gebhart/patrepeval huggingface dataset:
Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro (2004)

Endothelial progenitor cells (EPCs) play a role in the repair of ischemic or injured tissue. Because endothelial injury can be associated with apoptosis, we have investigated whether apoptotic bodies from mature endothelial cells (ECs) may affect growth and differentiation of EPCs in vitro. A 24-hour incubation of isolated human EPCs with apoptotic bodies-rich medium (ABRM) from ECs led to a significant increase in the number of spindle-shaped attached cells. EPCs were characterized by DiI-Ac-LDL/lectin staining and measurement of CD34 and kinase insert domain receptor (KDR) expression. The treatment with ABRM resulted in a 2-fold increase of DiI-Ac-LDL/lectin-positive cells and up-regulation of CD34 (22% +/- 2% versus 13% +/- 3%, P < .05 and KDR (49% +/- 12% versus 19% +/- 7%, P < .05). Fluorescence and confocal laser microscopy demonstrated the uptake of apoptotic bodies by the EPCs. Apoptotic bodies-depleted medium had no effect, whereas the incubation with suspension of apoptotic bodies induced effects similar to those of ABRM. Our results suggest that apoptotic bodies from ECs are taken up by EPCs, increasing their number and differentiation state. Such a mechanism may facilitate the repair of injured endothelium and may represent a new signaling pathway between progenitor and damaged somatic cells.
Conditional Mutations in the Mitotic Chromosome Binding Function of the Bovine Papillomavirus Type 1 E2 Protein (2005)

The papillomavirus E2 protein is required for viral transcriptional regulation, DNA replication and genome segregation. We have previously shown that the E2 transactivator protein and BPV1 genomes are associated with mitotic chromosomes; E2 links the genomes to cellular chromosomes to ensure efficient segregation to daughter nuclei. The transactivation domain of the E2 protein is necessary and sufficient for association of the E2 protein with mitotic chromosomes. To determine which residues of this 200-amino-acid domain are important for chromosomal interaction, E2 proteins with amino acid substitutions in each conserved residue of the transactivation domain were tested for their ability to associate with mitotic chromosomes. Chromatin binding was assessed by using immunofluorescence on both spread and directly fixed mitotic chromosomes. E2 proteins defective in the transactivation and replication functions were unable to associate with chromosomes, and those that were competent in these functions were attached to mitotic chromosomes. However, several mutated proteins that were defective for chromosomal interaction could associate with chromosomes after treatment with agents that promote protein folding or when cells were incubated at lower temperatures. These results indicate that precise folding of the E2 transactivation domain is crucial for its interaction with mitotic chromosomes and that this association can be modulated.
Handbook of Experimental Immunology. (1968)

There are now many medium sized rheu- matology books, but Drs Morrow and Isenberg have written a good rheumato- logical overview.They have gone along an immunological pathway, concentrating on the autoimmune aspects of rheumatic diseases.This fills a previous void.They have a deliberately restricted view, and focus predominantly on connective tissue diseases.After setting the immunological scene and outlining immunological methods they journey through the individual diseases.They start with systemic lupus erythematosus, and then progress through rheumatoid arthritis towards the overlap syndromes and systemic vasculitis.I do not consider rheumatoid arthritis or scleroderma as autoimmune diseases, and some of their opinions seem rather too immuno- logical, especially concerning the pathogenesis of connective tissue disorders.Nevertheless, this is an enjoyable and readable account of the rheumatic diseases.It is well illustrated with understandable and topical line drawings.Its tables give up to date summaries.I was also taken with the introductions to each disease showing the mile- stones in their history.
Hierarchical organization of certification authorities for secure environments (2002)

The paper presents a model of hierarchical organization of certification authorities which can be applied to any open system network. In order to study the feasibility of the proposed model, a pilot experiment within a university environment is being carried out. The authors have developed an application which provides the users with security services using X.509 certificates. The authors have also developed a security server to provide RSA keys and management of certificates. The hierarchical infrastructure that is being created needs a multi-level policy which implies the use of various types of documents which are managed by people with different roles. One of the objectives being followed is to formalize the treatment of the information about policy, for which some components of the extensions field of the version 3 certificate have been used and other new ones are proposed.
Regression Models in Clinical Studies: Determining Relationships Between Predictors and Response (1988)

Multiple regression models are increasingly being applied to clinical studies. Such models are powerful analytic tools that yield valid statistical inferences and make reliable predictions if various assumptions are satisfied. Two types of assumptions made by regression models concern the distribution of the response variable and the nature or shape of the relationship between the predictors and the response. This paper addresses the latter assumption by applying a direct and flexible approach, cubic spline functions, to two widely used models: the logistic regression model for binary responses and the Cox proportional hazards regression model for survival time data.
G-Protein β3 Subunit Gene ( GNB3 ) Variant in Causation of Essential Hypertension (1998)

-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.
NetPhosYeast: prediction of protein phosphorylation sites in yeast (2007)

The NetPhosYeast prediction service is available as a public web server at http://www.cbs.dtu.dk/services/NetPhosYeast/.
Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea (1997)

A new fungal immunomodulatory protein (Fip) has been purified from the edible mushroom, Volvariella volvacea, and designated Fip-vvo. Analysis of the purified protein by SDS/PAGE followed by Coomassie Blue staining demonstrated that Fip-vvo is a single polypeptide with an apparent molecular mass of 15 kDa. Periodic acid/Schiff staining showed that this single polypeptide lacks carbohydrates. Using an in vitro bioassay measuring blast-formation stimulatory activity, Fip-vvo was shown to stimulate the maximum proliferation of human peripheral blood lymphocytes at a concentration of 5 microg/ml. Fip-vvo was capable of agglutinating rat red blood cells. Neither haemagglutination nor mitogenic activities were inhibited by mono- or dimeric sugars. In vivo, repeat administration of Fip-vvo greatly reduced the production of BSA-induced Arthus reaction in mice, whereas little effect was observed on the prevention of systemic anaphylaxis reactions. The selectively enhanced transcriptional expression of interleukin (IL)-2, IL-4, interferon-gamma, tumour necrosis factor-alpha, lymphotoxin and IL-2 receptor by Fip-vvo was also demonstrated by reverse transcriptase-PCR. This finding suggests that Fip-vvo exerts its immunomodulatory effects via cytokine regulation. In addition, the complete amino acid sequence of Fip-vvo was obtained by direct protein sequencing. This protein consists of 112 amino acid residues with a blocked N-terminal end and has a calculated molecular mass of 12667 Da not including the N-terminal blocking group. By gel filtration analysis, Fip-vvo exhibited a molecular mass of 26 kDa for the native molecules in PBS. This result indicates that native Fip-vvo is most likely a non-covalently associated homodimeric molecule.
Nonredundant roles for Stat5a/b in directly regulating Foxp3 (2007)

Stats (signal transducers and activators of transcription) regulate multiple aspects of T-cell fate. T regulatory (Treg) cells are a critical subset that limits immune responses, but the relative importance of Stat5a/b versus Stat3 for Treg cell development has been contentious. We observed that peripheral CD25(+)CD4(+) T cells were reduced in Stat5(DeltaN) mice; however, the levels of Foxp3, a transcription factor that is critical for Treg cells, were normal in splenic CD4(+) T cells even though they were reduced in the thymus. In contrast, complete deletion of Stat5a/b (Stat5(-/-)) resulted in dramatic reduction in CD25- or Foxp3-expressing CD4(+) T cells. An intrinsic requirement was demonstrated by reduction of Stat5a/b in CD4-expressing cells and by stem cell transplantation using Stat5(-/-) fetal liver cells. Stat5a/b were also required for optimal induction of Foxp3 in vitro and bound directly to the Foxp3 gene. Reduction of Stat3 in T cells did not reduce the numbers of Treg cells in the thymus or spleen; however, Stat3 was required for IL-6-dependent down-regulation of Foxp3. Therefore, we conclude that Stat5a/b have an essential, nonredundant role in regulating Treg cells, and that Stat3 and Stat5a/b appear to have opposing roles in the regulation of Foxp3.
Cytological aspects of isolated microspore culture of Brassica napus (1988)

Preculture cytological events within anthers of two genotypes of Brassica napus were examined to detect differences between microspores that have embryogenic potential and those that do not. Microspores of five anthers per bud were cultured, while the sixth anther was fixed for cytological observation. A series of buds of increasing maturity were individually sampled from specific racemes. Correlations of bud, anther, microspore, and nuclear size were drawn to establish physical parameters for each cytological stage. Cytological events and cytophotometrically monitored DNA content were noted for spores of each anther size class. Best embryogenic responses were among populations of microspores in the late uninucleate stage, immediately prior to first pollen mitosis. Typical, rod-shaped, cotyledonous embryos could be generated within 30 days from microspores at this stage at a rate up to 1300/anther. Slightly younger or older microspores had a drastically reduced embryogenic performance. Postculture observations (within 6 h after culture) indicated that the embryogenic spores appeared spherically swollen, distinctly vacuolate, and with a clear cytoplasm.
Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm (1996)

To determine the distribution of nitric oxide synthase (NOS) in the primate cerebral artery nervi vasorum and to examine the potential role of NOS in cerebral vasospasm after subarachnoid hemorrhage (SAH) in primates, the distribution of NOS immunoreactivity (NOS-IR) in the major cerebral arteries was examined immunohistochemically in cynomolgus monkeys by the use of whole, mounted preparations of the circle of Willis. In four normal monkeys, NOS-IR was localized to the endothelial and adventitial layers of the large cerebral arteries. On the abluminal side, NOS-IR staining was densely concentrated in perivascular nerve fibers (nervi vasorum) of the anterior circulation. Staining was less prominent in the posterior circulation. In six monkeys with vasospasm on Day 7 after placement of preclotted arterial blood to form an SAH around the right middle cerebral artery (MCA) (42% +/- 8.3% decrease of MCA area, mean +/- standard deviation), NOS-IR was virtually absent in nerve fibers around the spastic right MCA but was normal on the contralateral side. In five monkeys in which vasospasm resolved by Day 14 after SAH (36% +/- 14% decrease of right MCA area on Day 7, and 5% +/- 14% decrease on Day 14), NOS-IR was also absent in the right MCA adventitial nerve fibers and remained normal in the left MCA. Adventitial NOS-IR was also normal in cerebral vessels of a sham-operated, nonspastic monkey. These findings provide further evidence that nitric oxide (NO) functions as a neuronal transmitter to mediate vasodilation in primates and indicate a role for adventitial NO in the pathogenesis of cerebral vasospasm after SAH in humans.
Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models. (2000)

Although insulin-like growth factor binding protein-5 (IGFBP-5) has been shown to be implicated in prostate cancer progression, the functional role of IGFBP-5 in progression to androgen-independence remains largely undefined. Here, we demonstrate substantial up-regulation of IGFBP-5 during castration-induced regression and androgen-independent (AI) progression in the mouse androgen-dependent (AD) Shionogi tumor model. To analyze the functional significance of these changes in IGFBP-5, human AD LNCaP prostate cancer cells were stably transfected with IGFBP-5 gene, and IGFBP-5-overexpressing LNCaP tumors progressed significantly faster to androgen independence after castration compared with controls. Antisense mouse IGFBP-5 oligodeoxynucleotides (ODNs) were then designed that reduced IGFBP-5 expression in Shionogi tumor cells in vitro in a dose-dependent and sequence-specific manner. Growth of Shionogi tumor cells was inhibited by antisense IGFBP-5 ODN treatment in a time- and dose-dependent manner, which could be reversed by exogenous IGF-I. However, antisense IGFBP-5 ODN treatment had no additive inhibitory effect on Shionogi tumor cell growth when IGF-I activity was neutralized by anti-IGF-I antibody. Antisense IGFBP-5 ODN treatment resulted in decreased mitogen-activated protein kinase activity and number of cells in the S + G2-M phases of the cell cycle that directly correlated with reduced proliferation rate of Shionogi tumor cells. Systemic administration of antisense IGFBP-5 ODN in mice bearing Shionogi tumors after castration significantly delayed time to progression to androgen independence and inhibited growth of AI recurrent tumors. These findings suggest that up-regulation of IGFBP-5 after castration serves to enhance IGF bioactivity and raise the possibility that the response of prostate cancer to androgen withdrawal can be enhanced by strategies, such as antisense IGFBP-5 ODN therapy, that target IGF signal transduction.
METABOLISM OF GLUCOSE AND REDUCTION OF RETINALDEHYDE IN RETINAL PHOTORECEPTORS1 (1970)

Abstract —The capacity of a variety of substrates to support reduction of retinaldehyde to retinol by preparations of outer segments from photoreceptor cells of bovine retina, the requirement for supplements, the effect of iodoacetate, and the stoichiometry of the metabolism of glucose and the reduction of retinaldehyde have been studied. Metabolism of glucose supported reduction of retinaldehyde by preparations of outer segments at approximately the rate observed for the intact retina. Throughout the physiological range of pH, the dehydrogenase reactions of the pentose cycle in outer segments provided virtually all of the reduced pyridine nucleotides that were utilized for reduction of retinaldehyde. It was concluded that reduction of retinaldehyde during light adaptation is exclusively dependent upon NADPH.
A molecular tool kit for the variable design of logic operations (NOR, INH, EnNOR) (2006)

A simple set of five components was used to design molecular logic gates based on phthalimide-sensitised Tb(III) luminescence, including the first report of an enabled NOR (EnNOR) gate.
Associons: A Program Notation with Tuples Instead of Variables (1981)

A program notation without variables is proposed. The state of a computation is recorded as a set of "associons." Each associon is a tuple of names representing a relation between the entities with those names. The state of the computation can be changed by the creation of new associons representing new relations deducible from those already recorded. The building block prescribing such deductions is called the "closure statement."
The core and carboxyl-terminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding (1994)

The integrase protein of human immunodeficiency virus type 1 removes two nucleotides from the 3' ends of reverse-transcribed human immunodeficiency virus type 1 DNA (3' processing) and covalently inserts the processed ends into a target DNA (DNA strand transfer). Mutant integrase proteins that lack the amino-and/or carboxyl-terminal domains are incapable of catalyzing 3' processing and DNA strand transfer but are competent for an apparent reversal of the DNA strand transfer reaction (disintegration) in vitro. Here, we investigate the binding of integrase to DNA by UV cross-linking. Cross-linked complexes form with a variety of DNA substrates independent of the presence of divalent metal ion. Analysis with amino- and carboxyl-terminal deletion mutant proteins shows that residues 213 to 266 of the 288-residue protein are required for efficient cross-linking in the absence of divalent metal ion. Carboxyl-terminal deletion mutants that lack this region efficiently cross-link only to the branched disintegration DNA substrate, and this reaction is dependent on the presence of metal ion. Both the core and C-terminal domains of integrase therefore contribute to nonspecific DNA binding.
A high-quality SOI structure fabricated by low-temperature technology with B+/H+co-implantation and plasma bonding (2006)

In order to decrease the heating temperature of Smart-Cut technology, plasma activation and B+/H+ co-implantation were used. B+/H+ co-implantation gave rise to a decrease of splitting temperature, and finally a high-quality silicon-on-insulator (SOI) structure was fabricated at 300 °C. A diluted Secco etching test indicated that the top Si surface defect density was 104–105 cm−2. An atomic force microscope (AFM) image showed that the surface roughness of the top Si layer was much smaller than that of the SOI structure formed from the H-only implanted wafer. The diluted Secco etching test also indicated that the top Si surface defect density would decrease with the increase of annealing temperature, and 500 °C was a critical temperature for reducing the defect density.
Complement components C1r/C1s, bone morphogenic protein 1 and Xenopus laevis developmentally regulated protein UVS.2 share common repeats (1991)

Property patterns were constructed, based on an alignment of related domains in human complement subcomponents C1r and C1s as well as in the sea urchin protein uEGF. This kind of consensus pattern was able to identify similar domains in a human bone morphogenic protein, in a Xenopus laevis embryonal protein involved in dorsoanterior development and in a calcium-dependent serine protease secreted from malignant hamster embryo fibroblast cells. Because of the high level of overall sequence homology this protease may be the hamsters' equivalent of the human complement subcomponent C1s. The resulting multiple alignment of all studied domains suggests functionally and structurally important regions.
Red Blood Cell Fatty Acid Patterns and Acute Coronary Syndrome (2009)

RBC-FA profiles contribute significantly to the discrimination of ACS cases, especially when combined with standard risk factors. The utility of FA patterns in risk prediction warrants further investigation.
Viral RNA Patterns and High Viral Load Reliably Define Oropharynx Carcinomas with Active HPV16 Involvement (2012)

Oropharyngeal squamous cell carcinomas (OPSCC) that are associated with human papilloma virus (HPV) infection carry a more favorable prognosis than those that are HPV-negative. However, it remains unclear which biomarker(s) can reliably determine which OPSCC specimens are truly driven by HPV infection. In this study, we analyzed 199 fresh-frozen OPSCC specimens for HPV DNA, viral load, RNA expression patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV-targeted tumor suppressor protein p16(INK4a) as markers for HPV infection. In this set of specimens, there was a 49% prevalence of DNA for the cancer-associated HPV type 16 (HPV(+)). However, there was only a 16% prevalence of high viral load and only a 20% prevalence of CxCaRNA(+), a marker of HPV16 carcinogenic activity. Among the CxCaRNA(+) tumors, 78% of the specimens exhibited overexpression of p16(INK4a), which also occurred in 14% of the HPV-negative tumors. Using a multivariate survival analysis with HPV negativity as the reference group, CxCaRNA(+) as a single marker conferred the lowest risk of death [HR = 0.28, 95% confidence interval (CI), 0.13-0.61] from oropharyngeal cancer, closely followed by high viral load (HR = 0.32, 95% CI, 0.14-0.73). In contrast, a weaker inverse association was found for OPSCC that were HPV(+) and p16(INK4a) high (HR = 0.55, 95% CI, 0.29-1.08). In summary, our findings argued that viral load or RNA pattern analysis is better suited than p16(INK4a) expression to identify HPV16-driven tumors in OPSCC patient populations.
Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy (2015)

Recent progress in tumor immunology has revealed that tumors generate immunologically restrained milieu during the process of their growth, which facilitates the escape of tumors from host immune systems. Immune checkpoint molecules, which transduce co-inhibitory signals to immuno-competent cells, are one of the most important components conferring the immunosuppressive capacity in the tumor microenvironment. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) are typical immune checkpoint molecules intimately involved in the suppression of anti-tumor immunity. Antibodies against those molecules have been developed, such as ipilimumab (anti-CTLA-4 antibody), nivolumab and pembrolizumab (anti-PD-1 antibody), and have been approved by regulatory agencies and used in some countries. Treatment with these antibodies demonstrates previously unobserved clinical efficacies superior to the conventional therapies. In this review, we first discuss the escape mechanisms of cancer from host immune systems, and then focus on the recent advances in immune checkpoint blockade therapy and on the new findings of related immune reactions, aiming to provide a better understanding of the novel cancer immunotherapies.