gebhart/patrepeval huggingface dataset:
Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease (2001)

Increasing evidence suggests that apoptosis may be the underlying cell death mechanism in the selective loss of dopaminergic neurons in Parkinson's disease. Because the inhibition of caspases provides only partial protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP(+)) model of Parkinson's disease, we investigated the role of the proapoptotic c-Jun N-terminal kinase (JNK) signaling cascade in SH-SY5Y human neuroblastoma cells in vitro and in mice in vivo. MPTP/MPP(+) led to the sequential phosphorylation and activation of JNK kinase (MKK4), JNK, and c-Jun, the activation of caspases, and apoptosis. In mice, adenoviral gene transfer of the JNK binding domain of JNK-interacting protein-1 (a scaffold protein and inhibitor of JNK) inhibited this cascade downstream of MKK4 phosphorylation, blocked JNK, c-Jun, and caspase activation, the death of dopaminergic neurons, and the loss of catecholamines in the striatum. Furthermore, the gene transfer resulted in behavioral benefit. Therefore, inhibition of the JNK pathway offers a new treatment strategy for Parkinson's disease that blocks the death signaling pathway upstream of the execution of apoptosis in dopaminergic neurons, providing a therapeutic advantage over the direct inhibition of caspases.
Round window membrane permeability to golimumab in guinea pigs: A pilot study (2013)

NA. Laryngoscope, 123:2840-2844, 2013.
CHIP-SCALE ATOMIC DEVICES (2006)

Chip-scale atomic devices combine elements of precision atomic spectroscopy, silicon micromachining, and advanced diode laser technology to create compact, low-power, and manufacturable instruments with high precision and stability. Microfabricated alkali vapor cells are at the heart of most of these technologies, and the fabrication of these cells is discussed in detail. We review the design, fabrication, and performance of chip-scale atomic clocks, magnetometers, and gyroscopes and discuss many applications in which these novel instruments are being used. Finally, we present prospects for future generations of miniaturized devices, such as photonically integrated systems and manufacturable devices, which may enable embedded absolute measurement of a broad range of physical quantities.
Lipid Nanoparticles Improve Activity of Single-Stranded siRNA and Gapmer Antisense Oligonucleotides in Animals (2013)

We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed for LNP-formulated agents compared to unformulated drugs when gene silencing was evaluated after a single dose in the livers of mice. An unformulated ss-siRNA modified with a metabolically stable phosphate mimic 5'-(E)-vinylphosphonate showed dose-dependent reduction of PTEN mRNA in mice, albeit at doses significantly higher than those observed for formulated ss-siRNA. These results demonstrate that LNPs can be used to deliver functional antisense and ss-siRNA therapeutics to the liver, indicating that progress in the field of siRNA delivery is transferable to other classes of nucleic acid-based drugs.
Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group. (1993)

Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG #160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels.
Magnetic Levitation in the Analysis of Foods and Water (2010)

This paper describes a method and a sensor that use magnetic levitation (MagLev) to characterize samples of food and water on the basis of measurements of density. The sensor comprises two permanent NdFeB magnets positioned on top of each other in a configuration with like poles facing and a container filled with a solution of paramagnetic ions. Measurements of density are obtained by suspending a diamagnetic object in the container filled with the paramagnetic fluid, placing the container between the magnets, and measuring the vertical position of the suspended object. MagLev was used to estimate the salinity of water, to compare a variety of vegetable oils on the basis of the ratio of polyunsaturated fat to monounsaturated fat, to compare the contents of fat in milk, cheese, and peanut butter, and to determine the density of grains.
Selective T cell depletion of donor allogeneic marrow with anti-CD6 monoclonal antibody: rationale and results. (1993)

Acute and chronic graft-versus-host disease (GVHD) are responsible for a significant fraction of the morbidity and mortality of allogeneic bone marrow transplantation. Attempts to reduce the incidence of GVHD by exhaustive T cell depletion of donor marrow have frequently been associated with an increase in graft failure and disease relapse. For the past 10 years, we have evaluated the use of a monoclonal antibody (T12) that selectively targets the CD6 determinant on mature T cells. 171 patients with hematologic malignancies have received donor marrow depleted of mature T cells with anti-CD6 and rabbit complement. Initial engraftment in recipients of HLA-matched marrow has been > 98% with 96% of patients showing stable hematologic reconstitution. The incidence of acute GVHD in this population was only 15%. Chronic GVHD has developed in 5% of patients. Overall, transplant-related mortality was 17%. Examination of peripheral blood lymphocyte reconstitution in the early post-BMT period has been helpful in predicting which patients will ultimately go on to develop GVHD. Treatment of recipients of CD6 depleted marrow with low doses of interleukin-2 post-BMT can expand the number of circulating NK cells and may be associated with a decrease in disease relapse rate.
Molecular Targeting of Drug Delivery Systems to Cancer (2004)

This review presents molecular targeting approaches in anticancer drug delivery systems (DDS) and identifies new developments in these systems. Targeting approaches include passive targeting (enhanced permeability and retention effect), targeting specific tumor conditions, topical delivery and active targeting, namely, targeting organs, cells, intracellular organelles and molecules, sandwich targeting, promoter targeting, indirect targeting and targeting by external stimuli. A novel advanced proapoptotic anticancer DDS that utilizes several molecular targets will be considered. Experimental data suggest that this DDS can simultaneously: (1) induce cell death, (2) prevent adverse effects on healthy tissues; (3) suppress and prevent multidrug resistance; and (4) inhibit cellular antiapoptotic defense.
The effect of food composition on serum testosterone levels after oral administration of Andriol® Testocaps® (2007)

Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.
Comparative efficacy of oral administrated afoxolaner (NexGard™) and fluralaner (Bravecto™) with topically applied permethrin/imidacloprid (Advantix®) against transmission of Ehrlichia canis by infected Rhipicephalus sanguineus ticks to dogs (2016)

The speed of kill of the two recently registered systemic compounds against R. sanguineus was not sufficiently fast to prevent transmission of E. canis and resulted in only low partial blocking and protection capacity while Advantix(®) effectively blocked transmission of E. canis to dogs in the challenge period and thus provided adequate protection for dogs against monocytic ehrlichiosis.
Physiologic disposition of nabilone, a cannabinol derivative, in man (1977)

Nabilone is a cannabinoid that is being evaluated in man as a potentially useful psychoactive drug. We found that nabilone was readily absorbed from the human gastrointestinal tract when administered orally as a coprecipitate with polyvinyl-pyrrolidone. The absorbed drug disappeared from plasma rather rapidly (half-life, approximately 2 hr), evidently due to extensive tissue distribution and rapid metabolism. The metabolites of nabilone persist in plasma for extended periods (half-life of total radioactivity exceeds 20 hr). Circulating metabolites include isomeric carbinols formed by reduction of the ketone in the 9-position of nabilone. Nabilone is eliminated in feces (about 65% of dose) and urine (20%). The excretory products in urine have not been identified, but metabolites that are labile to hydrolysis by beta-glucuronidase or sulfatase do not appear to be formed in significant amounts. A metabolite of nabilone in feces has been identified as a diol formed by reduction of the 9-keto group plus oxidation at the penultimate carbon of the dimethylheptyl side chain. The long duration of action of nabilone in the face of rapid and extensive metabolic elimination suggests that the pharmacologic effects, at least in part, may be exerted by one or more active metabolites.
Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity (2000)

Exclusive breast feeding seems to have a protective effect against some risk factors for cardiovascular disease in later life.
Cross-linking of HLA class II antigens modulates the release of tumor necrosis factor-alpha by the EBV-B lymphoblastoid cell line JY. (1993)

In addition to their functional role as peptide-binding proteins HLA class II Ag can also act as signal-transducing molecules. The present study showed that cross-linking of HLA class II Ag by the anti-HLA-DR mAb L243 or by the anti-HLA-DR,-DP mAb IVA12 significantly (p < 0.05) increased the release of TNF-alpha by the EBV-B lymphoblastoid cell line JY. In contrast, the anti-HLA-DR mAb 2.06 or the superantigens staphylococcal exotoxin toxic shock syndrome toxin-1 and staphylococcal enterotoxin B that bind to HLA-DR,-DQ Ag did not affect the release of TNF-alpha by JY cells. The accumulation of TNF-alpha in the culture medium of JY cells peaked at 24 h, decreased thereafter, and was found to be dependent on the dose of mAb L243 or mAb IVA12 used to cross-link HLA class II Ag. mAb L243 or staphylococcal exotoxin toxic shock syndrome toxin-1 enhanced the spontaneous homotypic aggregation of JY cells and mediated a dose-dependent inhibition of JY cell proliferation. These phenomena were not mediated by TNF-alpha released in response to cross-linking of HLA class II Ag; polyclonal anti-TNF-alpha neutralizing antibody did not affect JY cell aggregation and the inhibition of JY cell proliferation mediated by mAb L243. In contrast, TNF-alpha secreted by JY cells enhanced a nuclear factor-kB-like activity through the binding to the 75-kDa TNF-alpha receptor. These results demonstrate an additional role of HLA class II Ag as signal-transducing molecules regulating the production of bioactive TNF-alpha by EBV-B cells. The release of TNF-alpha after the triggering of HLA class II molecules could be relevant to different aspects of B cell biology and might play a role in the pathogenesis of human diseases in which antibodies cross-reactive to HLA class II Ag have been identified.
Cytokines as biomarkers of Crimean‐Congo hemorrhagic fever (2015)

Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe disease caused by CCHF virus. As in other viral hemorrhagic fevers, it is considered that the course and outcome of the disease depend on the viral load and the balance among the immune response mediators, and that a fatal outcome is the result of a "cytokine storm." The level of 27 cytokines was measured in serum samples taken from 29 patients during the acute phase of the disease. Two cases were fatal. Among survivors, significant differences between severe and non-severe cases were observed in the levels of IP-10, and MCP-1, while the levels of IL-1b, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IP-10, MCP-1, TNF-α, and RANTES differed significantly between fatal and non-fatal cases (P < 0.05). RANTES was negatively correlated with the outcome of the disease. A striking similarity with the cytokine patterns seen in Ebola virus disease was observed. A weak Th1 immune response was seen. The viral load was positively correlated with IL-10, IP-10, and MCP-1 levels, and negatively correlated with the ratio IL-12/IL-10. Especially IP-10 and MCP-1 were significantly associated with the viral load, the severity and outcome of the disease, and they could act as biomarkers and, probably, as potential targets for treatment strategies design.
A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats (2013)

Our data suggest that hepcidin lowering agents may provide a new therapeutic strategy to improve iron availability for erythropoiesis in CKD.
Clusterin Expression and Univariate Analysis of Overall Survival in Human Breast Cancer (2006)

The aim of this research is to investigate the significance of clusterin (CLU) expression as a risk factor for breast cancer through tissue microarray technology and univariate analysis of overall survival. Formalin-fixed, paraffin-embedded tissues from 158 cases of breast cancer and 31 cases of normal adjacent tissues assembled into a tissue microarray. Cytoplasmic CLU expression in tumor tissues was measured by immunochemistry. Survival analysis was used to investigate the relationship between CLU expression and prognosis, tumor volume, pathological classification, and recurrence. Survival time of patients with CLU expression, lymph node metastasis, and limited post-surgery chemotherapy (<6 cycles of treatment) was significantly shorter than that of patients with no detectable CLU expression (P=0.000), without lymph node metastasis (P=0.000) and more comprehensive post-surgery chemotherapy (>/=6 cycles of treatment) (P=0.035). CLU expression in tumor cells was higher than in normal adjacent breast epithelial cells (P=0.03). The CLU expression staining coefficient of cancer tissues with lymph node metastasis was higher than those without lymph node metastasis (P=0.000). Cytoplasmic CLU expression was found to be a prognostic factor for human breast cancer.
Prevalence of Nasal Polyps in Adults: The Skovde Population-Based Study (2003)

Patients with nasal polyps present repeatedly in otorhinolaryngology practices, but the prevalence of nasal polyps in the general population is not known. Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age, gender, asthma, and aspirin intolerance. A random sample of 1,900 inhabitants over the age of 20 years, stratified for age and gender, was drawn from the municipal population register in Skövde, Sweden, in December 2000. The subjects were called to clinical visits that included questions about rhinitis, asthma, and aspirin intolerance and examination by nasal endoscopy. In total, 1,387 volunteers (73% of the sample) were investigated. The sample size was adequate, with a good fit to the whole population. The prevalence of nasal polyps was 2.7% (95% confidence interval, 1.9-3.5), and polyps were more frequent in men (2.2 to 1), the elderly (5% at > or = 60 years of age), and asthmatics. Subjective symptoms of aspirin intolerance were not found to correlate with polyps. Nasal polyps were more common in adults than was stated by the a priori estimate. The Skövde population-based study is considered representative for the Swedish population.
High-Resolution Interferometric Spectrophotopolarimetry (1981)

Spectrophotopolarimetric capability can be added to a laboratory interferometer-spectrometer by use of a specially designed module described herein. With the instrument so augmented, high-resolution spectra can be obtained of the Stokes parameters of the reference beam and the beams diffusely reflected or transmitted by a sample medium of interest. For any such beam, the exponential Fourier transforms of the two interferograms obtained with a polarizer-analyzer oriented along the 0 ° and the 90 ° directions provide the spectra of I and Q, separately. Within experimental (and numerical) noise, this I spectrum should be the same as the one obtained with the polarizer removed. The remaining Stokes parameters U and V are obtained with a third interferogram recorded with the polarizer along the 45° direction. The complete theory of this instrument is described including the detailed analysis of the polarization-interferograms it provides.
Empirical evaluation of the influence of side chains on the conformational entropy of the polypeptide backbone (1995)

Changes in amino acid side chains have long been recognized to alter the range and distribution of phi, psi angles found in the main chain of polypeptides. Altering the range and distribution of phi, psi angles also alters the conformational entropy of the flexible denatured state and may thus stabilize or destabilize it relative to the comparatively conformationally rigid native state. A database of 12,320 residues from 61 nonhomologous, high resolution crystal structures was examined to determine the phi, psi conformational preferences of each of the 20 amino acids. These observed distributions in the native state of proteins are assumed to also reflect the distributions found in the denatured state. The distributions were used to approximate the energy surface for each residue, allowing the calculation of relative conformational entropies for each residue relative to glycine. In the most extreme case, replacement of glycine by proline, conformational entropy changes will stabilize the native state relative to the denatured state by -0.82 +/- 0.08 kcal/mol at 20 degrees C. Surprisingly, alanine is found to be the most ordered residue other than proline. This unexpected result is a result of the high percentage of alanines found in helical conformations. This either indicates that the observed distributions in the native state do not reflect the distributions in the denatured state, or that alanine is much more likely to adopt a helical conformation in the denatured state than residues with longer side chains.(ABSTRACT TRUNCATED AT 250 WORDS)
Apoptosis as a Novel Target for Cancer Chemoprevention (2004)

Cancer chemopreventive agents are typically natural products or their synthetic analogs that inhibit the transformation of normal cells to premalignant cells or the progression of premalignant cells to malignant cells. These agents are believed to function by modulating processes associated with xenobiotic biotransformation, with the protection of cellular elements from oxidative damage, or with the promotion of a more differentiated phenotype in target cells. However, an increasing number of chemopreventive agents (e.g., certain retinoids, nonsteroidal anti-inflammatory drugs, polyphenols, and vanilloids) have been shown to stimulate apoptosis in premalignant and malignant cells in vitro or in vivo. Apoptosis is arguably the most potent defense against cancer because it is the mechanism used by metazoans to eliminate deleterious cells. Many chemopreventive agents appear to target signaling intermediates in apoptosis-inducing pathways. Inherently, the process of carcinogenesis selects against apoptosis to initiate, promote, and perpetuate the malignant phenotype. Thus, targeting apoptosis pathways in premalignant cells--in which these pathways are still relatively intact--may be an effective method of cancer prevention. In this review, we construct a paradigm supporting apoptosis as a novel target for cancer chemoprevention by highlighting recent studies of several chemopreventive agents that engage apoptosis pathways.
Homogeneous development of electrical excitability via heterogeneous ion channel expression (1996)

Synchronous differentiation of delayed-rectifier potassium current regulates electrical excitability and calcium entry in motor, sensory, and interneurons of the developing amphibian spinal cord. Although Kv1 and Kv2 potassium channel transcripts are detectable in these cells, it is not known which transcript contributes to functional expression. Overexpression of a Kv1 dominant-negative subunit indicates that 20% of neurons have only Kv1 potassium currents. In other neurons, non-Kv1 channels function because the dominant-negative subunit either only partially suppresses or has no effect on current. Thus, diverse embryonic neurons coordinate differentiation of excitability yet rely on heterogeneous potassium channel gene expression.
Analysis of Transmembrane Segment 10 of the Glut1 Glucose Transporter by Cysteine-scanning Mutagenesis and Substituted Cysteine Accessibility (2002)

The Glut1 glucose transporter has been proposed to form an aqueous sugar translocation pathway through the lipid bilayer via the clustering of several transmembrane helices (Mueckler, M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I., Morris, H. R., Allard, W. J., Lienhard, G. E., and Lodish, H. F. (1985) Science 229, 941-945). The participation of transmembrane helix 10 in the formation of this putative aqueous tunnel was tested using cysteine-scanning mutagenesis in conjunction with the membrane-impermeant, sulfhydryl-specific reagent, p-chloromercuribenzenesulfonate (pCMBS). A series of 21 mutants was created from a fully functional, cysteine-less, parental Glut1 molecule by changing each residue within putative transmembrane segment 10 to cysteine. Each mutant was then expressed in Xenopus oocytes, and its plasma membrane content, 2-deoxyglucose uptake activity, and sensitivity to pCMBS were measured. Helix 10 exhibited a highly distinctive reaction profile to scanning mutagenesis whereby cysteine substitution at residues within the cytoplasmic N-terminal half of the helix tended to increase specific transport activity, whereas substitution at residues within the exoplasmic C-terminal half of the helix tended to decrease specific transport activity. Four residues within helix 10 were clearly accessible to pCMBS as judged by inhibition or stimulation of transport activity. All four of these residues were clustered along one face of a putative alpha-helix. These results combined with previously published data suggest that transmembrane segment 10 of Glut1 forms part of the sugar permeation pathway. Two-dimensional models for the conformation of the 12 transmembrane helices and the exofacial glucose-binding site of Glut1 are proposed that are consistent with existing experimental data.