gebhart/patrepeval huggingface dataset:
Ex vivo treatment of antigen-presenting cells with CTLA4Ig and encephalitogenic peptide prevents experimental autoimmune encephalomyelitis in the Lewis rat (1996)

We used a novel approach to study the role of CD28-B7 T cell costimulatory blockade in experimental autoimmune encephalomyelitis (EAE) in the Lewis rat model. APCs were incubated in vitro with CTLA4Ig and the encephalitogenic peptide p71-90 of myelin basic protein. Systemic injection of APCs treated ex vivo with p71-90 and CTLA4Ig before immunization protected animals from clinical EAE. Systemic injection of APCs treated with CTLA4Ig alone, CTLA4Ig and control peptide, peptide alone, or peptide and control Ig was not protective. Injection of APCs treated ex vivo with CTLA4Ig and p71-90 on the day of immunization was also protective, but delaying the injection till day 7 after immunization impaired the protective effect. Immunohistologically, protected animals had decreased inflammatory responses, with inhibition of Th1 and sparing of Th2 cytokines in the brain. Preincubation of APCs with p71-90 and a mutant form of CTLA4Ig that binds only B7-1 also protected animals from developing EAE. These results suggest that ex vivo blockade of CD28-B7-1 leads to the generation of regulatory cells, presumably Th2, which inhibit the generation or priming of encephalitogenic T cells and suppress the autoimmune response to the specific Ag in vivo. These observations have therapeutic implications for autoimmune diseases and transplantation.
Tobacco-specific nitrosamines in mainstream smoke of West Gennan cigarettes-tar alone is not a sufficient index for the carcinogenic potential of cigarette smoke (1989)

Fifty-five types of commercial cigarettes on the West German market were analyzed for tobacco-specific nitrosamines (TSNA) in mainstream smoke. The cigarettes included filter and nonfilter cigarettes with very high, high, medium, low and ultra-low tar and nicotine yields. The observed range for N'-nitrosonornicotine was from 5 to 625 ng/cigarette and for 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone from not detected (less than 4 ng/cigarette) to 432 ng/cigarette. The highest TSNA values were obtained for nonfilter cigarettes made of dark tobaccos and the lowest values for nonfilter Oriental-type cigarettes. Relatively high TSNA yields were also observed in filter cigarettes with moderate and lower tar deliveries. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstrain smoke. The TSNA deliveries in mainstream smoke depended on the actual tobacco composition. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke.
STAT3 Inhibition Induces Apoptosis in Cancer Cells Independent of STAT1 or STAT2. (2013)

Signal transducers and activators of transcription (STATs) were originally discovered as mediators of signal transduction. Persistent aberrant activation of STAT3 is part of the malignant phenotype of hormone-refractory prostate cancer and pancreatic cancer; this is thought to be mediated by homodimers of phosphorylated STAT3, which translocate to the nucleus. One consequence of persistently-activated STAT3 in malignant cells is that they depend upon it for survival. STAT3 is observed to heterodimerize with STAT1 and STAT2; however the contributions of STAT3:STAT1 and STAT3:STAT2 heterodimers to the survival of malignant cells have not been investigated in detail. Previously we reported that single-stranded oligonucleotides containing consensus STAT3 binding sequences (13410 and 13411) were more effective for inducing apoptosis in prostate cancer cells than antisense STAT3 oligonucleotides. Control oligonucleotides (scrambled sequences) had no effect. STAT3-inhibiting oligonucleotide 13410, but not scrambled-sequence oligonucleotides, induced apoptosis in pancreatic cancer cells as well. Here we report that 13410 and derivative olignucleotides induced apoptosis in STAT1-null and STAT2-null fibrosarcoma cell lines U3A and U6A, as well as in the parental fibrosarcoma cell line 2fTGH. The cell lines expressed constitutively-activated STAT3 and depended on its activity for survival. Forty-eight hr after transfection of 13410 or related oligonucleotides, significant apoptosis was observed in 2fTGH, U3A and U6A cells. Scrambled-sequence oligonucleotides had no effect on survival. These data indicate that neither STAT1 nor STAT2 play significant roles in the maintenance of these cells, and by extension that STAT3:STAT1 and STAT3:STAT2 heterodimers regulate a different set of genes from STAT3:STAT3 homodimers.
Thermal effect limits in ultrahigh-density magnetic recording (1999)

In current longitudinal magnetic recording media, high areal density and low noise are achieved by statistical averaging over several hundred weakly coupled ferromagnetic grains per bit cell. Continued scaling to smaller bit and grain sizes, however, may prompt spontaneous magnetization reversal processes when the stored energy per particle starts competing with thermal energy, thereby limiting the achievable areal density. Charap et al. have predicted this to occur at about 40 Gbits/in/sup 2/. This paper discusses thermal effects in the framework of basic Arrhenius-Neel statistical switching models. It is emphasized that magnetization decay is intimately related to high-speed-switching phenomena. Thickness-, temperature- and bit-density dependent recording experiments reveal the onset of thermal decay at "stability ratios" (K/sub u/V/K/sub B/T)/sub 0//spl sime/35 /spl plusmn/ 2. The stability requirement is grain size dispersion dependent and shifts to about 60 for projected 40 Gbits/in/sup 2/ conditions and ten-year storage times. Higher anisotropy and coercivity media with reduced grain sizes are logical extensions of the current technology until write field limitations are reached. Future advancements will rely on deviations from traditional scaling. Squarer bits may reduce destabilizing stray fields inside the bit transitions. Perpendicular recording may shift the onset of thermal effects to higher bit densities. Enhanced signal processing may allow signal retrieval with fewer grains per bit. Finally, single grain per bit recording may be envisioned in patterned media, with lithographically defined bits.
Total contact casting in diabetic patients with neuropathic foot ulcerations. (1984)

This study investigated total contact casting in the treatment of diabetic foot ulcerations and factors affecting the rate of ulcer healing. Twenty-two diabetic patients with foot ulcerations were rated on the basis of age, weight, ulcer size, and ulcer grade. After treatment with total contact casting, 16 patients (72.7%) healed in an average of 38.3 days, 3 refused treatment, 1 developed a small tibial ulceration, and the remainder were discontinued due to excessive edema. A significant (p less than 0.01) t test for differences between means was calculated comparing ulcer duration prior to casting to healing rate during casting. All patient variables were intercorrelated, and significant (p less than 0.01) intercorrelations among patient variables were as follows: age with grade, 0.58; grade with healing time, 0.49; size with healing time, 0.50; age with ulcer size, 0.36; weight with ulcer size, 0.37; age with healing time, 0.32. A multiple correlation of 0.69 (p less than 0.01) was found for age, grade, size, and weight with healing time. Ulcer grade and size contributed most directly to the total multiple correlation; age contributed equally to size, grade, and healing time; and weight contributed primarily to ulcer size. These results suggest the following: 1) total contact casting is an extremely valuable method of treatment for diabetic foot ulcerations, and 2) when using this treatment technique associated factors (ulcer size, ulcer grade, patient age, patient weight) may be utilized to help predict patient healing.
Influence of Yucca shidigera extract on ruminal ammonia concentrations and ruminal microorganisms (1994)

An extract of the desert plant Yucca shidigera was assessed for its possible benefit in ruminal fermentation. The extract bound ammonia in aqueous solution when concentrations of ammonia were low (up to 0.4 mM) and when the extract was added at a high concentration to the sample (20%, vol/vol). The apparent ammonia-binding capability was retained after autoclaving and was decreased slightly following dialysis. Acid-precipitated extract was inactive. No evidence of substantial ammonia binding was found at higher ammonia concentrations (up to 30 mM). When Y. shidigera extract (1%, vol/vol) was added to strained rumen fluid in vitro, a small (6%) but significant (P < 0.05) decrease in ammonia concentration occurred, apparently because of decreased proteolysis. Inclusion of Y. shidigera extract (1%, vol/vol) in the growth medium of the rumen bacterium Streptococcus bovis ES1 extended its lag phase, while growth of Butyrivibrio fibrisolvens SH13 was abolished. The growth of Prevotella (Bacteroides) ruminicola B(1)4 was stimulated, and that of Selenomonas ruminantium Z108 was unaffected. Protozoal activity, as measured by the breakdown of 14C-leucine-labelled S. ruminantium in rumen fluid incubated in vitro, was abolished by the addition of 1% extract. The antimicrobial activities were unaffected by precipitating tannins with polyvinylpyrrolidone, but a butanol extract, containing the saponin fraction, retained its antibacterial and antiprotozoal effects. Saponins from other sources were less effective against protozoa than Y. shidigera saponins. Y. shidigera extract, therefore, appears unlikely to influence ammonia concentration in the rumen directly, but its saponins have antimicrobial properties, particularly in suppressing ciliate protozoa, which may prove beneficial to ruminal fermentation and may lead indirectly to lower ruminal ammonia concentrations.
A Canadian in Reggio Emilia: The May 1997 Study Tour. (1997)

We aimed to evaluate the inhibitory effect and mechanism of plantaricin YKX on <i>S. aureus</i>. The mode of action of plantaricin YKX against the cells of <i>S. aureus</i> indicated that plantaricin YKX was able to cause the leakage of cellular content and damage the structure of the cell membranes. Additionally, plantaricin YKX was also able to inhibit the formation of <i>S. aureus</i> biofilms. As the concentration of plantaricin YKX reached 3/4 MIC, the percentage of biofilm formation inhibition was over 50%. Fluorescent dye labeling combined with fluorescence microscopy confirmed the results. Finally, the effect of plantaricin YKX on the AI-2/LuxS QS system was investigated. Molecular docking predicted that the binding energy of AI-2 and plantaricin YKX was -4.7 kcal/mol and the binding energy of bacteriocin and luxS protein was -183.701 kcal/mol. The expression of the <i>luxS</i> gene increased significantly after being cocultured with plantaricin YKX, suggesting that plantaricin YKX can affect the QS system of <i>S. aureus</i>.
Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer (2001)

The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer.
Enhancing Effects of Fatty Acids on Piroxicam Permeation Through Rat Skins (2000)

To increase the skin permeation of piroxicam from the Poloxamer 407 gel, fatty acid was added as a penetration enhancer to the Poloxamer 407 gel containing 1% piroxicam. The enhancing effects of the enhancer on the skin permeation of piroxicam were evaluated using Franz diffusion cells fitted with intact excised rat skins. To elucidate the modes of the action of enhancers, thermal analysis and histological examinations were conducted. Among fatty acids tested, linoleic acid showed the highest enhancing effects, with an enhancement factor (EF) of 1.76. From the thermal analysis results, fatty acids have fluidizing effects on the stratum corneum. The skin pretreated with the Poloxamer 407 gels containing piroxicam including linoleic acid showed a loosely layered stratum corneum and wide intercellular space.
DEVELOPMENTAL DETERMINANTS OF BLOOD PRESSURE IN ADULTS (2005)

Over the past 20 years a large and varied body of research has attempted to make the case for the developmental origins of elevated adult blood pressure (BP). Experimental animal research has identified plausible biological mechanisms through which fetal nutritional insufficiency may affect adult BP. The majority of human epidemiologic studies demonstrate an inverse association of birth weight (the most commonly used marker of fetal nutrition) with adult BP and higher risk of hypertension among individuals with lower weight at birth. The most adverse BP outcomes occur among individuals who were small at birth but relatively large as adults, a finding that suggests a role for postnatal growth. We critically review the literature on proposed mechanisms and epidemiologic evidence for developmental origins of adult BP and hypertension, considering associations with birth weight, maternal nutrition during pregnancy, child growth patterns, and infant feeding.
Acid Denaturation and Refolding of Green Fluorescent Protein (2004)

Green fluorescent protein from the jellyfish Aequorea victoria can serve as a good model protein to understand protein folding in a complex environment with molecular chaperones and other macromolecules such as those in biological cells, but little is known about the detailed mechanisms of the in vitro folding of green fluorescent protein itself. We therefore investigated the kinetic refolding of a mutant (F99S/M153T/V163A) of green fluorescent protein, which is known to mature more efficiently than the wild-type protein, from the acid-denatured state; refolding was observed by chromophore fluorescence, tryptophan fluorescence, and far-UV CD, using a stopped-flow technique. In this study, we demonstrated that the kinetics of the refolding of the mutant have at least five kinetic phases and involve nonspecific collapse within the dead time of a stopped-flow apparatus and the subsequent formation of an on-pathway intermediate with the characteristics of the molten globule state. We also demonstrated that the slowest phase and a major portion of the second slowest phase were rate-limited by slow prolyl isomerization in the intermediate state, and this rate limitation accounts for a major portion of the observed kinetics in the folding of green fluorescent protein.
Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re-esterification by the glucocorticoid dexamethasone (2004)

Hepatic VLDL (very-low-density lipoprotein) assembly is a complex process that is largely regulated by the provision of lipid for apolipoprotein B assembly. Intracellular stored TAG (triacylglycerol) undergoes an initial lipolysis followed by re-esterification of the lipolytic products to form TAG prior to their incorporation into a VLDL particle. TGH (TAG hydrolase) is a lipase that hydrolyses intracellular TAG within the hepatocyte. We have utilized both dexamethasone-injected mouse and primary hepatocyte models to address whether stimulation of TAG biosynthesis by the synthetic glucocorticoid, dexamethasone, altered hepatic lipolysis and re-esterification and the provision of stored TAG for lipoprotein secretion. Dexamethasone treatment resulted in decreased TGH expression, primarily due to a dexamethasone-induced decrease in TGH mRNA stability. The expression and activities of diacylglycerol acyltransferases 1 and 2 were stimulated by dexamethasone. The combination of reduced intracellular TAG lipolysis and increased TAG biosynthesis contributed to the accumulation of TAG within the livers of dexamethasone-injected mice. The rate of hepatic TAG secretion in dexamethasonetreated mice was maintained at similar levels as in control mice. Our data demonstrate that stimulation of de novo TAG synthesis by dexamethasone increased the proportion of secreted TAG that was derived from de novo sources, while the utilization of stored TAG for secretion was reduced. The results show that, during markedly increased TAG synthesis, some TAGs are diverted from the cytosolic storage pool and are utilized directly for VLDL assembly within the endoplasmic reticulum lumen.
Superposition of two mesoscopically distinct quantum states: Coupling a Cooper-pair box to a large superconducting island (2001)

We consider a system of two superconducting islands, each of which is coupled to a bulk superconductor via Josephson tunneling. One of the islands represents a ``Cooper-pair box,'' i.e., it is an effective two-level system. The other island has a smaller charging energy and approximates a harmonic oscillator. A capacitive interaction between the islands results in a dependence of the oscillator frequency on the quantum state of the box. Placing the latter in a coherent superposition of its eigenstates and exciting coherent oscillations in the large island will lead to a phase shift of these oscillations depending on the box quantum state, thereby producing a coherent superposition of two ``mesoscopically distinct'' quantum states in the large island.
Detection of feline coronavirus RNA in feces, tissues, and body fluids of naturally infected cats by reverse transcriptase PCR (1995)

A nested reverse transcriptase PCR (RT-nPCR) was developed for the detection of feline coronavirus (FCoV) RNA in the feces, tissues, and body fluids of infected cats. The RT-nPCR was targeted to the highly conserved 3'-untranslated region of the viral genome and will detect most, if not all, feline coronaviruses in the field. With the RT-nPCR, FCoV RNA was detected in plasma samples from experimentally infected cats as early as 2 days postinoculation. FCoV RNA was also detected in serum, plasma, or ascitic fluid samples from 14 of 18 cats (78%) with naturally occurring feline infectious peritonitis (FIP). The use of RT-PCR for FIP diagnosis is limited because of the occurrence of apparently healthy FCoV carriers. These asymptomatic cats shed the virus in the feces and, in a number of cases, also had detectable virus in the plasma. Because of the nature of FCoV infections, our RT-PCR assay with plasma or serum cannot be used to establish a definite diagnosis of FIP. However, this assay does provide a new means to identify asymptomatic FCoV carriers. As such, RT-nPCR will be of use to screen cats before their introduction into FCoV-free catteries. Moreover, this assay provides an important tool to study the epidemiology of FCoV.
Quantitative Characterization of Ligand Binding (1995)

Introduction: The Analysis of Simple Binding Responses. Experimental Methods Based on Phase Separation. Spectral Studies of Ligand Binding. Other Direct Procedures for Characterizing Ligand Binding. Binding Constants from Competitive Binding Assays. Sigmoidal Binding Curves: Analysis and Interpretation. Complicating Factors in the Analysis of Binding Curves. Studies of DNA-Ligand Interactions. Concluding Remarks. Glossary of Symbols. References. Index.
Conformational changes in chicken thyroid hormone receptor .alpha.1 induced by binding to ligand or to DNA (1993)

A classic model of steroid/thyroid hormone receptor activation postulates that a conformational change or "transformation" occurs upon ligand binding as a first step toward regulation of gene transcription. In order to test this model, physical studies have been carried out using purified full-length chicken thyroid hormone receptor alpha 1 (cT3R-alpha 1) expressed in Escherichia coli. Circular dichroism spectroscopic studies reveal that cT3R-alpha 1 adopts a different conformation upon specific binding to a cognate ligand triiodothyroacetic acid as well as to a thyroid hormone response element, an idealized inverted repeat AGGTCA TGACCT. These results suggest that cT3R-alpha 1 may adopt distinct conformations whether free or bound to ligand or to DNA. These states may reflect the changes in the conformation of steroid/thyroid hormone receptors in the signal transduction pathway.
Exhaustion of Racing Sperm in Nature‐Mimicking Microfluidic Channels During Sorting (2013)

Fertilization is central to the survival and propagation of a species, however, the precise mechanisms that regulate the sperm's journey to the egg are not well understood. In nature, the sperm has to swim through the cervical mucus, akin to a microfluidic channel. Inspired by this, a simple, cost-effective microfluidic channel is designed on the same scale. The experimental results are supported by a computational model incorporating the exhaustion time of sperm.
Role of CD4+ CD25+ Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways (2001)

It has recently been shown that CD4(+) CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T cell-mediated organ-specific autoimmune diseases. To determine whether CD4(+) CD25(+) T cells downregulate Th2 cell-mediated allergic inflammation in the airways, we studied antigen-induced eosinophil recruitment in the airways in BALB/c Rag-2(-)(/-) mice transferred with CD4(+) CD25(+) T cell-depleted or unfractionated T cells from ovalbumin-specific TCR transgenic mice. Antigen-induced eosinophil recruitment into the airways was significantly decreased in the mice transferred with CD4(+) CD25(+) T cell-depleted splenocytes as compared with those transferred with unfractionated splenocytes. On the other hand, the depletion of CD4(+) CD25(+) T cells increased antigen-induced neutrophil and T cell recruitment in the airways of the mice. The depletion of CD4(+) CD25(+) T cells also decreased antigen-induced IL-4 and IL-5 production in the airways of the mice. Finally, the depletion of CD4(+) CD25(+) T cells prevented antigen-induced Th2 cell differentiation in vitro but increased the differentiation of Th1 cells. These results indicate that CD4(+) CD25(+) T cells modulate the Th1 and Th2 cell balance toward Th2 cells and thus upregulate Th2 cell-mediated allergic inflammation in the airways.