gebhart/patrepeval huggingface dataset:
Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus Transcription through Phosphorylation of CDK9 at Threonine 29 (2008)

Positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 (CDK9) and cyclin T, is a global transcription factor for eukaryotic gene expression, as well as a key factor for human immunodeficiency virus (HIV) transcription elongation. P-TEFb phosphorylates the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II), facilitating the transition from nonprocessive to processive transcription elongation. Recently, the bromodomain protein Brd4 has been shown to interact with the low-molecular-weight, active P-TEFb complex and recruit P-TEFb to the HIV type 1 long terminal repeat (LTR) promoter. However, the subsequent events through which Brd4 regulates CDK9 kinase activity and RNAP II-dependent transcription are not clearly understood. Here we provide evidence that Brd4 regulates P-TEFb kinase activity by inducing a negative pathway. Moreover, by analyzing stepwise initiation and elongation complexes, we demonstrate that P-TEFb activity is regulated in the transcription complex. Brd4 induces phosphorylation of CDK9 at threonine 29 (T29) in the HIV transcription initiation complex, inhibiting CDK9 kinase activity. P-TEFb inhibition is transient, as Brd4 is released from the transcription complex between positions +14 and +36. Removal of the phosphate group at T29 by an incoming phosphatase released P-TEFb activity, resulting in increased RNAP II CTD phosphorylation and transcription. Finally, we present chromatin immunoprecipitation studies showing that CDK9 with phosphorylated T29 is associated with the HIV promoter region in the integrated and transcriptionally silent HIV genome.
Relation between systemic hypertension and sleep hypoxaemia or snoring: analysis in 748 men drawn from general practice. (1990)

It is unlikely that snoring and sleep hypoxaemia from occult sleep apnoea are important causes of diurnal systemic hypertension when compared with age, obesity, and alcohol consumption. The increased prevalence of cardiovascular complications reported in snorers may be due to the confounding variable of obesity or to nocturnal rises in blood pressure that are not reflected in the daytime figures.
Suppression of immunological response against a novel gene product delivered by implants of genetically modified fibroblasts. (1990)

We have recently demonstrated the feasibility of genetically modifying autologous primary rat fibroblasts to deliver in vivo a foreign gene product, human growth hormone. However, in this model for gene replacement therapy, all recipient animals developed extremely high titres of antibodies against human growth hormone within two weeks of grafting. We now report on two approaches to suppress this immune-response. First, rats implanted with human growth hormone-secreting rat fibroblasts were treated with an immunosuppressant, cyclosporine A, at 20 mg/kg body weight per day. The production of anti-human growth hormone antibodies in the treated animals was completely blocked during the 12-week course of treatment. Secondly, by using immunologically immature neonatal rats as recipients, the rapid antibody response to the human growth hormone was also avoided. However, after a delay of one month, these rats also developed an extremely high titre of antibodies against the human growth hormone. In comparison, rats in the adolescent, mature and aged groups developed and maintained high titres of antibodies soon after implantation. Therefore, antigenic response against novel gene products can be suppressed either totally by cyclosporine A or temporarily in neonatal animals. The combination of early implantation and subsequent immuno-suppression should be considered in somatic gene therapy for those patients who are negative for cross-reacting-material and may be expected to mount an antigenic response to the replacement gene product.
Study of the Michael Addition of β‐Cyclodextrin—Thiol Complexes to Conjugated Alkenes in Water. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells (2020)

Regulatory T cells (Tregs) are critical mediators of immune homeostasis. The co-stimulatory molecule CD27 is a marker of highly suppressive Tregs, although the role of the CD27-CD70 receptor-ligand interaction in Tregs is not clear. Here we show that after prolonged in vitro stimulation, a significant proportion of human Tregs gain stable CD70 expression while losing CD27. The expression of CD70 in expanded Tregs is associated with a profound loss of regulatory function and an unusual ability to provide CD70-directed co-stimulation to TCR-activated conventional T cells. Genetic deletion of CD70 or its blockade prevents Tregs from delivering this co-stimulatory signal, thus maintaining their regulatory activity. High resolution targeted single-cell RNA sequencing of human peripheral blood confirms the presence of CD27<sup>-</sup>CD70<sup>+</sup> Treg cells. These findings have important implications for Treg-based clinical studies where cells are expanded over extended periods in order to achieve sufficient treatment doses.
Short-Chain Carbohydrates and Functional Gastrointestinal Disorders (2013)

Carbohydrates occur across a range of foods regularly consumed including grains such as wheat and rye, vegetables, fruits, and legumes. Short-chain carbohydrates with chains of up to 10 sugars vary in their digestibility and subsequent absorption. Those that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These two effects alone may underlie most of the induction of gastrointestinal symptoms after they are ingested in moderate amounts via luminal distension in patients with visceral hypersensitivity. This has been the basis of the use of lactose-free diets in those with lactose malabsorption and of fructose-reduced diets for fructose malabsorption. However, application of such dietary approaches in patients with functional bowel disorders has been restricted to observational studies with uncertain efficacy. As all dietary poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. In patients with irritable bowel syndrome, there is now an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders, and that a diet low in FODMAPs offers considerable symptom relief in the majority of patients who use it.
Morphological Changes Induced in Mouse Mammary Gland by Porcine and Human Relaxin (1984)

The effects of pure porcine relaxin and of human decidual extracts with relaxin-like activity on the mammary gland of virgin mice primed with estrogen have been studied by the light microscope. Porcine relaxin enhanced the changes induced by estrogen alone; the effect was different in the various mammary tissues. In the stroma, relaxin only slightly increased the loosening of connective tissue, the extent of the adipose tissue and of the capillary bed, as well as the degranulation of the mast cells. The changes in the parenchyma, such as elongation and branching of ducts, are strikingly enhanced. Moreover, relaxin seems to promote differentiation of the cells forming the walls of distal ducts, and of the myoepithelial cells. Tissue extracts of human decidua with relaxin-like activity induce changes in the mammary gland similar to those due to porcine relaxin. Such data indicate that relaxin synergizes with estrogen to cause growth of ducts of the mammary gland and that tissue extracts of human decidua have a similar effect, thus providing further evidence that decidua may be a source of relaxin in humans.
Raman microprobe and microscope with laser excitation (1975)

Abstract New devices, have been developed to generate maps or images of heterogeneous samples using a characteristic Raman frequency line and to obtain the surface distribution of a given compound. Samples are illuminated by a laser beam causing Raman lines of the different substances to be emitted. Different techniques using a triple monochromator or a holographic grating system are described. Several examples of Raman images of heterogeneous samples are presented.
Labdane Diterpenes from the Aerial Parts of Curcuma comosa Enhance Fetal Hemoglobin Production in an Erythroid Cell Line (2010)

Three new labdane diterpenes, curcucomosins A-C (1-3), four known labdane diterpenes, 4-7, and a known diarylheptanoid, 8, were isolated from the aerial parts of Curcuma comosa. The structures of the new diterpenes were elucidated by spectroscopic data analysis. The fetal hemoglobin (Hb F) induction potency of the isolated compounds was examined using a K562 reporter cell line harboring the enhanced green fluorescence protein (EGFP) gene under the control of a (G)gamma-globin promoter. Compound 6, isocoronarin D, exhibited the highest Hb F induction effect of 1.6-fold at 20 microM.
Spatio–Temporal Memories for Machine Learning: A Long-Term Memory Organization (2009)

Design of artificial neural structures capable of reliable and flexible long-term spatio-temporal memory is of paramount importance in machine intelligence. To this end, we propose a novel, biologically inspired, long-term memory (LTM) architecture. We intend to use it as a building block of a neuron-level architecture that is able to mimic natural intelligence through learning, anticipation, and goal-driven behavior. A mutual input enhancement and blocking structure is proposed, and its operation is discussed in detail. The paper focuses on a hierarchical memory organization, storage, recognition, and recall mechanisms. Simulation results of the proposed memory show its effectiveness, adaptability, and robustness. Accuracy of the proposed method is compared to other methods including Levenshtein distance method and a Markov chain.
Cytomegalovirus: development and progression of cytopathic effects in human cell culture. (1980)

Cytopathic effects of cytomegalovirus infection were studied in human cell cultures at various time intervals. Cells derived from human embryonic thyroid, skin-muscle, and lung were infected with five different strains of cytomegalovirus at multiplicities of infection of approximately 5 plaque forming units per cell. Under these conditions, cell rounding and early cytoplasmic inclusions were first apparent at 5 hours postinfection, whereas nuclear inclusions were first observed as a homogenous eosinophilic bead at 24 hours postinfection. Cytoplasmic and nuclear inclusions underwent extensive morphogenesis through 96 to 120 hours postinfection. Development of nuclear inclusions included the formation of distinctive beadlike subunits, which increased in size from their first appearance at 48 to 72 hours postinfection and underwent apparent contraction and breakup after 96 hours postinfection. While the cytopathology induced by various cytomegalovirus strains studied was generally similar, the kinetics of their development was different and independent of both the multiplicities of infection and the source of the fibroblastic cells. Such cytomegalovirus strain-associated differences in cytopathology could result from variances in biologic characteristics of the strains studied.
Cd40–Cd40 Ligand Interactions in Vivo Regulate Migration of Antigen-Bearing Dendritic Cells from the Skin to Draining Lymph Nodes (1999)

Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand -/- mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand -/- mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-alpha production and was corrected by injecting recombinant TNF-alpha or an agonistic anti-CD40 monoclonal antibody. Thus, CD40-CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-alpha production and play a vital role in the initiation of acquired T cell-mediated immunity.
Transformation of follicular lymphoma to diffuse large B-cell lymphoma may occur by divergent evolution from a common progenitor cell or by direct evolution from the follicular lymphoma clone (2009)

To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node. On the basis of the father/son model, this CPC must be long-lived, providing a possible explanation for the incurable nature of this disease.
Locally Controlled Release of Basic Fibroblast Growth Factor from Multilayered Capsules (2008)

Biodegradable multilayered capsules encapsulating basic fibroblast growth factor (bFGF) were developed as a cytokine release carrier for drug delivery systems. The multilayered hollow capsules were fabricated via the layer-by-layer (LbL) assembly of chitosan (CT) and dextran sulfate (Dex). The bFGF was encapsulated into the CT/Dex multilayered capsules by controlling the membrane permeability, and the local and sustained release of bFGF from the capsules was examined. At pH < 8.0, the capsule membrane tightened, and FITC-dextran ( Mw = 4000) could not enter the capsules. However, FITC-dextran ( M w = 250000) easily entered the capsules at pH > 8.0, which can be attributed to the electrostatic repulsion of Dex caused by the deprotonation of the amine group in CT. After treatment with acetic acid buffer (pH 5.6), FITC-dextran or bFGF was successfully encapsulated into the capsules. The amount of encapsulated bFGF was approximately 34 microg/1 mg of capsule. Initially, about 30% of the encapsulated bFGF was released in serum-free medium within a few hours, however, the release was sustained over 70 h. When the bFGF encapsulating capsules were added to cell culture medium (serum-free), the mouse L929 fibroblast cells proliferated well for 2 weeks as compared to cultures, where bFGF was added to the medium or where bFGF and empty hollow capsules were added separately. The proliferation is due to the local and sustained release of bFGF from the adsorbent capsule to the cell surface.
Patch Control Mechanism for Large Scale Software (1995)

Applying patches to large scale software is often difficult because unofficial patches and user modifications conflict with any ‘‘official’ ’ patches. Version control systems such as RCS[1], CVS[2], and configuration management[3,4,5] are useful solutions for this problem when the baseline of the software is fixed. However, an official patch that is developed externally changes the baseline and any local changes based on this become obsolete. Thus we must re-apply various unofficial patches and modifications, identify the causes of conflict, change or remove patches, and repeat the patch and unpatch operations. This paper presents a mechanism for (1) managing versions of a software package based on patches, (2) automating the application of unofficial patches and modifications by the user, and (3) rebuilding the package using file versions instead of timestamps. Using this mechanism, it becomes easy to apply patches and re-build software.
Efficient organic light-emitting diodes with phosphorescent platinum complexes containing N∧C∧N-coordinating tridentate ligand (2005)

We describe the phosphorescent characteristics of two platinum complexes containing an N∧C∧N-coordinating tridentate ligand: platinum(II) 3,5-di(2-pyridyl)toluene chloride [Pt(dpt)Cl] and a newly synthesized platinum(II) 3,5-di(2-pyridyl)toluene phenoxide [Pt(dpt)(oph)], together with the performance of organic light-emitting diodes (OLEDs) prepared with these complexes as phosphors. Films containing each one of the complexes in a 4,4’-N,N’-dicalbazolylbiphenyl (CBP) host showed highly efficient photoluminescence. The fabricated OLEDs exhibited high efficiencies; the maximum external quantum efficiency of the device with Pt(dpt)(oph) phosphor after correction of angular dependence of emission was found to be 16.5%. The luminance half decay time of the Pt(dpt)(oph) device under a constant-current operation was considerably longer than that of the Pt(dpt)Cl device.
Preparation of a Stable Intravenous Gamma‐Globulin: Process Design and Scale‐Up (1980)

Intravenous gamma-globulin has been prepared on a pilot scale by the process of reduction with dithiothreitol and alkylation with iodoacetamide. The spent reagents are removed by diafiltration followed by ultrafiltration. The product is stabilized with maltose to minimize precipitation. Process design concepts as well as product characteristics are discussed.
Efficient random mutagenesis method with adjustable mutation frequency by use of PCR and dITP (1993)

Journal Article Efficient random mutagenesis method with adjustable mutation frequency by use of PCR and dITP Get access Johan H. Spee, Johan H. Spee Molecular Genetics Group of the Department of Biophysical Chemistry, Netherlands Institute for Dairy Research (NIZO)PO Box 20, 6710 BA Ede, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Willem M. de Vos, Willem M. de Vos Molecular Genetics Group of the Department of Biophysical Chemistry, Netherlands Institute for Dairy Research (NIZO)PO Box 20, 6710 BA Ede, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Oscar P Kuipers Oscar P Kuipers * Molecular Genetics Group of the Department of Biophysical Chemistry, Netherlands Institute for Dairy Research (NIZO)PO Box 20, 6710 BA Ede, The Netherlands * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 3, 11 February 1993, Pages 777–778, https://doi.org/10.1093/nar/21.3.777 Published: 11 February 1993 Article history Received: 28 October 1992 Revision received: 22 December 1992 Accepted: 22 December 1992 Published: 11 February 1993
Molecular characterization of human TRPM‐2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration (1994)

The TRPM-2/clusterin gene and its cognate protein has been characterized in a number of species. Although the functional role, or roles, of the TRPM-2/clusterin protein remains to be firmly established, the gene has been implicated in a variety of physiological processes, including sperm maturation, lipid transport, membrane remodelling and inhibition of the complement cascade. TRPM-2/clusterin is induced de novo during the regression of the prostate and other hormone-dependent tissues after hormone ablation, and is over-expressed in several human neurodegenerative diseases including Alzheimer's disease, epilepsy and retinitis pigmentosa. We describe the genomic structure of the human TRPM-2/clusterin gene which is organized into nine exons, ranging in size from 47 bp (exon I) to 412 bp (exon V), spanning a region of 16,580 bp. Comparison with sequences registered in the databases shows that it has extensive similarity to the human protein designated as SP-40,40 or complement-lysis inhibitor (CLI), a protein that appears to block the membrane-attack complex of complement. However, the cDNA sequences reported for SP-40,40 and CLI diverge significantly in the 5' untranslated region of the mRNA (coded for by exon I), raising the possibility that the TRPM-2/clusterin gene is present in the human genome as a small multi-gene family or that there are several alternate exon I sequences in the TRPM-2 gene. Southern analysis and fluorescent in situ hybridization suggest that the clusterin gene is a single-copy gene, and that, if alternative exon I sequences are present in the genome, they lie outside of the lambda clones that have been characterized. Analysis of the promoter region of the human TRPM-2/clusterin gene shows many similarities to the rat TRPM-2/clusterin promoter including a putative control region containing several potential regulatory elements that may regulate the complex tissue-specific control of the gene which must be constitutively expressed in some tissues but is inducible in others.
Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy (1995)

We have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of > 4 cm. Results at 807 nm show a DPF of 4.16(+/- 18.8%) for adult arm, 5.51(+/- 18%) for adult leg, 6.26(+/- 14.1%) for adult head and 4.99(+/- 9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.
A novel AβPP mutation exclusively associated with cerebral amyloid angiopathy (2005)

Mutations in AbetaPP cause deposition of Abeta amyloid fibrils in brain parenchyma and cerebral vessels, resulting in Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA). We report a novel mutation (L705V) within the Abeta sequence of AbetaPP in a family with autosomal dominant, recurrent intracerebral hemorrhages. Pathological examination disclosed severe CAA, without parenchymal amyloid plaques or neurofibrillary tangles. This variant highlights the vascular tropism of mutated Abeta, resulting in CAA instead of the pathological hallmarks of AD.