gebhart/patrepeval huggingface dataset:
Fragile X-related protein and VIG associate with the RNA interference machinery (2002)

RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.
Leukocyte phosphoinositide-3 kinase γ is required for chemokine-induced, sustained adhesion under flow in vivo (2006)

During inflammation, leukocytes roll along the wall of postcapillary venules scanning the surface for immobilized CXCL1, a chemokine that triggers firm adhesion by activating CXCR2 on the neutrophil. PI-3K are signaling molecules important in cellular processes, ranging from cellular differentiation to leukocyte migration. PI-3Kgamma can be activated directly by the betagamma dimer of heterotrimeric G proteins coupled to CXCR2. Here, we used in vivo and ex vivo intravital microscopy models to test the role of PI-3Kgamma in leukocyte arrest. PI-3Kgamma null mice showed an 80% decrease in CXCL1-induced leukocyte adhesion in venules of the exteriorized mouse cremaster muscle. In wild-type mice, rolling leukocytes showed rapid and sustained adhesion, but in PI-3Kgamma(-/-) mice, adhesion was not triggered at all or was transient, suggesting that absence of PI-3Kgamma interferes with integrin bond strengthening. Wild-type mice reconstituted with PI-3Kgamma null bone marrow showed a 50% decrease in CXCL1-induced leukocyte adhesion. In a blood-perfused micro-flow chamber, leukocytes from PI-3Kgamma(-/-) mice showed a defect in adhesion on a P-selectin/ICAM-1/CXCL1 substrate, indicating that leukocyte PI-3Kgamma was required for adhesion. The adhesion defect in PI-3Kgamma(-/-) mice was as severe as that in mice lacking LFA-1, the major integrin responsible for neutrophil adhesion. We conclude that the gamma isoform of PI-3K must be functional in leukocytes to allow efficient adhesion from rolling in response to chemokine stimulation.
Protocols for Distributed Management (2012)

We survey approaches to distributed management and highlight an architecture thatis especially suited for distributed management in a large network. We then discuss indetail two fundamental classes of protocols that execute within such an architecture.The rst is the class of Echo protocols, which can be used for distributed polling, globalstate estimation, resource discovery, and distributed conguration. The second classis that of GAP protocols, whose main application is continuous real-time monitoring.Both classes are based on distributed trees, which are created during the executionof the protocols. Furthermore, both protocols perform in-network aggregation of theresults from local operations on network elements. When presenting the protocols, wediscuss their underlying distributed algorithms, their performance properties, such asoverhead and execution times, and possible extensions for operational use. We limitthe discussion to a single administrative domain.
CEST and PARACEST Agents for Molecular Imaging (2014)

In this chapter, small-molecule chemical exchange saturation transfer (CEST) agents are divided into classifications of diamagnetic (DIACEST) and paramagnetic (PARACEST) agents. Paramagnetic CEST agents represent class of chemical exchange systems that offer some potential advantages and disadvantages over DIACEST agents. Although PARACEST agents show considerable promise as responsive magnetic resonance imaging (MRI) agents in vitro, translation of these sensors to in vivo measurements has so far been limited, especially for those PARACEST systems that operate through a water exchange mechanism. LipoCEST agents display exceptional sensitivity in the picomolar concentration range without the need for high saturation powers. Although the poor sensitivity of small-molecule CEST agents may still present a problem for molecular imaging applications, the design of supramolecular and nanosized systems with much lower detection limits could potentially resolve this issue.
Positional Cloning of a Type 2 Diabetes Quantitative Trait Locus; Tomosyn-2, a Negative Regulator of Insulin Secretion (2011)

We previously mapped a type 2 diabetes (T2D) locus on chromosome 16 (Chr 16) in an F2 intercross from the BTBR T (+) tf (BTBR) Lep(ob/ob) and C57BL/6 (B6) Lep(ob/ob) mouse strains. Introgression of BTBR Chr 16 into B6 mice resulted in a consomic mouse with reduced fasting plasma insulin and elevated glucose levels. We derived a panel of sub-congenic mice and narrowed the diabetes susceptibility locus to a 1.6 Mb region. Introgression of this 1.6 Mb fragment of the BTBR Chr 16 into lean B6 mice (B6.16(BT36-38)) replicated the phenotypes of the consomic mice. Pancreatic islets from the B6.16(BT36-38) mice were defective in the second phase of the insulin secretion, suggesting that the 1.6 Mb region encodes a regulator of insulin secretion. Within this region, syntaxin-binding protein 5-like (Stxbp5l) or tomosyn-2 was the only gene with an expression difference and a non-synonymous coding single nucleotide polymorphism (SNP) between the B6 and BTBR alleles. Overexpression of the b-tomosyn-2 isoform in the pancreatic β-cell line, INS1 (832/13), resulted in an inhibition of insulin secretion in response to 3 mM 8-bromo cAMP at 7 mM glucose. In vitro binding experiments showed that tomosyn-2 binds recombinant syntaxin-1A and syntaxin-4, key proteins that are involved in insulin secretion via formation of the SNARE complex. The B6 form of tomosyn-2 is more susceptible to proteasomal degradation than the BTBR form, establishing a functional role for the coding SNP in tomosyn-2. We conclude that tomosyn-2 is the major gene responsible for the T2D Chr 16 quantitative trait locus (QTL) we mapped in our mouse cross. Our findings suggest that tomosyn-2 is a key negative regulator of insulin secretion.
Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma (1997)

The LOH of tumor suppressor genes is frequent in HCCs and LOH of the p53 gene and accumulated LOHs are related to poorly differentiated HCC. Abnormalities of the p53 gene or the accumulated abnormalities of the tumor suppressor genes may play a role in the aggressive progression of HCC.
Resequencing Analysis of the Human Tyrosine Kinase Gene Family in Pancreatic Cancer (2009)

Our genome-wide resequencing approach revealed novel oncogenic pathways in pancreatic cancers.
Pharmacokinetics of morphine in cerebrospinal fluid and plasma after epidural administration in man. (1988)

The morphine concentration in serum as well as in cerebrospinal fluid (CSF) after epidural administration of 0.1 mg/kg morphine to 10 patients undergoing aortic abdominal surgery, was determined. Model independent pharmacokinetic parameters in serum and CSF i.e. mean residence time (MRT), clearance (Cl) and apparent volume of distribution were calculated from the concentration time curves using a non-linear square regression fitting programme. Peak concentration of morphine in serum (86 ng/ml) and in CSF (2610 ng/ml) was reached after 10 min respectively 40 min of epidural injection.
Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas. (1993)

Seventy-nine esophageal carcinoma patients were studied for genetic abnormalities in the p53 and Rb tumor suppressor genes. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect p53 point mutations, Northern blotting was used to examine abnormal expression of p53 and Rb, and polymerase chain reaction and Southern blotting were used to analyze allelic loss. Twenty-five cases were analyzed by DNA sequencing to detect mutations in p53. Fourteen samples contained mutations within exons 5 through 9 of p53; seven had missense mutations giving rise to single amino acid substitutions. The remaining seven (50%) contained nonsense mutations leading to premature termination, five due to single base pair substitutions, and two that were the result of frameshift mutations. In other human tumors, p53 mutations are predominantly missense mutations, but our data as well as those from other groups show that nonsense mutations are common in human esophageal cancer. All but one of the constitutionally heterozygous samples containing mutations also manifested loss of the normal p53 allele; the one exception without allelic loss contained a silent mutation, which should not have had any affect on the p53 protein product. In addition, Northern blotting analysis revealed abnormalities (altered transcript size or mRNA levels) in 5 of 7 cases involving p53 and in 2 of 7 cases analyzed for Rb. Thirty-four cases were informative for allelic loss studies of both p53 and Rb; of these, 25 (74%) lost heterozygosity of p53, Rb, or both. When point mutations and mRNA expression abnormalities were also considered, 33 of 45 (73%) tumors informative for allelic loss assays of both genes as well as for mRNA or point mutation studies showed one or more abnormalities in p53 or Rb. Our results strongly suggest that a unique profile of molecular alterations involving p53 and Rb characterizes human esophageal cancer and that these specific genetic lesions are important in the development and/or progression of most human esophageal carcinomas.
The Vaginal Epithelium of Immature Rats Metabolizes Androgens through an Aromatase-Like Reaction: Changes during the Time of Puberty1 (1989)

Testosterone (T) at physiological levels can induce precocious vaginal opening without advancing the time of first ovulation. The present experiments were undertaken to test the hypothesis that the vaginal epithelium has the ability to aromatize androgens to estrogens. Using standardized conditions, we estimated aromatase activity using both 3H2O-release from [1 beta-3H]T and thin-layer chromatographic (TLC) characterization of estrogen formed after incubations with [1,2,6,7-3H] testosterone. Vaginal aromatase-like activity, as measured by the 3H2O-release assay, increased between the juvenile and peripubertal phases of development and remained elevated throughout puberty. In contrast, ovarian aromatase increased markedly during the early proestrus (EP) and late (first) proestrus (LP) phases of puberty but declined after the first ovulation. Vaginal aromatase-like activity was induced in vivo by either stimulation of ovarian steroidogenesis with pregnant mare's serum gonadotropin (PMSG), or by producing EP levels of serum T via testosterone-containing Silastic capsules. 4-Hydroxy androstenedione, a potent aromatase inhibitor, decreased both vaginal and ovarian aromatase activity in vitro in a concentration-dependent manner. Although the principal product of ovarian aromatase derived from [1,2,6,7-3H] T was identified as estradiol (E2), the identity of the vaginal estrogen product could not be firmly established. The vaginal metabolite comigrated with 16-keto-E2 in two TLC systems before and one TLC system after acetylation but failed to recrystallize as 16-keto-E2 diacetate and failed to co-elute with 16-keto-E2 diacetate on high performance liquid chromatography. This vaginal metabolite does not correspond to any of 13 steroids tested, including 2-hydroxy-E2, and it does not represent a 5 alpha-reduced metabolite of T.(ABSTRACT TRUNCATED AT 250 WORDS)
The soluble methane mono-oxygenase of Methylococcus capsulatus (Bath). Its ability to oxygenate n-alkanes, n-alkenes, ethers, and alicyclic, aromatic and heterocyclic compounds (1977)

1. Methane mono-oxygenase of Methylococcus capsulatus (Bath) catalyses the oxidation of various substituted methane derivatives including methanol. 2. It is a very non-specific oxygenase and, in some of its catalytic properties, apparently resembles the analogous enzyme from Methylomonas methanica but differs from those found in Methylosinus trichosporium and Methylomonas albus. 3. CO is oxidized to CO2. 4. C1-C8 n-alkanes are hydroxylated, yielding mixtures of the corresponding 1- and 2-alcohols; no 3- or 4-alcohols are formed. 5. Terminal alkenes yield the corresponding 1,2-epoxides. cis- or trans-but-2-ene are each oxidized to a mixture of 2,3-epoxybutane and but-2-en-1-ol with retention of the cis or trans configuration in both products; 2-butanone is also formed from cis-but-2-ene only. 6. Dimethyl ether is oxidized. Diethyl ether undergoes sub-terminal oxidation, yielding ethanol and ethanal in equimolar amounts. 7. Methane mono-oxygenase also hydroxylates cyclic alkanes and aromatic compounds. However, styrene yields only styrene epoxide and pyridine yields only pyridine N-oxide. 8. Of those compounds tested, only NADPH can replace NADH as electron donor.
Picosecond Dynamics of Silver Nanoclusters. Photoejection of Electrons and Fragmentation (1998)

Silver colloids of particle diameter 40−60 nm have been synthesized using a chemical reduction method in aqueous medium. These nanoclusters are photoactive and exhibit transient bleaching in the 400−500 nm region followed by a strong absorption in the visible−near-infrared region when subjected to 355 nm laser-pulse excitation. The transient bleaching of the surface plasmon absorption band is a monophotonic process, while the absorption growth in the red region is a biphotonic process arising from the photoejection of electrons. The 40−60 nm clusters were observed to break up into smaller clusters (5−20 nm) with 355 nm laser-pulse excitation. The choice of excitation wavelength provides the size selectivity in the fragmentation of the clusters. For example, when the excitation wavelength was switched to 532 nm, only larger (or irregularly shaped) particles were found to break up.
Cap‐independent translation of maize Hsp101 (2005)

Maize embryonic axes contain stored mRNAs, some of which are able to undergo cap-independent translation initiation during germination. The Hsp101 mRNA, encoding a heat shock protein, is essential for thermo-tolerance induction and is present among the stored transcripts. This research aimed to investigate whether the Hsp101 transcript is IRES-driven regulated upon heat stress. Hsp101 transcribed either in vitro or in vivo was efficiently translated via a cap-independent mechanism. This was observed either in an animal in vitro translation system containing proteolytically cleaved eukaryotic initiation factor eIF4G or in a plant system lacking both eIF4E and eIFiso4E initiation factors. Deletion of the 5' untranslated region (UTR) from the Hsp101 mRNA abolished its cap-independent translation indicating that this nucleotide sequence is required to confer cap-independent initiation. Bicistronic constructs containing the Hsp101 mRNA 5'UTR in sense and anti-sense directions between two reporter genes were translated in both cap-independent systems. A similar bicistronic construct containing a viral internal ribosome entry site (IRES) element between the reporter genes was used as control. Internal translation of the second reporter gene was observed when the Hsp101 5'UTR was in the sense but not in the anti-sense orientation in the bicistronic construct. Taken together, these data suggest that the 5'UTR of maize Hsp101, a plant cellular mRNA, functions as an IRES-like element accounting for its cap-independent translation during heat stress.
Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. (1981)

DNA strand breaks can be detected with great sensitivity by exposing crude cell lysates to alkaline solutions and monitoring the rate of strand unwinding. As little as one strand break per chromosome can be detected. Previous methods for measuring strand unwinding have required physical separation of single- from double-stranded molecules. We now describe conditions under which unwinding can be monitored directly using a fluorescent dye, thus greatly simplifying the analysis. Breaks due to irradiation of blood samples by 60Co gamma-rays at doses as low as 0.05 to 0.1 gray (5 to 10 rads) were detectable. Rapid rejoining of strand breaks during in vitro incubation at 37 degrees could readily be observed following a dose of one gray. Since the procedure is very rapid and cells can be analyzed directly without the requirement for culturing or radiolabeling, the procedure could be useful in cancer chemotherapy if in vivo damage is to be monitored or for testing the in vitro sensitivity of cells to drugs.
Inefficiency of expression of luciferase reporter from transfected murine leukaemia proviral DNA may be partially overcome by providing a strong polyadenylation signal (1991)

HepG2 human hepatoma cells were transfected with the luciferase reporter gene, linked with a liver-specific enhancer plus a minimal promoter, contained within either pBR/pUC or Moloney murine leukaemia virus (MMLV) proviral plasmid contexts. Reporter expression from the proviral plasmid was decreased 10- to 20-fold, regardless of whether or not the orientation within the proviral DNA was appropriate for the use of the poly(A) signal in the 3' long terminal repeat (LTR). Efficient reporter expression was restored when the proviral transcription unit was provided with a simian virus 40 poly(A) signal. These results imply that the MMLV LTR poly(A) signal is inefficient. Therefore, strategies to maximize expression of internal transcription units from retroviral vectors should include the provision of an efficient (unidirectional) poly(A) signal (its requiring insertion in the reverse orientation to that of viral transcription).
Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. (1992)

Persistent microvascular hyperpermeability to plasma proteins even after the cessation of injury is a characteristic but poorly understood feature of normal wound healing. It results in extravasation of fibrinogen that clots to form fibrin, which serves as a provisional matrix and promotes angiogenesis and scar formation. We present evidence indicating that vascular permeability factor (VPF; also known as vascular endothelial growth factor) may be responsible for the hyperpermeable state, as well as the angiogenesis, that are characteristic of healing wounds. Hyperpermeable blood vessels were identified in healing split-thickness guinea pig and rat punch biopsy skin wounds by their capacity to extravasate circulating macromolecular tracers (colloidal carbon, fluoresceinated dextran). Vascular permeability was maximal at 2-3 d, but persisted as late as 7 d after wounding. Leaky vessels were found initially at the wound edges and later in the subepidermal granulation tissue as keratinocytes migrated to cover the denuded wound surface. Angiogenesis was also prominent within this 7-d interval. In situ hybridization revealed that greatly increased amounts of VPF mRNA were expressed by keratinocytes, initially those at the wound edge, and, at later intervals, keratinocytes that migrated to cover the wound surface; occasional mononuclear cells also expressed VPF mRNA. Secreted VPF was detected by immunofluoroassay of medium from cultured human keratinocytes. These data identify keratinocytes as an important source of VPF gene transcript and protein, correlate VPF expression with persistent vascular hyperpermeability and angiogenesis, and suggest that VPF is an important cytokine in wound healing.
Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with magnesium-ATP and peptide inhibitor (1993)

The structure of a ternary complex of the catalytic subunit of cAMP-dependent protein kinase, MgATP, and a 20-residue inhibitor peptide was determined at a resolution of 2.7 A using the difference Fourier technique starting from the model of the binary complex (Knighton et al., 1991a). The model of the ternary complex was refined using both X-PLOR and TNT to an R factor of 0.212 and 0.224, respectively. The orientation of the nucleotide and the interactions of MgATP with numerous conserved residues at the active site of the enzyme are clearly defined. The unique protein kinase nucleotide binding site consists of a five-stranded antiparallel beta-sheet with the base buried in a hydrophobic site along beta-strands 1 and 2 and fixed by hydrogen bonds to the N6 amino and N7 nitrogens. The small lobe secures the nucleotide via a glycine-rich loop and by ion pairing with Lys72 and Glu91. While the small lobe fixes the nontransferable alpha- and beta-phosphates in this inhibitor complex, the gamma-phosphate is secured by two Mg2+ ions and interacts both directly and indirectly with several residues in the large lobe--Asp184, Asn171, Lys168. Asp166 is positioned to serve as a catalytic base. The structure is correlated with previous chemical evidence, and the features that distinguish this nucleotide binding motif from other nucleotide binding proteins are delineated.
Modern Separation Techniques for the Efficient Workup in Organic Synthesis (2002)

The shift of paradigm in combinatorial chemistry, from large compound libraries (of mixtures) on a small scale towards defined compound libraries where each compound is prepared in an individual well, has stimulated the search for alternative separation approaches. The key to a rapid and efficient synthesis is not only the parallel arrangement of reactions, but simple work-up procedures so as to circumvent time-consuming and laborious purification steps. During the initial development stages of combinatorial synthesis it was believed that rational synthesis of individual compounds could only be achieved by solid-phase strategies. However, there are a number of problems in solid-phase chemistry: most notably there is the need for a suitable linker unit, the limitation of the reaction conditions to certain solvents and reagents, and the heterogeneous reaction conditions. Further disadvantages are: the moderate loading capacities of the polymeric support and the limited stability of the solid support. In the last few years several new separation techniques have been developed. Depending on the chemical problem or the class of compounds to be prepared, one can choose from a whole array of different approaches. Most of these modern separation approaches rely on solution-phase chemistry, even though some of them use solid-phase resins as tools (for example, as scavengers). Several of these separation techniques are based on liquid-liquid phase separation, including ionic liquids, fluorous phases, and supercritical solvents. Besides being benign with respect to their environmental aspects, they also show a number of advantages with respect to the work-up procedures of organic reactions as well as simplicity in the isolation of products. Another set of separation strategies involves polymeric supports (for example, as scavengers or for cyclative cleavage), either as solid phases or as soluble polymeric supports. In contrast to solid-phase resins, soluble polymeric supports allow reactions to be performed under homogeneous conditions, which can be an important factor in catalysis. At the same time, a whole set of techniques has been developed for the separation of these soluble polymeric supports from small target molecules. Finally, miscellaneous separation techniques, such as phase-switchable tags for precipitation by chemical modification or magnetic beads, can accelerate the separation of compounds in a parallel format.