gebhart/patrepeval huggingface dataset:
Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir (2000)

Human herpesvirus 8 (HHV8) open reading frame (ORF) 21 is predicted to encode a protein similar to the thymidine kinase (TK) enzyme of other herpesviruses. Expressed in mammalian cells, ORF 21 was found to have low TK activity, based on poor growth in media containing hypoxanthine-aminopterin-thymidine (HAT) and low incorporation of [(3)H]thymidine into high-molecular-weight DNA. Kinetic analysis using HHV8 TK as a purified glutathione S-transferase (GST) fusion protein showed that the enzyme has a comparatively high K(m) for thymidine (dThd) of approximately 33.2 microM. Nearly 50% of the phosphorylated product of the reaction with dThd was thymidylate. This monophosphate kinase activity was more pronounced with 3'-azido-3'-deoxythymidine (AZT), in which 78% of the reaction product was AZT diphosphate. Thymidine analogs competitively inhibited dThd phosphorylation by HHV8 TK, while 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, and corresponding analogs did not. Further competition experiments revealed that the nucleoside analog ganciclovir (GCV), at up to 1,000-fold molar excess, could not significantly inhibit dThd phosphorylation by the enzyme. In support of these data, 143B TK(-) cells expressing HHV8 TK phosphorylated GCV very poorly and were not susceptible to GCV toxicity compared to parental cells. Phosphorylation of [(3)H]GCV by a purified GST-HHV8 TK fusion protein was not detected by high-pressure liquid chromatography analysis. Structural features of HHV8 TK substrate recognition were investigated. Therapeutic implications of these findings are discussed.
Pathology and Pathogenesis of Hepatocellular Carcinoma (2001)

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and among the most common cancers worldwide. The distribution pattern of HCC shows geographical variation and its pathogenesis is multifactorial. Environmental, infectious, nutritional, metabolic, and endocrine factors contribute directly or indirectly to hepatocarcinogenesis. The synchronous occurrence of different risk factors, such as chronic viral hepatitis B and C, aflatoxin exposure, alcohol consumption or iron overload, in a single patient or patient population further increases the risk. HCC is commonly associated with chronic hepatitis and liver cirrhosis. Different genes have been implicated in the pathogenesis of HCC, and may be divided into four major groups: genes regulating DNA damage response; genes involved in cell cycle control; genes involved in growth inhibition and apoptosis, and genes responsible for cell-cell interaction and signal transduction. Hepatocarcinogenesis is mediated by loss of heterozygosity, somatic mutation, de novo methylation, and/or functional inactivation. As yet, there is no evidence for an ordered sequence of genomic events leading to hepatocarcinogenesis. The pattern of genomic alterations shows great variability, often between two different HCCs from a single patient. HCC evolves from precancerous lesions, and well-differentiated HCC further progresses to a less differentiated form. However, there is still great need for the definition of objective morphological, phenotypic and genetic markers for the progression of HCC.
Mixtures of Plant Growth-Promoting Rhizobacteria Enhance Biological Control of Multiple Cucumber Pathogens (1998)

ABSTRACT Plant growth-promoting rhizobacteria (PGPR) strains INR7 (Bacillus pumilus), GB03 (Bacillus subtilis), and ME1 (Curtobacterium flaccumfaciens) were tested singly and in combinations for biological control against multiple cucumber pathogens. Investigations under greenhouse conditions were conducted with three cucumber pathogens-Colletotrichum orbiculare (causing anthracnose), Pseudomonas syringae pv. lachrymans (causing angular leaf spot), and Erwinia tracheiphila(causing cucurbit wilt disease)-inoculated singly and in all possible combinations. There was a general trend across all experiments toward greater suppression and enhanced consistency against multiple cucumber pathogens using strain mixtures. The same three PGPR strains were evaluated as seed treatments in two field trials over two seasons, and two strains, IN26 (Burkholderia gladioli) and INR7 also were tested as foliar sprays in one of the trials. In the field trials, the efficacy of induced systemic resistance activity was determined against introduced cucumber pathogens naturally spread within plots through placement of infected plants into the field to provide the pathogen inoculum. PGPR-mediated disease suppression was observed against angular leaf spot in 1996 and against a mixed infection of angular leaf spot and anthracnose in 1997. The three-way mixture of PGPR strains (INR7 plus ME1 plus GB03) as a seed treatment showed intensive plant growth promotion and disease reduction to a level statistically equivalent to the synthetic elicitor Actigard applied as a spray.
Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature (2007)

The objective of our study is to describe patient characteristics, clinical, endoscopic, and pathologic features and management of adult eosinophilic esophagitis (EE). A retrospective review of adults with EE (20 or more eosinophils per high-power field) diagnosed between 1997 and 2006, and a systematic review of the medical literature was performed. Forty-two patients (31 male; 11 female) had EE. Mean (SD) age at diagnosis was 44 (15.8) years, with highest prevalence (48%) at age 20-39. Predominant symptoms were dysphagia (81%); median duration, 8 years; range, 1-30 years and food impaction (55%). Forty-three percent had allergy or atopy, 36% had asthma, 54% had peripheral eosinophilia, and 10% had a first-degree relative with dysphagia. Endoscopic findings included ringed esophagus (55%), linear furrows (33%), narrow esophagus (10%), normal esophagus (7%), and esophageal strictures (38%). Mean number of dilations was 2 (range, 1-5). There were no perforations, but superficial mucosal tears occurred in 31% of dilations. Nine patients were treated with topical fluticasone with clinical improvement in all four (100%) patients who were seen in follow-up. Pathologic findings included 20 or more eosinophils per high-power field from proximal or mid-esophageal biopsy specimens. A systematic review of 14 studies (11 manuscripts, 2 abstracts, and this case series) with 212 patients showed similar findings. EE should be suspected in young men with unexplained dysphagia or food impaction even in the absence of typical endoscopic findings of rings or corrugations, linear furrows, and narrow esophagus; diagnosis is confirmed by 20 or more eosinophils per high-power field on proximal or mid-esophageal biopsies; EE is associated with allergic or atopic disorders; topical steroids are effective in the management of EE; dilation of esophageal strictures is reasonably safe in EE.
Obesity-Associated Decrease in Growth Hormone-Releasing Hormone Gene Expression: A Mechanism for Reduced Growth Hormone mRNA Levels in Genetically Obese Zucker Rats (1993)

The secretion of growth hormone (GH) is impaired in the genetically obese Zucker rat where GH gene expression and plasma GH levels are depressed; however, the underlying mechanism of this abnormality remains unclear. We have evaluated the potential causative role of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) gene expression in the onset of the decreased GH mRNA levels by studying both GHRH and SRIH mRNA and peptide levels in obese and lean rats at 5 weeks of age when the decrease in GH mRNA is first detected. At that age both GHRH content and GHRH mRNA were significantly reduced in obese rats as compared to lean controls; hypothalamic SRIH content was also decreased in obese rats, but SRIH mRNA levels did not differ. Since GHRH is capable of stimulating GH gene expression, the decreased GHRH mRNA level could be a critical factor in causing the attenuation in GH gene expression and consequent diminution of circulating plasma GH.
Design, synthesis and structure of non-macrocyclic inhibitors of FKBP12, the major binding protein for the immunosuppressant FK506 (1995)

We have synthesized a series of non-macrocyclic ligands to FKBP12 that are comparable in binding potency and peptidyl prolyl isomerase (PPIase) inhibition to FK506 itself. We have also solved the structure of one of these ligands in complex with FKBP12, and have compared that structure to the FK506-FKBP12 complex. Consistent with the observed inhibitory equipotency of these compounds, we observe a strong similarity in the conformation of the two ligands in the region of the protein that mediates PPIase activity. Our compounds, however, are not immunosuppressive. In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its 'effector domain', projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. In contrast, our compounds bind within the surface envelope of FKBP12, and induce significant changes in the structure of the FKBP12 protein which may also affect calcineurin binding indirectly.
Image Classification using Random Forests and Ferns (2007)

We explore the problem of classifying images by the object categories they contain in the case of a large number of object categories. To this end we combine three ingredients: (i) shape and appearance representations that support spatial pyramid matching over a region of interest. This generalizes the representation of Lazebnik et al., (2006) from an image to a region of interest (ROI), and from appearance (visual words) alone to appearance and local shape (edge distributions); (ii) automatic selection of the regions of interest in training. This provides a method of inhibiting background clutter and adding invariance to the object instance 's position; and (iii) the use of random forests (and random ferns) as a multi-way classifier. The advantage of such classifiers (over multi-way SVM for example) is the ease of training and testing. Results are reported for classification of the Caltech-101 and Caltech-256 data sets. We compare the performance of the random forest/ferns classifier with a benchmark multi-way SVM classifier. It is shown that selecting the ROI adds about 5% to the performance and, together with the other improvements, the result is about a 10% improvement over the state of the art for Caltech-256.
Segmentation for efficient browsing of chronical video recorded by a wearable device (2010)

Video segmentation is often the first and a key step in many video analysis problems, such as in analyzing chronically recorded daily life video using a wearable device. Pre-segmentation is conducted based on shot boundary detection in multiple feature spaces. Subsequent boundary merging and refinement are based on shot duration thresholds and keyframe comparisons. Different from traditional keyframes, our key frames have statistical characteristics which best match those of the video segments they represent. Experiment results demonstrate that our method is effective in rapid video browsing.
Optimal Inventory Policies for Assembly Systems Under Random Demands (1989)

This paper considers an inventory model of an assembly system with random demands and proportional costs of production and stock holding activities. The model is a generalization of the facilities in series model of Clark and Scarf. Under an assumption on the initial stock levels that in any case should appear in the long run (Long-Run Balance), it is demonstrated that the assembly system can be remodeled as a series system. Hence, simple reorder policies are optimal and the computational requirements are drastically reduced. Simple approximate policies are suggested for the generally short period of time when systems might be out of long-run balance. There is some discussion of extensions.
Rapamycin-Resistant mTORC1 Kinase Activity Is Required for Herpesvirus Replication (2010)

Human cytomegalovirus (HCMV) infection has been shown to activate the mTORC1 signaling pathway. However, the phosphorylation of mTORC1 targets is differentially sensitive to the mTORC1 inhibitor rapamycin, and the drug inhibits HCMV replication to a modest extent. Using Torin1, a newly developed inhibitor that targets the catalytic site of mTOR kinase, we show that HCMV replication requires both rapamycin-sensitive and rapamycin-resistant mTOR activity. The treatment of infected cells with Torin1 inhibits the phosphorylation of rapamycin-sensitive and rapamycin-resistant mTOR targets and markedly blocks the production of virus progeny. The blockade of mTOR signaling with Torin1, but not rapamycin, disrupts the assembly of the eIF4F complex and increases the association of the translational repressor 4EBP1 to the 7-methylguanosine cap-binding complex. Torin1 does not affect HCMV entry and only modestly reduces the accumulation of the immediate-early and early viral proteins that were tested despite the disruption of the eIF4F complex. In contrast, Torin1 significantly decreases the accumulation of viral DNA and the pUL99 viral late protein. Similar mTOR signaling events were observed during murine cytomegalovirus (MCMV) infection, and we utilized murine fibroblasts containing several different mutations to dissect the mechanism by which Torin1 inhibits MCMV replication. This approach demonstrated that mTORC2 and the Akt1 and Akt2 kinases are not required for the Torin1-mediated inhibition of cytomegalovirus replication. The inhibition of MCMV replication by Torin1 was rescued in cells lacking 4EBP1, demonstrating that the inactivation of 4EBP1 by mTORC1 is critical for cytomegalovirus replication. Finally, we show that Torin1 inhibits the replication of representative members of the alpha-, beta-, and gammaherpesvirus families, demonstrating the potential of mTOR kinase inhibitors as broad-spectrum antiviral agents.
Supramolecular self-assembly directed by carborane C–H‥F interactions (2000)

The synthesis and crystallization of 9,12-bis-(4-fluorophenyl)-1,2-carborane 1 and 9,12-bis-(3,5-difluorophenyl)-1,2-carborane 2 provide the first examples of a supramolecular assemblage directed by C–Hcarborane⋯F interactions.
NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia (2005)

The myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis and dysplasia. A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene. Using a NUP98-HOXD13 fusion gene, we have developed a mouse model that faithfully recapitulates all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia, and apoptosis, and transformation to acute leukemia. The MDS that develops in NUP98-HOXD13 transgenic mice is uniformly fatal. Within 14 months, all of the mice died of either leukemic transformation or severe anemia and leucopenia as a result of progressive MDS. The NUP98-HOXD13 fusion gene inhibits megakaryocytic differentiation and increases apoptosis in the bone marrow, suggesting a mechanism leading to ineffective hematopoiesis in the presence of a hypercellular bone marrow. These mice provide an accurate preclinical model that can be used for the evaluation of MDS therapy and biology.
Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks (1992)

In this study, we evaluated the individual in vitro sensitivity of fresh acute myeloid leukemia (AML) cells to VP-16, and attempted to correlate VP-16 cytotoxicity with AML cell growth characteristics and drug-induced DNA single-strand breaks (SSB). Primary (PE1) colony inhibition assays allowed us to characterize two distinct groups of AML: group I (patients 1 through 6), which displayed sensitivity to VP-16 similar to that of normal CFU-GM (IC90 of 20.52 +/- 2.44 micrograms/mL v 20.48 +/- 2.23 micrograms/mL after 1 hour drug exposure, respectively); and group II (patients 7 through 11), which was more sensitive to VP-16 (IC90 of 7.26 +/- 2.93 micrograms/mL, P = .004). Subsequently, groups I and II were termed normosensitive and hypersensitive, respectively. This objective VP-16 sensitivity classification, as determined by PE1, remained unaltered when assessed by secondary (PE2) colony inhibition assay (evaluating the self-renewal fraction of AML progenitors), or by cytofluorometric viability assay (evaluating the ultimately differentiated blast cell population). These findings would suggest that individual sensitivity to VP-16 of a particular cell population is maintained throughout CFU-AML differentiation. Finally, we report that sensitivity of AML cells to VP-16 did not correlate either with cell growth characteristics or with SSB generation. Indeed, AML cell sensitivity to VP-16 appeared more closely related to DNA repair kinetics after drug removal, ie, hypersensitivity being essentially characterized by a prolonged retention of SSB during the posttreatment period. Interestingly, the established HL-60 cell line, which presented greater sensitivity to VP-16 cytotoxicity than KG1, HEL, and K562, was also found to exhibit delayed DNA SSB repair kinetics, as compared with the other AML cell lines. These results suggest that hypersensitivity to VP-16 of some AML cells may be related to a deficient DNA-repair mechanism.
Modeling the mashup ecosystem: structure and growth (2009)

Mashups combine data and services provided by third parties through open APIs (such as Google Maps and Flickr), as well as internal data sources owned by users. The creation of mashups is supported by a complex ecosystem of interconnected data providers, mashup platforms, and users. In this paper, we examine the structure of the mashup ecosystem and its growth over time. Several observations follow from our analysis. First, we can conclude that while the number of new APIs and mashups over time follows a linear growth pattern, the distribution of mashups over APIs is not uniform but follows a power law. This implies that a small number of APIs provides the basis for the majority of mashups, and the other APIs are only used in certain application niches. Second, our analysis suggests that mashup platforms were introduced in response to the increasing complexity of mashups, as mashups evolved from one-feature mashups (widgets). Third, we observe that complementary relationships between open APIs are formed based on the position of the APIs in the ecosystem. The propensity of two APIs to be used together in the same mashup depends on the existing number of mashups to which they both contribute. The growth of the mashup ecosystem follows a pattern where keystone data providers or ‘powerful hubs’ attract niche data providers as complementors, and the positions of keystones in the ecosystem are mutually reinforcing.
Antivin, a novel and divergent member of the TGFβ superfamily, negatively regulates mesoderm induction (1999)

Mesoderm induction and patterning are mediated by members of the TGFbeta superfamily. We have isolated a novel zebrafish member, antivin, that structurally is highly related to mouse lefty. Overexpression of antivin completely abolishes mesoderm induction at blastula stage, yet resultant embryos develop well-patterned epidermal and neural derivatives. The mesoderm-inhibiting activity of antivin can be mimicked by lefty and is suppressed by increasing levels of the mesodermal inducer Activin or its receptors. On the basis of its expression and activity, we propose that Antivin normally functions as a competitive inhibitor of Activin to limit mesoderm induction in the early embryo.
Multivariate stochastic approximation using a simultaneous perturbation gradient approximation (1992)

The problem of finding a root of the multivariate gradient equation that arises in function minimization is considered. When only noisy measurements of the function are available, a stochastic approximation (SA) algorithm for the general Kiefer-Wolfowitz type is appropriate for estimating the root. The paper presents an SA algorithm that is based on a simultaneous perturbation gradient approximation instead of the standard finite-difference approximation of Keifer-Wolfowitz type procedures. Theory and numerical experience indicate that the algorithm can be significantly more efficient than the standard algorithms in large-dimensional problems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates: I. Effects of anti-T11 antibodies on the circulating T cell pool (1985)

The effects of in vivo administration of three monoclonal antibodies specific for T11, the E rosette receptor on T lymphocytes, were examined in the rhesus monkey (Macaca mulatta). These three monoclonal antibodies were of different isotypes and were shown in in vitro studies to have differing affinities for the monkey T11 structure. Furthermore, each antibody induced antigenic modulation of T11 from the cell membrane of the lymphocytes to varying degrees in vitro. In vivo infusion of each of these antibodies into normal rhesus monkeys caused remarkably different effects on the circulating T lymphocyte pool. Infusion of these antibodies at doses of 2 mg/kg caused the coating of circulating T lymphocytes with antibody, the modulation of T11 off the T cell surface and the transient clearance of T cells from the circulation. Yet, the variation in the extent to which these effects were seen with these different antibodies indicates that extrapolating from studies of the in vivo use of one antibody to the use of another may be quite difficult. These studies clearly indicate the strengths of this nonhuman primate system for exploring the uses of monoclonal antilymphocyte antibodies as therapeutic agents. They, however, also demonstrate that differences may exist in the affinity of a particular antibody for homologous lymphocyte surface structures in humans and in a nonhuman primate species. These differences may make it difficult to predict the precise effects that the infusion of an antibody will cause in humans on the basis of alterations it induces in nonhuman primates.
A nucleic acid probe labeled with desmethyl thiazole orange: a new type of hybridization-sensitive fluorescent oligonucleotide for live-cell RNA imaging (2012)

A new fluorescent nucleotide with desmethyl thiazole orange dyes, D'(505), has been developed for expansion of the function of fluorescent probes for live-cell RNA imaging. The nucleoside unit of D'(505) for DNA autosynthesis was soluble in organic solvents, which made the preparation of nucleoside units and the reactions in the cycles of DNA synthesis more efficient. The dyes of D'(505)-containing oligodeoxynucleotide were protonated below pH 7 and the oligodeoxynucleotide exhibited hybridization-sensitive fluorescence emission through the control of excitonic interactions of the dyes of D'(505). The simplified procedure and effective hybridization-sensitive fluorescence emission produced multicolored hybridization-sensitive fluorescent probes, which were useful for live-cell RNA imaging. The acceptor-bleaching method gave us information on RNA in a specific cell among many living cells.