gebhart/patrepeval huggingface dataset:
IL-17A Enhances Vitamin D3-Induced Expression of Cathelicidin Antimicrobial Peptide in Human Keratinocytes (2008)

Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.
Neuroprotective Effects of Glycine for Therapy of Acute Ischaemic Stroke (2000)

The aim of this randomized, double-blind, placebo-controlled trial was to assess the safety and the efficacy of the pharmaceutic drug glycine in 200 patients with acute (<6 h) ischaemic stroke in the carotid artery territory. Fifty patients received placebo, 49 glycine 0.5 g/day, 51 glycine 1.0 g/day and 50 glycine 2.0 g/day for 5 days in each group. The efficacy of glycine was assessed by clinical analysis, by an enzyme-linked immunosorbent assay of levels of blood serum autoantibodies to NMDA-binding proteines, by detection of excitatory (glutamate, aspartate) and inhibitory (glycine, GABA) amino acid concentrations and lipid peroxidation products (TBARS) in CSF. The trial confirmed the safety profile of the glycine treatment. Slight sedation was observed in 9 patients (4. 5%) as a side-effect. Other marked side-effects or adverse events were absent. The glycine treatment at the dose of 1.0-2.0 g/day was accompanied by a tendency to a decreased 30-day mortality (5.9% in 1. 0 g/day glycine and 10% in 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in 0.5 g/day glycine groups), to an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke Scale (p < 0.01) and to a favourable functional outcome on the Barthel index (p < 0.01 in 1.0 g/day glycine vs. placebo group in patients with no or mild disability). An early normalization of autoantibody titres to NMDA-binding proteins in serum was found (p < 0.01 vs. placebo), a reduction of glutamate and aspartate levels (p < 0.05 vs. placebo), an increase in GABA concentrations (p < 0.01 vs. placebo in severe stroke patients) and also a reduction of TBARS levels (p < 0.05 vs. placebo) in CSF by day 3. Thus, the trial suggests that sublingual application of 1.0-2. 0 g/day glycine started within 6 h after the onset of acute ischaemic stroke in the carotid artery territory is safe and can exert favourable clinical effects. These results will be verified in further trials with a larger number of patients.
Down-Regulation of β-Catenin by Activated p53 (2001)

beta-Catenin is a cytoplasmic protein that participates in the assembly of cell-cell adherens junctions by binding cadherins to the actin cytoskeleton. In addition, it is a key component of the Wnt signaling pathway. Activation of this pathway triggers the accumulation of beta-catenin in the nucleus, where it activates the transcription of target genes. Abnormal accumulation of beta-catenin is characteristic of various types of cancer and is caused by mutations either in the adenomatous polyposis coli protein, which regulates beta-catenin degradation, or in the beta-catenin molecule itself. Aberrant accumulation of beta-catenin in tumors is often associated with mutational inactivation of the p53 tumor suppressor. Here we show that overexpression of wild-type p53, by either transfection or DNA damage, down-regulates beta-catenin in human and mouse cells. This effect was not obtained with transcriptionally inactive p53, including a common tumor-associated p53 mutant. The reduction in beta-catenin level was accompanied by inhibition of its transactivation potential. The inhibitory effect of p53 on beta-catenin is apparently mediated by the ubiquitin-proteasome system and requires an active glycogen synthase kinase 3beta (GSK3beta). Mutations in the N terminus of beta-catenin which compromise its degradation by the proteasomes, overexpression of dominant-negative DeltaF-beta-TrCP, or inhibition of GSKbeta activity all rendered beta-catenin resistant to down-regulation by p53. These findings support the notion that there will be a selective pressure for the loss of wild-type p53 expression in cancers that are driven by excessive accumulation of beta-catenin.
Enhanced Cellular Activation with Single Walled Carbon Nanotube Bundles Presenting Antibody Stimuli (2008)

Efficient immunotherapy can be accomplished by expanding T cells outside the body using single walled carbon nanotube (SWNT) bundles presenting antibody stimuli. Owing to the large surface area of these bundles, which can reach 1560 m (2)/g, T cell stimulating antibodies such as anti-CD3, can be presented at high local concentrations inducing potent activation of T cells. We show that anti-CD3 adsorbed onto SWNT bundles stimulate cells more effectively than equivalent concentrations of soluble anti-CD3. Stimulation by antibody adsorbed onto SWNT is significantly higher than other high surface area materials (activated carbon, polystyrene, and C60 nanoparticles), suggesting unique properties of SWNT bundles for stimuli presentation. We demonstrate the surface area tunability of these bundles by chemical treatment and its effect on antibody adsorption and subsequent T cell activation. In addition, the T cell response varied with the concentration of SWNT in a concentration dependent manner. Antibody stimuli adsorbed onto SWNT bundles represent a novel paradigm for efficient activation of lymphocytes, useful for basic science applications and clinical immunotherapy.
IgG4 breaking the rules (2002)

Immunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L-chain) among IgG4. This process results in bispecific antibodies that in most situations will behave as functionally monovalent antibodies. The structural basis for the abnormal behaviour of IgG4 seems to be largely the result of a single amino acid change relative to human IgG1: the change of a proline in core hinge of IgG1 to serine. This results in a marked shift in the equilibrium between interchain disulphide bridges and intrachain disulphide bridges, which for IgG4 results in 25-75% absence of a covalent interaction between the H-chains. Because of strong non-covalent interactions between the CH3 domains (and possibly also between the CH1 domain and the trans-CH2 domain) IgG4 is a stable four-chain molecule and does not easily exchange half-molecules under standard physiological conditions in vitro. We postulate that the exchange is catalysed in vivo by protein disulphide isomerase (PDI) and/or FcRn (the major histocompatibility complex (MHC)-related Fc receptor) during transit of IgG4 in the endosomal pathway in endothelial cells. Because IgG4 is predominantly expressed under conditions of chronic antigen exposure, the biological relevance of this exchange of half-molecules is that it generates antibodies that are unable to form large immune complexes and therefore have a low potential for inducing immune inflammation. In contrast to monovalent immunoglobulin fragments, these scrambled immunoglobulins have a normal half-life. The significance of the ensuing bispecificity needs further evaluation, because this will be relevant only in situations where high IgG4 responses are found to two unrelated antigens that happen to be present in the body at the same time and place. In this context the significance of IgG4 autoreactivity might have to be re-evaluated. The main function of IgG4, however, is presumably to interfere with immune inflammation induced by complement-fixing antibodies, or, in the case of helminth infection or allergy, by IgE antibodies.
An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression (2001)

The cDNA microarray is one technological approach that has the potential to accurately measure changes in global mRNA expression levels. We report an assessment of an optimized cDNA microarray platform to generate accurate, precise and reliable data consistent with the objective of using microarrays as an acquisition platform to populate gene expression databases. The study design consisted of two independent evaluations with 70 arrays from two different manufactured lots and used three human tissue sources as samples: placenta, brain and heart. Overall signal response was linear over three orders of magnitude and the sensitivity for any element was estimated to be 2 pg mRNA. The calculated coefficient of variation for differential expression for all non-differentiated elements was 12-14% across the entire signal range and did not vary with array batch or tissue source. The minimum detectable fold change for differential expression was 1.4. Accuracy, in terms of bias (observed minus expected differential expression ratio), was less than 1 part in 10 000 for all non-differentiated elements. The results presented in this report demonstrate the reproducible performance of the cDNA microarray technology platform and the methods provide a useful framework for evaluating other technologies that monitor changes in global mRNA expression.
Zn2+-Dependent Peptide Nucleic Acids Probes (2004)

Binding of bis-picolylamine-naphthalene diimide-peptide nucleic acid conjugates to complementary DNA is strongly dependent upon Zn2+; ultimately, hybridization is switched ON in the presence muM Zn2+.
Dissociation between adipose tissue fluxes and lipogenic gene expression inob/obmice (2006)

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using (2)H(2)O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 microg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.
A 640-Mb/s 2048-Bit Programmable LDPC Decoder Chip (2006)

A 14.3-mm/sup 2/ code-programmable and code-rate tunable decoder chip for 2048-bit low-density parity-check (LDPC) codes is presented. The chip implements the turbo-decoding message-passing (TDMP) algorithm for architecture-aware (AA-)LDPC codes which has a faster convergence rate and hence a throughput advantage over the standard decoding algorithm. It employs a reduced complexity message computation mechanism free of lookup tables, and features a programmable network for message interleaving based on the code structure. The chip decodes any mix of 2048-bit rate-1/2 (3,6)-regular AA-LDPC codes in standard mode by programming the network, and attains a throughput of 640 Mb/s at 125 MHz for 10 TDMP-decoding iterations. In augmented mode, the code rate can be tuned up to 14/16 in steps of 1/16 by augmenting the code. The chip is fabricated in 0.18-/spl mu/m six-metal-layer CMOS technology, operates at a peak clock frequency of 125 MHz at 1.8 V (nominal), and dissipates an average power of 787 mW.
Tau-Targeted Immunization Impedes Progression of Neurofibrillary Histopathology in Aged P301L Tau Transgenic Mice (2011)

In Alzheimer's disease (AD) brains, the microtubule-associated protein tau and amyloid-β (Aβ) deposit as intracellular neurofibrillary tangles (NFTs) and extracellular plaques, respectively. Tau deposits are furthermore found in a significant number of frontotemporal dementia cases. These diseases are characterized by progressive neurodegeneration, the loss of intellectual capabilities and behavioral changes. Unfortunately, the currently available therapies are limited to symptomatic relief. While active immunization against Aβ has shown efficacy in both various AD mouse models and patients with AD, immunization against pathogenic tau has only recently been shown to prevent pathology in young tau transgenic mice. However, if translated to humans, diagnosis and treatment would be routinely done when symptoms are overt, meaning that the histopathological changes have already progressed. Therefore, we used active immunization to target pathogenic tau in 4, 8, and 18 months-old P301L tau transgenic pR5 mice that have an onset of NFT pathology at 6 months of age. In all age groups, NFT pathology was significantly reduced in treated compared to control pR5 mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Taken together, our data suggests that tau-targeted immunization slows the progression of NFT pathology in mice, with practical implications for human patients.
Neonatal exposure of rats to recombinant follicle stimulating hormone increases adult Sertoli and spermatogenic cell numbers (1996)

It is believed that Sertoli cells support a finite number of germ cells and that Sertoli cell number may help determine the spermatogenic capacity of the adult. In the rat, Sertoli cells divide during fetal and early postnatal life, a process controlled in part by FSH. This study examined the effect of recombinant human FSH on postnatal testicular development and the impact of neonatal FSH exposure on the adult animal. Sprague-Dawley rats received FSH (200 IU/kg s.c.) daily from birth (Day 1) until Day 5, 10, 15, and 20. In a second experiment, animals received FSH for the first 10 or 15 days of life and were killed at Day 90. Sertoli and spermatogenic cell numbers were determined by stereological methods (the optical disector technique). FSH treatment significantly (p < 0.001) increased testicular weights (135%, 193%, and 173% of controls at Days 10, 15, and 20, respectively). The absolute volume of the epithelium and interstitium increased significantly as a result of increases in tubule diameter and length. In response to FSH treatment, the number of Sertoli cells increased significantly (p < 0.01) to 168%, 139%, and 151% of control numbers at Days 10, 15, and 20, respectively. After 15 days of FSH treatment, the numbers of spermatogonia and spermatocytes also increased (169% and 220% of control, p < 0.01, p < 0.001, respectively). The labeling index of Sertoli cell nuclei, as determined by bromodeoxyuridine incorporation, was unaffected by FSH treatment, with cessation of Sertoli cell division occurring as normal at Day 15. FSH treatment for the first 10 or 15 days of neonatal life resulted in testicular hypertrophy in adulthood (testis weight 118% and 124% of control, respectively). Similar increases were seen in the absolute volume of seminiferous epithelium and lumen, which were attributed to an increase in tubule length. Sertoli cell numbers increased to 113% and 149% of control after 10 and 15 days, respectively, of FSH exposure, with similar increases in round and elongated spermatid numbers. We conclude that exposure of the neonatal rat to recombinant FSH results in testicular hypertrophy with increases in seminiferous tubule volume and length and proportionate increases in Sertoli and germ cell numbers. This trophic effect of increased perinatal FSH exposure persists into adulthood to augment the spermatogenic potential of the rat.
The Automatic Vehicles Access Control System Of The Historical Centre Of Rome (2002)

The continuous increase of vehicles inside cities leads to un unsustainable traffic flow that, in historical cities such as Rome, in Italy, leads to a congestion situation characterized by a high environmental pollution due to the vehicles emissions. It this paper we illustrate an automatic vehicle access control system which is capable of controlling and reducing the traffic inside the historical centre.
Umbilical Cord Blood Transplantation (2003)

Transplantation of allogeneic hematopoietic stem cells (HSC) derived either from sibling or unrelated donor bone marrow (BM) or mobilized peripheral blood (PB) have been successfully utilized in the treatment of high risk or recurrent hematological malignancies, BM failure syndromes, hemoglobinopathies, selected hereditary immunodeficiency states, and inborn errrors of metabolism (1). However, a number of limitations exist that impede the successful use of such HSC transplant therapy. The first of these is the unavailability of suitable donors. With current trends in family size in the U.S. fewer than 35% of patients will have an human leukocyte antigen (HLA)-matched sibling (2). While there are currently more than 5 million HLA-typed marrow donors registered in BM donor registries worldwide, substantial numbers of patients are still unable to find an available, suitably HLA-matched BM donor. For example, although an initial search may identify at least one potential HLA-matched donor for 85% of Caucasian patients, 40% of African-American or Asian-Pacific-Islanders will not have a matched donor (3–5). Further, because of the heterogeneity of HLA haplotypes seen in some racial groups, such as African-Americans, HLA-matched BM may be unavailable regardless of registry size (6). Also, the unrelated BM donor search process can be lengthy, taking 3.7 mo on average (5).
Release of Prolactin as well as Adrenocorticotropin after Administration of Arginine-Vasopressin to Healthy Men (1996)

The study was undertaken to obtain simultaneous measurements of circulating anterior pituitary hormone levels after the i.v. injection of arginine-vasopressin (AVP). Nine healthy men, mean age 31 years (range 24-41), received single blind with at least one week apart, after resting in the supine position for 30 min, AVP 0.26 microgram/kg body weight i.v. (Pitressin, Parke-Davis) or saline in randomized order. Blood samples were taken at 0, 10, 20, 30, 45 and 60 min for analyses of serum or plasma levels of ACTH, prolactin, TSH, GH, FSH, LH and AVP. The hormone responses after AVP or saline were calculated as the area under the curve (AUC) 0-60 min as well as the change in hormone levels from 0 to 10 min to pick up possible short lasting effects when there was no significant difference in AUC between AVP and control. As expected the highest plasma concentration of AVP was measured 10 min after the injection of AVP and well comparable to those in other studies where AVP was observed to release ACTH. The AUC:s for both ACTH and prolactin levels were significantly increased after AVP in comparison with saline (p = 0.008 and p = 0.038, respectively). The AUC:s for the other hormones measured were not significantly changed after AVP, but there were small but significant changes in the 0-10 min values for TSH and LH after AVP compared to saline. It is concluded that AVP has the potency to release not only ACTH but also prolactin in healthy men.
Purification and Characterization of Bovine Follicle-Stimulating Hormone: Comparison with Ovine Follicle-Stimulating Hormone* (1979)

Highly purified FSH was obtained from several batches of bovine pituitaries by sequential application of the following procedures: 1) extraction with an alcoholic sodium acetate buffer, 2) fractionation with metaphosphoric acid, 3) fractionation with ammonium sulfate, 4) gel filtration on Sephadex G-150, 5) ion exchange chromatography on CM-Sephadex, 6) chromatography on hydroxylapatite, 7) gel filtration on Sephadex G-100, and 8) preparative acrylamide disc gel electrophoresis, followed by another gel filtration on Sephadex G-100. pproximately 1.3 mg FSH, containing activity equivalent to 47 U NIH-FSH-Sl/mg, were obtained from 1 kg glands. This FSH contained less than 0.01 U NIH-LH-Sl/mg, as determined by the ovarian ascorbic acid depletion assay. The subunits of bovine FSH (bFSH) were isolated by treatment of the hormone with 8 M urea, followed by ion exchange chromatography on DEAESephadex and gel filtration on Sephadex G-100. bFSH was similar to its ovine counterpart with regard to its electrophoretic properties, molecular weight, and amino acid content. The apparent molecular weights of bFSH and its a- and ∧-subunits were 37,300, 12,600, and 18,500, respectively. bFSH contained high amounts of aspartic acid, threonine, glutamic acid, half-cystine, and lysine, but only low amounts of methionine, histidine, and tryptophan. bFSH differed from its obvine counterpart with regard to its carbohydrate content and biological properties. Although bFSH contained the same sugars as ovine FSH, it possessed twice as much galactosamine, but only 66% of the sialic acid. bFSH was only one third as potent biologically in the augmentation bioassay as the ovine hormone.
Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction (2016)

We present a scalable, integrated strategy for coupled protein and RNA detection from single cells. Our approach leverages the DNA polymerase activity of reverse transcriptase to simultaneously perform proximity extension assays and complementary DNA synthesis in the same reaction. Using the Fluidigm C1™ system, we profile the transcriptomic and proteomic response of a human breast adenocarcinoma cell line to a chemical perturbation, benchmarking against in situ hybridizations and immunofluorescence staining, as well as recombinant proteins, ERCC Spike-Ins, and population lysate dilutions. Through supervised and unsupervised analyses, we demonstrate synergies enabled by simultaneous measurement of single-cell protein and RNA abundances. Collectively, our generalizable approach highlights the potential for molecular metadata to inform highly-multiplexed single-cell analyses.
Hematopoietic Cell Growth Factors And Their Receptors (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Restricted antigenic variability of the epitope recognized by the neutralizing gp41 antibody 2F5 (1996)

Sequence analysis of a variety of primary isolates suggests that the major determinant of MAb 2F5 binding corresponds to the amino-acid sequence LDKW. Naturally occurring and in vitro selected neutralization-resistant viruses contained changes in the D and K positions of the ELDKWA motif.