gebhart/patrepeval huggingface dataset:
Structure-activity relationships in an imidazole-based series of thromboxane synthase inhibitors (1987)

Analogues of 4-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl] ethoxy]methyl]benzoic acid (5m) were prepared and evaluated as thromboxane synthase inhibitors. A series of esters of 5m showed a parabolic relationship between lipophilicity and inhibition of TxB2 generation in intact platelets, with activities up to 50 times greater than that of dazoxiben. However, on administration to rabbits the ethyl ester 5d had a short duration of action, due to rapid metabolism and excretion via deesterification and beta-glucuronidation. Attempts at replacing the carboxylate group with other potential pharmacophores were unsuccessful.
Spectral analysis of periodic fluctuations in electrocardiographic repolarization (1999)

Repolarization alternans (RPA) indicates alternate-beat fluctuations in the temporal or spatial characteristics of the echocardiogram (ECG) STU segment which may represent dispersion in repolarization. Spectral decomposition has revealed microvolt-level RPA which has been found to correlate with ventricular tachycardia (VT) and fibrillation, and is increasingly being used for clinical risk stratification. However, while interruptions in periodicity are known to affect spectral decomposition, their quantitative impact on RPA and its clinical utility have been poorly described. We therefore studied the effect of variable alignment, extrasystoles, dissimilar beats and beat exclusion on RPA magnitude in simulations and on the sensitivity and specificity of RPA for VT in a pilot clinical study. RPA magnitude was exquisitely sensitive to QRS alignment such that +/- 1 ms random beat misalignment reduced it by 68% in simulations. Correspondingly, suboptimal QRS alignment in clinical ECG's caused the sensitivity of RPA for inducible VT to fall from 93% to as low as 63%; while JT alignment was also less effective for RPA recovery. As an experiment in minimizing morphometric irregularities in clinical ECG's, we found that RPA magnitude actually fell when replacing either measurably dissimilar or ectopic beats with more representative beats. In addition, inserting or deleting beats also reduced RPA magnitude in clinical sequences and simulations. These statistical analyses suggest that the precision of beat alignment and interruptions to ECG periodicity, which may occur physiologically, may greatly reduce the clinical utility of RPA for VT. Dynamic alterations in RPA in response to sequence irregularities require further study before RPA may be optimally applied to screen for ventricular arrhythmias.
The Use of Fluorescein-Labelled Lectins in the Detection and Identification of Fungi Pathogenic for Man: A Preliminary Study (1978)

Fluorescein-labelled lectins of known specificities for different sugars were used in an attempt to identify fungi in paraffin sections of surgical and post-mortem material. Aspergillus fumigatus, Blastomyces dermatitidis, Candida albicans, Cryptococcus neoformans, Paracoccidioides brasiliensis and Rhizopus oryzae have been studied with five fluorescein-labelled lectins and with basis of differences in their reactions with these stains. The results accord well with what is known of the chemistry of the organisms and the method offers promise to practising histopathologists.
Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels (2016)

Fluid secretion by the ciliary body plays a critical and irreplaceable function in vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure. Here, we identify TRPV4 (transient receptor potential vanilloid isoform 4) channels as key osmosensors in nonpigmented epithelial (NPE) cells of the mouse ciliary body. Hypotonic swelling and the selective agonist GSK1016790A (EC50 ∼33 nM) induced sustained transmembrane cation currents and cytosolic [Formula: see text] elevations in dissociated and intact NPE cells. Swelling had no effect on [Formula: see text] levels in pigment epithelial (PE) cells, whereas depolarization evoked [Formula: see text] elevations in both NPE and PE cells. Swelling-evoked [Formula: see text] signals were inhibited by the TRPV4 antagonist HC067047 (IC50 ∼0.9 μM) and were absent in Trpv4(-/-) NPE. In NPE, but not PE, swelling-induced [Formula: see text] signals required phospholipase A2 activation. TRPV4 localization to NPE was confirmed with immunolocalization and excitation mapping approaches, whereas in vivo MRI analysis confirmed TRPV4-mediated signals in the intact mouse ciliary body. Trpv2 and Trpv4 were the most abundant vanilloid transcripts in CB. Overall, our results support a model whereby TRPV4 differentially regulates cell volume, lipid, and calcium signals in NPE and PE cell types and therefore represents a potential target for antiglaucoma medications.
Rat Phospholipid-hydroperoxide Glutathione Peroxidase (1995)

Phospholipid-hydroperoxide glutathione peroxidase (PhGPx) is a selenoenzyme that reduces hydroperoxides of phospholipid, cholesterol, and cholesteryl ester. Previous studies suggested that both the mitochondrial and nonmitochondrial forms of PhGPx are approximately 170 amino acids long. In this study, we isolated a full-length cDNA clone encoding rat testis PhGPx. Based on sequence analysis, the cDNA encodes a protein of 197 amino acids, with translation initiating at AUG61. The additional 27 amino acids at the N terminus contain the features of a mitochondrial targeting sequence. In vitro translation of the full-length PhGPx mRNA initiated predominantly at AUG61. However, translation initiated at AUG141 when AUG61 was deleted. An RNase protection assay was used to map the 5'-ends of PhGPx mRNAs in rat tissues. We identified two major windows of transcription initiation that are tissue-specific. Rat testis predominantly expresses larger transcripts that encode the 197-amino acid protein containing the potential mitochondrial targeting signal. The predominant smaller transcripts in somatic tissues lack AUG61 and encode a 170-amino acid protein, which may represent the nonmitochondrial forms of PhGPx. Our results suggest that the use of alternative transcription and translation start sites determines the subcellular localization of PhGPx in different tissues.
The Physics of Macropore Formation in Low Doped n‐Type Silicon (1993)

Macropore formation in n‐type silicon is a self‐adjusting phenomenon characterized by a specific current density at the pore tip. At this specific current density, the dissolution reaction changes from the charge‐transfer‐limited to the mass‐transfer‐limited regime. The passivation of the pore walls in hydrofluoric acid is caused by a depletion of holes due to the n‐type doping of the substrate. Equations based on these findings are presented and allow us to precalculate the dimensions of the pores. The validity of the model and its mathematical description is verified in experiments. Pores of a depth up to the wafer thickness and aspect ratios of 250 were etched using this method.
Active Anti-Interferon-α Immunization: A European-Israeli, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in 242 HIV-1-Infected Patients (the EURIS Study) (1999)

This randomized, double-blind, placebo-controlled, phase II/III study was designed to evaluate safety, immunogenicity, and efficacy of an active anti-interferon-alpha (anti-IFN-alpha) vaccine in asymptomatic HIV-1-infected patients. The active immunization was aimed at inducing anti-IFN-alpha antibodies to counteract IFN-alpha overproduction. In all, 242 patients, recruited between December 1995 and July 1996 in eight centers in Europe and Israel, with CD4+ counts from 100 to 634 cells/mm3 who were receiving or not receiving antiretroviral therapy (including protease inhibitors) were randomized to receive either anti-IFN-alpha vaccine or placebo. The anti-IFN-alpha immunization regimen consisted of three priming injections delivered intramuscularly at 1-month intervals in a water-in-oil emulsion of inactivated recombinant IFN-alpha-2b (i-IFN-alpha) followed by intramuscular booster injections of i-IFN-alpha adsorbed onto calcium phosphate every 3 months. Immunogenicity to vaccine was defined as an increase of anti-IFN-alpha antibody level of more than twofold the preimmunization value. Clinical progression, changes in antiretroviral treatment, and decrease of CD4+ counts to <200 cells/mm3 were considered endpoints for efficacy evaluation. Contrary to our previous experience, in which six to seven oil priming injections induced a >90% response rate, the three oil-adjuvanted injections in this trial were suboptimal because only 40 of 122 vaccinees (33%) had raised anti-IFN-alpha antibody following immunization. In vaccinees, both antibody responders (AbRV) and nonresponders (AbNRV), the tolerance to the vaccine was good and was without evidence of significant safety concerns. During the course of the trial, 62% of vaccine responders, 64% of nonresponders, and 63% of placebo patients elected to add protease inhibitor-containing regimens as new treatment guidelines were established, resulting in a marked decrease in clinical and laboratory progression such that the expected endpoints of the study could not be achieved and further follow-up was halted. Despite the unexpectedly low immunogenicity and fewer than expected endpoints, anti-IFN-alpha vaccine recipients, in comparison with placebo recipients, showed a lower rate of disease progression, nonelective treatment changes, and/or CD4+ count decrease to <200 cells/mm3, but the difference was not statistically significant. Nevertheless, the subgroup of patients immunized to IFN-alpha who experienced a rise in anti-IFN-alpha antibodies had a significantly lower rate of occurrence of HIV-1-related events and of any combination of the endpoints compared with those of either placebo patients or vaccinees who failed to develop anti-IFN-alpha antibodies, the latter two groups behaving similarly. Further studies of this approach are warranted because these data suggest a beneficial effect of this adjuvant approach.
Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells (1999)

Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.
Atrial size, atrial fibrillation, and stroke (1986)

M-mode and two-dimensional echocardiographic images were reviewed retrospectively in 20 patients with atrial fibrillation and ischemic stroke with no known valvular disease and in 20 patients with atrial fibrillation without known stroke. Left atrial size was measured and analyzed without knowledge of patient grouping. Two-dimensional echocardiography showed that 90% of the stroke patients had left atrial enlargement compared with only 20% in the nonstroke group. This finding suggests that left atrial enlargement may convey additional stroke risk in patients with atrial fibrillation.
Nuclease activity of 1,10-phenanthroline-copper: sequence-specific targeting. (1986)

The nuclease activity of 1,10-phenanthroline-copper ion can be targeted to specific DNA sequences by attachment of the ligand to the 5' end of complementary deoxyoligonucleotides via a phosphoramidate linkage. To synthesize the adduct, the phosphorimidazolide of the deoxyoligonucleotide is prepared using a water-soluble carbodiimide and is then coupled to 5-glycylamido-1,10-phenanthroline. After hybridization to the target DNA, sequence-specific cleavage is observed upon the addition of cupric ion and 3-mercaptopropionic acid. Two methods of assaying the cutting of the operator sequence of the lac operon have been employed using the oligonucleotide 5'-AATTGTTATCCGCTCACAATT-3' representing sequence positions 21-1 of the template strand. In the first, the single-stranded DNA of the phage M13mp8 was the target, and cuts were detected using a primer-extension assay. In the second, the substrate was an EcoRI fragment 3' labeled in the nontemplate strand. After denaturation and reannealing to the oligonucleotide-1,10-phenanthroline adduct, cupric ion and 3-mercaptopropionic acid were added, and the products were analyzed directly on a sequencing gel. With the phenanthroline moiety attached to position 21 of the oligonucleotide carrier, cutting was observed at positions 20-25 using both assays.
Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS (2016)

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (T<sub>max1</sub> ≈ 0.75 h, T<sub>max2</sub> ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L<sup>-1</sup> or 24625.1 ± 1563.8 mg·h·L<sup>-1</sup>, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L<sup>-1</sup> or 1394.6 ± 868.1 mg·h·L<sup>-1</sup>, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.
Structure-Activity Relationship of Calcitonin Gene Related Peptide (1989)

Chicken, human(alpha) CGRPs and their analogues were synthesized to investigate the relationship between structure and serum calcium and phosphate lowering effects. The native hormones contain 37 amino acid residues with only four positions (3, 14, 15 and 23) that differ. Chicken CGRP exhibits stronger and longer lasting activities than the human hormone. A chicken CGRP analogue with replacement of Asp at position 14 by Gly (as in human CGRP) showed great reduction of activity. The converse replacement of Gly at position 14 by Asp in human CGRP enhanced this analogue activity. Among the synthetic analogues, des-1-Ala-des-alpha-amino chicken CGRP, exhibited the most potent and long lasting biological activity.
Treatment with Tin Prevents the Development of Hypertension in Spontaneously Hypertensive Rats (1989)

Cytochrome P-450-dependent metabolites of arachidonic acid (AA) increased in the kidneys of young, spontaneously hypertensive rats (SHRs) during the period of rapid elevation of blood pressure (BP) but not in adult SHRs or in Wistar Kyoto rats (WKYs) with normal BP. Treatment of SHRs and WKYs with stannous chloride (SnCl2), which selectively depletes renal cytochrome P-450, restored BP to normal, coincident with a natriuresis, in young but not in adult SHRs and did not affect either BP or sodium excretion in WKYs. Depletion of renal cytochrome P-450 was associated with decreased generation of these AA metabolites only in young SHRs. The antihypertensive effect of SnCl2 in young SHRs was greatly reduced by prevention of its cytochrome P-450-depleting action.
Requirement of the Chemokine Receptor CXCR3 for Acute Allograft Rejection (2000)

Chemokines provide signals for activation and recruitment of effector cells into sites of inflammation, acting via specific G protein-coupled receptors. However, in vitro data demonstrating the presence of multiple ligands for a given chemokine receptor, and often multiple receptors for a given chemokine, have led to concerns of biologic redundancy. Here we show that acute cardiac allograft rejection is accompanied by progressive intragraft production of the chemokines interferon (IFN)-gamma-inducible protein of 10 kD (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T cell alpha chemoattractant (I-TAC), and by infiltration of activated T cells bearing the corresponding chemokine receptor, CXCR3. We used three in vivo models to demonstrate a role for CXCR3 in the development of transplant rejection. First, CXCR3-deficient (CXCR3(-/)-) mice showed profound resistance to development of acute allograft rejection. Second, CXCR3(-/)- allograft recipients treated with a brief, subtherapeutic course of cyclosporin A maintained their allografts permanently and without evidence of chronic rejection. Third, CXCR(+/+) mice treated with an anti-CXCR3 monoclonal antibody showed prolongation of allograft survival, even if begun after the onset of rejection. Taken in conjunction with our findings of CXCR3 expression in rejecting human cardiac allografts, we conclude that CXCR3 plays a key role in T cell activation, recruitment, and allograft destruction.
miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer (2018)

Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b-FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.
Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. (1987)

Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were also seen in a 16-residue segment. On extraction, the islet amyloid is particulate and insoluble like the core particles of Alzheimer disease. Their monomers have similar molecular masses, each having a hydropathic region that can probably form beta-pleated sheets. The accumulation of amyloid, including diabetes-associated peptide, in islets may impair islet function in type 2 diabetes mellitus.
A token passing network for powerline communications (1991)

The AC powerline is the ideal communications medium for enabling control and monitoring applications in the home. The authors describe a low-level network architecture for reliable powerline communications. It uses a robust token passing protocol that supports network access and device response under worst-case powerline impairments. The approach is hierarchical, building upon both a spread-spectrum physical layer enabling short-duration powerline transmissions and adaptation to changing powerline conditions and upon a packet structure designed for error correction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Optimal scaffold design and effective progenitor cell identification for the regeneration of vascularized bone (2011)

Bone tissue engineering offers perhaps the most attractive treatment option for bone repair/regeneration as it eliminates complications of other bone grafting options (i.e., availability and immunogenicity issues of autografts and allografts, respectively). However, scaffold-based bone tissue engineering is largely limited by inadequate vascaularization, and as a result, bone formation is often restricted to the construct's periphery. In this study, we offer a two-pronged approach to overcome periphery-limited bone and vascular formation. We have developed optimally designed, mechanically strong, biodegradable scaffolds with increased porosity and interconnectivity. We have also identified and isolated superior, clinically-relevant cell populations (peripheral blood-derived endothelial progenitor cells (EPCs), and bone marrow-derived mesenchymal stem cells (MSCs)). In combination, we have developed a synthetic graft system suitable for the regeneration of vascularized bone.
Modulation of alpha-crystallin chaperone activity in diabetic rat lens by curcumin. (2005)

We demonstrate that curcumin, at the levels close to dietary consumption, prevented the loss of chaperone-like activity of alpha-crystallin vis-a-vis cataractogenesis due to diabetes in rat lens.