gebhart/patrepeval huggingface dataset:
Ionizing irradiation increases transcription of the von Willebrand factor gene in endothelial cells (1996)

Ionizing irradiation damage to the vasculature results in an increase in procoagulant activity of endothelial cells, including elevated von Willebrand factor (vWf) secretion. We investigated the mechanism of irradiation induction of vWf release and demonstrated that vWf mRNA levels were increased when either human or bovine endothelial cells were exposed to 20 Gy irradiation. This response to irradiation was independent to de novo protein synthesis, but required new transcription. Nuclear run-on experiments indicated that increased vWf transcriptional activity was partly responsible for the higher levels of the mRNA accumulation. Transfection analyses with plasmids in which a human growth hormone structural gene was under the control of the endothelial-cell-specific vWf promoter demonstrated that irradiation increased promoter activity. Deletion analyses demonstrated that sequences necessary for irradiation induction of the promoter activity were located within the 112-bp sequences (-90 to +22) that constitute the non-endothelial-cell-specific core promoter region of the vWf gene. Results of gel mobility assays and deletion analyses demonstrated that a site in the vWf promoter other than the putative NF-kB binding site is involved in the mechanism of irradiation induction of the vWf.
Structure-Function Analyses Point to a Polynucleotide-Accommodating Groove Essential for APOBEC3A Restriction Activities (2010)

Members of the human APOBEC3 family of editing enzymes can inhibit various mobile genetic elements. APOBEC3A (A3A) can block the retrotransposon LINE-1 and the parvovirus adeno-associated virus type 2 (AAV-2) but does not inhibit retroviruses. In contrast, APOBEC3G (A3G) can block retroviruses but has only limited effects on AAV-2 or LINE-1. What dictates this differential target specificity remains largely undefined. Here, we modeled the structure of A3A based on its homology with the C-terminal domain of A3G and further compared the sequence of human A3A to those of 11 nonhuman primate orthologues. We then used these data to perform a mutational analysis of A3A, examining its ability to restrict LINE-1, AAV-2, and foreign plasmid DNA and to edit a single-stranded DNA substrate. The results revealed an essential functional role for the predicted single-stranded DNA-docking groove located around the A3A catalytic site. Within this region, amino acid differences between A3A and A3G are predicted to affect the shape of the polynucleotide-binding groove. Correspondingly, transferring some of these A3A residues to A3G endows the latter protein with the ability to block LINE-1 and AAV-2. These results suggest that the target specificity of APOBEC3 family members is partly defined by structural features influencing their interaction with polynucleotide substrates.
Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs. (2001)

Nasopharyngeal carcinoma (NPC) is universally associated with EBV infection. We have shown that the phosphonated nucleoside analog, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)-propyl]cytosine (HPMPC) strongly inhibits growth of NPC xenografts in nude mice by causing apoptosis (J. Neyts et al., Cancer Res., 58, 384-388, 1998). We, therefore, tested two additional members of this drug family that have different degrees of antiviral activity, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-2-(R)-(phosphonomethoxy)propyladenine (PMPA). Intratumoral injection of PMEA (75 microl of 2% solution) in C15 NPC xenografts, which are latently infected with EBV, slowed tumor growth moderately, whereas PMPA (75 microl of 2% solution) slowed tumor growth only marginally. Compared with the previous results showing complete regression of tumor, PMEA had less antitumoral effect than HPMPC, and PMPA had the least. After 4 weeks of preventive treatment, tumors formed in 12.5, 50, and 100% of mice treated with HPMPC, PMEA, and PMPA, respectively, in contrast to the development of tumors in all of the PBS-treated control mice. We also investigated the effect of each drug on the EBV-positive epithelial cell line NPC-KT in vitro. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed inhibition of growth of NPC-KT cells by HPMPC and PMEA, but not by PMPA, which correlates with the results observed in tumor xenografts. Growth inhibition was attributable to induction of apoptosis in NPC-KT cells as indicated by a DNA fragmentation assay. Cleavage of poly(ADP-ribose) polymerase after treatment of NPC-KT cells with HPMPC was observed, which suggested that the apoptosis may be mediated by caspase(s). The apoptotic effects of the drugs are independent of any effects on EBV DNA polymerase, which is not expressed in these latently infected NPCs. These results suggest that HPMPC as well as PMEA could provide an adjunctive treatment for NPC.
Protein kinase C-dependent and -independent pathways of mitogen-activated protein kinase activation in macrophages by stimuli that activate phospholipase A2. (1994)

The activation of mitogen-activated protein kinase (MAP kinase) in macrophages and the involvement of protein kinase C (PKC) in MAP kinase activation was investigated in macrophages exposed to agents that have previously been shown to activate the 85-kDa cytosolic phospholipase A2 (PLA2) and induce arachidonic acid release. Phorbol 12-myristate 13-acetate (PMA) and zymosan maximally stimulated MAP kinase activity by 5 and 15 min, respectively, whereas the response to okadaic acid was maximal by 60-90 min. MAP kinase activation correlated with tyrosine phosphorylation of p44 MAP kinase in PMA-stimulated cells and p44 and p42 MAP kinases in zymosan- and okadaic acid-stimulated cells. MAP kinase activity was not elevated in A23187-stimulated macrophages. Inhibition of PKC with the inhibitor, bisindolylmaleimide (GF109203X), or by prolonged exposure to PMA suppressed both arachidonic acid release and MAP kinase activation in PMA- and zymosan-stimulated macrophages but not in okadaic acid or A23187-treated cells. However, prolonged exposure to PMA did not suppress the increased cytosolic PLA2 activity in agonist-treated macrophages. This approach was complicated since initial exposure to PMA to down-regulate PKC increased cytosolic PLA2 activity which remained elevated for 16 h. In contrast, GF109203X treatment suppressed the increase in cytosolic PLA2 activity in response to zymosan and PMA but not to okadaic acid or A23187. The results demonstrate that PMA and zymosan trigger PKC activation that leads to the activation of MAP kinase and PLA2, whereas these responses are PKC independent in okadaic acid-treated cells. In addition, the results are consistent with a role for MAP kinase activation in regulating the activation of the 85-kDa PLA2 and arachidonic acid release in PMA-, zymosan-, and okadaic acid-stimulated cells, whereas these responses in A23187-treated cells are MAP kinase-and PKC-independent.
In‐situ enzyme histochemistry on plastic‐embedded plant material. The development of an artefact‐free β‐glucuronidase assay (1992)

Summary An in‐situ enzyme histochemical method is described that preserves the tissue and cell structure as well as the enzyme activities. Flower buds at different developmental stages from wild‐type and transgenic Brassica napus plants, the latter containing the GUS gene under the control of a tapetum‐specific promoter, were used as starting material. The method is based on the following principles: processing of the tissue on crushed ice, no fixation but a pretreatment with spermidine, partial dehydration with acetone, and a final embedding in a water‐miscible glycol methacrylate resin at 5°C. This method was used to set up a sensitive p‐glucuronidase histochemical assay with a high resolution. A succinate dehydrogenase assay was included as a control for tissue and cell viability as well as a standard for the relative metabolic activities between different tissues and cell types.
L-arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats. (1993)

The effect(s) of L-arginine administration on the renal function of rats with untreated diabetes mellitus was examined. Rats received streptozotocin (N = 11) or vehicle (N = 12): Group 1 (normal rats, N = 6) drank tap water; Group 2 (normal rats, N = 6) drank tap water containing 1% L-arginine; Group 3 (diabetic rats, N = 5) drank tap water; and Group 4 (diabetic rats, N = 6) drank tap water with 1% L-arginine. Rats were fed a standard rat chow diet (22.8% protein, 142% L-arginine) with free access to food and water for 14 wk. Diabetic rats gained less weight, had significantly lower plasma levels of albumin and L-arginine, and had greater values for 24-h urine volumes and urine excretion of glucose, protein, urea, creatinine, nitrate, and nitrite than control rats. Diabetic rats given L-arginine (Group 4) had significantly lower protein and cGMP excretion in the urine than did rats of Group 3. The administration of L-arginine did not affect the plasma levels of glucose or L-arginine in Groups 2 or 4 compared with those of their respective controls. Group 3 had significantly higher values for GFR than did the other three groups of rats, but values for effective RPF, mean arterial pressure, hematocrit, and renal vascular resistance were not significantly different between Groups 3 and 4. There was no significant difference in glomerular morphology among the four groups of rats as determined by light microscopy, and both groups of diabetic rats exhibited the Armanni-Ebstein lesion in their tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Cortisone in Ulcerative Colitis (1955)

In a preliminary report (Truelove and Witts, 1954) we have given the immediate results of a controlled trial of cortisone in the treatment of chronic ulcerative colitis.
Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring (2011)

A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.
Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease (2020)

Prevalence of sarcopenia is high in patients with chronic kidney disease (CKD), especially in those with dialysis. Various pathological conditions related to CKD, such as chronic inflammation, insulin resistance, and endothelial dysfunction, are thought to be associated with the development and progression of sarcopenia. Advanced glycation end products (AGE), one of the representative uremic toxins, have been shown to contribute to various CKD-associated complications. This study investigated the role of AGE in frailty and sarcopenia in patients and animals with CKD, respectively. In patients undergoing dialysis, serum AGE levels were significantly increased according to the frailty status and inversely associated with physical performance and activity. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD.
Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. (1996)

In the tissue-engineered heart valve leaflet, transplanted autologous cells generated a proper matrix on the polymer scaffold in a physiological environment at a period of 8 weeks after implantation.
Monoclonal Rat Antibodies to Rat Carcinoembryonic Antigen (1988)

An IgM-class rat monoclonal antibody, designated 5B1, was produced against rat carcinoembryonic antigen. This antibody, which can be considered an autoantibody, formed a single precipitation line in a gel diffusion test with an extract of the CEA-positive rat colonic adenocarcinoma, RCA-1. This line gave a reaction of complete identity with a line formed by a rabbit antiserum specific for rat CEA. 5B1 also bound to extracts of the RCA-1 tumor in EIA, but did not bind at all to extracts of the CEA-negative rat colonic adenocarcinoma, RCA-2, nor to extracts of normal rat tissues including liver, kidney and intestine. Inhibition tests showed that the activity of the monoclonal antibody in EIA was abolished by extracts of RCA-1 tumor, but was hardly affected by extracts of the other tissues.
Conformational Stability and Disassembly of Norwalk Virus-like Particles (2006)

Greater than 99% of the Norwalk virus (NV) capsid consists of 180 copies of a single 58-kDa protein. Recombinantly expressed monomers self-assemble into virus-like particles (VLPs) with a well defined icosahedral structure. NV-VLPs are an appropriate vaccine antigen since the antigenic determinants of the parent virion are preserved. They also constitute very simple models to study the mechanisms of assembly and disassembly of viral capsids. This work examines the inherent stability of NV-VLPs over a range of pH and temperature values and provides detailed insight into structural perturbations that accompany disassembly. The NV-VLP structure was monitored using a variety of biophysical techniques including intrinsic and extrinsic fluorescence, high resolution second-derivative UV absorption spectroscopy, circular dichroism (CD), dynamic light scattering, differential scanning calorimetry, and direct observation employing transmission electron microscopy. The data demonstrate that NV-VLPs are highly stable over a pH range of 3-7 and up to 55 degrees C. At pH 8, however, reversible capsid dissociation was correlated with increased solvent exposure of tyrosine residues and subtle changes in secondary structure. Above 60 degrees C NV-VLPs undergo distinct phase transitions arising from secondary-, tertiary-, and quaternary-level protein structural perturbations. By combining the spectroscopic data employing a multidimensional eigenvector phase space approach, an empirical phase diagram for NV-VLP was constructed. This strategy of visualization provides a comprehensive description of the physical stability of NV-VLP over a broad range of pH and temperature. Complementary, differential scanning calorimetric analyses suggest that the two domains of VP1 unfold independently in a pH-dependent manner.
Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells (1991)

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases the product of the c-kit proto-oncogene was detected by immunoblotting with anti-c-kit antibody. The expression of c-kit transcripts and protein was barely detectable in normal bone marrow cells as a control. The expression of c-kit transcript did not correlate with the French-American-British classification nor clinical manifestations. In 6 of 11 cases that expressed c-kit product, AML cells were found to proliferate in response to recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the synergistic stimulation of AML cells was observed by rhSCF and granulocyte- macrophage colony-stimulating factor. Immunoblotting with anti- phosphotyrosine antibody showed that the c-kit receptor protein was detectably phosphorylated in 7 of 12 cases tested before the stimulation with rhSCF, while the rhSCF treatment resulted in an increased tyrosine phosphorylation of c-kit in AML cells. These results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.
Interleukin-4 and lnterleukin-13: Their Similarities and Discrepancies (1998)

Interleukin-4 (IL-4) and the closely related cytokine, interleukin-13 (IL-13) share many biological and immunoregulatory functions on B lymphocytes, monocytes, dendritic cells and fibroblasts. Both IL-4 and IL-13 genes are located in the same vicinity on chromosome 5 and display identical major regulatory sequences in their respective promoters, thus explaining their restricted secretion pattern to activated T cells and mast cells. The IL-4 and IL-13 receptors are multimeric and share at least one common chain called IL-4R alpha. Recent progress made in the description of IL-4 and IL-13 receptor complex have demonstrated the existence of two types of IL-4 receptors: one constituted by the IL-4R alpha and the gamma c chain, and a second constituted by the IL-4 R alpha and the IL-13R alpha 1 and able to transduce both IL-4 and IL-13 signals. Specific IL-13 receptors are results from the association between the IL-4R alpha and the IL-13R alpha 2 or between two IL-13R alpha. Furthermore, similarities in IL-4 and IL-13 signal transduction have been also described, thus explaining the striking overlapping of IL-4- and IL-13-induced biological activities such as regulation of antibody production and inflammation. However, the restricted expression of IL-4 to type 2 helper T lymphocytes as well as the inability of IL-13 to regulate T cell differentiation due to a lack of IL-13 receptors on T lymphocytes represent the major differences between these cytokines. This would indicate that although IL-4 and IL-13 share a large number of properties, precise mechanisms of regulation are also present to guarantee their distinct functions.
Component-based design approach for multicore SoCs (2002)

This paper presents a high-level component-based methodology and design environment for application-specific multicore SoC architectures. Component-based design provides primitives to build complex architectures from basic components. This bottom up approach allows design-architects to explore efficient custom solutions with best performances. This paper presents a high-level component-based methodology and design environment for application-specific multicore SoC architectures. The system specifications are represented as a virtual architecture described in a SystemC-like model and annotated with a set of configuration parameters. Our component-based design environment provides automatic wrapper-generation tools able to synthesize hardware interfaces, device drivers, and operating systems that implement a high-level interconnect API. This approach, experimented over a VDSL system, shows a drastic design time reduction without any significant efficiency loss in the final circuit.
Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. (1994)

We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX-2 mRNA and protein coincided with the production of PGs in the pouch tissue and cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to macrophages obtained from the fluid exudate as well as to the inner surface layer of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the stomach. Furthermore, NS-398, a selective COX-2 inhibitor, and indomethacin, a nonselective COX-1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the air pouch. In contrast, only indomethacin blocked gastric PG and, additionally, produced gastric lesions. These results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects (e.g., gastric ulcers) associated with the nonselective, COX-1-directed antiinflammatory drugs.
Enhancing the quality of pre-service teachers’ learning in teaching practicum (2013)

This study aims to explore the relationship between the supporting factors and learning outcomes of a teaching practicum model for an initial teacher education programme in Hong Kong. Identifying the predictive relationships of the supporting factors for pre-service teachers’ teaching practicum and their learning outcome could help promoting the quality of the programme. There were 229 pre-service teachers participated to a questionnaire survey of a quasi-experimental design. Confirmatory factor analysis and reliability test were used to confirm the constructed validity and reliability of the survey instrument. A Structural Equation Model was applied to explore the predictive relationship between the supporting factors and their learning outcomes. Results show that campus-based courses, school mentor support and pre-service teacher’s self-efficacy were identified to be the supporting factors for their learning outcomes which include instructional design, managing learning activities and assessment. Strengthening school partnerships, providing mentor training and enhancing the element of assessment for learning in campus based course are recommended to the teacher education programme.
Past, present and future perspectives on sexing sperm (2003)

Development of flow cytometry for sorting mammalian sperm according to their sex chromosomes began in the late 1970s and early 1980s. This technology, which has recently been commercialized for bovine sperm, is based on the differences in DNA content between X- and Y-chromosome-bearing sperm. Under ideal conditions, 5000 live bovine sperm of each sex can be sorted per second at 90% accuracy. Pregnancy rates of 50% have been achieved routinely in well-managed heifers with sex-sorted, cryopreserved bovine sperm compared to 60–80% with unsexed control sperm. About 90% of offspring have been of the selected sex. Sorting sperm according to sex chromosome content is similarly successful in many other mammals including exotic species, but sorting efficiencies are somewhat less for sperm from some species. Key words: Mammals, sex chromosomes, flow cytometer, cell sorter, DNA content, X and Y sperm, Hoechst 33342
PANCREAS(PX) TRANSPLANTATION (TX) ALONE (PTA) FOR NON-UREMIC DIABETIC PATIENTS: A 20 YEAR EXPERIENCE. (2000)

Sutherland, David E.R.1; Gruessner, Rainer W.G.1; Humar, Abhinav1; Kandaswamy, Raja1; Najarian, John S.1; Dunn, David L.1; Gruessner, Angelika C.1 Author Information