gebhart/patrepeval huggingface dataset:
Immune Response of Elderly Individuals to a Live Attenuated Varicella Vaccine (1992)

The Oka strain live attenuated varicella-zoster virus (VZV) vaccine was administered subcutaneously to 202 VZV-immune individuals who were 55 to greater than 87 years old. The dose administered varied from 1100 to 12,000 pfu. One cohort received 3000 pfu with a 3000 pfu booster 3 months later. The vaccine was well tolerated. VZV-specific immunologic responses were evaluated over a 24-month period. The mean anti-VZV antibody level was significantly increased for 12 months after vaccination. Interferon-gamma production in vitro by peripheral blood mononuclear cells (PBMC) of vaccinees was also increased for 6 months after vaccination. Most significantly, VZV-specific proliferating T cells in PBMC of vaccinees were increased in frequency from 1 in 68,000 to 1 in 40,000. This vaccine-enhanced frequency of VZV-responding T cells is similar to the frequency observed in 35- to 40-year-old adults. Dose and age of the vaccinees did not significantly influence the magnitude of the mean cell-mediated immune response. The data indicate that VZV immunity in the elderly can be boosted by active immunization. If the increased incidence of herpes zoster that accompanies aging results from the natural waning of immunity, active immunization may prevent or attenuate zoster in the elderly.
Current-Driven Magnetization Reversal and Spin-Wave Excitations in Co/Cu/Co Pillars (2000)

Using thin film pillars approximately 100 nm in diameter, containing two Co layers of different thicknesses separated by a Cu spacer, we examine the process by which the scattering from the ferromagnetic layers of spin-polarized currents flowing perpendicular to the layers causes controlled reversal of the moment direction in the thin Co layer. The well-defined geometry permits a quantitative analysis of this spin-transfer effect, allowing tests of competing theories for the mechanism and also new insight concerning magnetic damping. When large magnetic fields are applied, the spin-polarized current no longer fully reverses the magnetic moment, but instead stimulates spin-wave excitations.
New dawn for Botswana. Offering free HIV treatment -- and hope. (2004)

Although the prevalence of HIV/AIDS in Botswana is one of the highest in the world with infection estimates of about 37.4% of adults a public- private partnership for addressing the epidemic has brought hope to the country. One critical component of the African Comprehensive HIV/AIDS Partnerships (a collaboration between Botswanas government the Bill & Melinda Gates Foundation and the Merck Foundation/Merck & Co Inc) is Masa (a Setswana word meaning new dawn) an ambitious program involving offering free antiretroviral drugs to all Botswana citizens who require treatment (http://www.achap.org/MASA.htm). Overseeing Masas efforts is Ernest Darkoh MD MPH an American-born son of Ghanian parents who grew up in Africa and later received his medical and public health degrees from Harvard University and an MBA from Oxford University. JAMA recently spoke with him about how the program is progressing. (excerpt)
Evidence Map of Prevention and Treatment Interventions for Depression in Young People (2012)

Introduction. Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care. Methods. "Evidence mapping" methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains. Results. Prevention research is dominated by cognitive-behavioral- (CBT-) based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking. Conclusions. This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies.
Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. (2000)

Aberrant inhibition of programmed cell death (apoptosis) prevents normal homeostasis and promotes tissue tumorigenesis, but whether it also influences the outcome of common cancers has remained arguable. The expression of a novel IAP apoptosis inhibitor, survivin, in breast cancer and its association with tumor cell apoptosis and overall prognosis were examined in this study. Immunohistochemical analysis showed that survivin expression was positive in 118 of 167 cases (70.7%) of breast carcinomas of histological stages I to IH. In contrast, no expression of survivin in adjacent normal tissue was detected. Although survivin expression was not correlated with p53 mutations, survivin-positive cases were strongly associated with bcl-2 expression (78.0% versus 47.5%; P = 0.0005) and reduced apoptotic index (0.62% +/- 0.51% versus 1.27% +/- 1.37%; P < 0.0001). In addition, patients with low apoptotic index (<0.52%) had worse survival rates than the group with high apoptotic index (> or =0.52%; P = 0.028), and multivariate Cox proportional hazard model analysis identified apoptotic index as an independent prognostic factor (P = 0.024). The results suggest that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is a significant prognostic parameter of worse outcome in breast carcinoma.
DNA demethylation in the Arabidopsis genome (2007)

Cytosine DNA methylation is considered to be a stable epigenetic mark, but active demethylation has been observed in both plants and animals. In Arabidopsis thaliana, DNA glycosylases of the DEMETER (DME) family remove methylcytosines from DNA. Demethylation by DME is necessary for genomic imprinting, and demethylation by a related protein, REPRESSOR OF SILENCING1, prevents gene silencing in a transgenic background. However, the extent and function of demethylation by DEMETER-LIKE (DML) proteins in WT plants is not known. Using genome-tiling microarrays, we mapped DNA methylation in mutant and WT plants and identified 179 loci actively demethylated by DML enzymes. Mutations in DML genes lead to locus-specific DNA hypermethylation. Reintroducing WT DML genes restores most loci to the normal pattern of methylation, although at some loci, hypermethylated epialleles persist. Of loci demethylated by DML enzymes, >80% are near or overlap genes. Genic demethylation by DML enzymes primarily occurs at the 5' and 3' ends, a pattern opposite to the overall distribution of WT DNA methylation. Our results show that demethylation by DML DNA glycosylases edits the patterns of DNA methylation within the Arabidopsis genome to protect genes from potentially deleterious methylation.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA (1997)

We have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted ‘knock-in’ event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue-specific expression and regulation of CFTR function when animal models are used in gene therapy studies.
Nature of Functional Estrogen Receptors at the Plasma Membrane (2006)

Although rapid signaling by estrogen at the plasma membrane is established, it is controversial as to the nature of the receptor protein. Estrogen may bind membrane proteins comparable to classical nuclear estrogen receptors (ERs), but some studies identify nonclassical receptors, such as G protein-coupled receptor (GPR)30. We took several approaches to define membrane-localized estrogen-binding proteins. In endothelial cells (ECs) from ERalpha/ERbeta combined-deleted mice, estradiol (E2) failed to specifically bind, and did not activate cAMP, ERK, or phosphatidyinositol 3-kinase or stimulate DNA synthesis. This is in contrast to wild-type ECs, indicating the lack of any functional estrogen-binding proteins in ERalpha/ERbeta combined-deleted ECs. To directly determine the identity of membrane and nuclear-localized ER, we isolated subcellular receptor pools from MCF7 cells. Putative ER proteins were trypsin digested and subjected to tandem array mass spectrometry. The output analysis identified membrane and nuclear E2-binding proteins as classical human ERalpha. We also determined whether GPR30 plays any role in E2 rapid actions. MCF7 (ER and GPR30 positive) and SKBR-3 (ER negative, GPR30 positive) cells were incubated with E2. Only MCF7 responded with significantly increased signaling. In MCF7, the response to E2 was not different in cells transfected with small interfering RNA to green fluorescent protein or GPR30. In contrast, interfering RNA to ERalpha or ER inhibition prevented rapid signaling and resulting biology in MCF7. In breast cancer and ECs, nuclear and membrane ERs are the same proteins. Furthermore, classical ERs mediate rapid signals induced by E2 in these cells.
Segmental bioelectrical impedance analysis: theory and application of a new technique (1994)

Bioelectrical impedance analysis (BIA) for body composition has been based on the volume conductor model that results in the mathematical relationship Ht2/R approximately FFM, where Ht is body height, R is whole body resistance or impedance, and FFM is fat-free mass. Although this relationship exists in the human subject, its strength and usefulness have been subject to conflicting reports. This study reassessed the theory and methodology of BIA and describes a new technique for measuring segmental impedance that may resolve some major limitations associated with the current whole body impedance methodology. By use of data from 200 adult subjects, a new theory and methodology for BIA were developed in four steps: 1) a rationale was presented for replacing the Ht2/R model by one based on electrical resistivity, 2) a practical six-electrode technique for segmental BIA that uses only peripheral electrode sites was described, 3) prediction equations for fat weight based on the new segmental BIA technique were developed, and 4) prediction equations for fat distribution, a potential new use of impedance methodology, were developed using a new measure of fat distribution, the impedance index.
Adaptation of U.K. Teletext System for 525/60 Operation (1980)

The United Kingdom (UK) Teletext System has now been in service in the UK f or four years. It is also being transmitted on a regular basis in more than six European countries and Australia. Experience has confirmed the soundness of the original system design concept which has lead to television sets equipped with decoders from a number of sources. These combine economy, ease of use, and rugged system performance. The small added cost for installing the teletext decoder has been one of the most important factors in establishing the service in Britain.
PAPR reduction via a fixed frequency-domain weighting across multiple OFDM bauds (2004)

The paper introduces a PAPR reduction technique for OFDM that uses the same PAPR reduction weights over multiple OFDM bauds. The PAPR reduction weights are applied on each subcarrier in the frequency domain and are designed to be either fixed over a group of subcarriers (in addition to multiple bauds) or parameterized by time taps. The advantage of these methods is to simplify channel estimation by not destroying the channel frequency correlation (for weights fixed over groups of subcarriers) or by increasing the effective length of the channel to be estimated (for the weights parameterized by time taps). Simulation results show up to a 6.0 dB decrease in PAPR where PAPR is measured over an OFDM baud.
Seroepidemiology of hepatitis C virus infection in Taiwan (1991)

The prevalence of antibody to hepatitis C virus among Chinese subjects in Taiwan was evaluated using a commercially available enzyme immunoassay. The overall prevalence of antibody to hepatitis C virus was 0.28% among 1,419 healthy subjects, 0.8% among 500 unselected paid blood donors and 0.4% among 793 pregnant women. The three offspring of the mothers positive for antibody to hepatitis C virus were all found to be positive for antibody to hepatitis C virus at birth but all became negative by the age of 6 mo. Among healthy subjects, none of 1,000 school children and young adolescents had antibody to hepatitis C virus. Among patients in selected "high-risk" groups, antibody to hepatitis C virus was detected in 100% of 9 hemophiliac patients who were positive for antibody to human immunodeficiency virus, in 53% of 115 intravenous drug abusers, in 34.4% of 96 hemodialysis patient and in 15.8% of 19 homosexual men who were positive for antibody to human immunodeficiency virus. Only 7.1% of 196 prostitutes, 5.9% of 34 spouses of patients positive for antibody to hepatitis C virus and 0.5% of 201 brothelgoers had antibody to hepatitis C virus. These findings suggest that hepatitis C virus is transmitted mainly by the parenteral route in Taiwan. Transmission from mother to infant is not an important mode of spread of hepatitis C virus.
Local pH domains regulate NHE3-mediated Na+reabsorption in the renal proximal tubule (2014)

The proximal tubule Na(+)/H(+) exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na(+) reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.
Zero-Strain Intercalation Cathode for Rechargeable Li-Ion Cell (2001)

No strain, big gain: the possibility of producing more-efficient rechargeable lithium batteries is offered by a zero-strain LiCoO2 cathode material produced by coating particles with thin films of high-fracture-toughness oxides. This method suppresses the changes in the lattice constant during electrochemical cycling and thereby suppresses phase transitions (see scheme). The order of capacity retention correlates with the fracture toughness of the coating thin-film oxides. The ZrO2-coated sample does not show any noticeable capacity fading over 70 electrochemical cycles.
Neuropeptides : basics and perspectives (1990)

List of contributors. Foreword (W.H. Gispen, J.M. van Ree and Tj.B. van Wimersma Greidanus). Preface (R. Guillemin). David de Wied: a biographical sketch (P.G. Smelik and A. Witter). I. Effects of peptide hormones on behavior (D. de Wied). II. Gene expression, biosynthesis and processing of pro-opiomelanocortin peptides and vasopressin (J.P.H. Burbach and V.M. Wiegant). III. Central neurohypophyseal hormone receptors and receptor mediated cellular responses (E.R. de Kloet, M. Joels and I.J.A. Urban). IV. Neural mechanisms of action of neuropeptides: macromolecules and neurotransmitters (P.N.E. de Graan, P. Schotman and D.H.G. Versteeg). V. Neurotropic effects of ACTH/MSH-like peptides in the peripheral nervous system (P.R. Bar, L.H. Schrama and W.H. Gispen). VI. Neuropeptides and behavioral adaptation: structure-activity relationships (J.W. Van Nispen and Tj.B. Van Wimersma Greidanus). VII. Neuropeptides, behavior, and the autonomic nervous system (B. Bohus and G. Croiset). VIII. Neuro-opioid peptides and blood pressure control (P.L.M. van Giersbergen and W. de Jong). IX. Neuropeptides and psychopathology (J.M. Van Ree, J. Jolles and W.M.A. Verhoeven). X. Neuropeptides and brain aging (B.M. Spruijt, A.B. Oestreicher and J.A.D.M. Tonnaer).
MEK1/2 Induces STAT5-Mediated Germline Transcription of the TCRγ Locus in Response to IL-7R Signaling (2008)

The IL-7R plays an essential role in gammadelta T cell development by inducing V-J recombination of the TCRgamma locus through STAT5. Although tyrosine residues in the intracellular domain of the mouse IL-7R alpha-chain (IL-7Ralpha) have been implicated in STAT5 activation, it is still unknown whether they are essential for gammadelta T cell development. In this study, we showed that those IL-7Ralpha tyrosine residues are not essential for gammadelta T cell development, because phenylalanine replacement of four intracellular tyrosine residues (IL-7R-FFFF) partially rescued gammadelta T cell development of IL-7Ralpha-/- progenitors. To examine signaling pathways activated by IL-7R-FFFF, we introduced a chimeric receptor consisting of the human IL-4R alpha-chain and mouse IL-7R-FFFF (4R/7R-FFFF) into an IL-7-dependent pre-B cell line and found that 4R/7R-FFFF induced TCRgamma germline transcription and STAT5 activation. Treatment of cells with MEK1/2 inhibitors significantly decreased levels of TCRgamma germline transcription and STAT5 tyrosine phosphorylation mediated by 4R/7R-FFFF, suggesting that MEK1/2 plays an alternative role in STAT5 activation by IL-7R. MEK1/2 associated with STAT5 and induced STAT5 tyrosine phosphorylation and DNA binding activity. Furthermore, MEK1 directly phosphorylated a STAT5 tyrosine residue in vitro. Finally, active MEK1 partially rescued TCRgamma germline transcription by IL-7R in a pre-T cell line. These results demonstrate that MEK1/2 induces TCRgamma germline transcription by phosphorylating STAT5 through IL-7R-FFFF and suggest a potential role for MAPK in IL-7R tyrosine-independent activation of STAT5.
DIRECT EVIDENCE FOR HAGEMAN FACTOR (FACTOR XII) ACTIVATION BY BACTERIAL LIPOPOLYSACCHARIDES (ENDOTOXINS) (1974)

Purified precursor Hageman factor has been demonstrated to bind to soluble bacterial lipopolysaccharide (LPS, endotoxin) isolated from Escherichia coli 0111:B4, and this complex has been shown to have the capacity to convert prekallikrein to its active form. In addition, LPS-activated Hageman factor substantially reduces clotting times in XII-deficient plasma. The capacity to activate Hageman factor has been demonstrated to reside in the lipid A region of the LPS molecule. Activation of Hageman factor by LPS contrasts with fluid-phase activation (e.g., by kallikrein or trypsin) in that no cleavage to lower molecular weight fragments occurs. High concentrations of LPS inhibit the activity of Hageman factor, probably by a direct LPS-Hageman factor interaction.
Synthesis and Evaluation of Coumermycin A1 Analogues that Inhibit the Hsp90 Protein Folding Machinery (2006)

[structure: see text] The coumarin antibiotics are not only potent inhibitors of DNA gyrase but also represent the most effective C-terminal inhibitors of 90 kDa heat shock proteins (Hsp90) reported thus far. In contrast to the N-terminal ATP-binding site, little is known about the Hsp90 C-terminus. In addition, very limited structure-activity relationships exist between this class of natural products and Hsp90. In this letter, the syntheses of dimeric coumarin analogues are presented along with their inhibitory values in breast cancer cell lines.
Cannabinoids in health and disease (2007)

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.
Linear Siloxane—Acetylene Polymers as Precursors to High-Temperature Materials (1995)

Novel linear polymers containing alternating diacetylene and siloxane units have been prepared in high yields. The syntheses are one-pot procedures which involve the reaction of 1,4-dilithiobutadiyne with the appropriate dichlorosiloxane compound. IR and NMR analyses of the products support the proposed polymer structures. The polymers are processable and are thermally cross-linked, forming hard, void-free thermosets. The thermosets have excellent thermo-oxidative stabilities. They are stable to ~400 °C in air, and retain most of their mass when heated to 1000 °C in air or nitrogen.