3900(12) Å, b = 11.618(2) Å, c = 10.8822(14) Å, beta = 98.245(8) degrees, Z = 2; 2, orthorhombic space group Pbca, a = 12.777(6) Å, b = 17.841(10) Å, c = 21.010(8) Å, Z = 8; 3, monoclinic space group P2(1)/c, a = 9.087(2) Å, b = 11.889(2) Å, c = 22.456(4) Å, beta = 98.780(13) degrees, Z = 4.
Enhanced prime editing systems by manipulating cellular determinants of editing outcomes (2021)

While prime editing enables precise sequence changes in DNA, cellular determinants of prime editing remain poorly understood. Using pooled CRISPRi screens, we discovered that DNA mismatch repair (MMR) impedes prime editing and promotes undesired indel byproducts. We developed PE4 and PE5 prime editing systems in which transient expression of an engineered MMR-inhibiting protein enhances the efficiency of substitution, small insertion, and small deletion prime edits by an average 7.7-fold and 2.0-fold compared to PE2 and PE3 systems, respectively, while improving edit/indel ratios by 3.4-fold in MMR-proficient cell types. Strategic installation of silent mutations near the intended edit can enhance prime editing outcomes by evading MMR. Prime editor protein optimization resulted in a PEmax architecture that enhances editing efficacy by 2.8-fold on average in HeLa cells. These findings enrich our understanding of prime editing and establish prime editing systems that show substantial improvement across 191 edits in seven mammalian cell types.
Anisotropic Properties of Ice/Water Interface: A Molecular Dynamics Study (1995)

Ice/water interface structures were studied using a molecular dynamics method. The simulations were carried out for both ice {0001}/water and ice {101̄0}/water interfaces. The results strongly suggest that each interface has a diffuse structure and that the physical properties of the interfacial region differ from each other between the interfaces. The anisotropy in the structures and dynamic properties of ice/water interfaces, that is, the difference in the structures and dynamic properties between the interfaces were observed for the first time in this molecular dynamics simulation.
Assessment of Drug Therapy Management and the Prevalence of Heart Failure in a Managed Care Population With Hypertension (2004)

The study results indicate a deficit in the treatment of HTN among HF patients with and without diabetes, including failure to achieve blood pressure goals (< 130/85 mm Hg at the time of this study period). More aggressive quality improvement programs are necessary to educate providers and patients on the importance of treating blood pressure to nationally accepted goal using antihypertensives proven beneficial for hypertensive patients with HF.