gebhart/patrepeval huggingface dataset:
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro (2000)

The protein kinase Chk2, the mammalian homolog of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases, is phosphorylated and activated in response to DNA damage by ionizing radiation (IR), UV irradiation, and replication blocks by hydroxyurea (HU). Phosphorylation and activation of Chk2 are ataxia telangiectasia-mutated (ATM) dependent in response to IR, whereas Chk2 phosphorylation is ATM-independent when cells are exposed to UV or HU. Here we show that in vitro, ATM phosphorylates the Ser-Gln/Thr-Gln (SQ/TQ) cluster domain (SCD) on Chk2, which contains seven SQ/TQ motifs, and Thr68 is the major in vitro phosphorylation site by ATM. ATM- and Rad3-related also phosphorylates Thr68 in addition to Thr26 and Ser50, which are not phosphorylated to a significant extent by ATM in vitro. In vivo, Thr68 is phosphorylated in an ATM-dependent manner in response to IR, but not in response to UV or HU. Substitution of Thr68 with Ala reduced the extent of phosphorylation and activation of Chk2 in response to IR, and mutation of all seven SQ/TQ motifs blocked all phosphorylation and activation of Chk2 after IR. These results suggest that in vivo, Chk2 is directly phosphorylated by ATM in response to IR and that Chk2 is regulated by phosphorylation of the SCD.
Low degree of relatedness between Campylobacter pyloridis and enteropathogenic Campylobacter species as revealed by DNA-DNA blot hybridization and immunoblot studies (1987)

Campylobacter pyloridis, an organism recently described in association with antrum gastritis and peptic lesions, shares a number of morphological and growth characteristics with other Campylobacter species such as C. jejuni or C. coli. The degree of relationship between these microorganisms was studied on molecular level using DNA-DNA blot hybridization and immunoblot techniques. SDS-PAGE protein profiles and immunoblot patterns of total lysates of C. pyloridis were fundamentally different from those of C. jejuni and C. coli. In accordance with those results positive hybridization signals between chromosomal DNA of the different species were not seen by the blot hybridization method. C. pyloridis isolates that differed in respect to urea hydrolysis and plasmid content, on the other hand, shared a number of major proteins and their blotted DNAs hybridized strongly. Some differences in protein patterns of different C. pyloridis strains became more apparent when studied by immunoblot analysis.
Multicomponent Nanomaterials with Complex Networked Architectures from Orthogonal Degradation and Binary Metal Backfilling in ABC Triblock Terpolymers (2015)

Selective degradation of block copolymer templates and backfilling the open mesopores is an effective strategy for the synthesis of nanostructured hybrid and inorganic materials. Incorporation of more than one type of inorganic material in orthogonal ways enables the synthesis of multicomponent nanomaterials with complex yet well-controlled architectures; however, developments in this field have been limited by the availability of appropriate orthogonally degradable block copolymers for use as templates. We report the synthesis and self-assembly into cocontinuous network structures of polyisoprene-block-polystyrene-block-poly(propylene carbonate) where the polyisoprene and poly(propylene carbonate) blocks can be orthogonally removed from the polymer film. Through sequential block etching and backfilling the resulting mesopores with different metals, we demonstrate first steps toward the preparation of three-component polymer-inorganic hybrid materials with two distinct metal networks. Multiblock copolymers in which two blocks can be degraded and backfilled independently of each other, without interference from the other, may be used in a wide range of applications requiring periodically ordered complex multicomponent nanoarchitectures.
Wide Variety of Genotypes and Geographic Origins of Hepatitis B Virus in Belgian Children (2001)

In this series, the wide variety of geographic origins is confirmed by the molecular characteristics of HBV. In Belgium, HBV infection of children is currently essentially an imported infection.
Degradation of Basement Membrane by Murine Tumor Cells2 (1977)

Tumor cells from the murine T241 fibrosarcoma, which rapidly and reproducibility produces pulmonary metastases, were tested in vitro for their ability to degrade isolated pulmonary basement membrane. Degradation of basement membrane substrate was quantified by the culture of the substrate with tumor cells and measurement of the solubilized hydroxyproline and hexose glycoprotein at neutral pH. It was found that tumor cells collected in the tumor venous drainage were associated with a significantly greater solubilization of basement membrane than were tumor cells obtained from the primary tumor mass. Tumor cells were also assayed for their ability to solubilize type I collagen purified from human dura. Venous effluent tumor cells solubilized collagen to a significantly greater level than primary tumor cells, spleen cells, or liver cells. These findings raised the possibility that metastasizing tumor cells may be a distinct tumor subpopulation with regard to invasive potential.
Tumor-Induced Immune Suppression and Immune Escape (2006)

A large body of evidence supports the notion that both the adaptive and nonadaptive immune systems play an important role in the control of tumor progression in patients with malignant disease. These findings have provided the rationale for the development of active specific immunotherapy for the treatment of malignant disease. The enthusiastic application of active specific immunotherapy in a large number of patients has conclusively shown that: These disappointing findings are likely to reflect, at least in part, the ability of tumor cells to manipulate the ongoing TA-specific immune response as well as evade immune recognition and destruction, utilizing multiple mechanisms. The latter include tumor cell-induced qualitative and/or quantitative defects in the generation and maintenance of TA-specific immune responses, tumor cell-induced immune suppression, and/or changes in the antigenic profile of tumor cells because of their genetic instability. These topics are reviewed in this chapter, following a brief description of the essential components of a TA-specific immune response. Lastly, potential strategies to counteract tumor immune suppression and immune escape mechanisms are discussed, because these approaches may improve the outcome of immunotherapy in patients with malignant disease.
‘Race no more’: an alternative approach to cloning the 5′end of transcripts (1994)

Journal Article ‘ Race no more ’: an alternative approach to cloning the 5′end of transcripts Get access John H. Weis John H. Weis Division of Cell Biology and Immunology, Department of Pathology, University of Utah School MedicineSalt Lake City, UT 84132, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 22, Issue 16, 25 August 1994, Pages 3427–3428, https://doi.org/10.1093/nar/22.16.3427 Published: 25 August 1994 Article history Received: 08 June 1994 Revision received: 24 July 1994 Accepted: 24 July 1994 Published: 25 August 1994
Platelet-Activating Factor-Induced Aggregation of Human Platelets Specifically Inhibited by Triazolobenzodiazepines (1984)

Platelet-activating factor (PAF), a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms by which PAF acts are largely unknown, partly because of the lack of specific inhibitors for PAF-elicited responses. It was found that in washed human platelets the psychotropic triazolobenzodiazepine drugs alprazolam and triazolam potently inhibited PAF-induced changes in shape, aggregation, and secretion. The effects were specific for PAF activation, since the responses of human platelets to adenosine diphosphate, thrombin, epinephrine, collagen, arachidonate, and the calcium ionophore A23187 were not inhibited by the triazolobenzodiazepines. These psychotropic drugs should be useful in investigating the possibility that PAF or PAF-like phospholipids play a role in neuronal function and in elucidating biochemical mechanisms activated specifically by PAF in a variety of cells.
Solubilization and Display of G Protein-Coupled Receptors on Beads for Real-Time Fluorescence and Flow Cytometric Analysis (2000)

G protein-coupled receptors (GPCR) and cellular signaling elements are prime targets for drug discovery. Sensitive real-time methods that expand the analytical capabilities for these elements can play significant roles in basic research and drug discovery. Here, we describe novel approaches for the real-time fluorescence analysis of GPCRs. Using the G protein-coupled N-formyl peptide receptor (FPR) as a model system in concert with a fluorescent ligand, we showed the quantitative solubilization of his-tagged FPRs in 1% dodecyl maltoside. Solubilized receptors reconstitute in dodecyl maltoside with a mixture of bovine brain Gi/Go showing an apparent Kd of 100 nM. Solubilized receptors were also bound to Ni(2+)-silica particles and were detected in a flow cytometer by the binding of fluorescent ligand. The efficiency of receptor uptake by the particles was in excess of 80% with an apparent affinity for the bead in the nM range. The receptors had largely homogeneous dissociation characteristics, an appropriate Kd for the ligand in the low nM range and a high site number, with several million receptor molecules per particle. However, the G protein reconstitution was not detected on the beads, apparently for steric reasons. These approaches for displaying receptors could prove useful in drug discovery and in the analysis of the molecular assemblies in signal transduction.
Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles (2002)

Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.
Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major (1998)

Deferiprone does not adequately control body iron burden in patients with thalassemia and may worsen hepatic fibrosis.
Hematopoietic Precursor Cells Transiently Reestablish Permissiveness for X Inactivation (2006)

Xist is the trigger for X inactivation in female mammals. The long noncoding Xist RNA localizes along one of the two female X chromosomes and initiates chromosome-wide silencing in the early embryo. In differentiated cells, Xist becomes dispensable for the maintenance of the inactive X, and its function for initiation of silencing is lost. How Xist mediates gene repression remains an open question. Here, we use an inducible Xist allele in adult mice to identify cells in which Xist can cause chromosome-wide silencing. We show that Xist has the ability to initiate silencing in immature hematopoietic precursor cells. In contrast, hematopoietic stem cells and mature blood cells are unable to initiate ectopic X inactivation. This indicates that pathways critical for silencing are transiently activated in hematopoietic differentiation. Xist-responsive cell types in normal female mice show a change of chromatin marks on the inactive X. However, dosage compensation is maintained throughout hematopoiesis. Therefore, Xist can initiate silencing in precursors with concomitant maintenance of dosage compensation. This suggests that Xist function is restricted in development by the limited activity of epigenetic pathways rather than by a change in the responsiveness of chromatin between embryonic and differentiated cell types.
Haloalkane Dehalogenases:  Structure of aRhodococcusEnzyme, (1999)

The hydrolytic haloalkane dehalogenases are promising bioremediation and biocatalytic agents. Two general classes of dehalogenases have been reported from Xanthobacter and Rhodococcus. While these enzymes share 30% amino acid sequence identity, they have significantly different substrate specificities and halide-binding properties. We report the 1.5 A resolution crystal structure of the Rhodococcus dehalogenase at pH 5.5, pH 7.0, and pH 5.5 in the presence of NaI. The Rhodococcus and Xanthobacter enzymes have significant structural homology in the alpha/beta hydrolase core, but differ considerably in the cap domain. Consistent with its broad specificity for primary, secondary, and cyclic haloalkanes, the Rhodococcus enzyme has a substantially larger active site cavity. Significantly, the Rhodococcus dehalogenase has a different catalytic triad topology than the Xanthobacter enzyme. In the Xanthobacter dehalogenase, the third carboxylate functionality in the triad is provided by D260, which is positioned on the loop between beta7 and the penultimate helix. The carboxylate functionality in the Rhodococcus catalytic triad is donated from E141. A model of the enzyme cocrystallized with sodium iodide shows two iodide binding sites; one that defines the normal substrate and product-binding site and a second within the active site region. In the substrate and product complexes, the halogen binds to the Xanthobacter enzyme via hydrogen bonds with the N(eta)H of both W125 and W175. The Rhodococcusenzyme does not have a tryptophan analogous to W175. Instead, bound halide is stabilized with hydrogen bonds to the N(eta)H of W118 and to N(delta)H of N52. It appears that when cocrystallized with NaI the Rhodococcus enzyme has a rare stable S-I covalent bond to S(gamma) of C187.
Knockout mouse model for Fxr2: a model for mental retardation (2002)

Fragile X syndrome is a common form of mental retardation caused by the absence of the FMR1 protein, FMRP. Fmr1 knockout mice exhibit a phenotype with some similarities to humans, such as macro-orchidism and behavioral abnormalities. Two homologs of FMRP have been identified, FXR1P and FXR2P. These proteins show high sequence similarity, including all functional domains identified in FMRP, such as RNA binding domains. They have an overlap in tissue distribution to that of FMRP. Interactions between the three FXR proteins have also been described. FXR2P shows high expression in brain and testis, like FMRP. To study the function of FXR2P, we generated an Fxr2 knockout mouse model. No pathological differences between knockout and wild-type mice were found in brain or testis. Given the behavioral phenotype in fragile X patients and the phenotype previously reported for the Fmr1 knockout mouse, we performed a thorough evaluation of the Fxr2 knockout phenotype using a behavioral test battery. Fxr2 knockout mice were hyperactive (i.e. traveled a greater distance, spent more time moving and moved faster) in the open-field test, impaired on the rotarod test, had reduced levels of prepulse inhibition, displayed less contextual conditioned fear, impaired at locating the hidden platform in the Morris water task and were less sensitive to a heat stimulus. Interestingly, there are some behavioral phenotypes in Fxr2 knockout mice which are similar to those observed in Fmr1 knockout mice, but there are also some different behavioral abnormalities that are only observed in the Fxr2 mutant mice. The findings implicate a role for Fxr2 in central nervous system function.
The effects of fire on nitrogen cycling processes within Bandelier National Monument, NM (1996)

Nitrogen is often the nutrient limiting production in conifer forests. Fire acts as a mineralizing agent, releasing nutrients in available forms. However, nitrogen is lost during fires, which can further deplete this limiting nutrient. Without fire, nitrogen becomes tied up in partially decomposed litter (needles and woody debris). The problems faced by managers of these forest systems are how and when to use fire from a nutrient perspective. A chronosequence of fire intervals in ponderosa pine forests (Pinus ponderosa) was studied to determine (1) if nitrogen cycling processes (mineralization and nitrification) decrease and (2) if concentrations of organics that inhibit these processes increase along the fire chronosequence. Patterns were not statistically significant, but fairly clear trends occurred. Nitrogen mineralization and nitrification patterns were higher in sites recentry burned (within two years) and were lowest in sites without fire since the 1890's. The patterns at intermediate age sites varied, perhaps because of differential usage by elk and variable amounts of needle scorch which resulted in differential needle litterfall after fire. Within a site, concentrations of certain monoterpenes were consistently negatively correlated with rates of nitrification and mineralization. In these systems, fire promotes more rapid cycling of nitrogen, in part through combustion of monoterpene inhibitors.
Adenosine A2Areceptors play a role in the pathogenesis of hepatic cirrhosis (2006)

1. Adenosine is a potent endogenous regulator of inflammation and tissue repair. Adenosine, which is released from injured and hypoxic tissue or in response to toxins and medications, may induce pulmonary fibrosis in mice, presumably via interaction with a specific adenosine receptor. We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2. As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3. Adenosine A(2A) receptors are expressed on rat and human hepatic stellate cell lines and adenosine A(2A) receptor occupancy promotes collagen production by these cells. Liver sections from mice treated with the hepatotoxins carbon tetrachloride (CCl(4)) (0.05 ml in oil, 50 : 50 v : v, subcutaneously) and thioacetamide (100 mg kg(-1) in PBS, intraperitoneally) released more adenosine than those from untreated mice when cultured ex vivo. 4. Adenosine A(2A) receptor-deficient, but not wild-type or A(3) receptor-deficient, mice are protected from development of hepatic fibrosis following CCl(4) or thioacetamide exposure. 5. Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl(4) or thioacetamide. 6. These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis.
ADENOVIRUS MEDIATED CYTOSINE DEAMINASE GENE TRANSDUCTION AND 5-FLUOROCYTOSINE THERAPY SENSITIZES MOUSE PROSTATE CANCER CELLS TO IRRADIATION (2000)

The combination of adenovirus mediated cytosine deaminase plus 5-fluorocytosine and radiation therapy resulted in radiation sensitization with clinically relevant doses of radiation suggesting a potential usefulness of this treatment in patients with prostate cancer.
The Cooltown User Experience (2001)

ubiquitous, user, interface, web, handheld, wireless The Cooltown project at HP Labs applies Web technology to develop systems that support the users of wireless, handheld devices interacting with their environment, anywhere they may be. The basic elements of Web technology useful for ubiquitous computing are described in several papers and on-line resources from the Cooltown project [1-5]. Here we will give a flavor of the Cooltown user experience, discuss ways that context can be used in web systems, and explain why we think a web-based system for ubiquitous computing can achieve network effects. In our conclusion we will mention some of the many remaining challenges and our initial user studies platform.
Phase transitions of multivalent proteins can promote clustering of membrane receptors (2014)

Clustering of proteins into micrometer-sized structures at membranes is observed in many signaling pathways. Most models of clustering are specific to particular systems, and relationships between physical properties of the clusters and their molecular components are not well understood. We report biochemical reconstitution on supported lipid bilayers of protein clusters containing the adhesion receptor Nephrin and its cytoplasmic partners, Nck and N-WASP. With Nephrin attached to the bilayer, multivalent interactions enable these proteins to polymerize on the membrane surface and undergo two-dimensional phase separation, producing micrometer-sized clusters. Dynamics and thermodynamics of the clusters are modulated by the valencies and affinities of the interacting species. In the presence of the Arp2/3 complex, the clusters assemble actin filaments, suggesting that clustering of regulatory factors could promote local actin assembly at membranes. Interactions between multivalent proteins could be a general mechanism for cytoplasmic adaptor proteins to organize membrane receptors into micrometer-scale signaling zones.
Aroma Extract Dilution Analysis of a Beeflike Process Flavor from Extruded Enzyme-Hydrolyzed Soybean Protein (2001)

Aroma-active compounds from a beeflike process flavor, produced by extrusion of enzyme-hydrolyzed vegetable protein (E-HVP), were analyzed using aroma extract dilution analysis. The number of aroma-active compounds and the aroma intensity were increased by the addition of aroma precursors prior to extrusion. The most intense compound was 2-methyl-3-furanthiol having a cooked rice/vitamin-like/meaty aroma note. Several sulfur-containing furans, such as 2-methyl-3-(methylthio)furan, 2-methyl-3-(methyldithio)furan, and bis(2-methylfuryl)disulfide, were detected with high flavor dilution (FD) factors. Some pyrazines, such as 2-ethyl-3,5-dimethylpyrazine, 2,6-diethylpyrazine, and 3,5-diethyl-2-methylpyrazine, also had high FD factors. It is hypothesized that sulfur-containing amino acids and thiamin were important precursors in aroma formation in process flavor from E-HVP.
Respiratory Syncytial Virus and Human Bronchial Epithelium (1998)

This model closely mirrors human RSV disease and affords a unique opportunity to study interepithelial cell interactions, cytokine responses from cells of different donors, and ciliary activity of live cells undergoing RSV infection.