gebhart/patrepeval huggingface dataset:
Chromatin : a practical approach (1998)

1: Isolation and fractionation of chromatin and linker histones. 2: Extraction and separation of core histones and non-histone chromosomal proteins. 3: Mapping chromatin structure in Drosophila. 4: In vivo footprint and chromatin analysis by LMPCR. 5: Analysis of nuclear scaffold attachment regions. 6: Electron microscopy of chromatin. 7: Counting nucleosome cores on circular DNA using topoisomerase I. 8: In vitro reconstitution of chromatin and analysis of nucleosome positioning. 9: Transcriptional and structural analysis of chromatin assembled in vivo. 10: An assembly of chromatin and nuclear structures in Xenopus egg extracts. Appendix: List of Suppliers. Index
Ketamine as a new treatment for depression: A review of its efficacy and adverse effects (2013)

Current research on the antidepressant effects of ketamine has consistently shown rapid and substantial improvement in mood in the majority of patients. However, these effects have often been found to be short-lived. Future research should focus on identifying predictors of response (e.g. clinical, genetic, pharmacokinetic, environmental), examining different dosing regimens and routes of administration, and strategies to maintain the antidepressant response.
Contribution of Plasmid DNA to Inflammation in the Lung after Administration of Cationic Lipid:pDNA Complexes (1999)

Cationic lipid-mediated gene transfer to the mouse lung induces a dose-dependent inflammatory response that is characterized by an influx of leukocytes and elevated levels of the cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). We have examined the contribution of plasmid DNA (pDNA) to this observed toxicity, specifically the role of unmethylated CpG dinucleotides, which have been previously shown to be immunostimulatory. We report here that complexes of cationic lipid GL-67 and unmethylated pDNA (pCF1-CAT) instilled into the lungs of BALB/c mice induced highly elevated levels of the cytokines TNF-alpha, IFN-gamma, IL-6, and IL-12 in the bronchoalveolar lavage fluids (BALF). In contrast, BALF of animals administered either GL-67 alone or GL-67 complexed with SssI-methylated pDNA contained low levels of these cytokines. Similar results were observed using a plasmid (pCF1-null) that does not express a transgene, demonstrating that expression of chloramphenicol acetyltransferase (CAT) was not responsible for the observed inflammation. The response observed was dose dependent, with animals receiving increasingly higher amounts of unmethylated pDNA exhibiting progressively higher levels of the cytokines. Concomitant with this increase in cytokine levels were also elevated numbers of neutrophils in the BALF, suggesting a possible cause- and-effect relationship between neutrophil influx and generation of cytokines. Consistent with this proposal is the observation that reduction of neutrophils in the lung by administration of antibodies against Mac-1alpha and LFA-1 also diminished cytokine levels. This reduction in cytokine levels in the BALF was accompanied by an increase in transgene expression. In an attempt to abate the inflammatory response, sequences in the pDNA encoding the motif RRCGYY, shown to be most immunostimulatory, were selectively mutagenized. However, instillation of a plasmid in which 14 of the 17 CpG sites were altered into BALF/c mice did not reduce the levels of cytokines in the BALF compared with the unmodified vector. This suggests that other unmethylated motifs, in addition to RRCGYY, may also contribute to the inflammatory response. Together, these findings indicate that unmethylated CpG residues in pDNA are a major contributor to the induction of specific proinflammatory cytokines associated with instillation of cationic lipid:pDNA complexes into the lung. Strategies to abate this response are warranted to improve the efficacy of this nonviral gene delivery vector system for the treatment of chronic diseases.
Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis (2007)

Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD) and several other visual disorders, but the underlying mechanisms remain elusive. Recently, increased expression of monocyte chemoattractant protein 1 (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic retinopathy as well as in the brain tissues of patients with neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Here we report that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an experimental model of RD. RD led to increased MCP-1 expression in the Müller glia and increased CD11b+ macrophage/microglia in the detached retina. An MCP-1 blocking antibody greatly reduced macrophage/microglia infiltration and RD-induced photoreceptor apoptosis. Confirming these results, MCP-1 gene-deficient mice showed significantly reduced macrophage/microglia infiltration after RD and very little photoreceptor apoptosis. In primary retinal mixed cultures, MCP-1 was cytotoxic for recoverin+ photoreceptors, and this toxicity was eliminated through immunodepleting macrophage/microglia from the culture. In vivo, deletion of the gene encoding CD11b/CD18 nearly eliminated macrophage/microglia infiltration to the retina after RD and the loss of photoreceptors. Thus, MCP-1 expression and subsequent macrophage/microglia infiltration and activation are critical for RD-induced photoreceptor apoptosis. This pathway may be an important therapeutic target for preventing photoreceptor apoptosis in RD and other CNS diseases that share a common etiology.
Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy (2003)

Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic beta cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (Vmax) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.
Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases (2012)

Vascular endothelial growth factors (VEGFs) belong to the platelet-derived growth factor supergene family, and they play central roles in the regulation of angiogenesis and lymphangiogenesis. VEGF-A, the major factor for angiogenesis, binds to two tyrosine kinase (TK) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and regulates endothelial cell proliferation, migration, vascular permeability, secretion and other endothelial functions. VEGFR-2 exhibits a strong TK activity towards pro-angiogenic signals, whereas the soluble VEGFR-1 (sFlt-1) functions as an endogenous VEGF inhibitor. sFlt-1 is abnormally overexpressed in the placenta of preeclampsia patients, resulting in the major symptoms of the disease due to abnormal trapping of VEGFs. The VEGF-VEGFR system is crucial for tumour angiogenesis, and anti-VEGF-VEGFR molecules are now widely used in the clinical field to treat cancer patients. The efficacy of these molecules in prolonging the overall survival of patients has been established; however, some cancers do not respond well and reduced tumour sensitivity to anti-VEGF signals may occur after long-term treatment. The molecular basis of tumour refractoriness should be determined to improve anti-angiogenic therapy.
Disposition of a 14C-labeled bioerodible polyorthoester and its hydrolysis products, 4-hydroxybutyrate and cis,trans-1,4-bis(hydroxymethyl)cyclohexane, in rats. (1985)

Disposition of the 14C-labeled bioerodible polymer poly(2,2-dioxy-cis,trans-1,4-cyclohexane dimethylene tetrahydrofuran) (ALZAMER C101ct) and its ultimate hydrolysis products, 4-hydroxybutyrate (4HB) and cis,trans-1,4-bis(hydroxymethyl)cyclohexane (CHDM), was assessed in vivo in rats 24 hr after sc administration of the 14C-labeled polymer or hydrolysis products. The hydrolysis products were rapidly metabolized and eliminated, whether administered directly or via in vivo erosion of the polymer. At 24 hr, fractional distribution of carbon-14 derived from 4HB was 65 to 75% in expired CO2, 5 to 10% in urine, 1 to 2% in feces, and 15 to 19% in tissues. For CHDM, distribution was 92 to 96% in urine, 2 to 3% in feces, and 0.3 to 3% in tissues. Hydrolysis products or metabolites were not sequestered in specific tissues. Pretreatment with unlabeled polymer for 28 days had little effect on the disposition of carbon-14. Minor differences in disposition between the polymer and its hydrolysis products are discussed.
The NB Protein of Influenza B Virus Is Not Necessary for Virus Replication In Vitro (2003)

The NB protein of influenza B virus is thought to function as an ion channel and therefore would be expected to have an essential function in viral replication. Because direct evidence for its absolute requirement in the viral life cycle is lacking, we generated NB knockout viruses by reverse genetics and tested their growth properties both in vitro and in vivo. Mutants not expressing NB replicated as efficiently as the wild-type virus in cell culture, whereas in mice they showed restricted growth compared with findings for the wild-type virus. Thus, the NB protein is not essential for influenza B virus replication in cell culture but promotes efficient growth in mice.
Mixed-Element Capture Agents:  A Simple Strategy for the Construction of Synthetic, High-Affinity Protein Capture Ligands (2003)

Demonstration of a simple strategy to generate synthetic high-affinity protein capture agents of practical utility for protein-detecting microarrays. The model study highlights capture of the MBP-Mdm2 fusion protein on a solid support by a linear sequence of peptides that bind to the two individual polypeptide chains.
Immunological and functional characterization of proteins of the Mycobacterium tuberculosis antigen 85 complex using synthetic peptides (1993)

As tuberculosis re-emerges as an important health problem worldwide, new drugs, better diagnostic tests and vaccines are being sought. In order to identify potentially useful peptides for the development of a synthetic vaccine against tuberculosis, immunological and functional studies were performed using proteins of the antigen 85 complex. Western blot (immuno-blot) analysis and a lymphoproliferation study was used to investigate the B- and T-cell immune response of tuberculosis patients, healthy household contacts and normal controls to proteins of the Mycobacterium tuberculosis antigen 85 complex. Peptides derived from the 85A amino acid sequence were synthesized and used in fibronectin-binding and in ELISA assays. A peptide with the sequence CQPACRKAGCQTYKWEC bound to radiolabelled fibronectin in a time-dependent manner and was recognized by human sera in ELISA. This peptide was identified as a potential component of a synthetic vaccine against tuberculosis.
The Role of ABC Transporters in Drug Resistance, Metabolism and Toxicity (2004)

ATP Binding Cassette (ABC) transporters form a special family of membrane proteins, characterized by homologous ATP-binding, and large, multispanning transmembrane domains. Several members of this family are primary active transporters, which significantly modulate the absorption, metabolism, cellular effectivity and toxicity of pharmacological agents. This review provides a general overview of the human ABC transporters, their expression, localization and basic mechanism of action. Then we shortly deal with the human ABC transporters as targets of therapeutic interventions in medicine, including cancer drug resistance, lipid and other metabolic disorders, and even gene therapy applications. We place a special emphasis on the three major groups of ABC transporters involved in cancer multidrug resistance (MDR). These are the classical P-glycoprotein (MDR1, ABCB1), the multidrug resistance associated proteins (MRPs, in the ABCC subfamily), and the ABCG2 protein, an ABC half-transporter. All these proteins catalyze an ATP-dependent active transport of chemically unrelated compounds, including anticancer drugs. MDR1 (P-glycoprotein) and ABCG2 preferentially extrude large hydrophobic, positively charged molecules, while the members of the MRP family can extrude both hydrophobic uncharged molecules and water-soluble anionic compounds. Based on the physiological expression and role of these transporters, we provide examples for their role in Absorption-Distribution-Metabolism-Excretion (ADME) and toxicology, and describe several basic assays which can be applied for screening drug interactions with ABC transporters in the course of drug research and development.
Molecular cloning of a murine N-acetylgalactosamine transferase cDNA that determines expression of the T lymphocyte-specific CT oligosaccharide differentiation antigen. (1994)

Two monoclonal antibodies termed CT1 and CT2 define a cell surface oligosaccharide molecule expressed on restricted populations of murine lymphocytes. This oligosaccharide structure is largely associated with the extracellular domain of the CD45 family of tyrosine phosphatases, molecules required for lymphocytes to proliferate in response to antigen stimulation. Previous work has shown that the oligosaccharide structure recognized by the CT antibodies is identical, at least in part, to that of the human Sda blood group, a structure formed through enzymatic addition of N-acetylgalactosamine in beta 1,4-linkage to a sub-terminal galactose substituted with an alpha 2,3-linked N-acetylneuraminic acid residue. We have used a mammalian transient expression cloning approach to isolate a murine cDNA that determines expression of an oligosaccharide structure recognized by the CT antibodies as well as human anti-Sda serum. The nucleotide sequence predicts a 510-amino acid type II transmembrane protein characteristic of other mammalian glycosyltransferases. Enzymatic characterization of the protein expressed by this cDNA demonstrates that it encodes a beta 1,4-N-acetylgalactosamine transferase activity that can add to the low molecular weight acceptor 3'-sialyl-N-acetyllactosamine, to form the nonreducing terminal tetrasaccharide Sda blood group structure. This cDNA shares 51% nucleotide sequence identity with a cDNA encoding the human GM2/GD2 synthase, particularly throughout the regions encoding their putative catalytic domains. Southern blot analysis demonstrates that these two cDNA's represent distinct loci in the murine genome. The CT-GalNAc transferase cDNA isolated here represents a tool with which to define the role(s) of lymphocyte cell surface CT determinants, and may facilitate the isolation of the human Sda blood group locus through cross-hybridization approaches.
Real-time detection of airborne viruses on a mass-sensitive device (2008)

We present real-time detection of airborne Vaccinia viruses using quartz crystal microbalance (QCM) in an integrated manner. Vaccinia viruses were aerosolized and neutralized using an electrospray aerosol generator, transported into the QCM chamber, and captured by a QCM crystal. The capture of the viruses on the QCM crystal resulted in frequency shifts proportional to the number of viruses. The capture rate varied linearly with the concentration of initial virus suspensions (8.5x10(8)-8.5x10(10) particlesml) at flow rates of 2.0 and 1.1 lmin. This work demonstrates the general potential of mass sensitive detection of nanoscale biological entities in air.
Anti-Oxidant, Anti-Inflammatory and Anti-Allergic Activities of Luteolin (2008)

Luteolin is a flavone which occurs in medicinal plants as well as in some vegetables and spices. It is a natural anti-oxidant with less pro-oxidant potential than the flavonol quercetin, the best studied flavonoid, but apparently with a better safety profile. It displays excellent radical scavenging and cytoprotective properties, especially when tested in complex biological systems where it can interact with other anti-oxidants like vitamins. Luteolin displays specific anti-inflammatory effects at micromolar concentrations which are only partly explained by its anti-oxidant capacities. The anti-inflammatory activity includes activation of anti-oxidative enzymes, suppression of the NFkappaB pathway and inhibition of pro-inflammatory substances. In vivo, luteolin reduced increased vascular permeability and was effective in animal models of inflammation after parenteral and oral application. Although luteolin is only a minor component in our nutrition (less than 1 mg/day) epidemiological studies indicate that it has the potential to protect from diseases associated with inflammatory processes such as cardiovascular disease. Luteolin often occurs in the form of glycosides in plants, but these are cleaved and the aglycones are conjugated and metabolized after nutritional uptake which has to be considered when evaluating in vitro studies. Some data for oral and topical bioavailability exist, but more quantitative research in this field is needed to evaluate the physiological and therapeutical potential of luteolin.
V-edge: fast self-constructive power modeling of smartphones based on battery voltage dynamics (2013)

System power models are important for power management and optimization on smartphones. However, existing approaches for power modeling have several limitations. Some require external power meters, which is not convenient for people to use. Other approaches either rely on the battery current sensing capability, which is not available on many smartphones, or take a long time to generate the power model. To overcome these limitations, we propose a new way of generating power models from battery voltage dynamics, called V-edge. V-edge is selfconstructive and does not require current-sensing. Most importantly, it is fast in model building. Our implementation supports both component level power models and per-application energy accounting. Evaluation results using various benchmarks and applications show that the V-edge approach achieves high power modeling accuracy, and is two orders of magnitude faster than existing selfmodeling approaches requiring no current-sensing. 1
Antiandrogenic properties of nomegestrol acetate. (1995)

Nomegestrol acetate (NOM-Ac; TX 066, 17 alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione, CAS 58652-20-3), a 19-nor-progesterone derivative showed a significant antiandrogenic effect on ventral prostate and seminal vesicles weights of immature castrated rats treated with testosterone. However, this effect was 20 times less potent than that of cyproterone acetate (CYP-Ac). In contrast to norethindrone acetate, a 19-nor-testosterone derivative. NOM-Ac was totally devoid of androgenic effect on male accessory sex organs. Relative binding affinity against 3H-testosterone for androgen receptor of rat ventral prostate showed an IC50 of 22.6 +/- 4.0 and 21.1 +/- 5.3 nmol/l for NOM-Ac and CYP-Ac, respectively, while Dixon analysis disclosed a Ki of 7.58 +/- 0.94 and 4.30 +/- 0.17 nmol/l. Then, Scatchard plot analysis of 3H-NOM-Ac binding revealed a KD of 20.9 +/- 3.1 nmol/l and a Bmax of 217 +/- 27 fmol/mg protein.
ChemInform Abstract: Synthesis of Isoxazolo(2,3‐a)quinoxalines and Pyrrolo(1,2‐a)quinoxalines by 1,3‐Dipolar Cycloaddition Reaction. (1990)

Abstract Depending on the conditions the title reaction of the N‐oxide (I) with the ester (II) yields the fused isoxazoles (III) or the fused pyrroles (IV).
Financial difficulties, smoking habits, composition of the diet and birthweight in a population of pregnant women in the South West of England. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. (1998)

The quality of diet in pregnancy falls with increasing difficulty in affording food. However, this does not appear to affect mean birthweight of infants born after 32 weeks gestation.
Cyclic Electron Flow around Photosystem I in C3 Plants. In Vivo Control by the Redox State of Chloroplasts and Involvement of the NADH-Dehydrogenase Complex (2002)

Cyclic electron flow around photosystem (PS) I has been widely described in vitro in chloroplasts or thylakoids isolated from C 3 plant leaves, but its occurrence in vivo is still a matter of debate. Photoacoustic spectroscopy and kinetic spectrophotometry were used to analyze cyclic PS I activity in tobacco (Nicotiana tabacum cv Petit Havana) leaf discs illuminated with far-red light. Only a very weak activity was measured in air with both techniques. When leaf discs were placed in anaerobiosis, a high and rapid cyclic PS I activity was measured. The maximal energy storage in far-red light increased to 30% to 50%, and the half-time of the P 700 re-reduction in the dark decreased to around 400 ms; these values are comparable with those measured in cyanobacteria and C 4 plant leaves in aerobiosis. The stimulatory effect of anaerobiosis was mimicked by infiltrating leaves with inhibitors of mitochondrial respiration or of the chlororespiratory oxidase, therefore, showing that changes in the redox state of intersystem electron carriers tightly control the rate of PS I-driven cyclic electron flow in vivo. Measurements of energy storage at different modulation frequencies of far-red light showed that anaerobiosis-induced cyclic PS I activity in leaves of a tobacco mutant deficient in the plastid Ndh complex was kinetically different from that of the wild type, the cycle being slower in the former leaves. We conclude that the Ndh complex is required for rapid electron cycling around PS I.
Detection of a variable number of 18S-5.8S-26S and 5S ribosomal DNA loci by fluorescent in situ hybridization in diploid and tetraploid Arachis species (1999)

In order to obtain new information on the genome organization of Arachis ribosomal DNA, more particularly among A. hypogaea and its close relatives, the distribution of the 18S-5.8S-26S and 5S ribosomal RNA gene families on the chromosomes of 21 diploid and tetraploid Arachis species, selected from six of nine taxonomic sections, was analyzed by in situ hybridization with pTa71 (18S-5.8S-26S rDNA) and pTa794 (5S rDNA) clones. Two major 18S-5.8S-26S rDNA loci with intense signals were found in the nucleolus organizer regions (NOR) of each of the diploid and tetraploid species. In addition to extended signals at major NORs, two to six medium and (or) minute-sized signals were also observed. Variability in the number, size, and location of 18S-5.8S-26S sites could generally distinguish species within the same genome as well as between species with different genomes. The use of double fluorescence in situ hybridization enabled us to locate the positions of 5S rRNA genes in relation to the chromosomal location of 18S-5.8S-26S rRNA genes in Arachis chromosomes which were difficult to karyotype. Two or four 5S rDNA loci and 18S-5.8S-26S rDNA loci were generally located on different chromosomes. The tandemly repeated 5S rDNA sites were diagnostic for T and C genomes. In one species, each of B and Am genomes, the two ribosomal gene families were observed to occur at the same locus. Barring A. ipaensis and A. valida, all the diploid species had characteristic centromeric bands in all the 20 chromosomes. In tetraploid species A. hypogaea and A. monticola only 20 out of 40 chromosomes showed centromeric bands. Comparative studies of distribution of the two ribosomal gene families, and occurrence of centromeric bands in only 20 chromosomes of the tetraploid species suggests that A. villosa and A. ipaensis are the diploid progenitors of A. hypogaea and A. monticola. This study excludes A. batizocoi as the B genome donor species for A. hypogaea and A. monticola.Key words: Arachis species, 5S rRNA, 18S-5.8S-26S rRNA, in situ hybridization, evolution.