gebhart/patrepeval huggingface dataset:
Effects of I Domain Deletion on the Function of the β2 Integrin Lymphocyte Function-associated Antigen-1 (2000)

A subset of integrin alpha subunits contain an I domain, which is important for ligand binding. We have deleted the I domain from the beta2 integrin lymphocyte function-asssociated antigen-1 (LFA-1) and expressed the resulting non-I domain-containing integrin (DeltaI-LFA-1) in an LFA-1-deficient T cell line. DeltaI-LFA-1 showed no recognition of LFA-1 ligands, confirming the essential role of the I domain in ligand binding. Except for I domain monoclonal antibodies (mAbs), DeltaI-LFA-1 was recognized by a panel of anti-LFA-1 mAbs similarly to wild-type LFA-1. However, DeltaI-LFA-1 had enhanced expression of seven mAb epitopes that are associated with beta2 integrin activation, suggesting that it exhibited an "active" conformation. In keeping with this characteristic, DeltaI-LFA-1 induced constitutive activation of alpha4beta1 and alpha5beta1, suggesting intracellular signaling to these integrins. This "cross-talk" was not due to an effect on beta1 integrin affinity. However, the enhanced activity was susceptible to inhibition by cytochalasin D, indicating a role for the cytoskeleton, and also correlated with clustering of beta1 integrins. Thus, removal of the I domain from LFA-1 created an integrin with the hallmarks of a constitutively active receptor mediating signals into the cell. These findings suggest a key role for the I domain in controlling integrin activity.
Targeted disruption of the arylsulfatase B gene results in mice resembling the phenotype of mucopolysaccharidosis VI. (1996)

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with autosomal recessive inheritance caused by a deficiency of the enzyme arylsulfatase B (ASB), which is involved in degradation of dermatan sulfate and chondroitin 4-sulfate. A MPS VI mouse model was generated by targeted disruption of the ASB gene. Homozygous mutant animals exhibit ASB enzyme deficiency and elevated urinary secretion of dermatan sulfate. They develop progressive symptoms resembling those of MPS VI in humans. Around 4 weeks of age facial dysmorphia becomes overt, long bones are shortened, and pelvic and costal abnormalities are observed. Major alterations in bone formation with perturbed cartilaginous tissues in newborns and widened, perturbed, and persisting growth plates in adult animals are seen. All major parenchymal organs show storage of glycosaminoglycans preferentially in interstitial cells and macrophages. Affected mice are fertile and mortality is not elevated up to 15 months of age. This mouse model will be a valuable tool for studying pathogenesis of MPS VI and may help to evaluate therapeutical approaches for lysosomal storage diseases.
Endogenous nerve growth factor regulates the sensitivity of nociceptors in the adult rat (1998)

Nerve growth factor (NGF) has a well characterized role in the development of the nervous system and there is evidence that it interacts with nociceptive primary afferent fibres. Here we applied a synthetic tyrosine kinase A IgG (trkA-IgG) fusion molecule for 10-12 days to the innervation territory of the purely cutaneous saphenous nerve in order to bind, and thereby neutralize endogenous NGF in adult rats. Using neurophysiological analysis of 152 nociceptors we now show that sequestration of NGF results in specific changes of their receptive field properties. The percentage of nociceptors responding to heat dropped significantly from a normal 57% to 32%. This was accompanied by a rightward shift and a reduced slope of the stimulus response function relating the intracutaneous temperature to the neural response. The number of nociceptors responding to application of bradykinin was also significantly reduced from a normal of 28% to 8%. In contrast, the threshold for mechanical stimuli and the response to suprathreshold stimuli remained unaltered, as did the percentage of nociceptors responding to noxious cold. The reduced sensitivity of primary afferent nociceptors was accompanied by a reduction in the innervation density of the epidermis by 44% as assessed with quantitative immunocytochemical analysis of the panaxonal marker PGP 9.5. This demonstrates that endogenous NGF in the adult specifically modulates the terminal arborization of unmyelinated fibres and the sensitivity of primary afferent nociceptors to thermal and chemical stimuli in vivo.
Zooming in on the Human–Mouse Comparative Map: Genome Conservation Re-examined on a High-Resolution Scale (1997)

Over the past decade, conservation of genetic linkage groups has been shown in mammals and used to great advantage, fueling significant exchanges of gene mapping and functional information especially between the genomes of humans and mice. As human physical maps increase in resolution from chromosome bands to nucleotide sequence, comparative alignments of mouse and human regions have revealed striking similarities and surprising differences between the genomes of these two best-mapped mammalian species. Whereas, at present, very few mouse and human regions have been compared on the physical level, existing studies provide intriguing insights to genome evolution, including the observation of recent duplications and deletions of genes that may play significant roles in defining some of the biological differences between the two species. Although high-resolution conserved marker-based maps are currently available only for human and mouse, a variety of new methods and resources are speeding the development of comparative maps of additional organisms. These advances mark the first step toward establishment of the human genome as a reference map for vertebrate species, providing evolutionary and functional annotation to human sequence and vast new resources for genetic analysis of a variety of commercially, medically, and ecologically important animal models.
Noninvasive delivery of an α‐synuclein gene silencing vector with magnetic resonance–guided focused ultrasound (2018)

These results demonstrate that magnetic resonance-guided focused ultrasound can effectively, noninvasively, and simultaneously deliver viral vectors targeting α-synuclein to multiple brain areas. Importantly, this approach may be useful to alter the progression of Lewy pathology along selected neuronal pathways, particularly as prodromal PD markers improve early diagnoses. © 2018 International Parkinson and Movement Disorder Society.
Rifaximin Treatment of Pathogen‐Negative Travelers’ Diarrhea: Table 1 (2007)

More than one third of patients with travelers' diarrhea had pathogen-negative illness. Rifaximin was effective in treating the illness without associated side effects. These results are consistent with the hypothesis that undetected bacterial pathogens are the most likely cause of travelers' diarrhea without definable cause.
Detection of testosterone esters in blood (2015)

Injections of synthetic esters of testosterone are among the most common forms of testosterone application. In doping control, the detection of an intact ester of testosterone in blood gives unequivocal proof of the administration of exogenous testosterone. The aim of the current project was to investigate the detection window for injected testosterone esters as a mixed substance preparation and as a single substance preparation in serum and plasma. Furthermore, the suitability of different types of blood collection devices was evaluated. Collection tubes with stabilizing additives, as well as non-stabilized serum separation tubes, were tested. A clinical study with six participants was carried out, comprising a single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido(®)) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanon(®)). Blood was collected throughout a testing period of 60 days. The applied analytical method for blood analysis included liquid-liquid extraction and preparation of oxime derivatives, prior to TLX-sample clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. All investigated testosterone esters could be detected in post-administration blood samples. The detection time depended on the type of ester administered. Furthermore, results from the study show that measured blood concentrations of especially short-chained testosterone esters are influenced by the type of blood collection device applied. The testosterone ester detection window, however, was comparable.
The effect of aqueous surfactant solutions on alcohol dehydrogenase (LADH) (1993)

Abstract Alcohol dehydrogenase (LADH) was studied in aqueous solutions of surfactants to determine its structural and catalytic characteristics. Fluorescence, circular dichroism (CD), and electron paramagnetic resonance (ERP) techniques were used to study structural changes to the enzyme. The activity of LADH in catalyzing the oxidation of ethanol was investigated. Short‐chain alkyl sulfonates and sulfates did not deactivate LADH or alter its structure. Longer and branched alkyl sulfates and sulfonates, as well as a cationic surfactant (CTAB), affected both LADH activity and conformation. © 1993 John Wiley &amp; Sons, Inc.
Chloroplast Transcription at Different Light Intensities. Glutathione-Mediated Phosphorylation of the Major RNA Polymerase Involved in Redox-Regulated Organellar Gene Expression (2001)

Previous studies using purified RNA polymerase from mustard (Sinapis alba) chloroplasts showed control of transcription by an associated protein kinase. This kinase was found to respond to reversible thiol/disulfide formation mediated by glutathione (GSH), although at concentrations exceeding those thought to exist in vivo. In the present study, several lines of evidence are presented to substantiate the functioning of this regulation mechanism, also in vivo: (a) Studies on the polymerase-associated transcription kinase revealed that at appropriate ATP levels, GSH concentrations similar to those in vivo are sufficient to modulate the kinase activity; (b) GSH measurements from isolated mustard chloroplasts showed considerable differences in response to light intensity; (c) this was reflected by run-on transcription rates in isolated chloroplasts that were generally higher if organelles were prepared from seedlings incubated under high-light as compared with growth-light conditions; (d) the notion of a general transcriptional switch was strengthened by in vitro experiments showing that the kinase not only affects the transcription of a photosynthetic gene (psbA) but also that of a non-photosynthetic gene (trnQ); and (e) the polymerase-kinase complex revealed specific differences in the phosphorylation state of polypeptides depending on the light intensity to which the seedlings had been exposed prior to chloroplast isolation. Taken together, these data are consistent with GSH and phosphorylation-dependent regulation of chloroplast transcription in vivo.
Molecular mediators of angiogenesis in bladder cancer. (1998)

Bladder tumors are characterized by markedly increased angiogenesis when compared to the normal urothelium (NU) from which they are derived. Here, we use both cultured cells and immunohistochemistry to demonstrate a primary regulatory role for thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in the development of bladder tumor angiogenesis. Secretions from bladder cancer (CA) cells stimulated endothelial cell migration and corneal neovascularization, whereas those from NU cells were inhibitory. The antiangiogenic activity of NU cells was primarily due to secreted TSP-1 because neutralizing antibodies completely relieved the inhibition. Neutralizing antibodies to several putative angiogenesis inducers identified vascular endothelial growth factor (VEGF) and, to a lesser extent, basic fibroblast growth factor as the primary inducers secreted by bladder cancer cells. The secretion of TSP-1 by low- and high-grade cancer cells was reduced >94% when compared to NU cells, and this loss of inhibitory TSP-1 accounted for the development of an angiogenic phenotype because both NU cells and cancer cells secreted similar levels of total stimulatory activity and VEGF. Immunohistochemistry showed that TSP-1 was significantly reduced in all grades of bladder cancer when compared to NU, whereas VEGF staining remained relatively constant. Taken together, these data suggest that down-regulation of TSP-1 secretion is a key event in the switch from an antiangiogenic to an angiogenic phenotype, which occurs early in the development of bladder cancer.
A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model (2006)

In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions. We developed small molecule inhibitors against ligand-dependent phosphorylation of c-Fms and examined the effects of these compounds on osteolytic bone destruction in a bone metastasis model. We discovered a novel quinoline-urea derivative, Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl]urea), which is a c-Fms tyrosine kinase inhibitor. The IC(50)s of Ki20227 to inhibit c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta were found to be 2, 12, 451, and 217 nmol/L, respectively. Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro. Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibited the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner. In in vivo studies, oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. Moreover, Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo. Therefore, Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases.
Creatine Kinase Isoenzymes in Chicken Cerebellum: Specific Localization of Brain‐type Creatine Kinase in Bergmann Glial Cells and Muscle‐type Creatine Kinase in Purkinje Neurons (1994)

Creatine kinase isoenzymes were localized in the chicken cerebellum by the use of isoenzyme-specific anti-chicken creatine kinase antibodies. Brain-type creatine kinase was found in high amounts in the molecular layer, particularly in Bergmann glial cells but also in other cells of the cerebellar cortex, e.g. in astrocytes and in the glomerular structures, as well as in cells of the deeper nuclei. A mitochondrial creatine kinase isoform was primarily localized to the glomerular structures in the granule cell layer and was also identified in Purkinje neurons. Surprisingly, a small amount of the muscle-type creatine kinase isoform was identified in cerebellar extracts by immunoprecipitation, immunoblotting and native enzyme electrophoresis, and was shown to be localized exclusively in Purkinje neurons. Cell type-specific expression of brain- and muscle-type creatine kinase in Bergmann glial cells and Purkinje neurons, respectively, may serve to adapt cellular ATP regeneration to the different energy requirements in these specialized cell types. The presence of brain-type creatine kinase in Bergmann glial cells and astrocytes is discussed within the context of the energy requirements for ion homeostasis (K+ resorption), as well as for metabolite and neurotransmitter trafficking. In addition, the presence of muscle-type creatine kinase in Purkinje neurons, which also express other muscle-specific proteins, is discussed with respect to the unique calcium metabolism of these neurons and their role in cerebellar motor learning.
One-chip solution in 0.35 μm standard CMOS for electronic ballasts for fluorescent lamps (2004)

An ASIC for full digital control of electronic ballasts for fluorescent lamps is presented. The one-chip solution is the functional integration of 3 chips, an IC for the PFC, a lamp management ASIC and a half bridge driver IC. The ASIC has 3 V compatible high precision ADC and comparator inputs, a fully digital controlled PFC, a digital regulation of the lamp power and a state machine establishing the lamp management. The outputs are 13 V high speed FET drivers that are directly controlled by the digital logic. The paper presents the topology of the electronic ballast, the interfaces to the two main control loops, and the main analog and digital blocks. The ASIC is fabricated in a 0.35 /spl mu/m standard CMOS process. The system building blocks and the topology can be used for various highly integrated power electronics applications.
Nondegradative Sulfation of Polysaccharides. Synthesis and Structure Characterization of Biologically Active Heparan Sulfate Mimetics (2005)

Reproducible and nondegradative preparation of sulfated molecules exhibiting diverse biological properties requires caring out sulfation reactions under ready controlled mild conditions. Although, to date, sulfur trioxide is the most used sulfation agent, its highly acid character has brought its use in association with different nitrogen bases as sulfur trioxide−nitrogen base complexes and/or by introduction of basic solvents as pyridine. We have applied sulfur trioxide and other sulfation agents including protocols for the synthesis of biologically active sulfated polysaccharides and demonstrated that these agents provoke cleavage of glycosidic bonds and other acid labile functions as amides, esters and even ethers. These facts prompted us to develop new reaction conditions for a general and nondestructive sulfation protocol. Our approach consists of the introduction of 2-methyl-2-butene as an acid scavenger of neutral character. Application of the method leads to an efficient, reproducible, and controlled synthesis of acid labile dextran derivatives well-known to be active in tissue repair and recently proposed for example as a new therapeutic agent for prion diseases. A novel 1H NMR structural analysis of this kind of macromolecules is presented. This method offers a new advance for more efficient synthesis of biologically active sulfated macromolecules.
Classifying Bad Chips and Ordering Test Sets (2006)

This paper shows data related to choosing a pair of test sets for digital IC production test. This data demonstrates that the choice of the second set of the pair should take into account the test metric used for the first test set. An approach for making this choice by taking defect coverage and total test length into account is presented
Threshold switching mechanism by high-field energy gain in the hopping transport of chalcogenide glasses (2008)

Chalcogenide glasses are widely used in phase-change nonvolatile memories and in optical recording media for their ability to rapidly change their structure to crystalline, thus obtaining different electrical resistance and optical reflectivity. Chalcogenide glasses universally display threshold switching, that is a sudden, reversible transition from a high-resistivity state to a low-resistivity state observed in the current-voltage $(I\text{\ensuremath{-}}V)$ characteristic. Since threshold switching controls the operating voltage and speed of phase-change memories, the predictability of the switching voltage, current, and speed is of critical importance for selecting the proper chalcogenide material for memory applications. Although threshold switching has long been recognized to be an electronic process with an intimate relation to localized states, its detailed physical mechanism is still not clear. In this work, threshold switching is explained by the field-induced energy increase in electrons in their hopping transport, moderated by the energy relaxation due to phonon-electron interaction. The energy increase leads to an enhancement of conductivity and a collapse of the electric field within the amorphous chalcogenide layer, accounting for the observed negative differential resistance at switching. Threshold switching is found to obey to a constant electrical-power condition. The proposed model generally applies to low-mobility semiconductors featuring a deep Fermi level and hopping-type conduction, and can predict the thickness, temperature, and material dependence of threshold voltage and current.
Role of cardiac glutathione transferase and of the glutathione S-conjugate export system in biotransformation of 4-hydroxynonenal in the heart. (1986)

There is a remarkable difference in the isozyme pattern between cardiac and hepatic glutathione S-transferases in rat (Ishikawa, T., and Sies, H. (1984) FEBS Lett. 169, 156-160), and one near-neutral isozyme (pI = 6.9) of the cardiac glutathione S-transferases was found to have a significantly high activity toward 4-hydroxynonenal. The isozyme was inhibited by the resulting glutathione S-conjugate of 4-hydroxynonenal competitively with GSH and noncompetitively with 4-hydroxynonenal. The kinetic parameters estimated for the isozyme were: kcat = 460 mol X min-1 X mol enzyme-1, Km = 50 microM for 4-hydroxynonenal, Ki = 85 microM. When the heart was perfused with 4-hydroxynonenal, a marked decrease was observed in the intracellular GSH level, accompanied by an increase of glutathione S-conjugate of 4-hydroxynonenal in the heart. The rate of the conjugation reaction was more than 30 times the rate of the spontaneous reaction, the half-life of 4-hydroxynonenal in the heart being less than 4 s. The glutathione S-conjugate of 4-hydroxynonenal was released from the heart into the perfusion medium. Saturation kinetics were observed for the release with respect to the intracellular level of the S-conjugate (Vmax = 12 nmol X min-1 X g heart-1), and there was a competition by the S-conjugate for GSSG release. The release of the glutathione S-conjugate is considered as a carrier-mediated process and to be important not only in interorgan glutathione metabolism but also in diminishing the inhibitory effect of the S-conjugate on glutathione S-transferases and glutathione reductase.
Reviews in Food and Nutrition Toxicity (2003)

Heavy Metals in Breast Milk: Implications for Toxicity, C. Gundacker and B. Zodl Selenium Toxicity and Its Adverse Health Effects, U. Tinggi Arsenic in Fish: Implications for Human Toxicity, M. De Gieter and W. Baeyens Biological and Toxicological Considerations of Dietary Sulfur, L.A. Komarnisky and T.K. Basu Fluoride - Toxic and Pathologic Aspects: Review of Current Literature on Some Aspects of Fluoride Toxicity, T.F.X. Collins and R.L. Sprando Bacterial Contamination of Ready-to-Eat Foods: Concern for Human Toxicity, T.J. Fang T-2 Mycotoxin in the Diet and Its Effects on Tissues, Z.W. Jaradat Aflatoxin B1 and Cell Cycle Perturbation, R. Ricordy, E. Cacci, and G. Augusti-Tocco Cycad Consumption and Neurological Disease, J.D. Schulz, E.L. Hawkes, and C.A. Shaw Dietary Lectins and the Immune Response, T.M. Rosenkilde Kjaer and H. Frokiaer Index