gebhart/patrepeval huggingface dataset:
Normobaric oxygen as a sensitizer in radiotherapy for advanced head and neck cancer. (1995)

The aim of this study was to evaluate radiosensitizing effect of normobaric oxygen breathing in radiotherapy for advanced head and neck cancers. Forty seven patients with advanced squamous cell carcinomas of the head and neck (7% in Stage III and 93% in Stage IV) were entered in the study. Breathing the pure, normobaric oxygen was given for 15-20 min in the treatment room. Irradiation started immediately after oxygen breathing. Conventional, megavoltage radiotherapy to the total doses in the range of 46-67.5 Gy was used. The control group was 46 patients with the same diagnosis and stage treated by radiotherapy alone. Locoregional tumor control was 36% in the study group compared to 15% in the control (p < 0.05). Mean survival time was 15.8 and 11.8 months, and 3-year survival was 19% and 2%, respectively (p < 0.05). Survival depended on total tumor dose and total nodal dose. No significant influence of the tumor location on local control and importance of the size of dose per fraction and overall treatment time were found. The most common failure in both groups was persistent tumor. Mean recurrence time was 5 months in the study group and 8 months in the control. Present results suggest that the use of normobaric oxygen breathing prior to irradiation could increase effectiveness of conventional radiotherapy for advanced squamous cell carcinomas of head and neck.
Stopped Flow Fluorescence Energy Transfer Measurement of the Rate Constants Describing the Reversible Formation and the Irreversible Rearrangement of the Elastase-α1-Proteinase Inhibitor Complex (1998)

Serpins are thought to inhibit proteinases by first forming a Michaelis-type complex that later converts into a stable inhibitory species. However, there is only circumstantial evidence for such a two-step reaction pathway. Here we directly observe the sequential appearance of two complexes by measuring the time-dependent change in fluorescence resonance energy transfer between fluorescein-elastase and rhodamine-alpha1-protease inhibitor. A moderately tight initial Michaelis-type complex EI1 (Ki = 0.38-0.52 microM) forms and dissociates rapidly (k1 = 1.5 x 10(6) M-1 s-1, k-1 = 0.58 s-1). EI1 then slowly converts into EI2 (k2 = 0.13 s-1), the fluorescence intensity of which is stable for at least 50 s. The two species differ by their donor-acceptor energy transfer efficiency (0. 41 and 0.26, respectively). EI2 might be the final product of the elastase + inhibitor association because its transfer efficiency is the same as that of a complex incubated for 30 min. The time-dependent change in fluorescence resonance energy transfer between fluorescein-elastase and rhodamine-eglin c, a canonical inhibitor, again allows the fast formation of a complex to be observed. However, this complex does not undergo any fluorescently detectable transformation.
Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development (1996)

TIE is a receptor tyrosine kinase expressed in both mature endothelial cells and their precursors, as well as in some hematopoietic cells. Mouse embryos homozygous for a disrupted Tie allele die at midgestation due to impaired endothelial cell integrity and resulting hemorrhage. Here we have performed chimeric analysis to study further the function of the murine TIE in the development of embryonic vasculature and in the hematopoietic system. Cells lacking a functional Tie gene (tie(lcz)/tie(lczn-) cells) contributed to the embryonic vasculature at E10.5 as efficiently as cells heterozygous for a targeted Tie allele (tie(lcz)/+ cells). Thus, TIE does not play a significant role in vasculogenesis or in early angiogenic processes, such as formation of the intersomitic arteries and limb bud vascularization. At E15.5 tie(lcz)/tie(lczn-) cells still readily contributed to major blood vessels and to endothelial cells of organs such as lung and heart, which have been suggested to be vascularized by angioblast differentiation. In contrast, the tie(lcz)/tie(lczn-) cells were selected against in the capillary plexuses of several angiogenically vascularized tissues, such as brain and kidney. Our results thus support a role for TIE in late phases of angiogenesis but not vasculogenesis. Furthermore, the results suggest that different mechanisms regulate early and late angiogenesis and provide support for a model of differential organ vascularization by vasculogenic or angiogenic processes. Analysis of adult chimeras suggested that TIE is required to support the survival or proliferation of certain types of endothelial cells demonstrating heterogeneity in the growth/survival factor requirements in various endothelial cell populations. Chimeric analysis of adult hematopoietic cell populations, including peripheral platelets and bone marrow progenitor cells, revealed that tie(lcz)/tie(lczn-) cells were able to contribute to these cell types in a way indistinguishable from tie(lcz)/+ or wild-type cells. Thus, the primary function of TIE appears to be restricted to the endothelial cell lineage.
Cloud-based security mechanisms for critical information infrastructure protection (2013)

In this paper the suitability of cloud-based security services (SECaaS) for critical information infrastructure protection (CIIP) is discussed. A background of cloud-based security services is provided. The suitability of these services for CIIP is discussed, and it is concluded that a mixed cloud and traditional solution is best. A model for providing cloud-based protection to critical infrastructure in this manner is proposed.
Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells (2004)

Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.
NG2 Is a Major Chondroitin Sulfate Proteoglycan Produced after Spinal Cord Injury and Is Expressed by Macrophages and Oligodendrocyte Progenitors (2002)

Several extracellular matrix (ECM) molecules have been identified as potent inhibitors of neurite outgrowth in vitro and are believed to limit axonal growth after CNS injury. Recent studies have shown that different members of the chondroitin sulfate proteoglycan (CSPG) class of putatively inhibitory ECM molecules are expressed after a number of CNS injuries. The purpose of this study was to evaluate the relative amounts of individual CSPGs expressed after spinal cord injury (SCI) and identify their cells of origin. Evaluation of total soluble CSPGs 2 weeks after dorsal column lesion in the rat demonstrated that NG2 is highly upregulated and is a major CSPG species. Immunocytochemical analysis further demonstrated that NG2 expression is upregulated within 24 hr of injury, peaks at 1 week, and remains elevated for at least an additional 7 weeks. NG2 expression results from a multicellular response to injury, including both reactive macrophages and oligodendrocyte progenitors; astrocytes were not identified as a major source of NG2. Immunocytochemical analysis of other CSPG family members 7 d after injury showed moderate upregulation of versican, brevican, and neurocan, and downregulation of phosphacan. Axonal tracing experiments demonstrated dense NG2 labeling adjacent to the forward processes of transected corticospinal tract axons in a spatial profile that could restrict axonal growth. Thus, NG2 is a major component of this putatively inhibitory class of ECM molecules expressed at sites of SCI and may restrict axonal regeneration.
Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom) (2010)

Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the mixed lineage leukemia (MLL) partners in leukemia such as ENL, AF9/MLLT3, AF17/MLLT6, and AF10/MLLT10, as well as the known Wnt pathway modifiers TRRAP, Skp1, and beta-catenin. We demonstrated that the human DotCom is indeed capable of trimethylating H3K79 and, given the association of beta-catenin, Skp1, and TRRAP, we investigated, and found, a role for Dot1 in Wnt/Wingless signaling in an in vivo model system. Knockdown of Dot1 in Drosophila results in decreased expression of a subset of Wingless target genes. Furthermore, the loss of expression for the Drosophila homologs of the Dot1-associated proteins involved in the regulation of H3K79 shows a similar reduction in expression of these Wingless targets. From yeast to human, specific trimethylation of H3K79 by Dot1 requires the monoubiquitination of histone H2B by the Rad6/Bre1 complex. Here, we demonstrate that depletion of Bre1, the E3 ligase required for H2B monoubiquitination, leads specifically to reduced bulk H3K79 trimethylation levels and a reduction in expression of many Wingless targets. Overall, our study describes for the first time the components of DotCom and links the specific regulation of H3K79 trimethylation by Dot1 and its associated factors to the Wnt/Wingless signaling pathway.
117. Diazaindenes and their quaternary salts. Part II. The cyclisation of isopropyl methyl ketone 3-pyridylhydrazone (1961)

G. E. Ficken and J. D. Kendall, J. Chem. Soc., 1961, 584 DOI: 10.1039/JR9610000584
A new chiral ligand for the asymmetric conjugate addition of organocopper reagents to enones (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new chiral ligand for the asymmetric conjugate addition of organocopper reagents to enonesAlexandre Alexakis, Stephane Mutti, and Jean F. NormantCite this: J. Am. Chem. Soc. 1991, 113, 16, 6332–6334Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/ja00016a094https://doi.org/10.1021/ja00016a094research-articleACS PublicationsRequest reuse permissionsArticle Views649Altmetric-Citations93LEARN 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 Get e-Alerts
Anticlusterin treatment of breast cancer cells increases the sensitivities of chemotherapy and tamoxifen and counteracts the inhibitory action of dexamethasone on chemotherapy-induced cytotoxicity (2007)

These data suggest that combined treatment with antibodies to clusterin or antisense clusterin oligodeoxynucleotides and paclitaxel, doxorubicin, or tamoxifen could be a novel and attractive strategy to inhibit the progression of breast carcinoma by regulation of the clusterin function. Moreover, glucocorticoid activation in breast cancer cells regulates survival signaling by the direct transactivation of genes like clusterin which encode proteins that decrease susceptibility to apoptosis. Given the widespread clinical administration of dexamethasone before chemotherapy, understanding glucocorticoid-induced survival mechanisms is essential for achieving optimal therapeutic responses.
Oligomerization of DNMT3A Controls the Mechanism of de Novo DNA Methylation (2011)

DNMT3A is one of two human de novo DNA methyltransferases essential for regulating gene expression through cellular development and differentiation. Here we describe the consequences of single amino acid mutations, including those implicated in the development of acute myeloid leukemia (AML) and myelodysplastic syndromes, at the DNMT3A·DNMT3A homotetramer and DNMT3A·DNMT3L heterotetramer interfaces. A model for the DNMT3A homotetramer was developed via computational interface scanning and tested using light scattering and electrophoretic mobility shift assays. Distinct oligomeric states were functionally characterized using fluorescence anisotropy and steady-state kinetics. Replacement of residues that result in DNMT3A dimers, including those identified in AML patients, show minor changes in methylation activity but lose the capacity for processive catalysis on multisite DNA substrates, unlike the highly processive wild-type enzyme. Our results are consistent with the bimodal distribution of DNA methylation in vivo and the loss of clustered methylation in AML patients. Tetramerization with the known interacting partner DNMT3L rescues processive catalysis, demonstrating that protein binding at the DNMT3A tetramer interface can modulate methylation patterning. Our results provide a structural mechanism for the regulation of DNMT3A activity and epigenetic imprinting.
Decoding a Substantial Set of Samples in Parallel by Massive Sequencing (2011)

There has been a dramatic increase of throughput of sequenced bases in the last years but sequencing a multitude of samples in parallel has not yet developed equally. Here we present a novel strategy where the combination of two tags is used to link sequencing reads back to their origins from a pool of samples. By incorporating the tags in two steps sample-handling complexity is lowered by nearly 100 times compared to conventional indexing protocols. In addition, the method described here enables accurate identification and typing of thousands of samples in parallel. In this study the system was designed to test 4992 samples using only 122 tags. To prove the concept of the two-tagging method, the highly polymorphic 2(nd) exon of DLA-DRB1 in dogs and wolves was sequenced using the 454 GS FLX Titanium Chemistry. By requiring a minimum sequence depth of 20 reads per sample, 94% of the successfully amplified samples were genotyped. In addition, the method allowed digital detection of chimeric fragments. These results demonstrate that it is possible to sequence thousands of samples in parallel without complex pooling patterns or primer combinations. Furthermore, the method is highly scalable as only a limited number of additional tags leads to substantial increase of the sample size.
Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection (2016)

Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV-cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Memory T cells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.
Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol (2016)

In conclusion, our study demonstrates a dose-dependent physiological effect of human IDOL on LDL metabolism in mice. This provides a potential model for preclinical testing of IDOL inhibitors for reduction of LDL-C levels.
Induction of an Inflammatory Loop by Interleukin-1β and Tumor Necrosis Factor-α Involves NF-kB and STAT-1 in Differentiated Human Neuroprogenitor Cells (2013)

Proinflammatory cytokines secreted from microglia are known to induce a secondary immune response in astrocytes leading to an inflammatory loop. Cytokines also interfere with neurogenesis during aging and in neurodegenerative diseases. The present study examined the mechanism of induction of inflammatory mediators at the transcriptional level in human differentiated neuroprogenitor cells (NPCs). Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced the expression of cytokines and chemokines in differentiated human NPCs as shown by an immune pathway-specific array. Network motif (NM) analysis of these genes revealed 118 three-node NMs, suggesting complex interactions between inflammatory mediators and transcription factors. Immunofluorescent staining showed increases in the levels of IL-8 and CXCL10 proteins in neurons and glial cells. Findings from Taqman low density array suggested the synergistic actions of IL-1β and TNF-α in the induction of a majority of inflammatory genes by a mechanism involving NF-kB and STAT-1. Nuclear localization of these transcription factors in differentiated NPCs was observed following exposure to IL-1α and TNF-α. Further studies on CXCL10, a chemokine known to be elevated in the Alzheimer's brain, showed that TNF-α is a stronger inducer of CXCL10 promoter when compared to IL-1β. The synergy between these cytokines was lost when ISRE or kB elements in CXCL10 promoter were mutated. Our findings suggest that the activation of inflammatory pathways in neurons and astrocytes through transcription factors including NF-kB and STAT-1 play important roles in neuroglial interactions and in sustaining the vicious cycle of inflammatory response.
A high-efficiency electromechanical battery (1993)

The electromechanical battery (EMB) is considered as an alternative energy storage system for electric utilities and other applications. An EMB is a modular unit consisting of an evacuated housing containing a fiber-composite rotor. The rotor is supported by magnetic bearings and contains an integrally mounted permanent magnet array. Recent developments in high-strength fibers, in permanent-magnet materials, and in solid-state power electronics allow the design of small (1 kW-h) modular EMBs for full-or hybrid-electric vehicles, and larger size modules (25 kW-h) for a variety of stationary storage needs. Design issues for EMBs with rotors made up of nested cylinders are addressed. Rotational stability, stress distributions, generator/motor power and efficiency, power conversion, and cost are discussed. It is concluded that the use of EMBs in electric autos could result in a fivefold reduction (relative to the IC engine) in the primary energy input required for urban driving, with a concommitant major positive impact on the economy and on air pollution.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Surface‐Modified Dendrimer Set for Potential Application as Drug Delivery Vehicles: Synthesis, In Vitro Toxicity, and Intracellular Localization (2004)

The synthesis, cytotoxicity, and behavior in cell culture of a new set of first- (G1) and second-generation (G2) dendrimers is reported. The surface functionality of these dendrimers has been varied to see whether structure/toxicity relations can be observed. The outermost functional groups are amines that are decorated either with protons, tert-butoxycarbonyl (Boc) or benzyloxycarbonyl (Cbz) protecting groups, Boc-protected or unprotected natural amino acid residues, ethylenediamine ligands, and/or dansyl fluorescence labels. The cytotoxicity was determined in vitro in concentration-dependent assays using the human MCF-7 breast cancer cell line. Cellular uptake and intracellular distribution was monitored by confocal fluorescence microscopy after internalization of the dansyl-labeled dendrimers by HeLa cells.
Anti-apoptotic proteins-targets for chemosensitization of tumor cells and cancer treatment. (2005)

Apoptosis or programmed cell death is an essential process not only for the normal development and function of multi-cellular organisms but it is also an important phenomenon in tumor cells killing. Numerous studies have indicated that non surgical cancer therapies eliminate tumor cells by activating apoptosis. The central regulators of apoptosis are proteins of the Bcl-2 family. In a wide variety of human tumors, the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-(XL)) was found. Moreover, it was revealed that high levels of these proteins block the action of many chemotherapeutic drugs. Due to this fact the inhibition of anti-apoptotic function of Bcl-2 proteins could be a strategy for either to restore the normal apoptotic process in tumor cells or to make them susceptible for chemo- and radio-therapeutic treatment. Three alternative therapeutic strategies for the repression of cytoprotective activity of anti-apoptotic proteins in tumor cells are reviewed in this article.
Higher Hydrocarbons.1 IV.2 Six Phenyleicosanes and Six Cyclohexyleicosanes (1947)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigher Hydrocarbons.1 IV.2 Six Phenyleicosanes and Six CyclohexyleicosanesFrank C. Whitmore, Robert W. Schiessler, C. S. Rowland, and J. N. CosbyCite this: J. Am. Chem. Soc. 1947, 69, 2, 235–237Publication Date (Print):February 1, 1947Publication History Published online1 May 2002Published inissue 1 February 1947https://pubs.acs.org/doi/10.1021/ja01194a016https://doi.org/10.1021/ja01194a016research-articleACS PublicationsRequest reuse permissionsArticle Views56Altmetric-Citations17LEARN 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 Get e-Alerts