gebhart/patrepeval huggingface dataset:
Use of a microsome-mediated test system to assess efficacy and mechanisms of cancer chemopreventive agents (1996)

There is a growing need for short-term assays which can assess the mechanisms and efficacy of cancer chemopreventive agents. In the present study we have employed a microsome-mediated test system concomitantly with DNA adduct detection to assess the efficacy of five chemopreventive agents, N-acetylcysteine, butylated hydroxytoluene (BHT), curcumin, oltipraz, and ellagic acid. 32P-Postlabeling analysis of DNA incubated with benzo[a]pyrene (BP) in the presence of Aroclor 1254-induced microsomes produced two major adducts: one derived from the interaction of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) with deoxyguanosine (dG) and the other from further activation of 9-OH-BP (309 and 34 adducts/10(7) nucleotides, respectively). With the exception of N-acetylcysteine, all test agents significantly altered BP-DNA adduct levels: Intervention with ellagic acid and oltipraz substantially (64-94%) inhibited both BPDE-dG and 9-OH-BP adducts, while intervention with curcumin and BHT inhibited the BPDE-dG adduct (57% and 38%, respectively) and enhanced the 9-OH-BP adduct (230% and 650%, respectively). Furthermore, ellagic acid was the only test agent observed to inhibit the anti BPDE-dG adduct in the absence of microsomal enzymes, which is consistent with the known conjugation of ellagic acid with BPDE. These results suggest that oltipraz may be acting as an inhibitor of P4501A1, the isozyme involved in activation of BP to BPDE, or by conjugation of the electrophilic species by a metabolite of oltipraz. A plausible mechanism for inhibition of the BPDE-dG adduct and enhancement of the 9-OH-BP adduct by curcumin and BHT includes inhibition of epoxide hydrolase. Our results also indicate that N-acetylcysteine does not act as an electrophilic trapping agent of BP metabolites but may exert its protective effect in vivo by various other means, including modulation of detoxification enzymes and altering DNA repair processes. These data suggest that this cell-free system in conjunction with the sensitive 32P-postlabeling DNA adduct analysis may prove a viable test system for assessing the mechanisms and efficacy of chemopreventive agents.
Complementary Deoxyribonucleic Acid Cloning of a Messenger Ribonucleic Acid Encoding Transforming Growth Factor β 4 from Chicken Embryo Chondrocytes (1988)

Using a human transforming growth factor beta 1 (TGF beta) cDNA probe, we have detected an RNA species migrating at about 1.7 kilobases in cultured primary chicken embryo chondrocytes that is distinct from chicken TGF beta 1. The cloning and sequencing of cDNAs corresponding to this chondrocyte RNA demonstrate that it represents a new member of the TGF beta family, which we have named TGF beta 4. Unlike previously described TGF beta which are 390 to 414 amino acids long, the predicted precursor protein of TGF beta 4 is only 304 amino acids and does not appear to contain a signal peptide. Also unique to this new TGF beta is an insertion of two amino acids near the N-terminus of the processed peptide which would result in a 114 amino acid mature protein after cleavage from the precursor at a tetrabasic arg-arg-arg-arg site. The nine cysteine residues characteristic of all TGF beta are conserved. TGF beta 4 shows 82%, 64%, and 71% identity with the amino acid sequences of processed TGF beta 1, 2, and 3, respectively.
Expression of the tumour necrosis factor receptor-associated factors 1 and 2 in Hodgkin's disease (2001)

The tumour necrosis factor receptor-associated factors (TRAFs) 1 and 2 participate in the signal transduction of various members of the tumour necrosis factor receptor (TNFR) family, including TNFR1, TNFR2, CD40, CD30, and the Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1). Previous in situ hybridization studies have demonstrated TRAF1 transcripts in the malignant cells of the majority of Hodgkin's disease (HD) tumours, where the expression of TRAF1 was higher in EBV-associated tumours than in their EBV-negative counterparts. In order to determine whether TRAF1 and also TRAF2 were expressed at the protein level in HD and whether there was any relationship to EBV status, immunohistochemistry has been used to detect these proteins in a series of HD specimens. TRAF1 protein was detected more frequently in Hodgkin/Reed-Sternberg (HRS) cells from EBV-positive tumours than in their EBV-negative counterparts. This difference was statistically significant (p=0.01). In contrast, TRAF2 expression by HRS cells appeared to be independent of EBV status. Using a sequential labelling approach, co-localization of LMP1 with either TRAF1 or TRAF2 was also demonstrated in HRS cells from EBV-positive tumours.
Synthesis and Biological Activity of 7-Alkylidenecephems (1995)

Several 7-alkylidenecephalosporins were synthesized and biologically evaluated as beta-lactamase inhibitors. The three beta-lactamase enzymes used in this study included two type C beta-lactamases, derived from Enterobacter cloacae P99 and E. cloacae SC12368, and one type A beta-lactamase, derived from Escherichia coli WC3310. Of the cephalosporins prepared, compound 7e, the sodium salt of 7-[(Z)-(2'-pyridyl)methylene]cephalosporanic acid sulfone, was found to have excellent inhibitory properties against both type C enzymes. Also, compound 7f, the sodium salt of 7-[(Z)-(tert-butoxycarbonyl)methylene]cephalosporanic acid sulfone showed high activity as an inhibitor of the type A enzyme. The inhibition kinetics of 7e were further explored. The IC50 value of 7e indicated that this compound was approximately 20-fold more active than tazobactam against the enzyme derived from E. cloacae P99 and 167-fold more active than tazobactam against the enzyme derived from E. cloacae SC12368. A plot of enzymatic activity vs incubation time with stoichiometric amounts of inhibitor reveals a rapid deactivation of the enzyme followed by an extremely slow reactivation. 7e exhibited a second-order rate constant of k3' = 5.3 x 10(6) L/mol.min, and a partition ratio of approximately 20:1 inhibitor:enzyme was determined for this inhibitor. After separation of excess inhibitor with Sephadex filtration, a rate constant of enzyme reactivation was measured at kreactiv = 1.0 x 10(-3) s-1. Following 24 h of incubation of enzyme with a large excess of inhibitor and sephadex filtration to remove excess inhibitor, the enzyme was able to recover only 43% of its original activity, indicating an irreversible component to the inhibition. Potential mechanisms of inhibition for both 7e and 7f are suggested.
Antifungal Activity of 5-, 7-, and 5,7-Substituted 2-Methyl-8-Quinolinols (1972)

2-Methyl-8-quinolinol and sixteen 5-, 7-, and 5,7-substituted derivatives with fluoro, chloro, bromo, iodo, nitro, and amino substituents were tested for in vitro antifungal activity against five fungi, Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria, and Trichophyton mentagrophytes. The 5,7-dichloro and 5,7-dibromo derivatives were the most fungitoxic of the compounds tested. With the exception of these two compounds and 5-iodo-2-methyl-8-quinolinol, the 2-methyl analogues were less active than the corresponding 8-quinolinols.
Mutations Affecting Export and Activity of Cytolysin A from Escherichia coli (2010)

Cytolysin A (known as ClyA, HlyE, and SheA) is a cytolytic pore-forming protein toxin found in several Escherichia coli and Salmonella enterica strains. The structure of its water-soluble monomeric form and that of dodecameric ClyA pores is known, but the mechanisms of ClyA export from bacterial cells and of pore assembly are only partially understood. Here we used site-directed mutagenesis to study the importance of different regions of the E. coli ClyA protein for export and activity. The data indicate that ClyA translocation to the periplasm requires several protein segments located closely adjacent to each other in the "tail" domain of the ClyA monomer, namely, the N- and C-terminal regions and the hydrophobic sequence ranging from residues 89 to 101. Deletion of most of the "head" domain of the monomer (residues 181 to 203), on the other hand, did not strongly affect ClyA secretion, suggesting that the tail domain plays a particular role in export. Furthermore, we found that the N-terminal amphipathic helix alphaA1 of ClyA is crucial for the formation and the properties of the transmembrane channel, and hence for hemolytic activity. Several mutations affecting the C-terminal helix alphaG, the "beta-tongue" region in the head domain, or the hydrophobic region in the tail domain of the ClyA monomer strongly impaired the hemolytic activity and reduced the activity toward planar lipid bilayer membranes but did not totally prevent formation of wild-type-like channels in these artificial membranes. The latter regions thus apparently promote membrane interaction without being directly required for pore formation in a lipid bilayer.
Inverse Diffraction and a New Reciprocity Theorem* (1968)

A solution is obtained to the inverse diffraction problem for a monochromatic scalar wave field propagated into the half space z&gt;0. It is shown how to determine the field distribution throughout the region 0≤z&lt;z1 from the knowledge of the field distribution in the plane z=z1&gt;0. The solution takes a particularly simple form when the spatial-frequency spectrum of the distribution in the plane z=z1 (or in any other plane z=const&gt;0) is bandlimited to a circle whose radius is equal to the wavenumber of the field. In this case, the solution to the inverse diffraction problem may be expressed in a form strictly similar to that for the direct-propagation problem (exterior boundary-value problem), given by Rayleigh’s diffraction formula of the first kind. A comparison of these two solutions leads to the formulation of a new reciprocity theorem, valid for a wide class of wave fields.
Screening for ovarian cancer (1999)

Computer simulation models predict that ovarian cancer screening could save at least three years of life per case1 and that screening is potentially cost effective.2 Such models have been developed and validated on data from published reports, but until now results from a randomised controlled trial have not been available. Jacobs et al recently described a randomised controlled trial of ovarian cancer screening in which 21 935 average risk postmenopausal women were randomised to three annual screens or to a control group.3 For their screening protocol Jacobs et al used the CA125 tumour marker as a first line screen and referred women to receive transvaginal sonography if CA125 concentrations were above 30 U/ml. If transvaginal sonography revealed an ovarian mass, women were referred for surgery. Designed as a pilot study, the trial was too small to show efficacy in terms of mortality reduction. However, its results are important for two reasons.

The Jacobs trial confirmed previous evidence4 that an acceptable positive predictive value is achieved by selecting women for evaluation by imaging on the basis of CA125 serum measurement. Neither transvaginal sonography nor CA125 is specific enough when used alone, but when the decision rule for surgical referral requires that both tests are positive the positive predictive value is 20%. Five operations …
Osmoregulation and glycerol metabolism in the yeastSaccharomyces cerevisiae (1997)

Glycerol is the main compatible solute in Saccharomyces cerevisiae. It is accumulated intracellularly when cells are exposed to decreased extracellular water activity. In general, increased intracellular accumulation of a solute may be caused by enhanced production, restricted dissimilation, increased retention by the plasma membrane and increased uptake from the medium. In this review, we evaluate current knowledge concerning mechanisms leading to the accumulation of glycerol in osmotically stressed cells of S. cerevisiae at the molecular and metabolic levels. An overview of glycerol metabolism in S. cerevisiae is provided.
Three-Dimensional Fibroblast Culture Implant for the Treatment of Diabetic Foot Ulcers: Metabolic Activity and Therapeutic Range (1998)

Dermagraft is three-dimensional, allogeneic, human neonatal dermal fibroblast culture grown on a degradable scaffold and cryopreserved. Clinical trials for treatment of diabetic foot ulcers showed optimal healing within a therapeutic range of metabolic activity, determined by 3[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) reduction. Actions of Dermagraft in wound repair include colonization by cells and provision of growth factors and cytokines, both activities dependent on living cells. Cells in the cryopreserved culture showed 60% viability by dye exclusion and, when isolated, were able to proliferate in monolayer culture. Protein synthesis by Dermagraft was inhibited 70-98% by cryopreservation, but, if within the therapeutic range, recovered to 45-85% of the prefreeze value over 48 h. Subtherapeutic Dermagraft showed variable, low recovery. Expression of mRNA for vascular endothelial growth factor (VEGF), platelet-derived growth factor A chain, and insulin-like growth factor-1 was reduced >83% in subtherapeutic compared with therapeutic Dermagraft. Granulocyte colony-stimulating factor and VEGF protein secretion, determined by enzyme-linked immunosorbent assay (ELISA), and angiogenic activity also depended on therapeutic range. VEGF secretion dropped sharply with MTT reductase in subtherapeutic tissue. The data demonstrate the critical dependence of the therapeutic properties of this living dermal implant on recovery of protein synthesis, growth factor expression, and angiogenesis, determined by metabolic activity.
HTML & CSS : the complete reference (2010)

Part I: Core Markup Chapter 1: Traditional HTML and XHTML Chapter 2: Introduction to HTML 5 Chapter 3: HTML and XHTML Element Reference Part II: Core Style Chapter 4: Introduction to CSS Chapter 5: CSS Syntax and Property Reference Chapter 6: CSS 3, Propertietary and Emerging Features Reference Appendices Appendix A: Character Entities Appendix B: Fonts Appendix C: Colors Appendix D: URLs Appendix E: Reading a Document Type Definition
Merozoite surface protein-3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes (1994)

Abstract We have previously found that the acquired protection against malaria implicates a mechanism of defense that relies on the cooperation between cytophilic antibodies and monocytes. Accordingly, an assay of antibody-dependent cellular inhibition (ADCI) of parasite growth was used as a means of selecting for molecules capable of inducing protective immunity to malaria. This allowed us to identify in the sera of clinically protected subjects an antibody specificity that promotes parasite killing mediated by monocytes. This antibody is directed to a novel merozoite surface protein (MSP-3) of a molecular mass of 48 kD. Purified IgG from protected subjects are effective in ADCI and those directed against MSP-3 are predominantly cytophilic. In contrast, in nonprotected individuals, whose antibodies are not effective in ADCI, anti-MSP-3 antibodies are mostly noncytophilic. A region in MSP-3 targetted by antibodies effective in the ADCI assay was identified and its sequence was determined; it contains an epitope not defined by a repetitive structure and does not appear to be polymorphic. Antibodies raised in mice against a peptide containing this epitope, as well as human antibodies immunopurified on this peptide, elicit a strong inhibition of Plasmodium falciparum growth in ADCI assay, whereas control antibodies, directed to peptides from other molecules, do not. The correlation between isotypes of antibodies produced against the 48- kD epitopes, clinical protection, and the ability of specific anti-MSP- 3 antibodies to block the parasite schizogony in the ADCI assay suggests that this molecule is involved in eliciting protective mechanisms.
Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes (2000)

Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor activation in human Valpha24JalphaQ T cell clones, DNA microarrays were used to quantitate changes in mRNA levels after anti-CD3 stimulation of clones derived from identical twins discordant for type 1 diabetes and IL-4 secretion. Activation resulted in significant modulation of 226 transcripts in the IL-4 secreting clone and 86 in the IL-4-null clone. Only 28 of these genes were in common. The differences observed suggest both ineffective differentiation of diabetic Valpha24JalphaQ T cells and a role for invariant T cells in the recruitment and activation of cells from the myeloid lineage.
Miniglucagon (Glucagon 19-29) (2002)

Miniglucagon, the COOH-terminal (19-29) fragment processed from glucagon, is a potent and efficient inhibitor of insulin secretion from the MIN 6 beta-cell line. Using the rat isolated-perfused pancreas, we investigated the inhibitory effect of miniglucagon on insulin secretion and evaluated the existence of an inhibitory tone exerted by this peptide inside the islet. Miniglucagon dose-dependently inhibited insulin secretion stimulated by 8.3 mol/l glucose, with no change in the perfusion flow rate. A concentration of 1 nmol/l miniglucagon had a significant inhibitory effect on a 1 nmol/l glucagon-like peptide 1 (7-36) amide-potentiated insulin secretion. A decrease in extracellular glucose concentration simultaneously stimulated glucagon and miniglucagon secretion from pancreatic alpha-cells. Using confocal and electron microscopy analysis, we observed that miniglucagon is colocalized with glucagon in mature secretory granules of alpha-cells. Perfusion of an anti-miniglucagon antiserum directed against the biologically active moiety of the peptide resulted in a more pronounced effect of a glucose challenge on insulin secretion, indicating that miniglucagon exerts a local inhibitory tone on beta-cells. We concluded that miniglucagon is a novel local regulator of the pancreatic islet physiology and that any abnormal inhibitory tone exerted by this peptide on the beta-cell would result in an impaired insulin secretion, as observed in type 2 diabetes.
Genetic Diversity and Selection Regulates Evolution of Infectious Bronchitis Virus (2012)

Conventional and molecular epidemiologic studies have confirmed the ability of infectious bronchitis virus (IBV) to rapidly evolve and successfully circumvent extensive vaccination programs implemented since the early 1950s. IBV evolution has often been explained as variation in gene frequencies as if evolution were driven by genetic drift alone. However, the mechanisms regulating the evolution of IBV include both the generation of genetic diversity and the selection process. IBV's generation of genetic diversity has been extensively investigated and ultimately involves mutations and recombination events occurring during viral replication. The relevance of the selection process has been further understood more recently by identifying genetic and phenotypic differences between IBV populations prior to, and during, replication in the natural host. Accumulating evidence suggests that multiple environmental forces within the host, including immune responses (or lack thereof) and affinity for cell receptors, as well as physical and biochemical conditions, are responsible for the selection process. Some scientists have used or adopted the related quasispecies frame to explain IBV evolution. The quasispecies frame, while providing a distinct explanation of the dynamics of populations in which mutation is a frequent event, exhibits relevant limitations which are discussed herein. Instead, it seems that IBV populations evolving by the generation of genetic variability and selection on replicons follow the evolutionary mechanisms originally proposed by Darwin. Understanding the mechanisms underlying the evolution of IBV is of basic relevance and, without doubt, essential to appropriately control and prevent the disease.
Fracture resistance of gamma radiation sterilized cortical bone allografts (2001)

Gamma radiation is widely used for sterilization of human cortical bone allografts. Previous studies have reported that cortical bone becomes brittle due to gamma radiation sterilization. This embrittlement raises concern about the performance of a radiation sterilized allograft in the presence of a stress concentration that might be surgically introduced or biologically induced. The purpose of this study was to investigate the effect of gamma radiation sterilization on the fracture resistance of human femoral cortical bone in the presence of a stress concentration. Fracture toughness tests of specimens sterilized at a dose of 27.5 kGy and control specimens were conducted transverse and longitudinal to the osteonal orientation of the bone tissue. The formation of damage was monitored with acoustic emission (AE) during testing and was histologically observed following testing. There was a significant decrease in fracture toughness due to irradiation in both crack growth directions. The work-to-fracture was also significantly reduced. It was observed that the ability of bone tissue to undergo damage in the form of microcracks and diffuse damage was significantly impaired due to radiation sterilization as evidenced by decreased AE activity and histological observations. The results of this study suggest that, for cortical bone irradiated at 27.5 kGy, it is easier to initiate and propagate a macrocrack from a stress concentration due to the inhibition of damage formation at and near the crack tip.
Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men (2005)

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.
OFDM PAPR reduction by pre-scrambling and clipping (2012)

This article presents a new method for Peak-to-Average Power Ratio (PAPR) reduction of Orthogonal Frequency Division Multiplexing (OFDM) signal. The proposed method is based on a relatively simple processing - pre-scrambling of OFDM symbol bit-block. The modified m-sequence with the least peak-factor for scrambling is used. The stability of pre-scrambled OFDM signal to the clipping is examined as well. C/C++ computer simulation of OFDM system with 64 subcarriers and frequency domain block-typepilot channel estimation is performed for AWGN multipath channel. As a result, bit error rate (BER) performance for various clipping levels is presented due to computer simulation. In addition, the Efficiency of joined pre-scrambling and clipping method is considered.