gebhart/patrepeval huggingface dataset:
A Splicing Variant of the Androgen Receptor Detected in a Metastatic Prostate Cancer Exhibits Exclusively Cytoplasmic Actions (2007)

The androgen receptor (AR) is a ligand-activated transcription factor that displays genomic actions characterized by binding to androgen-response elements in the promoter of target genes as well as nongenomic actions that do not require nuclear translocation and DNA binding. In this study, we report exclusive cytoplasmic actions of a splicing variant of the AR detected in a metastatic prostate cancer. This AR variant, named AR23, results from an aberrant splicing of intron 2, wherein the last 69 nucleotides of the intronic sequence are retained, leading to the insertion of 23 amino acids between the two zinc fingers in the DNA-binding domain. We show that the nuclear entry of AR23 upon dihydrotestosterone (DHT) stimulation is impaired. Alternatively, DHT-activated AR23 forms cytoplasmic and perinuclear aggregates that partially colocalize with the endoplasmic reticulum and are devoid of genomic actions. However, in LNCaP cells, this cytoplasmic DHT-activated AR23 remains partially active as evidenced by the activation of transcription from androgen-responsive promoters, the stimulation of NF-kappaB transcriptional activity and by the decrease of AP-1 transcriptional activity. Our data reveal novel cytoplasmic actions for this splicing AR variant, suggesting a contribution in prostate cancer progression.
Peptide-encoding for structure determination of nonsequenceable polymers within libraries synthesized and tested on solid-phase supports. (1993)

A method of indirectly determining the structure of nonpeptidic or nonsequenceable compounds that have been synthesized on individual particles of solid support is described. The technique permits the parallel synthesis of a compound that is not susceptible to Edman degradation (e.g., N-terminal-blocked peptide), or one containing components that cannot be identified by amino acid sequencing, together with a corresponding "coding" peptide. Each coupling step in the assembly of the nonsequenceable compound is followed by the coupling of an amino acid to a different attachment site of the same carrier particle, whereby the amino acid unambiguously codes for the previously coupled building block of the nonsequenceable compound. The rationale is to enable the sequence determination of a biologically active compound that has been identified through the screening of a library of nonequenceable compounds, by translating the sequence of its "coding" peptide, determined by Edman degradation, into the structure of the active compound. The technique facilitates the construction and screening of nonpeptidic libraries for the discovery of important pharmaceutical compounds.
Magnetic viscosity in high-density recording (1994)

For future ultrahigh-density magnetic recording, the magnetic viscosity in thin-film media will become an issue due to the drastic reduction in grain size. An algorithm combining a Monte Carlo method and molecular dynamics was employed to study the thermal effects in thin-film media. The component of the field perpendicular to the plane defined by the axes of shape anisotropy and uniaxial crystalline anisotropy makes it necessary to use the three-dimensional energy surface to find the minimum energy barrier. This barrier is used to sample the reversal rate and the elapsed time. Hysteresis loops for various KuV/kT ratios and sweep times are simulated. Isolated and di-bit transitions are written, taking into account thermally assisted switching. After the head field is turned off, the subsequent thermal decay is computed for time spans as long as 6 months. Significant aftereffect is found for grain volumes about twice that for ordinary superparamagnetism.
The hrp gene locus of Pseudomonas solanacearum, which controls the production of a type III secretion system, encodes eight proteins related to components of the bacterial flagellar biogenesis complex (1995)

Five transcription units of the Pseudomonas solanacearum hrp gene cluster are required for the secretion of the HR-inducing PopA1 protein. The nucleotide sequences of two of these, units 1 and 3, have been reported. Here, we present the nucleotide sequence of the three other transcription units, units 2, 4 and 7, which are together predicted to code for 15 hrp genes. This brings the total number of Hrp proteins encoded by these five transcription units to 20, including HrpB, the positive regulatory protein, and HpaP, which is apparently not required for plant interactions. Among the 18 other proteins, eight belong to protein families regrouping proteins involved in type III secretion pathways in animal and plant bacterial pathogens and in flagellum biogenesis, while two are related solely to proteins involved in secretion systems. For the various proteins found to be related to P. solanacearum Hrp proteins, those in plant-pathogenic bacteria include proteins encoded by hrp genes. For Hrp-related proteins of animal pathogens, those encoded by the spa and mxi genes of Shigella flexneri and of Salmonella typhimurium and by the ysc genes of Yersinia are involved in type III secretion pathways. Proteins involved in flagellum biogenesis, which are related to Hrp proteins of P. solancearum, include proteins encoded by fli and flh genes of S. typhimurium, Bacillus subtilis and Escherichia coli and by mop genes of Erwinia carotovora. P. solanacearum Hrp proteins were also found to be related to proteins of Rhizobium fredii involved in nodulation specificity.
Molecular Identification of GD3 as a Suppressor of the Innate Immune Response in Ovarian Cancer (2012)

Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion.
Development of an arabinose-fermenting Zymomonas mobilis strain by metabolic pathway engineering (1996)

The substrate fermentation range of the ethanologenic bacterium Zymomonas mobilis was expanded to include the pentose sugar, L-arabinose, which is commonly found in agricultural residues and other lignocellulosic biomass. Five genes, encoding L-arabinose isomerase (araA), L-ribulokinase (araB), L-ribulose-5-phosphate-4-epimerase (araD), transaldolase (talB), and transketolase (tktA), were isolated from Escherichia coli and introduced into Z. mobilis under the control of constitutive promoters that permitted their expression even in the presence of glucose. The engineered strain grew on and produced ethanol from L-arabinose as a sole C source at 98% of the maximum theoretical ethanol yield, based on the amount of consumed sugar. This indicates that arabinose was metabolized almost exclusively to ethanol as the sole fermentation product, with little by-product formation. Although no diauxic growth pattern was evident, the microorganism preferentially utilized glucose before arabinose, apparently reflecting the specificity of the indigenous facilitated diffusion transport system. This microorganism may be useful, along with the previously developed xylose-fermenting Z. mobilis (M. Zhang, C. Eddy, K. Deanda, M. Finkelstein, and S. Picataggio, Science 267:240-243, 1995), in a mixed culture for efficient fermentation of the predominant hexose and pentose sugars in agricultural residues and other lignocellulosic feedstocks to ethanol.
Effects of Sterilization on Wear in Total Knee Arthroplasty (1996)

Twenty-nine Ortholoc II ultrahigh molecular weight polyethylene tibial components were retrieved from 27 patients at revision surgery from the same hospital. The polyethylene material grade, method of sterilization, and sterilization dosage for 26 of the tibial components were determined by tracing the material lot number for each component. Each tibial surface was scored for wear using a qualitative scoring system that evaluated delamination, pitting, scratching, cold flow, abrasion, and burnishing. After the wear score analysis, 14 of the 26 components were analyzed to determine the physical and mechanical properties of the polyethylene including toughness and elongation. Seven of these 14 components were sterilized using ethylene oxide and 7 were sterilized using gamma radiation. Tibial components sterilized with gamma radiation had significantly higher wear rates than those sterilized with ethylene oxide. Thirteen of the 18 components sterilized with gamma radiation had delamination of the articular surface compared with 2 of 8 components sterilized with ethylene oxide. Mechanical properties were significantly affected by the sterilization method. Components sterilized with ethylene oxide had significantly higher toughness and percent elongation than those sterilized with gamma radiation. These findings suggest that ethylene oxide sterilization caused less microstructural damage to the polyethylene and resulted in significantly less wear than was found in those components sterilized with gamma radiation.
Detection of WT1 mRNA in urine from patients with kidney diseases (1999)

Detachment of glomerular epithelial cells (GEC) from glomerular basement membrane (GBM) could account for a part of the pathogenic mechanism of proteinuria seen in primary and secondary renal diseases. The Wilms' tumour suppresser gene (WT1) is strictly expressed in GEC in the adult kidney. Mutations of WT1 gene have been implicated in progressive renal damage. Utilizing nested RT-PCR we detected mRNA of WT1 in the urine of patients with renal diseases. Seven of 20 (35%) chronic glomerulonephritis (CGN), eight of 20 (40%) diabetes mellitus (DM) with proteinuria, and two of 24 (8.3%) rheumatic diseases were WT1 positive. Interestingly, only one of 51 (2%) DM without proteinuria was WT1 positive. None of the healthy volunteers or cystitis patients were WT1 positive. This is the first report describing the detection of endogenous WT1 mRNA, an important gene in progressive renal failure, from patients' urine. This technique could be a powerful tool in the search for information about glomerular damage in clinical settings as well as for WT1 mutations or isoform imbalance at the research level without renal biopsy.
Induction of the fibrinogen receptor on human platelets by intracellular mediators. (1987)

We have used platelets permeabilized with saponin to examine the mechanism by which platelet activation causes the exposure of surface receptors for fibrinogen. Receptor exposure was detected using 125I-fibrinogen and 125I-PAC1, a monoclonal antibody specific for the activated form of the fibrinogen receptor. The potential mediators that were studied included guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and guanosine 5'O-(thiotriphosphate) (GTP gamma S), which cause G protein-dependent phospholipase C activation in platelets; inositol 1,4,5-triphosphate (IP3), which causes Ca2+ release from the platelet dense tubular system; and diacylglycerol and phorbol ester, which activate protein kinase C. Each of these molecules caused fibrinogen and PAC1 binding. The effect of IP3 was mimicked by raising the cytosolic free Ca2+ concentration in the permeabilized platelets. However, IP3 and Ca2+-induced PAC1 binding were abolished by indomethacin or aspirin, which had no effect on PAC1 binding caused by Gpp(NH)p, phorbol ester, or diacylglycerol. This suggests that the response to IP3 and Ca2+ is due to the formation of metabolites of arachidonic acid. One such metabolite, TxA2, is believed to activate platelets by stimulating G protein-dependent phosphoinositide hydrolysis. Indeed, we found that the G protein inhibitor guanyl-5'-yl thiophosphate (GDP beta S) inhibited PAC1 binding caused by a thromboxane A2 analog (U46619), IP3, and Ca2+, but had no effect on diacylglycerol or phorbol ester-induced PAC1 binding. Thrombin-induced PAC1 binding and phosphoinositide hydrolysis were also inhibited by GDP beta S and by pertussis toxin. Increasing the thrombin concentration overcame the inhibition of PAC1 binding caused by GDP beta S but did not overcome the inhibition of phosphoinositide hydrolysis. These observations demonstrate that fibrinogen receptor exposure occurs by at least two routes. One of these, in response to agonists such as thrombin and U46619, is initiated by G protein-dependent phosphoinositide hydrolysis and involves the formation of IP3 and diacylglycerol. IP3 appears to act by stimulating Ca2+-dependent arachidonic acid metabolism which, in turn, triggers further phosphoinositide hydrolysis. Diacylglycerol acts by stimulating protein kinase C. A second route is activated by high concentrations of thrombin and is independent of phosphoinositide hydrolysis.
Mucin Biopolymers As Broad-Spectrum Antiviral Agents (2012)

Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system.
Nutrition and the prevention of cataracts (2007)

Supplementation with vitamin C, lutein, zeaxanthin, or a multivitamin may help certain populations, but is unlikely to affect the progression of cataracts in most patients.
Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances (2007)

Recent years have seen a dramatic increase in the number of clinical trials investigating the potential efficacy of medicinal cannabinoids for the symptomatic treatment of chronic pain and spasticity in multiple sclerosis (MS). A number of different cannabinoids have been used, including: delta9-tetrahydrocannabinol (THC) itself; the synthetic delta9-THC, dronabinol; a 1:1 ratio of delta9-THC:cannabidiol (Sativex); and the synthetic delta9-THC metabolites CT-3 and nabilone. Other Cannabis extracts have also been tested. While 2-3 years ago there was little consensus in the literature, now the majority of studies are beginning to suggest that cannabinoids are useful in the treatment of MS in at least a subset of individuals. Their adverse side-effect profile has generally been mild compared with other drugs used for pain and spasticity; nonetheless, there is still concern about potential long-term side effects, particularly psychiatric side effects and effects on fetal development.
Decreased expression of transcription factor GATA‐2 in haematopoietic stem cells in patients with aplastic anaemia (2001)

Aplastic anaemia is characterized by reduced haematopoiesis resulting in pancytopenia. It has been speculated that there is an injury in haematopoietic stem cells in the bone marrow; however, the precise nature of the injury has not been elucidated. In this study, the levels of expression of mRNAs for three transcription factors, GATA-2, SCL and AML1, which function in the early stages of haematopoiesis, were examined by quantitative polymerase chain reaction in patients with aplastic anaemia, idiopathic thrombocytopenic purpura (ITP) and normal subjects. Among these factors, expression of GATA-2 mRNA in purified CD34-positive cells was markedly decreased in aplastic anaemia compared with that in ITP and in normal subjects. The expression levels of SCL and AML1 mRNA in CD34-positive cells in aplastic anaemia were not different from those in normal subjects. When the expression of GATA-2 protein in CD34-positive cells was examined by immunocytochemical analysis, the percentage of GATA-2-positive cells in aplastic anaemia was lower than that in normal subjects. These findings strongly suggest that there is an aberrant expression of transcription factors in stem cells in aplastic anaemia, which may be responsible for the development of the disease.
Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin (2014)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE*3Leiden.CETP mice. Mice received a Western-type diet and were treated with alirocumab (3 or 10 mg/kg, weekly subcutaneous dosing) alone and in combination with atorvastatin (3.6 mg/kg/d) for 18 weeks. Alirocumab alone dose-dependently decreased total cholesterol (-37%; -46%, P < 0.001) and TGs (-36%; -39%, P < 0.001) and further decreased cholesterol in combination with atorvastatin (-48%; -58%, P < 0.001). Alirocumab increased hepatic LDL receptor protein levels but did not affect hepatic cholesterol and TG content. Fecal output of bile acids and neutral sterols was not changed. Alirocumab dose-dependently decreased atherosclerotic lesion size (-71%; -88%, P < 0.001) and severity and enhanced these effects when added to atorvastatin (-89%; -98%, P < 0.001). Alirocumab reduced monocyte recruitment and improved the lesion composition by increasing the smooth muscle cell and collagen content and decreasing the macrophage and necrotic core content. Alirocumab dose-dependently decreases plasma lipids and, as a result, atherosclerosis development, and it enhances the beneficial effects of atorvastatin in APOE*3Leiden.CETP mice. In addition, alirocumab improves plaque morphology.
A New Formula for Depigmenting Human Skin (1975)

Complete depigmentation of the noraml skin of adult male blacks was procured by the daily application for five to seven weeks of a formula consisting of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone, and hydrophilic ointment. Depigmentation was not attainable when any one of the components was omitted. The formula was therapeutically effective in treatment of melasma, ephelides, and postinflammatory hyperpigmentation. Senile lentigines were resistant to this therapy.
Breast feeding and obesity: cross sectional study (1999)

In industrialised countries promoting prolonged breast feeding may help decrease the prevalence of obesity in childhood. Since obese children have a high risk of becoming obese adults, such preventive measures may eventually result in a reduction in the prevalence of cardiovascular diseases and other diseases related to obesity.
Electromechanical Properties of Metallic, Quasimetallic, and Semiconducting Carbon Nanotubes under Stretching (2003)

An electromechanical system is constructed to explore the electrical properties of various types of suspended single-walled carbon nanotubes under the influence of tensile stretching. Small band-gap semiconducting (or quasimetallic) nanotubes exhibit the largest resistance changes and piezoresistive gauge factors ( approximately 600 to 1000) under axial strains. Metallic nanotubes exhibit much weaker but nonzero sensitivity. Comparison between experiments and theoretical predictions and potential applications of nanotube electromechanical systems for physical sensors (e.g., strain gauges, pressure sensors, etc.) are discussed.
Harnessing Nanoparticles for Immunomodulation and Vaccines (2017)

The first successful use of nanoparticles (NPs) for vaccination was reported almost 40 years ago with a virus-like particle-based vaccine against Hepatitis B. Since then, the term NP has been expanded to accommodate a large number of novel nano-sized particles engineered from a range of materials. The great interest in NPs is likely not only a result of the two successful vaccines against hepatitis B and Human Papilloma Virus (HPV) that use this technology, but also due to the versatility of those small-sized particles, as indicated by the wide range of applications reported so far, ranging from medicinal and cosmetics to purely technical applications. In this review, we will focus on the use of NPs, especially virus-like particles (VLPs), in the field of vaccines and will discuss their employment as vaccines, antigen display platforms, adjuvants and drug delivery systems.
Editor's Note (1998)

Our Winter 1996-97 and Summer 1997 issues explored new treatments of theories of history and Russian civilization. In this number we return to questions of historiography. Our guest editor is Thomas Sanders, a specialist in the study of the Russian historical profession in the late imperial period. He is editor of the forthcoming volume Historiography of Imperial Russia, to be published by M.E. Sharpe, Inc. He is currently assistant professor of history at the U.S. Naval Academy.
Examination of Etching Agent and Etching Mechanism on Femotosecond Laser Microfabrication of Channels Inside Vitreous Silica Substrates (2009)

We examined the physical chemistry underlying a wet chemical etching-assisted femtosecond laser microfabrication technique. Close scrutiny of etching reagents and the etching process has led to further refinement of the method for practical use such as microchips for chemical total analysis systems (μ-TAS). Microchannels as long as a centimeter scale with less than 60 μm diameter (aspect ratio of ∼200) were fabricated inside vitreous silica substrates. In this regard, we demonstrated that a concentrated aqueous solution of KOH is advantageous over commonly used aqueous HF because of least saturation behavior in elongating channel structures. Resultant nearly twice as large the etching selectivity of KOH as that of HF allowed substantial penetration depths within the laser-modified volume while leaving the unmodified regions practically intact. Furthermore, the mechanism of laser-modification that permits highly selective wet etching was investigated by photoluminescence and confocal Raman spectral measurements of the irradiated microvolumes. Based on the experimental results, we propose that the formation of a Si-rich structure is responsible for the remarkably enhanced etching rate of aqueous KOH, in addition to the densificaton of the silica structure previously advocated for the mechanism of waveguide formation.