gebhart/patrepeval huggingface dataset:
Myelodysplastic Syndromes with Myelofibrosis May Be a Target for the JAK2 V617F Tyrosine Kinase Mutation. (2005)

Abstract The JAK V617F tyrosine kinase mutation is responsible for development of the disease in chronic myeloproliferative disorders, including myelofibrosis (MF). Since MF is associated with various hematologic diseases as a terminal hematologic condition and is an important issue in managing patients, we searched for the V617F mutation in primary and secondary MF in various hematologic diseases using the sequence-specific primer-single molecule fluorescence detection assay (SSP-SMFD). Of the MF patients associated with acute myeloid leukemia and (n = 3), lymphoma (n = 3), and chronic myeloid leukemia (n = 3), none of them showed the mutation at the time of the diagnosis of MF. Approximately 40% of essential thrombocythemia (ET: n = 16) and primary MF (n = 4) showed the JAK2 V617F mutation, whereas 6 of 8 patients with polycythemia vera showed the mutation. Of note is that 2 of 6 patients with myelodysplastic syndromes (MDS) terminating in MF showed the mutation, while no MDS patient without MF (MDS: n = 3) had the JAK2 V617F mutation. Our study clearly demonstrated that MF in MDS patients is sometimes associated with JAK2 V617F mutation, while other underlying diseases developing MF may involve other pathways. Moreover, it permits speculation that clonal evolution in some MDS patients with the JAK2 V617F tyrosine kinase mutation may be responsible for secondary MF.
Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with myelocytic leukemia: Preliminary studies on therapeutic efficacy and toxicity (1998)

Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was shown to have pharmacological activity for the treatment of myelocytic leukemia in patients refractory to cytosine arabinoside (Ara C), retinoic acid, and other antileukemic drugs. Marked decreases in bone marrow myeloblasts as well as temporary remission of disease symptoms were observed when TPA was administered alone or in combination with vitamin D3 and Ara C. Additional studies with TPA after the determination of optimum dosing regimens are needed to determine whether long-lasting or permanent remissions of myelocytic leukemia can be achieved. Transient and reversible side effects were observed after a 1-mg i.v. dose of TPA, but these adverse effects became less intense or disappeared when a lower dose of TPA was used. The results of this study indicate a therapeutic effect of TPA in patients with myelocytic leukemia.
Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets (2000)

There remains a remarkable discordance between the results of observational epidemiological studies and intervention trials using beta-carotene as a potential chemopreventive agent. One question that needs to be examined is whether the adverse outcomes of human beta-carotene trials are related to the large doses of beta-carotene that were administered. In the present study, ferrets were given a physiological (low) dose or a pharmacological (high) dose of beta-carotene supplementation (0.43 mg versus 2.4 mg/kg body wt/day, which is equivalent to 6 mg versus 30 mg/day in humans) and exposed to cigarette smoke for 6 months. We investigated the effects of these doses of beta-carotene on retinoid concentrations, expression of retinoic acid receptors (RARs), activator protein 1 (AP-1; c-Jun and c-Fos), cyclin D1, proliferating cellular nuclear antigen (PCNA), and histopathological changes in the lungs of both normal and cigarette smoke-exposed ferrets. Thirty-six male ferrets were treated in six groups-control, smoke-exposed (SM), low-dose beta-carotene (LBC), high-dose beta-carotene (HBC), low-dose beta-carotene plus smoke exposure (LBC+SM) or high-dose beta-carotene plus smoke exposure (HBC+SM)-for 6 months. Retinoic acid concentration and RAR beta gene expression, but not expression of RAR alpha and RAR gamma, was reduced in the lung tissue of HBC+SM, HBC, SM and LBC+SM ferrets, but not in that of LBC ferrets, as compared with the control group. Expression of AP-1 and PCNA was greater in HBC+SM, HBC, SM and LBC+SM ferrets, but not in the LBC ferrets, as compared with the control group. Increased amounts of cyclin D1 and keratinized squamous metaplasia were observed in the lung tissue of HBC+SM, HBC and SM groups but not in that of the LBC+SM, LBC or control groups. These data suggest that, in contrast with a pharmacological dose of beta-carotene, a physiological dose of beta-carotene in smoke-exposed ferrets has no potentially detrimental effects and may afford weak protection against lung damage induced by cigarette smoke.
In Vivo Molecular Pharmacology and Antitumor Activity of the Targeted Akt Inhibitor PX-316 (2004)

Akt, a serine/threonine kinase that promotes cell survival, is activated by binding of its pleckstrin homology (PH) domain to membrane phosphatidylinositol (PtdIns)-3-phosphates formed by PtdIns-3-kinase. D-3-Deoxy-phosphatidyl-myo-inositols that cannot be phosphorylated on the 3-position of the myo-inositol group are inhibitors of the Akt PH domain. The most active compound is D-3-deoxy-phosphatidyl-myo-inositol 1-[(R)-2-methoxy-3-octadecyloxypropyl hydrogen phosphate] (PX-316). PX-316 administered intraperitoneally to mice at 150 mg/kg inhibits Akt activation in HT-29 human tumor xenografts up to 78% at 10 h with recovery to 34% at 48 h. Phosphorylation of GSK-3beta, a downstream target of Akt, is also inhibited. There is no decrease in PtdIns(3,4,5)-trisphosphate levels by PX-316, showing it is not an inhibitor of PtdIns-3-K in vivo. Gene expression profiling of HT-29 tumor xenografts shows many similarities between the effects of PX-316 and the PtdIns-3-K inhibitor wortmannin, with downregulation of several ribosomal-related genes, while PX-316 uniquely increases the expression of a group of mitochondrial-related genes. PX-316 has antitumor activity against early human MCF-7 breast cancer and HT-29 colon cancer xenografts in mice. PX-316 formulated in 20% hydroxypropyl-beta-cyclodextrin for intravenous administration is well tolerated in mice and rats with no hemolysis and no hematological toxicity. Thus, PX-316 is the lead compound of a new class of potential agents that inhibit Akt survival signaling.
Multicast function and its LSI implementation in a shared multibuffer ATM switch (2002)

There are several schemes to provide multicast function in an ATM switch. The authors have proposed a new multicast scheme in a shared buffering ATM switch. They discuss the cell-loss performance of ATM switch to compare various schemes. Computer simulation shows that this scheme achieves the best cell-loss performance and has a great advantage in the buffer size. Implementation of an LSI chip set and a 622 Mb/s 8/spl times/8 ATM switch board is also explained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Selective Interaction of Large or Charge-Transfer Aromatic Molecules with Metallic Single-Wall Carbon Nanotubes:  Critical Role of the Molecular Size and Orientation (2006)

Using first principles calculations, we report for the first time that large nearly neutral aromatic molecules, such as naphthalene and anthracene, and small charge-transfer aromatic molecules, such as TCNQ and DDQ, interact more strongly with metallic single-wall carbon nanotubes (SWNTs) versus their semiconducting counterparts as the molecular orientation of DDQ is taken into account. Hence two new mechanisms for separating metallic and semiconducting SWNTs via noncovalent pi-pi stacking or charge-transfer interaction are suggested.
Inter-Species Grafting Caused Extensive and Heritable Alterations of DNA Methylation in Solanaceae Plants (2013)

Our results demonstrate that inter-species grafting in plants could produce extensive and heritable alterations in DNA methylation. We suggest that these readily altered, yet heritable, epigenetic modifications due to interspecies hetero-grafting may shed one facet of insight into the molecular underpinnings for the still contentious concept of graft hybrid.
Human MI-ER1 Alpha and Beta Function as Transcriptional Repressors by Recruitment of Histone Deacetylase 1 to Their Conserved ELM2 Domain (2002)

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3' end of hmi-er1 produces two major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Using fusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.
Constructing the Collaborative Supply Logistics Operation Mode in Assembly System under JIT Environment (2011)

In the JIT assembly system, if any supplier does not deliver the raw materials or components on time, or in the right quantity, the core manufacturers will not assemble on the schedule, which will bring great loss to the whole supply chain and greatly reduce the competitiveness and collaboration of the entire supply chain. Based on a survey on supply chain collaboration and operation model, supply logistics in JIT environment are analyzed from both the inside and outside system with the research goal of coordinating the upstream supply logistics. In order to help manufacturers implement the JIT production, the VMI-Hub operation mode is proposed from the aspect of inside system, and from outside system, cross-docking dispatch operation mode is considered to coordinate the supply logistics in assembly system.
Genetically determined aberrant down-regulation of FcγRIIB1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus (1999)

Systemic lupus erythematosus (SLE) is a multigenic disease associated with IgG hypergammaglobulinemia, IgG anti-nuclear antibodies and immune complex (IC)-type glomerulonephritis. In both human and murine SLE, one susceptibility allele has been mapped to the interval linked to the IgG Fc receptor II (FcgammaRII) gene on chromosome 1. In spontaneous SLE models of NZB and (NZB x NZW) F(1) mice, expression of FcgammaRIIB1, which acts as a negative regulator for B cells, was abnormally down-regulated in follicular germinal center B cells from aged mice, compared to findings in non-SLE NZW, while levels in non-germinal center B cells were practically identical. Such strain differences were also evident in young mice upon in vivo stimulation with foreign antigens. In the FcgammaRIIB promoter region, the NZB allele has two deletion sites, including transcription factor-binding sites. Analyses using (NZB x NZW) F(1) x NZW backcross mice showed that this NZB allele was significantly linked to hyper-IgG, irrespective of the MHC haplotype, while high levels of IgG antibodies specific for DNA were regulated by a combinatorial effect of the F(1)-unique MHC haplotype and the NZB FcgammaRIIB allele. Therefore, the FcgammaRIIB promoter polymorphism may possibly predispose to SLE through germinal center B cells abnormally down-regulating FcgammaRIIB1 expression upon autoantigen stimulations and thus escaping negative signals for IgG production.
Inhibition of G1 to S Cell Cycle Progression by BCCIPb (2004)

The BCCIP alpha protein was identified as a BRCA2 and CDKN1A (p21, or p21(Waf1/Cip1)) Interacting Protein. It binds to a highly conserved domain proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK-inhibitor p21. Previous reports showed that BCCIP alpha enhances the inhibitory activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain tumor cells. Here we show that a second isoform, BCCIP beta, also binds to p21 and inhibits cell growth. The growth inhibition by BCCIP beta can be partially abrogated in p21 deficient cells. Overexpression of BCCIP beta delays the G1 to S progression and results in an elevated p21 expression. These data suggest BCCIP beta as a new regulator for the G1-S cell cycle progression and cell growth control.
Visualization of construction graphics in outdoor augmented reality (2005)

This paper describes research that investigates the application of augmented reality (AR) in 3D animation of simulated construction operations. The objective is an AR-based platform that can be used together with corresponding equipment (HMD, GPS receiver, and a portable computer) to generate a mixed view of the real world and superimposed virtual simulation objects in an outdoor environment. The characteristic that distinguishes the presented work from indoor AR applications is the capability to produce real time updated output as the user moves around while applying minimum constraints over the user's position and orientation. The ability to operate independently of environmental factors (e.g. lighting conditions and terrain variations) makes the described framework a powerful tool for outdoor AR applications. This paper presents initial results and an AR platform prototype (UM-AR-GPS-ROVER) that is able to place 3D graphical objects at any desired location in outdoor augmented space.
Transcriptional Analysis of an Ammonium-Excreting Strain of Azotobacter vinelandii Deregulated for Nitrogen Fixation (2017)

Biological nitrogen fixation is accomplished by a diverse group of organisms known as diazotrophs and requires the function of the complex metalloenzyme nitrogenase. Nitrogenase and many of the accessory proteins required for proper cofactor biosynthesis and incorporation into the enzyme have been characterized, but a complete picture of the reaction mechanism and key cellular changes that accompany biological nitrogen fixation remain to be fully elucidated. Studies have revealed that specific disruptions of the antiactivator-encoding gene <i>nifL</i> result in the deregulation of the <i>nif</i> transcriptional activator NifA in the nitrogen-fixing bacterium <i>Azotobacter vinelandii</i>, triggering the production of extracellular ammonium levels approaching 30 mM during the stationary phase of growth. In this work, we have characterized the global patterns of gene expression of this high-ammonium-releasing phenotype. The findings reported here indicated that cultures of this high-ammonium-accumulating strain may experience metal limitation when grown using standard Burk's medium, which could be amended by increasing the molybdenum levels to further increase the ammonium yield. In addition, elevated levels of nitrogenase gene transcription are not accompanied by a corresponding dramatic increase in hydrogenase gene transcription levels or hydrogen uptake rates. Of the three potential electron donor systems for nitrogenase, only the <i>rnf1</i> gene cluster showed a transcriptional correlation to the increased yield of ammonium. Our results also highlight several additional genes that may play a role in supporting elevated ammonium production in this aerobic nitrogen-fixing model bacterium.<b>IMPORTANCE</b> The transcriptional differences found during stationary-phase ammonium accumulation show a strong contrast between the deregulated (<i>nifL</i>-disrupted) and wild-type strains and what was previously reported for the wild-type strain under exponential-phase growth conditions. These results demonstrate that further improvement of the ammonium yield in this nitrogenase-deregulated strain can be obtained by increasing the amount of available molybdenum in the medium. These results also indicate a potential preference for one of two ATP synthases present in <i>A. vinelandii</i> as well as a prominent role for the membrane-bound hydrogenase over the soluble hydrogenase in hydrogen gas recycling. These results should inform future studies aimed at elucidating the important features of this phenotype and at maximizing ammonium production by this strain.
Helminths and the IBD hygiene hypothesis (2008)

Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.
Assay for the terminal enzyme of the stearoyl coenzyme A desaturase system using chick embryo liver microsomes (1977)

The NADH-dependent stearoyl CoA desaturase of hepatic microsomes (EC 1.14.99.5) is an enzyme system consisting of cytochrome b5 reductase (EC 1.6.2.2), cytochrome b5, and the terminal desaturase. We have developed a simple method for routine assay of the terminal enzyme based on complementation of the enzyme with chick embryo liver microsomes lacking desaturase activity. Desaturation of [1-14C]stearoyl CoA by the enzyme-microsome mixture is then assayed by thin-layer chromatography of the reaction products and determination of the amount of oleate formed. Microsomes from the livers of starved-refed rats were used as the source of the stearoyl CoA desaturase. The enzyme alone, solubilized and free from cytocrome b5 reductase and cytochrome b5, was unable to catalyze the desaturation of stearoyl CoA. However, after preincubation with chick embryo liver microsomes in the presence of 1% Triton X-100, the enzyme was active. The enzyme activity was linear with time and desaturase protein under the conditions described and depended on the concentrations of Triton X-100 present in the preincubation and the assay. The optimum concentrations of Triton X-100 were 1% for the preincubation and 0.1-0.15% in the assay. The desaturation activity was dependent on NADH and O2, and was inhibited 95% by 1 mM KCN. The use of chick embryo liver microsomes in this method eliminates the need to use purified cytochrome b5 reductase, cytochrome b5, and liposomes for routine assays and greatly reduces the complexities of timing and order of addition encountered in the existing assays.
Effects of Rhizosphere Colonization by Plant Growth-Promoting Rhizobacteria on Potato Plant Development and Yield (2008)

Two strains of fluorescent <i>Pseudomonas</i> spp. isolated from potato periderms and from celery roots significantly increased growth of potato plants up to 500% greater than controls in greenhouse assays. Mutants of these plant growth-promoting rhizobacteria (PGPR) resistant to rifampicin and nalidixic acid rapidly colonized rhizospheres of roots emerging from treated seed pieces in field tests. The bacteria colonized the entire rhizosphere of treated plants including developing daughter tubers and the apical roots of adjacent nontreated plants. PGPR rhizosphere populations were as great as 9.6 × 10<sup>5</sup> colony-forming units per centimeter (cfu/cm) of root 2 wk after plant emergence and averaged 10<sup>3</sup> cfu/cm throughout the season, but declined to approximately 10<sup>2</sup> cfu/cm at harvest time. PGPR populations were relatively constant throughout the root system. Field tests were done in various soil types with pH ranges from 6.8 to 7.8. PGPR rhizosphere colonization resulted in significant increases in stolon length 2 wk after plant emergence in all six sampled fields. The early season plant growth promotion caused by PGPR was followed by significant yield increases up to 17% compared to untreated controls in four of five harvested fields.
Differential Control of Yersinia pestis Biofilm Formation In Vitro and in the Flea Vector by Two c-di-GMP Diguanylate Cyclases (2011)

Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC) enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE), encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in c-di-GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hms-independent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP) and two DGCs (HmsT and Y3730) control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis.