gebhart/patrepeval huggingface dataset:
Glucocorticosteroids: current and future directions (2010)

Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2 to the activated inflammatory gene transcription complex (trans-repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti-inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans-activation). Glucocorticoids also have post-transcriptional effects and decrease stability of some pro-inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post-translational modifications of GR. Histone deacetylase-2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans-repression over trans-activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti-inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti-inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.
Effect of Guanine Nucleotides on the Conformation and Stability of Chloroplast Elongation Factor Tu (1989)

The effect of guanine nucleotides and kirromycin on the conformation and stability of the chloroplast elongation factor Tu (EF-Tuchl) from Euglena gracilis has been investigated. Free EF-Tuchl is quite thermolabile but the protein is greatly stabilized by guanine nucleotides. The temperature dependence of the thermal inactivation of EF-Tuchl was used to calculate the amount of stabilization energy conferred by the guanine nucleotides. GDP increases the activation energy for the denaturation process by 77 kcal/mol while GTP increases the activation energy by 51 kcal/mol. The difference in heat stability of free EF-Tuchl and the EF-Tuchl.GDP complex was used to determine a dissociation constant of 1.3 x 10(-7) M at 37 degrees C. The temperature dependence of the dissociation constant allowed the calculation of a delta H degree obsd of -55 kcal/mol and a delta S degree obsd of -146 cal/(mol degree) for GDP binding to EF-Tuchl.EF-Tuchl was found to have a trypsin-sensitive region similar to that observed for Escherichia coli EF-Tu. This loop region was protected by GTP and kirromycin but not by GDP.
The involvement of phospholipid:diacylglycerol acyltransferases in triacylglycerol production (2000)

We have characterized three CoA-independent types of enzyme, phospholipases, phospholipid:diacylglycerol acyltransferases (PDATs) and cholinephosphotransferases, responsible for the removal of unusual fatty acids from phosphatidylcholine (PC) in microsomal preparations from developing oil seeds. The metabolism of sn-2-[(14)C]acyl-PC was monitored in microsomal preparations from various oilseeds having either medium-chain, acetylenic, epoxy or hydroxy fatty acids as their major fatty acids in the oil. The results indicate that PDAT plays a major role in removing ricinoleic acid and vernolic acid from phospholipids in Ricinus communis and Crepis palaestina seeds, respectively. However, vernolic, crepenynic and capric acids are primarily removed from phospholipids by phospholipases in Euphorbia lagascae, Crepis rubra and elm seeds, respectively. Further, we show that significant PDAT activity is also present in vegetative tissues of Arabidopsis thaliana.
Highly Dispersible Molecular Sieve Carbon Nanoparticles (2004)

Molecular sieve carbon (MSC) nanoparticles were successfully synthesized by carbonization of poly(furfuryl alcohol) (PFA) particles using silica as a temporary barrier to prevent irreversible aggregation of nanoparticles, and they showed good dispersibility in various organic solvents.
On the way to individuality : methodological issues in behavioral genetics (1999)

Contents: Incorporating Development in the Search for Etiological Factors in Human Traits Adaptive and Maladaptive Pathways in Development: A Quantitative Genetic Perspective Variable Age of Expression: Implications for Developmental Genetic Model.
Genetic susceptibility to lymphoma (2007)

Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations.
Amino acid sequence of Mirabilis Antiviral Protein, Total Synthesis of Its Gene and Expression in Escherichia coli (1989)

We have determined the complete amino acid sequence of Mirabilis antiviral protein (MAP). MAP is composed of 250 amino acids having a combined molecular weight of 27,833 and contains 23 lysine residues and 7 arginine residues. The amino acid sequence of MAP has 24% homology with the Ricin D-A chain. To carry out systematic structure-function studies of MAP, we have accomplished the total synthesis of its gene. We designed a synthetic MAP gene containing 12 unique restriction sites that were on the average 65 base pairs apart. Thirty synthetic oligonucleotides were enzymatically joined to form DNA duplexes. These were strategically synthesized to have EcoRI and HindIII cohesive ends and were cloned in pUC19. Nine blocks of the synthetic fragments were assembled in pUC19 to form the MAP gene consisting of 759 base pairs. The correctness of the connecting reactions was confirmed by step-wise sequencing of each assembled fragment as well as the total gene. When expressed under control of the tac promoter in Escherichia coli, the synthetic gene gave a protein similar to the native MAP. This was confirmed by an enzyme-linked immunosorbent assay and Western blotting analysis.
Anti‐idiotypic antibody identifies the cellular receptor of reovirus type 3 (1985)

The binding and subsequent infectivity of reovirus to target cells are mediated by interaction with specific cell surface viral receptors. To gain a more detailed understanding of the biochemistry of the reovirus receptor and the cellular consequences of viral attachment, we have studied the binding of type 3 reovirus (Dearing strain) in a quantitative manner utilizing an antiidiotypic antibody probe. A syngeneic monoclonal antiidiotypic antibody (87.92.6) was prepared by immunization with hybridoma cells which secrete an antireovirus hemagglutinin-specific antibody. This antiidiotypic antibody was previously shown to specifically recognize the cell surface receptor for reovirus type 3. In this report, we demonstrate that antiidiotype mimicked reovirus tropism in binding to murine thymomas; antiidiotype inhibited the binding of reovirus to specific targets, but not the binding of anti-H-2; and cross linking of receptor-bound antiidiotype by antiimmunoglobulin induced patching, but not capping of reovirus receptors. Utilizing radiolabeled antiidiotype, we next quantitate the number of reovirus receptors on R1.1 and YAC thymoma cells and, finally, report on the preliminary identification of the reovirus receptor as a 67,000-Da membrane glycoprotein.
3D integration technologies for emerging microsystems (2010)

The next generation of small form factor (SFF) microsystem technologies can only keep up with increased functionality and performance demands by using the third dimension. 3D integration technologies can be grouped into following distinct technology approaches: (i) 3D-monolithic IC integration, (ii) 3D stacking of IC-dies, wafers and packages, and (iii) 3D integrated packaging. This paper provides an overview on the various 3D integration and enabling technologies as well as the associated challenges that exist for SFF wireless system implementation with optimum cost and performance.
In vitro Release Behavior of Insulin from Biodegradable Hybrid Hydrogel Networks of Polysaccharide and Synthetic Biodegradable Polyester (2002)

The controlled release of insulin from a series of biodegradable hybrid hydrogel network containing dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of composition ratio was investigated. Laser confocal scanning microscope was used to understand the insulin dispersion and release mechanism in the hydrogels. We found that the dispersion of insulin in the hydrogel network appeared to become less homogeneous as the PDLLAM composition in the hydrogel increased. The increase in hydrogel degradability imparted by PDLLAM incorporation shifted the hydrogel to a more open structure at a later release time, which facilitated the release rate and extent of insulin. From the result of release kinetics study (i.e., diffusion coefficient), insulin release occurred through diffusion and degradation controlled mechanisms. In addition, a comparison of the release characteristics of indomethacin, insulin and bovine serum albumin from the hydrogel network showed that the following parameters determined the release kinetics: drug molecular weight and size, hydrogel swellability and degradability, drug solubility in water and the hydrophobic interaction between drugs and the hydrogel network.
A recombinant human hyaluronidase sustained release gel for the treatment of post‐surgical edema (2013)

These results demonstrate sustained hyaluronidase enzymatic activity that promotes diffusion of accumulated post-surgical edematous fluid, suggesting that PH20 SR gel may be a useful adjuvant in promoting postoperative edema resolution.
Metabolic Regulation of the Gene Encoding Glutamine-Dependent Asparagine Synthetase in Arabidopsis thaliana (1994)

Here, we characterize a cDNA encoding a glutamine-dependent asparagine synthetase (ASN1) from Arabidopsis thaliana and assess the effects of metabolic regulation on ASN1 mRNA levels. Sequence analysis shows that the predicted ASN1 peptide contains a purF-type glutamine-binding domain. Southern blot experiments and cDNA clone analysis suggest that ASN1 is the only gene encoding glutamine-dependent asparagine synthetase in A. thaliana. The ASN1 gene is expressed predominantly in shoot tissues, where light has a negative effect on its mRNA accumulation. This negative effect of light on ASN1 mRNA levels was shown to be mediated, at least in part, via the photoreceptor phytochrome. We also investigated whether light-induced changes in nitrogen to carbon ratios might exert a metabolic regulation of the ASN1 mRNA accumulation. These experiments demonstrated that the accumulation of ASN1 mRNA in dark-grown plants is strongly repressed by the presence of exogenous sucrose. Moreover, this sucrose repression of ASN1 expression can be partially rescued by supplementation with exogenous amino acids such as asparagine, glutamine, and glutamate. These findings suggest that the expression of the ASN1 gene is under the metabolic control of the nitrogen to carbon ratio in cells. This is consistent with the fact that asparagine, synthesized by the ASN1 gene product, is a favored compound for nitrogen storage and nitrogen transport in dark-grown plants. We have put forth a working model suggesting that when nitrogen to carbon ratios are high, the gene product of ASN1 functions to re-direct the flow of nitrogen into asparagine, which acts as a shunt for storage and/or long-distance transport of nitrogen.
OBI-1, porcine recombinant Factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII. (2010)

Hemophilia A is caused by a deficiency in blood coagulation Factor (F)VIII. Treatment for acute bleeding in patients comprises prophylactic infusion with human plasma-derived (pd) or recombinant (r)FVIII to increase circulating FVIII levels. However, alloantibodies (inhibitor) may arise in patients, limiting the efficacy of replacement therapy, especially in patients who develop high-titer inhibitors. For these patients, FVIII-bypassing agents are proposed, but there is a rare risk of thrombotic events. Porcine pdFVIII successfully achieves hemostatic FVIII levels in patients in whom human FVIII was ineffective, but possible residual viral contamination and immunogenicity prevents routine use. OBI-1, being developed by Ipsen and Inspiration Biopharmaceuticals Inc, is a bioengineered form of porcine rFVIII that is highly purified. OBI-1 has the procoagulant and biochemical properties of porcine pdFVIII, with improvements in risk of toxicity, infection and ease of manufacture. OBI-1 demonstrated significantly less immunogenicity than pdFVIII in a murine model of hemophilia A. Moreover, in cynomolgus monkeys, OBI-1 did not generate detectable inhibitors. OBI-1 was effective in a phase II, open-label clinical trial in patients with hemophilia A and inhibitor against porcine FVIII, who were experiencing a non-life or -limb threatening bleed. OBI-1 was well tolerated, without drug-related serious adverse events and is promising for further studies.
Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential (1998)

We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a herpes simplex virus (HSV)-seropositive individual. Competition with well-characterized murine monoclonal antibodies and immunodetection of gD truncations revealed that this antibody recognizes the group Ib antigenic site of glycoprotein D, a highly conserved and protective type-common determinant. To our knowledge, this is the first human group Ib monoclonal antibody ever described. The antibody also displayed first-order neutralization kinetics and a high neutralization rate constant, was capable of completely inhibiting syncytium formation by a fusogenic strain of HSV type 1, and efficiently neutralized low-passage clinical isolates of both HSV serotypes. Taken together with our earlier observations of the in vivo antiviral activities of this human recombinant antibody in animal models of HSV infection, the present results support the high therapeutic potential of this antibody.
Phonons and electron-phonon interaction in halogen-fullerene compounds (1998)

We have investigated the optical spectra of different halogen-fullerene compounds: ${\mathrm{C}}_{60}{\mathrm{I}}_{4\ensuremath{-}x},$ ${\mathrm{C}}_{70}{\mathrm{I}}_{2},$ ${\mathrm{C}}_{60}{\mathrm{Br}}_{24},$ ${\mathrm{C}}_{60}{\mathrm{Cl}}_{24},$ and ${\mathrm{C}}_{70}{\mathrm{Cl}}_{17}.$ Two types of carbon-halogen bonding have been established: (a) ${\mathrm{C}}_{60}{\mathrm{I}}_{4\ensuremath{-}x}$ and ${\mathrm{C}}_{70}{\mathrm{I}}_{2}$ compounds are formed by a ${\mathrm{C}}_{60}$ or ${\mathrm{C}}_{70}$ molecule sublattice and an ${\mathrm{I}}_{2}$ molecule sublattice that weakly interact via van der Waals forces; (b) ${\mathrm{C}}_{60}{\mathrm{Br}}_{24},$ ${\mathrm{C}}_{60}{\mathrm{Cl}}_{24},$ and ${\mathrm{C}}_{70}{\mathrm{Cl}}_{17}$ compounds are characterized by covalent bonds between C and Br/Cl atoms. We have studied in detail the resonance effects in ${\mathrm{C}}_{60}{\mathrm{Cl}}_{24}$ using the methods of Raman scattering, infrared absorption, and absorption in the visible region. The effect originates from the interactions between the phonon subsystem and the electron band at 2.33 eV and manifests itself in a resonant enhancement of the Raman line intensities and in the repetition of the phonon and the luminescence spectra shifted by the frequency of Raman-active phonon at $1508{\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}.$ The group-theory analysis of phonon symmetries in rigid and nonrigid ${\mathrm{C}}_{60}{\mathrm{Br}}_{24}$ and ${\mathrm{C}}_{60}{\mathrm{Cl}}_{24}$ crystals has been performed.
Parametric Texture Model (2000)

See J Portilla and E P Simoncelli. A Parametric Texture Model based on Joint Statistics of Complex Wavelet Coefficients. Int'l Journal of Computer Vision. 40(1):49-71, October, 2000.
Staphylococcus aureus and food poisoning. (2003)

Food-borne diseases are of major concern worldwide. To date, around 250 different food-borne diseases have been described, and bacteria are the causative agents of two thirds of food-borne disease outbreaks. Among the predominant bacteria involved in these diseases, Staphylococcus aureus is a leading cause of gastroenteritis resulting from the consumption of contaminated food. Staphylococcal food poisoning is due to the absorption of staphylococcal enterotoxins preformed in the food. Here, we briefly review the latest data on staphylococcal enterotoxins and some papers exemplifying the interactions between S. aureus and the food matrix; environmental factors affecting staphylococcal enterotoxin production are discussed.
Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome (2016)

The growth hormone (GH)-activated transcription factor signal transducer and activator of transcription 5b (STAT5b) is a key regulator of sexually dimorphic gene expression in the liver. Suppression of hepatic STAT5b signaling is associated with lipid metabolic dysfunction leading to steatosis and liver cancer. In the companion publication, a STAT5b biomarker gene set was identified and used in a rank-based test to predict both increases and decreases in liver STAT5b activation status/function with high (≥ 97%) accuracy. Here, this computational approach was used to identify chemicals and hormones that activate (masculinize) or suppress (feminize) STAT5b function in a large, annotated mouse liver and primary hepatocyte gene expression compendium. Exposure to dihydrotestosterone and thyroid hormone caused liver masculinization, whereas glucocorticoids, fibroblast growth factor 15, and angiotensin II caused liver feminization. In mouse models of diabetes and obesity, liver feminization was consistently observed and was at least partially reversed by leptin or resveratrol exposure. Chemical-induced feminization of male mouse liver gene expression profiles was a relatively frequent phenomenon: of 156 gene expression biosets from chemically-treated male mice, 29% showed feminization of liver STAT5b function, while <1% showed masculinization. Most (93%) of the biosets that exhibited feminization of male liver were also associated with activation of one or more xenobiotic-responsive receptors, most commonly constitutive activated receptor (CAR) or peroxisome proliferator-activated receptor alpha (PPARα). Feminization was consistently associated with increased expression of peroxisome proliferator-activated receptor gamma (Pparg) but not other lipogenic transcription factors linked to steatosis. GH-activated STAT5b signaling in mouse liver is thus commonly altered by diverse chemicals, and provides a linkage between chemical exposure and dysregulated gene expression associated with adverse effects on the liver.
Concepts in Gene Therapy (1997)

Part 1 Methods of gene delivery: Retroviral vectors, Salmons, Gunzberg Adenoviral vectors, Yeh et al Herpes simplex virus mediated gene transfer to neurons, Goins et al Virus functions for artificial vectors, Sandig, Strauss Targeted gene delivery and expression in hepatocytes, Wu, Wu Particle-mediated gene delivery system for cancer research, Rakhmilevich, Yang. Part 2 Methods for inactivation or restoration of gene function: Gene inactivation by homologous recombination - animal models of plasma disorders, Willnow, Herz Potential antisense oligonucleotide therapies for neuro-degenerative diseases, Grifman et al Synthetic ribozymes - the Hammerhead ribozyne, Heidenreich, Eckstein Ribozymes as tools for the gene therapist, Milich, Sullenger. Part 3 Cellular target systems: Gene transfer and transgene expression in haematopoietic cells, Baum et al The liver as a target for gene therapy, Cichon, Strauss Gene therapy for Gaucher disease via genetically engineered primary myoblasts, Liu et al In Vivo secretion of therapeutic proteins from neo-organs, Bohl, Heard. Part 4 Genetic diseases: Gene therapy for cystic fibrosis - strategies, problems and perspectives, Coutelle Gene therapy for dystrophin deficiency, Dickson Gene therapy for familial hypercholesterolemia, Gotthardt, Schuster Therapeutic strategies for the lysosomal storage disorders, Barranger et al. Part 5 Non-genetic and infectious diseases: Gene therapy for arthritis, Ghivizzani et al Gene therapy for HIV-1 disease, Bohnlein. Part 6 Cancer: Suicide genes for the treatment of cancer, Culver Tumour cell vaccines using genetically modified cells coexpressing cytokines and the T cell costimulatory molecule B7, Cayeux et al Dosage impact on immunotherapy with cytokine-gene modified cancer vaccines, Schmidt Tumour suppressor gene therapy - growth arrest and programmed cell death, Strauss et al.
Multiple Glycolytic Enzymes Are Tightly Bound to the Fibrous Sheath of Mouse Spermatozoa1 (2006)

The fibrous sheath is a cytoskeletal structure located in the principal piece of mammalian sperm flagella. Previous studies showed that glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS), a germ cell-specific glycolytic isozyme that is required for sperm motility, is tightly bound to the fibrous sheath. To determine if other glycolytic enzymes are also bound to this cytoskeletal structure, we isolated highly purified fibrous sheath preparations from mouse epididymal sperm using a sequential extraction procedure. The isolated fibrous sheaths retain typical ultrastructural features and exhibit little contamination by axonemal or outer dense fiber proteins in Western blot analyses. Proteomic analysis using peptide-mass fingerprinting and MS/MS peptide fragment ion matching identified GAPDHS and two additional glycolytic enzyme subunits, the A isoform of aldolase 1 (ALDOA) and lactate dehydrogenase A (LDHA), in isolated fibrous sheaths. The presence of glycolytic enzymes in the fibrous sheath was also examined by Western blotting. In addition to GAPDHS, ALDOA, and LDHA, this method determined that pyruvate kinase is also tightly bound to the fibrous sheath. These data support a role for the fibrous sheath as a scaffold for anchoring multiple glycolytic enzymes along the length of the flagellum to provide a localized source of ATP that is essential for sperm motility.