gebhart/patrepeval huggingface dataset:
p53-independent apoptosis induced by paclitaxel through an indirect mechanism (1997)

The efficacy of chemotherapeutic agents may be determined by a number of different factors, including the genotype of the tumor cell. The p53 tumor suppressor gene frequently is mutated in human tumors, and this may contribute to chemotherapeutic resistance. We tested the requirement for wild-type p53 in the response of tumor cells to treatment with paclitaxel (trade name Taxol), an antineoplastic agent that stabilizes cellular microtubules. Although paclitaxel is broadly effective against human tumor xenografts in mice, including some known to carry p53 mutations, we found that p53-containing mouse tumor cells were significantly more sensitive to direct treatment with this drug than were p53-deficient tumor cells. In an attempt to reconcile this apparent discrepancy, we examined the requirement for p53 in the cytotoxic effects of tumor necrosis factor alpha (TNF-alpha), a cytokine released from murine macrophages upon paclitaxel treatment. Conditioned medium from paclitaxel-treated macrophages was capable of inducing p53-independent apoptosis when applied to transformed mouse embryonic fibroblasts and was inhibitable by antibodies against TNF-alpha. Furthermore, in response to direct treatment with TNF-alpha, both wild-type and p53-deficient tumor cells underwent apoptosis to similar extents and with similar kinetics. Our results suggest that the efficacy of paclitaxel in vivo may be due not only to its microtubule-stabilizing activity, but its ability to activate local release of an apoptosis-inducing cytokine.
Bile acids promote diethylnitrosamine-induced hepatocellular carcinoma via increased inflammatory signaling (2016)

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC, but the mechanisms are not known. We investigated the mechanisms of HCC tumor promotion by bile acids the diethylnitrosamine (DEN)-initiation-cholic acid (CA)-induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in threefold increase in number and size of DEN-induced liver tumors. All tumors observed in DEN-treated mice were well-differentiated HCCs. The HCCs observed in DEN-treated CA-fed mice exhibited extensive CD3-, CD20-, and CD45-positive inflammatory cell aggregates. Microarray-based global gene expression studies combined with Ingenuity Pathway Analysis revealed significant activation of NF-κB and Nanog in the DEN-treated 0.2% CA-fed livers. Further studies showed significantly higher TNF-α and IL-1β mRNA, a marked increase in total and phosphorylated-p65 and phosphorylated IκBα (degradation form) in livers of DEN-treated 0.2% CA-fed mice. Treatment of primary mouse hepatocytes with various bile acids showed significant induction of stemness genes including Nanog, KLF4, Sox2, and Oct4. Quantification of total and 20 specific bile acids in liver, and serum revealed a tumor-associated bile acid signature. Finally, quantification of total serum bile acids in normal, cirrhotic, and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.
Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. (1996)

Reactive oxygen species play a central role in vascular inflammation and atherogenesis, with enhanced superoxide (O2.-) production contributing significantly to impairment of nitric oxide (.NO)-dependent relaxation of vessels from cholesterol-fed rabbits. We investigated potential sources of O2.- production, which contribute to this loss of endothelium-dependent vascular responses. The vasorelaxation elicited by acetylcholine (ACh) in phenylephrine-contracted, aortic ring segments was impaired by cholesterol feeding. Pretreatment of aortic vessels with either heparin, which competes with xanthine oxidase (XO) for binding to sulfated glycosaminoglycans, or the XO inhibitor allopurinol resulted in a partial restoration (36-40% at 1 muM ACh) of ACh-dependent relaxation. Furthermore, O2.(-)-dependent lucigenin chemiluminescence, measured in intact ring segments from hypercholesterolemic rabbits, was decreased by addition of heparin, allopurinol or a chimeric, heparin-binding superoxide dismutase. XO activity was elevated more than two-fold in plasma of hypercholesterolemic rabbits. Incubation of vascular rings from rabbits on a normal diet with purified XO (10 milliunits/ml) also impaired .NO-dependent relaxation but only in the presence of purine substrate. As with vessels from hypercholesterolemic rabbits, this effect was prevented by heparin and allopurinol treatment. We hypothesize that increases in plasma cholesterol induce the release of XO into the circulation, where it binds to endothelial cell glycosaminoglycans. Only in hypercholesterolemic vessels is sufficient substrate available to sustain the production of O2.- and impair NO-dependent vasorelaxation. Chronically, the continued production of peroxynitrite, (ONOO-) which the simultaneous generation of NO and O2.- implies, may irreversibly impair vessel function.
Structure and electronic properties of a nongraphitic disordered carbon system and its heat-treatment effects (2003)

The heat-treatment effect on electronic properties is investigated in relation to structural change for pulsed-laser-deposited amorphous carbon thin films having ${\mathrm{sp}}^{2}{/sp}^{3}$ ratio $\ensuremath{\approx}9.$ The heat treatment at temperatures 200--400 $\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$ increases conductivity and modifies the hopping conduction mechanism at low temperatures, resulting in the generation of a Coulomb gap at ${E}_{\mathrm{F}}.$ This is attributed to the heat-treatment-induced modification of the disorder nature of the structure from atomic-scale ${\mathrm{sp}}^{2}{/sp}^{3}$ disorder to a disordered graphitic ${\mathrm{sp}}^{2}$-domain network by the migration of ${\mathrm{sp}}^{3}$ defects. In the heat-treatment temperature region above $600\ifmmode^\circ\else\textdegree\fi{}\mathrm{C},$ where the structure is featured with graphitic ${\mathrm{sp}}^{2}$ domains, considerably small positive thermoelectric power is suggestive of carrier compensation by the competition of hole and electron carriers that originate from the inhomogeneous charge distribution caused by the difference of Fermi levels among graphitic ${\mathrm{sp}}^{2}$ domains. In the high-heat-treatment-temperature region $800--1100\ifmmode^\circ\else\textdegree\fi{}\mathrm{C},$ the formation of an infinite percolation path network of the graphitic ${\mathrm{sp}}^{2}$ domains induces an insulator-to-metal transition, where the electron transport in the ${\mathrm{sp}}^{2}$-rich metallic state is featured by weakly temperature-dependent conductivity with majority hole and minority electron carriers.
Efficient four fragment cloning for the construction of vectors for targeted gene replacement in filamentous fungi (2008)

The new vectors designed for USER Friendly cloning provided a fast reliable method to construct vectors for targeted gene manipulations in fungi.
Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells. (1992)

The mammalian tachykinin system consists of three distinct peptides, substance P, substance K, and neuromedin K, and possesses three corresponding receptors. In this investigation we examined intracellular signal transduction of the individual tachykinin receptors by transfection and stable expression of these receptor cDNAs in Chinese hamster ovary cells. The three receptors commonly showed a rapid and marked stimulation in both phosphatidylinositol (PI) hydrolysis and cyclic AMP formation in response to tachykinin interaction. Direct linkage of the three receptors to both phospholipase C and adenylate cyclase was evidenced by the finding that tachykinin, added together with GTP, activated these enzyme activities in membrane preparations derived from tachykinin receptor-expressing cells. The stimulation of cyclic AMP formation was less efficient than that of PI hydrolysis in receptor-expressing cells as well as their membrane preparations (about 1 order of magnitude difference in the effective peptide concentrations). However, the stimulatory responses of the PI hydrolysis and cyclic AMP formation in both receptor-expressing cells and their membrane preparations were induced in complete agreement with the tachykinin binding selectivity of each subtype of the receptors. This investigation demonstrated unequivocally that the tachykinin receptors have the potential to couple directly to both phospholipase C and adenylate cyclase and to stimulate PI hydrolysis and cyclic AMP formation.
Identification of 43StreptococcusSpecies by Pyrosequencing Analysis of thernpBGene (2005)

Pyrosequencing technology was evaluated for identification of species within the Streptococcus genus. Two variable regions in the rnpB gene, which encodes the RNA subunit of endonuclease P, were sequenced in two reactions. Of 43 species, all could be identified to the species level except strains of the species pairs Streptococcus anginosus/S. constellatus and S. infantis/S. peroris. A total of 113 blood culture isolates were identified by pyrosequencing analysis of partial rnpB sequences. All but eight isolates could be unambiguously assigned to a specific species when the first 30 nucleotides of the two regions were compared to an rnpB database comprising 107 streptococcal strains. Principal coordinate analysis of sequence variation of strains from viridans group streptococci resulted in species-specific clusters for the mitis and the salivarius groups but not for the anginosus group. The identification capacity of pyrosequencing was compared to the biochemical test systems VITEK 2 and Rapid ID 32 Strep. The concordance between pyrosequencing and VITEK 2 was 75%, and for Rapid ID 32 Strep the corresponding figure was 77%. Isolates with discrepant identifications in the three methods were subjected to entire rnpB DNA sequence analysis that confirmed the identifications by pyrosequencing. In conclusion, pyrosequencing analysis of the rnpB gene can reliably identify Streptococcus species with high resolution.
Effect of Anti–IL-15 Administration on T Cell and NK Cell Homeostasis in Rhesus Macaques (2016)

IL-15 has been implicated as a key regulator of T and NK cell homeostasis in multiple systems; however, its specific role in maintaining peripheral T and NK cell populations relative to other γ-chain (γc) cytokines has not been fully defined in primates. In this article, we address this question by determining the effect of IL-15 inhibition with a rhesusized anti-IL-15 mAb on T and NK cell dynamics in rhesus macaques. Strikingly, anti-IL-15 treatment resulted in rapid depletion of NK cells and both CD4(+) and CD8(+) effector memory T cells (TEM) in blood and tissues, with little to no effect on naive or central memory T cells. Importantly, whereas depletion of NK cells was nearly complete and maintained as long as anti-IL-15 treatment was given, TEM depletion was countered by the onset of massive TEM proliferation, which almost completely restored circulating TEM numbers. Tissue TEM, however, remained significantly reduced, and most TEM maintained very high turnover throughout anti-IL-15 treatment. In the presence of IL-15 inhibition, TEM became increasingly more sensitive to IL-7 stimulation in vivo, and transcriptional analysis of TEM in IL-15-inhibited monkeys revealed engagement of the JAK/STAT signaling pathway, suggesting alternative γc cytokine signaling may support TEM homeostasis in the absence of IL-15. Thus, IL-15 plays a major role in peripheral maintenance of NK cells and TEM However, whereas most NK cell populations collapse in the absence of IL-15, TEM can be maintained in the face of IL-15 inhibition by the activity of other homeostatic regulators, most likely IL-7.
Electron Transfer between Electrodes and Heme Proteins in Protein−DNA Films (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTElectron Transfer between Electrodes and Heme Proteins in Protein−DNA FilmsAlaa-Eldin F. Nassar, James F. Rusling, and Naotoshi NakashimaView Author Information Department of Chemistry, Box U-60 University of Connecticut, Storrs, Connecticut 06269-4060 Department of Applied Chemistry, Faculty of Engineering Nagasaki University, Nagasaki 852, Japan Cite this: J. Am. Chem. Soc. 1996, 118, 12, 3043–3044Publication Date (Web):March 27, 1996Publication History Received8 January 1996Published online27 March 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja960065vhttps://doi.org/10.1021/ja960065vrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views552Altmetric-Citations136LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Bioinorganic chemistry,Charge transfer,Electrodes,Genetics,Peptides and proteins Get e-Alerts
Body composition studies with intravenous nutrition. (1995)

Intravenous nutrition is a complex nutritional support system which is used for patients who are unable to take food through the normal enteric route. The nutritional protocols are complex and the patients being studies have many complicating factors which make determination of outcome difficult to measure. Body composition measures have proven to be very accurate in determining appropriate protocols for patient care. Because most of the patients being studied have a short term nutritional problem, appropriate period of study was found to be two weeks. In this model we have been able to consistently measure small changes in groups of between 10-15 patients. A large change which may occur in a more severe case could be demonstrated in simple patients. This model has demonstrated that 0.3 g of nitrogen per kg per day and 40 kcal of energy are necessary to maintain body composition over a 14 day period. This nutritional input appeared to be similar whether the patient was in the post-operative non septic state or in the pre-operative depleted condition. Studies were undertaken to show that nutritional benefit of changing from all-glucose to a lipid containing solution did not affect the nutritional outcome of therapy. The nutritional gains seen over the first 14 day period were sustained in a longer study of a small group of patients who were studied at two weekly intervals for 3 months. Subsequent to these studies it has been considered important to determine whether peripheral intravenous nutrition would be as effective as central intravenous nutrition. By adjusting the nutritional protocol such that it fulfilled the rules obtained by central intravenous studies we have demonstrated that peripheral iv nutrition can maintain body composition but that the amount of glucose required for this to occur is at least 30% of non-protein calories.
Rate distortion cost modeling of skip mode and early skip mode selection for H.264/MPEG-4 AVC (2008)

This paper proposed a linear rate-distortion (RD) cost model for skip mode in H.264/MPEG-4 AVC. The proposed RD cost model is derived theoretically based on the quantization scheme of H.264, and the simulation results also verify that the proposed RD cost model can estimate the RD cost of skip mode accurately. Based on the proposed RD cost model, an early skip mode selection algorithm is provided. The proposed early skip mode selection method can terminate the mode selection process adaptively and works well for both low complexity and high complexity video. Experimental results show that the proposed early skip mode selection algorithm can save the encoding time up to 56% with negligible performance loss compared with the original reference encoder.
Novel Approach to the Development of Effective H5N1 Influenza A Virus Vaccines: Use of M2 Cytoplasmic Tail Mutants (2007)

Outbreaks of highly pathogenic H5N1 influenza viruses in avian species began in Asia and have since spread to other continents. Concern regarding the pandemic potential of these viruses in humans is clearly warranted, and there is an urgent need to develop effective vaccines against them. Previously, we and others demonstrated that deletions of the M2 cytoplasmic tail caused a growth defect in A/WSN/33 (H1N1) influenza A virus in vitro (K. Iwatsuki-Horimoto, T. Horimoto, T. Noda, M. Kiso, J. Maeda, S. Watanabe, Y. Muramoto, K. Fujii, and Y. Kawaoka, J. Virol. 80:5233-5240, 2006; M. F. McCown and A. Pekosz, J. Virol. 79:3595-3605, 2005; M. F. McCown and A. Pekosz, J. Virol. 80:8178-8189, 2006). We therefore tested the feasibility of using M2 tail mutants as live attenuated vaccines against H5N1 virus. First we generated a series of highly pathogenic H5N1 (A/Vietnam/1203/04 [VN1203]) M2 cytoplasmic tail deletion mutants and examined their growth properties in vitro and in vivo. We found that one mutant, which contains an 11-amino-acid deletion from the C terminus (M2del11 virus), grew as well as the wild-type virus but replicated in mice less efficiently. We then generated a recombinant VN1203M2del11 virus whose hemagglutinin (HA) gene was modified by replacing sequences at the cleavage site with those of an avirulent type of HA (M2del11-HAavir virus). This M2del11-HAavir virus protected mice against challenge with lethal doses of homologous (VN1203; clade 1) and antigenically distinct heterologous (A/Indonesia/7/2005; clade 2) H5N1 viruses. Our results suggest that M2 cytoplasmic tail mutants have potential as live attenuated vaccines against H5N1 influenza viruses.
체육철학 : 다문화사회에서 사회통합을 위한 체육의 역할과 정책방향 제고 (2014)

다문화는 한국사회에서 고령화만큼이나 속도가 빠르게 진행되기 때문에 방치할 경우 다양한 사회적 갈등을 유발시켜 사회통합을 저해할 가능성이 높다. 따라서 다문화사회는 한국사회에서 중요한 사회현상으로 간주하여 이를 해결하기 위한 정책적 노력이 체계적으로 시행되어야 할 것이다. 그리하여 이 연구는 다문화사회에서 사회통합을 위한 체육의 역할을 재확인하고, 이에 따른 체육정책의 방향성을 모색하는데 목적이 있다. 우리나라보다 다문화사회의 경험이 빠른 호주, 미국, 프랑스, 독일 등의 다문화정책 사례를 통해 체육정책을 통한 다문화가정의 사회통합 실천이 세계적 추세임을 확인할 수 있었다. 따라서 체육은 다문화사회에서 사회통합을 도모하기 위한 다문화정책의 효율적인 수단임을 재확인하였다. 즉 체육은 사회적 갈등과 사회적 비용을 최소화시키기 위한 중요한 정책적 수단인 것이다. 그럼에도 우리나라의 다문화정책 중 체육정책의 시행은 인식부족으로 우선순위에 채택되지 못하고 있다. 따라서 다문화사회에서 체육정책의 방향성은 우선적으로 다문화주의 가치의 합리적 수용성을 담아내는 의식개혁 정책과 다문화가정의 체육실태 조사, 프로그램 개발 등에 중점을 둔 현장개혁 정책 중심으로 제고되어야 할 것이다. 이와 함께 정책시행 주체(중앙정부와 지방정부)와 협력 주체(대학교, 연구소, NGO 등) 상호교차간 긴밀한 체계 구축이 동반될 때 건강한 다문화사회 만들기가 현실화될 것이다.
Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy (2017)

Three-dimensional (3D) optical imaging of whole biological organs with microscopic resolution has remained a challenge. Most versions of such imaging techniques require special preparation of the tissue specimen. Here we demonstrate microtomy-assisted photoacoustic microscopy (mPAM) of mouse brains and other organs, which automatically acquires serial distortion-free and registration-free images with endogenous absorption contrasts. Without tissue staining or clearing, mPAM generates micrometer-resolution 3D images of paraffin- or agarose-embedded whole organs with high fidelity, achieved by label-free simultaneous sensing of DNA/RNA, hemoglobins, and lipids. mPAM provides histology-like imaging of cell nuclei, blood vessels, axons, and other anatomical structures, enabling the application of histopathological interpretation at the organelle level to analyze a whole organ. Its deep tissue imaging capability leads to less sectioning, resulting in negligible sectioning artifact. mPAM offers a new way to better understand complex biological organs.
A programmable pAgo nuclease with universal guide and target specificity from the mesophilic bacterium Kurthia massiliensis (2021)

ABSTRACT Argonaute proteins are programmable nucleases that are found in both eukaryotes and prokaryotes and provide defense against invading genetic elements. Although some prokaryotic Argonautes (pAgos) were shown to recognize RNA targets in vitro , the majority of studied pAgos have strict specificity toward DNA, which limits their practical use in RNA-centric applications. Here, we describe a unique KmAgo nuclease from the mesophilic bacterium Kurthia massiliensis that can be programmed with either DNA or RNA guides and can precisely cleave both DNA and RNA targets. KmAgo preferentially binds 16-20 nt long 5′-phosphorylated guide molecules with no strict specificity for their sequence and is active in a wide range of temperatures. In bacterial cells, KmAgo is loaded with small DNAs with no obvious sequence preferences suggesting that it can uniformly target genomic sequences. Target cleavage by KmAgo depends on the formation of secondary structure indicating that KmAgo can be used for structural probing of RNA targets. Mismatches between the guide and target sequences greatly affect the efficiency and precision of target cleavage, depending on the mismatch position and the nature of the reacting nucleic acid. These properties of KmAgo open the way for its use for highly specific nucleic acid detection and cleavage.
Noncontact Infrared-Mediated Thermocycling for Effective Polymerase Chain Reaction Amplification of DNA in Nanoliter Volumes (2000)

We demonstrate that accurate thermocycling of nanoliter volumes is possible using infrared-mediated temperature control. Thermocycling in the presence of Taq polymerase and the appropriate primers for amplification of lambda-DNA in a total volume of 160 nL is shown to result in the successful amplification of a 500-base pair fragment of lambda-DNA. The efficiency of the amplification is sufficiently high so that as few as 10 cycles were required to amplify an adequate mass of DNA for analysis by capillary electrophoresis. This indicates that, as expected, PCR amplification of DNA in nanoliter volumes should not only require less Taq polymerase but require less cycling time to produce a detectable amount of product. This sets the stage for microchip integration of the PCR process in the nanoliter volumes routinely manipulated in electrophoretic microchips.