gebhart/patrepeval huggingface dataset:
Frataxin: a protein in search for a function (2013)

Reduced levels of the protein frataxin cause the neurodegenerative disease Friedreich's ataxia. Pathology is associated with disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload, and oxidative stress. Frataxin is a highly conserved iron-binding protein present in most organisms. Despite the intense interest generated since the determination of its pathology, identification of the cellular function of frataxin has so far remained elusive. In this review, we revisit the most significant milestones that have led us to our current understanding of frataxin and its functions. The picture that emerges is that frataxin is a crucial element of one of the most essential cellular machines specialized in iron-sulfur cluster biogenesis. Future developments, therefore, can be expected from further advancements in our comprehension of this machine.
Two-Component Systems of Helicobacter pylori Contribute to Virulence in a Mouse Infection Model (2003)

Helicobacter pylori encodes three histidine kinases and five response regulators belonging to the family of two-component regulatory systems which are involved in transcriptional control. Here we demonstrate that isogenic mutants of H. pylori P76 with deletions of the response regulator open reading frame (ORF) HP1365 and ORFs HP244, HP165, and HP1364 encoding histidine kinases are unable to colonize the stomachs of BALB/c mice, suggesting an essential role of these systems in the regulation of important virulence properties of H. pylori. Furthermore, we demonstrate that the genes under the control of the P(HP1408) and P(HP119) promoters which are regulated by the two-component system HP166-HP165 are not essential for single mutant colonization of mice but are required under competitive colonization conditions.
The human tumour suppressor gene SLC5A8 expresses a Na+–monocarboxylate cotransporter (2004)

The orphan cotransport protein expressed by the SLC5A8 gene has been shown to play a role in controlling the growth of colon cancers, and the silencing of this gene is a common and early event in human colon neoplasia. We expressed this protein in Xenopus laevis oocytes and have found that it transports small monocarboxylic acids. The electrogenic activity of the cotransporter, which we have named SMCT (sodium monocarboxylate transporter), was dependent on external Na(+) and was compatible with a 3 : 1 stoichiometry between Na(+) and monocarboxylates. A portion of the SMCT-mediated current was also Cl(-) dependent, but Cl(-) was not cotransported. SMCT transports a variety of monocarboxylates (similar to unrelated monocarboxylate transport proteins) and most transported monocarboxylates demonstrated K(m) values near 100 microm, apart from acetate and d-lactate, for which the protein showed less affinity. SMCT was strongly inhibited by 1 mm probenecid or ibuprofen. In the absence of external substrate, a Na(+)-independent leak current was also observed to pass through SMCT. SMCT activity was strongly inhibited after prolonged exposure to high external concentrations of monocarboxylates. The transport of monocarboxylates in anionic form was confirmed by the observation of a concomitant alkalinization of the cytosol. SMCT, being expressed in colon and kidney, represents a novel means by which Na(+), short-chain fatty acids and other monocarboxylates are transported in these tissues. The significance of a Na(+)-monocarboxylate transporter to colon cancer presumably stems from the transport of butyrate, which is well known for having anti-proliferative and apoptosis-inducing activity in colon epithelial cells.
Ideal Copolymers and the Second-Order Transitions of Synthetic Rubbers. I. Noncrystalline Copolymers (1953)

Abstract Theoretical and practical evidence is put forward to show that copolymers can be treated like solutions of small molecules in the interpretation of packing phenomena, and that ideal volume-additivity of the repeating units in copolymers is frequently realized. On this basis equations are derived for predicting θ, the second-order transition temperature, of binary copolymers from the two second-order transition temperatures of the pure polymers and their coefficients of expansion in the glassy and rubbery states. Previous mechanistic theories of the second-order transition temperature of such copolymers are thus superseded by a general reduction of the problem to the mechanism of thermal expansion. Practical applications to the choice of monomers in producing synthetic rubbers are outlined, and attention is drawn to the importance of second-order transitions in kinetic measurements on the reactions of polymers.
Vacuum Deposited Organic Light Emitting Devices for Full-Color Flat Panel Display Applications (2005)

Recently, both polymeric and molecular organic multilayer structures have been extensively investigated for their potential application to lightweight, inexpensive, full color flat panel displays. In this paper, we discuss the physical origin of electroluminescence in such devices, and its implications for the limits to device efficiency, operating voltage and device lifetime.
The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients (2009)

Platelet-derived microparticles (PDMP) play an important role in the pathogenesis of diabetic vasculopathy, and statins or eicosapentaenoic acid (EPA) have been shown to have a beneficial effect on atherosclerosis in hyperlipidemic patients. However, the influence of EPA and statins on PDMP and adiponectin in atherosclerosis is poorly understood. We investigated the effect of pitavastatin and EPA on circulating levels of PDMP and adiponectin in hyperlipidemic patients with type II diabetes. A total of 191 hyperlipidemic patients with type II diabetes were divided into three groups: group A received pitavastatin 2 mg once daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received both drugs (n = 72). PDMP and adiponectin were measured by ELISA at baseline and after 3 and 6 months of drug treatment. Thirty normolipidemic patients were recruited as healthy controls. PDMP levels prior to treatment in hyperlipidemic patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9 vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and adiponectin levels were lower than controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001). PDMP decreased significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p < 0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not significant). In contrast, group A exhibited a significant increase in adiponectin levels after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/- 0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant improvement in both PDMP and adiponectin levels after treatment (PDMP, before vs. 6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001; adiponectin, before vs. 6M, 3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of PDMP in combined therapy were significantly greater than those observed with EPA alone (p < 0.05 by ANOVA). In addition, soluble CD40 ligand exhibited almost the same change as PDMP in all therapy groups. These results suggest that pitavastatin possesses an adiponectin-dependent antiatherosclerotic effect, and this drug is able to enhance the anti-platelet effect of EPA. The combination therapy of pitavastatin and EPA may be beneficial for the prevention of vascular complication in hyperlipidemic patients with type II diabetes.
The role of neutrophils and inflammation in gastric mucosal injury (2000)

Gastric inflammation is a highly complex biochemical protective response to cellular/tissue injury. When this process occurs in an uncontrolled manner, the result is excessive cellular/tissue damage that results chronic inflammation and destruction of normal tissue. Current evidence suggests that Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) ingestion are major causative factors in the pathogenesis of gastric mucosal injury in humans. In response to H. pylori infection or NSAID, neutrophils are recruited to the site of inflammation and generate reactive oxygen and nitrogen species and proteases. However, neutrophils are not able to kill the bacteria that live in the gastric mucus, and compounds produced by activated neutrophils themselves may be potentially harmful for normal tissue. It has been shown that leukocyte-vascular endothelial cell interaction is regulated by various cell adhesion molecules, and that this interaction is directly or indirectly modified by many factors, the origin of which is H. pylori and NSAIDs. This review describes the potential role of neutrophils and neutrophil-associated inflammation for gastric oxidative stress and injury induced by H. pylori and/or NSAID.
A comparative assay of the in‐vitro and in‐vivo behavior of three chemically induced neoplasms of rat submandibular glands (1973)

Abstract. A new method has been developed for the reproducible induction of rat salivary adenocarcinomas. Conventional means were used to induce fibrosarcoma and squamous cell carcinomas. The three tumors were compared for their ability to grow in tissue culture and syngeneic irradiated hosts. Based on the evidence of this system, squamous cell carcinoma appears to show the least biologic activity of the three tumors, a fact which may be tentatively explained by a predominance of keratinizing rather than replicating cells in this tumor.
Second-order surface-plasmon assisted responsivity enhancement in germanium nano-photodetectors with bull’s eye antennas (2014)

The enhancement of photo-response in nanometer-scale germanium photodetectors through bull's eye antennas capable of supporting 2nd-order Bloch surface plasmon modes is demonstrated in theory and experiment. A detailed numerical investigation reveals that the presence of surface wave and its constructive interference with the directly incident light are incorporated into the main mechanisms for enhancing transmission through the central nanoaperture. With a grating period of 1500 nm, the area-normalized responsivity can be enhanced up to 3.8 times at 2 V bias for a 780 nm laser. It provides an easier fabrication path for ultra-short wavelength operations especially in devices using optically denser materials.
Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-κB (2001)

The human inducible nitric oxide synthase (hiNOS) gene is expressed in several disease states and is also important in the normal immune response. Previously, we described a cytokine-responsive enhancer between -5.2 and -6.1 kb in the 5'-flanking hiNOS promoter DNA, which contains multiple nuclear factor kappa beta (NF-kappa B) elements. Here, we describe the role of the IFN-Jak kinase-Stat (signal transducer and activator of transcription) 1 pathway for regulation of hiNOS gene transcription. In A549 human lung epithelial cells, a combination of cytokines tumor necrosis factor-alpha, interleukin-1 beta, and IFN-gamma (TNF-alpha, IL-1 beta, and IFN-gamma) function synergistically for induction of hiNOS transcription. Pharmacological inhibitors of Jak2 kinase inhibit cytokine-induced Stat 1 DNA-binding and hiNOS gene expression. Expression of a dominant-negative mutant Stat 1 inhibits cytokine-induced hiNOS reporter expression. Site-directed mutagenesis of a cis-acting DNA element at -5.8 kb in the hiNOS promoter identifies a bifunctional NF-kappa B/Stat 1 motif. In contrast, gel shift assays indicate that only Stat 1 binds to the DNA element at -5.2 kb in the hiNOS promoter. Interestingly, Stat 1 is repressive to basal and stimulated iNOS mRNA expression in 2fTGH human fibroblasts, which are refractory to iNOS induction. Overexpression of NF-kappa B activates hiNOS promoter-reporter expression in Stat 1 mutant fibroblasts, but not in the wild type, suggesting that Stat 1 inhibits NF-kappa B function in these cells. These results indicate that both Stat 1 and NF-kappa B are important in the regulation of hiNOS transcription by cytokines in a complex and cell type-specific manner.
Protein-tyrosine Phosphatase 1B Is a Negative Regulator of Insulin- and Insulin-like Growth Factor-I-stimulated Signaling (1996)

To understand the physiological role of protein-tyrosine phosphatase 1B (PTPase 1B) in insulin and insulin-like growth factor-I (IGF-I) signaling, we established clonal cell lines overexpressing wild type or inactive mutant (C215S) PTPase 1B in cells overexpressing insulin (Hirc) or IGF-I (CIGFR) receptors. PTPase 1B overexpression in transfected cells was verified by immunoblot analysis with a monoclonal PTPase 1B antibody. Subfractionation of parental cells demonstrated that greater than 90% of PTPase activity was localized in the Triton X-100-soluble particulate (P1) cell fraction. PTPase activity in the P1 fraction of cells overexpressing wild type PTPase 1B was 3-6-fold higher than parental cells but was unaltered in all fractions from C215S PTPase 1B-containing cells. The overexpression of wild type and C215S PTPase 1B had no effects on intrinsic receptor kinase activity, growth rate, or general cell morphology. The effects of PTPase 1B overexpression on cellular protein tyrosine phosphorylation were examined by anti-phosphotyrosine immunoblot analysis. No differences were apparent under basal conditions, but hormone-stimulated receptor autophosphorylation and/or insulin receptor substrate tyrosine phosphorylation were inhibited in cells overexpressing wild type PTPase 1B and increased in cells expressing mutant PTPase 1B, in comparison with parental cells. Metabolic signaling, assessed by ligand-stimulated [14C]glucose incorporation into glycogen, was also inhibited in cells overexpressing active PTPase 1B and enhanced in cells containing C215S PTPase 1B. These data strongly suggest that PTPase 1B acts as a negative regulator of insulin and IGF-I signaling.
Database system issues in nomadic computing (1993)

Mobile computers and wireless networks are emerging technologies that will soon be available to a wide variety of computer users. Unlike earlier generations of laptop computers, the new generation of mobile computers can be an integrated part of a distributed computing environment, one in which users change physical location frequently. The result is a new computing paradigm, nomadic computing. This paradigm will affect the design of much of our current systems software, including that of database systems.
Small molecule control of biological function (2008)

Attracted by the novel homodimeric glycosylated diazobenzo[b ]fluorene natural product lomaiviticin A and its monomeric cousins the kinamycins, we investigated the ability of simplified diazofluorenes to recapitulate DNA cleaving activity of kinamycin D. Under DTT mediated conditions, we obtained high percentages of DNA nicking by kinamycin D, 1-methoxydiazofluorene and 4-aminodiazofluorene. Upon further examination, the concentrations of both DTT and kinamycin D could be lowered significantly and still retain high DNA cleavage activity. This culminated in the identification that kinamycin D effectively cleaved DNA in a concentration, temperature, and time-dependent fashion by both DTT and glutathione under mild biomimetic conditions. The virulence and persistence of bacterial biofilm infections is responsible for many chronic illnesses as well as increased morbidity and mortality rates in a plethora of infectious diseases. Using the marine natural product oroidin as molecular inspiration, a library of reverse amide (RA) 2-aminoimidazole analogues were synthesized and assayed for anti-biofilm activity. A thorough and detailed structure-activity-relationship (SAR) culminated in the identification of a long linear aliphatic tridecyl RA analogue with sub-micromolar anti-biofilm activity against Pseudomonas aeruginosa and low micromolar activity against Acinetobacter baumannii. Additionally, a sub-class of aliphatic analogues lacking the amide moiety were synthesized that were very active at inhibiting and dispersing both P. aeruginosa and A. baumannii biofilms. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.
Introduction to plant tissue culture (2003)

Introduction and techniques: introductory history laboratory organization media aseptic manipulation. Basic aspects: cell culture cellular totipotency somatic embryogenesis. Applications to plant breeding: haploid production triploid production in vitro pollination and fertilization zygotic embryo culture somatic hybridisation and cybridisation genetic transformation somaclonal and gametoclonal variant selection. Application to horticulture and forestry: production of disease-free plants clonal propagation. General applications: industrial applications - secondary metabolite production germplasm conservation.
2,2-Dimethyl-5-nitroso-1,3-dioxan-5-yl benzoate, 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate and 5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate (2007)

The crystal structures of 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl benzoate, C(13)H(15)NO(5), (I), 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate, C(13)H(14)ClNO(5), (II), and 5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate, C(11)H(11)NO(5), (III), have been determined in order to gain insight into the conformational preference of alpha-benzoyloxynitroso. Unfavourable 1,3-diaxial interactions force (I) and (II) to crystallize in the 2,5 twist-boat conformation, whereas compound (III), lacking this destabilizing interaction, crystallizes in the chair conformation.
A Cascade of 24 Histatins (Histatin 3 Fragments) in Human Saliva (2004)

The systematic search by tandem mass spectrometry of human saliva from four different subjects, of 136 possible fragments originated from histatin 3, allowed the detection of 24 different peptides. They include, with the exception of histatin 4, all the known histatin 3 fragments, namely histatins 5-12 and the peptides corresponding to 15-24, 26-32, 29-32 residues, and 13 new fragments corresponding to 1-11, 1-12, 1-13, 5-13, 6-11, 6-13, 7-11, 7-12, 7-13, 14-24, 14-25, 15-25, and 28-32 residues of histatin 3. On the contrary, none of 119 possible fragments of histatin 1, including histatin 2, was detected. The results suggest that the genesis of histatin 3-related peptides, being under the principal action of trypsin-like activities, is probably not a random process but rather follows a sequential fragmentation pathway. Lack of detection of C-terminal fragments, with the exception of 26-32, 28-32, and 29-32 fragments, suggested that arginine 25 should be the first cleavage site, generating histatin 6 and 26-32 fragments. The genesis of 28-32 and 29-32 fragments and histatin 5 should implicate a subsequent exo-protease action. Similarly, lack of detection of fragments having Lys-5 and Arg-6 at the N terminus and Arg-25 at the C terminus strongly suggested that sequences KRKF (11-14 residues) and AKR (4-6 residues) should be the second and the third cleavage sites, respectively. Lys-17 and Arg-22 are not cleaved at all.
Covalent linkage of the DNA repair template to the CRISPR-Cas9 nuclease enhances homology-directed repair (2018)

The CRISPR-Cas9 targeted nuclease technology allows the insertion of genetic modifications with single base-pair precision. The preference of mammalian cells to repair Cas9-induced DNA double-strand breaks via error-prone end-joining pathways rather than via homology-directed repair mechanisms, however, leads to relatively low rates of precise editing from donor DNA. Here we show that spatial and temporal co-localization of the donor template and Cas9 via covalent linkage increases the correction rates up to 24-fold, and demonstrate that the effect is mainly caused by an increase of donor template concentration in the nucleus. Enhanced correction rates were observed in multiple cell types and on different genomic loci, suggesting that covalently linking the donor template to the Cas9 complex provides advantages for clinical applications where high-fidelity repair is desired.
Antigen‐coated immunoadsorbents utilized for in vivo depletion of antibodies and lymphocytes with specificity for the antigen (1983)

Hyperacute rejection of xenografts is thought to be triggered by humoral antibodies. It is known that natural antibodies against dog blood cells have been identified in sheep serum. Dog kidney antigen immunoadsorbent columns were placed in the extracorporeal lymph circuit of two sheep. In vivo studies have shown that these immunoadsorbent columns were effective in depleting the thoracic duct lymph of all antibodies with specificity for the dog kidney antigen. However, these columns were not effective in depleting the thoracic duct lymphocytes bearing surface receptors for the dog kidney antigen. When in vitro studies were carried out, the immunoadsorbent columns were effective in the depletion of both lymphocytes and antibody for the dog kidney antigen. Thus, since a humoral antibody response is thought to be responsible for the hyperacute rejection seen in xenografts, it is possible that these columns might be effective in prolonging xenograft survival.
Dose‐dependent pharmacokinetics of furosemide in the rat (1982)

The pharmacokinetics of furosemide were investigated in the rat at doses of 10 and 40 mg kg-1 corresponding to doses of 80 and 320 mg given to humans based on body surface area. A three-compartment open model with renal excretion taking place from the shallow peripheral compartment gave the best fit to the data. The terminal half-life of furosemide was found to change from 29 min for the 10 mg kg-1 dose to 49 min for the 40 mg kg-1 dose. This change could be detected as a change in the apparent volume of distribution caused by decreased protein binding at increasing plasma concentrations of furosemide. The total plasma clearance did not change significantly although metabolic and renal clearance both changed. The renal clearance was found to be dependent on the free fraction of furosemide in plasma and thus increased with increasing plasma concentrations. The metabolic clearance decreased with increasing dose indicating a saturable metabolism of furosemide.