gebhart/patrepeval huggingface dataset:
Enhanced photosensitivity in lightly doped standardtelecommunication fibreexposed to high fluence ArF excimer laser light (1995)

The core refractive index of Corning SMF-28 optical fibre exposed to ArF laser pulses increases with the square of the fluence per pulse. Bragg gratings with a refractive index modulation amplitude higher than 10-3 have been obtained. This is an order of magnitude improvement over previously reported values for this type of fibre in the absence of treatment to enhance the photosensitivity.
Preparation and Characterization of Antisense Oligonucleotide-Peptide Hybrids Containing Viral Fusion Peptides (1995)

We have developed a strategy for the synthesis of novel oligodeoxynucleotide (ODN)-peptide conjugates on a scale suitable for the investigation of their potential as antisense inhibitors of gene expression. These conjugates have the 3'-terminus of the antisense oligodeoxynucleotide linked covalently to the N-terminus of a peptide. This strategy allows the preparation of conjugates containing a peptide segment designed to facilitate intracellular delivery of the antisense oligodeoxynucleotide as well as providing protection against 3'-exonuclease digestion. To illustrate the synthetic approach we describe the preparation of a series of conjugates comprising antisense oligonucleotides to human immunodeficiency virus type 1 (HIV) linked to fusion peptides derived from the HIV transmembrane glycoprotein gp41. The conjugates were prepared by the total synthesis method, in which the peptide is assembled first by the N-(fluorenylmethoxycarbonyl) (Fmoc) solid-phase methodology. This is followed by derivatization of the amino terminus by reaction with an alpha,omega-hydroxycarboxylic acid derivative which converts the terminus to a protected aliphatic hydroxy group on which standard solid phase DNA synthesis by the phosphoramidite method is performed. The purified conjugates were characterized extensively by several analytical techniques including ion spray mass spectrometry. Thermal denaturation studies showed that the interaction of the ODN-peptide conjugate with its complementary strand was similar to that of unmodified oligonucleotides. Preparation by the total synthesis method gave the purified conjugate with overall yields in the range of 6-14%.
Gene sensor using ferrocenyl oligonucleotide (1997)

An electrochemical gene sensing system has been developed using a redox-active ferrocene-modified oligonucleotide and an oligonucleotide anchored on a gold electrode, both of which formed a sandwich-type ternary complex with the target DNA to give a redox current.
Activation of a muscle-specific actin gene promoter in serum-stimulated fibroblasts. (1992)

Treatment of AKR-2B mouse fibroblasts with serum growth factors or inhibitors of protein synthesis, such as cycloheximide, results in a stimulation of cytoskeletal beta-actin transcription but has no effect on transcription of muscle-specific isotypes, such as the vascular smooth muscle (VSM) alpha-actin gene. Deletion mapping and site-specific mutagenesis studies demonstrated that a single "CArG" element of the general form CC(A/T)6GG was necessary and possibly sufficient to impart serum and cycloheximide-inducibility to the beta-actin promoter. Although the VSM alpha-actin promoter exhibits at least three similar sequence elements, it remained refractory to serum and cycloheximide induction. However, deletion of a 33 base pair sequence between -191 and -224 relative to the transcription start site resulted in the transcriptional activation of this muscle-specific promoter in rapidly growing or serum-stimulated fibroblasts. Although the activity of this truncated promoter was potentiated by cycloheximide in a manner indistinguishable from that of the beta-actin promoter, this was dependent on a more complex array of interacting elements. These included at least one CArG box and a putative upstream activating element closely associated with the -191 to -224 inhibitory sequences. These results demonstrate that the expression of a muscle-specific actin gene in fibroblasts is suppressed by a cis-acting negative control element and that in the absence of this element, the promoter is responsive to growth factor-induced signal transduction pathways.
Sulfur-Substituted α-Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors:  Biological Activities, CoMFA Analysis, and Active Site Modeling (2005)

A series of phenethylamine derivatives with various ring substituents and with or without N-methyl and/or C-alpha methyl or ethyl groups was synthesized and assayed for their ability reversibly to inhibit monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Several compounds showed potent and selective MAO-A inhibitory activity (IC(50) in the submicromolar range) but none showed appreciable activity toward MAO-B. A three-dimensional quantitative structure-activity relationship study for MAO-A inhibition was performed on the series using comparative molecular field analysis (CoMFA). The resulting model gave a cross-validated q(2) of 0.72 and showed that in this series of compounds steric properties of the substituents were more important than electrostatic effects. Molecular modeling based on the recently published crystal structure of inhibitor-bound MAO-A provided detailed evidence for specific interactions of the ligands with the enzyme, supported by previous references and consistent with results from the CoMFA. On the basis of these results, structural determinants for selectivity of substituted amphetamines for MAO-A are discussed.
Prevention of autoimmune attack and disease progression in multiple sclerosis: current therapies and future prospects (2002)

Multiple sclerosis (MS) is an important cause of progressive neurological disability, typically commencing in early adulthood. There is a need for safe and effective therapy to prevent the progressive central nervous system (CNS) damage and resultant disability that characterize the disease course. Increasing evidence supports a chronic autoimmune basis for CNS damage in MS. In the present study, we review current concepts of autoimmune pathogenesis in MS, assess current therapies aimed at countering autoimmune attack and discuss potential therapeutic strategies. Among currently available therapies, beta-interferon and glatiramer acetate have a modest effect on reducing relapses and slowing the accumulation of disability in relapsing-remitting MS. Beta-interferon is of doubtful efficacy in secondary progressive MS and appears to aggravate primary progressive MS, possibly by increasing antibody-mediated CNS damage through inhibition of B-cell apoptosis. Mitoxantrone may reduce relapses and slow disability progression in relapsing-remitting and secondary progressive MS, but its use is limited by the risk of cardiomyopathy. There are currently no effective treatments for primary progressive MS. Many therapies that are effective in the animal model, experimental autoimmune encephalomyelitis (EAE), are either ineffective in MS or--in the case of gamma-interferon, lenercept and altered peptide ligands--actually make MS worse. This discrepancy may be explained by the occurrence in MS of defects in immunoregulatory mechanisms, the integrity of which is essential for the efficacy of these treatments in EAE. It is likely that the development of safe, effective therapy for MS will depend on a better understanding of immunoregulatory defects in MS.
Protein kinetics during and after long-duration spaceflight on MIR (1999)

Human spaceflight is associated with a loss of body protein. Bed rest studies suggest that the reduction in the whole body protein synthesis (PS) rate should be approximately 15%. The objectives of this experiment were to test two hypotheses on astronauts and cosmonauts during long-duration (>3 mo) flights on MIR: that 1) the whole body PS rate will be reduced and 2) dietary intake and the PS rate should be increased postflight because protein accretion is occurring. The 15N glycine method was used for measuring whole body PS rate before, during, and after long-duration spaceflight on the Russian space station MIR. Dietary intake was measured together with the protein kinetics. Results show that subjects lost weight during flight (4.64 +/- 1.0 kg, P < 0.05). Energy intake was decreased inflight (2,854 +/- 268 vs. 2,145 +/- 190 kcal/day, n = 6, P < 0.05), as was the PS rate (226 +/- 24 vs. 97 +/- 11 g protein/day, n = 6, P < 0.01). The reduction in PS correlated with the reduction in energy intake (r2 = 0.86, P < 0.01, n = 6). Postflight energy intake and PS returned to, but were not increased over, the preflight levels. We conclude that the reduction in PS found was greater than predicted from ground-based bed rest experiments because of the shortfall in dietary intake. The expected postflight anabolic state with increases in dietary intake and PS did not occur during the first 2 wk after landing.
Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell‐less mollusc (1998)

BACKGROUND Dolastatin 10 is an anticancer peptide isolated from the sea hare, Dolabela auricularia, which is currently in phase I trials. METHODS The effects of dolastatin 10 on the DU-145 human prostate cancer cell line were studied both in tissue culture and in athymic nude mice. In tissue culture, after dolastatin 10 treatment, cell cycle kinetics were measured using propidum iodide, apoptosis was estimated using the TUNEL assay, and tubulin architecture studied by direct immunofluorescence. RESULTS At concentrations of 1 nM (IC50 = 0.5 nM), dolastatin 10 completely inhibited the growth in tissue culture of human prostate cancer DU-145 cells. Growth inhibition was correlated with the arrest of these cells in G2/M and α-tubulin depolymerization. In athymic mice at a dose of 5 μg every 4 days i.p., dolastatin 10 blocked the diaphragmatic invasion of DU-145 tumor cells. CONCLUSIONS Dolastatin 10 is a novel marine-derived compound with activity in the treatment of human prostate cancer in animals. The mechanism of action of this agent involves tubulin depolymerization but not the induction of apoptosis. Prostate 34:175–181, 1998. © 1998 Wiley-Liss, Inc.
Menschenwürde und Arbeitswelt (1970)

Wenn von der" Wrde des Menschen im Sinne von Art. I Abs. I GG gehandelt wird, bleibt in der Regel die gegenwrtige Arbeitswelt, die Situation der Menschen in den Betrieben vllig auerhalb des Blickfelds. Dieser Diskussionsstand wird nicht beeinflut von dem Streit um die Drittwirkung von Grundrechten,
Reactions of Alkenediazonium Salts. Part 1. 2,2‐Diethoxyethene‐diazonium hexachloroantimonate: A diazonium, a carbenium or an oxonium salt? (1983)

Abstract Reactions of the title compound 1 with various nucleophiles have been studied. The salt behaves like an alkylating agent towards ethers, alcohols and water forming ethyl diazoacetate ( 2 ), which reacts further with excess of the nucleophile. A solvent cage mechanism accounting for the observed products is proposed. Thermal decomposition in inert solvents leads to the alkylation of the counter‐ion, i.e. formation of chloroethane, and in anisole, alkylation and chlorination of the solvent are also observed. With a standard coupling component, 2‐naphtholate ion, no azo coupling reaction of 1 is observed, but instead 14‐methyl‐14 H ‐dibenzo[ a , j ]xanthene ( 17 ) is formed. The products of the reaction with diethylamine are diethylcyanoformamide ( 18 ) and ethyl diethylcarbamate ( 19 ). None of the chemistry of salt 1 is explained by the intervention of vinyl cations expected to be formed in a heteroytic dediazoniation. The predominant pathways seem to involve reactions of an oxonium salt (alkylating properties) or, in the case of diethylamine, a carbenium salt (primary nucleophilic attack on the β‐C‐atom of 1 ). The free energy barrier to CC rotation in 1 is estimated to be 75 to 77 kJ/mol (18.0 to 18.5 kcal/mol), a value which falls between those expected for a double and a single bond.
Some comments on seabed propagation of ULF/ELF electromagnetic fields (1990)

A reference model for the electrical conductivity structure beneath the deep seafloor is proposed and justified using a variety of geophysical evidence. The model consists of relatively conductive sediment and crustal layers of 6.5 km extent overlying a resistive (≈10 −5 S/m) subcrustal channel of 30 km thickness and terminated in a deeper conductive layer and half‐space. Its seafloor‐to‐seafloor response to a horizontal electric dipole source is explored as a function of frequency and range, showing that, compared with the response for a half‐space with the lowest conductivity in the reference model, significant enhancement of the field amplitude can occur at long ranges (&gt;100 km) and low frequencies (&lt;1 Hz). At the same time, marked attenuation relative to the half‐space response is seen at higher frequencies. The field enhancement is due to trapping of electromagnetic energy in a leaky subcrustal waveguide, as demonstrated by computing the complex Poynting vector. The attenuation occurs in the relatively conductive sedimentary and crustal layers overlying the lithospheric waveguide when their electrical thickness exceeds a skin depth. The results indicate that attempts either to model controlled electromagnetic sources or to interpret controlled source data using half‐space models for the Earth can be badly misleading. The practicality of lithospheric communications in the real Earth is also investigated. Using measured receiver noise figures and the reference model, the receiver bandwidth necessary to achieve a given signal‐to‐noise ratio as a function of range and frequency is estimated for a seafloor horizontal source of strength 10 5 A‐m. The results indicate that significant (≈100 km) ranges can be achieved only around 1 Hz with a bandwidth of ≈1 Hz at a SNR of 10, yielding a very low data rate of &lt;3.5 bits/s. Longer ranges and higher frequencies are precluded by attenuation in the sediment and crustal layers and because the conductivity in the resistive channel is too large.
A pathway-based approach for identifying biomarkers of tumor progression to trastuzumab-resistant breast cancer (2014)

Although trastuzumab is a successful targeted therapy for breast cancer patients with tumors expressing HER2 (ERBB2), many patients eventually progress to drug resistance. Here, we identified subpathways differentially expressed between trastuzumab-resistant vs. -sensitive breast cancer cells, in conjunction with additional transcriptomic preclinical and clinical gene datasets, to rigorously identify overexpressed, resistance-associated genes. From this approach, we identified 32 genes reproducibly upregulated in trastuzumab resistance. 25 genes were upregulated in drug-resistant JIMT-1 cells, which also downregulated HER2 protein by >80% in the presence of trastuzumab. 24 genes were downregulated in trastuzumab-sensitive SKBR3 cells. Trastuzumab sensitivity was restored by siRNA knockdown of these genes in the resistant cells, and overexpression of 5 of the 25 genes was found in at least one of five refractory HER2 + breast cancer. In summary, our rigorous computational approach, followed by experimental validation, significantly implicate ATF4, CHEK2, ENAH, ICOSLG, and RAD51 as potential biomarkers of trastuzumab resistance. These results provide further proof-of-concept of our methodology for successfully identifying potential biomarkers and druggable signal pathways involved in tumor progression to drug resistance.
Regional Satellite Oceanography. Serge Victorov. London: Taylor & Francis, xiv + 306 p, illustrated, soft cover. ISBN 0-7484-0274-8. £24.95. (1997)

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Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3a (2010)

FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27(Kip1) and p21(Cip1), and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3'-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells.
Preparation of a 7-Arylthieno[3,2-d]pyrimidin-4-Amine Library (2007)

A focused kinase library of 7-arylthieno[3,2-d]pyrimidin-4-amine analogues is readily prepared via solution-phase parallel synthesis. This strategy relies on a key cyclization of a 3-aminothiophene-2-carboxamide with a formamide to construct the thienopyrimidine core. Further elaborations of this core via substitution and Suzuki coupling reactions allow the introduction of other diversity points. This methodology is demonstrated through the preparation of a 72-membered library of 7-arylthieno[3,2-d]pyrimidin-4-amines in good yields and high purities.
The complement SC5b-9 complex mediates cell adhesion through a vitronectin receptor. (1990)

Adhesion of cells to the terminal complement complex of C5b through C9 containing the serum S-protein (SC5b-9) was investigated using a microtiter plate attachment assay with L8 myoblast indicator cells. The skeletal muscle-derived L8 myoblasts bound and spread on substratum coated with SC5b-9, and with the vitronectin/S-protein component of SC5b-9. The myoblasts did not adhere to substratum coated with collagen, laminin, or fibronectin. The cell attachment was blocked by antibody to vitronectin/S-protein, whereas antibody to the other components C5, C6, C7, C8, or C9 had minimal effect. The cells were not bound to free vitronectin because attachment activity was removed by adsorption with an anti-C6 antibody column. The L8 cell attachment was dependent on divalent cations, was blocked by synthetic peptides containing the amino acid sequence Arg-Gly-Asp, and was inhibited by antivitronectin receptor antibody. These results indicate that cells adhere to the SC5b-9 complex through interaction of the vitronectin component with an integrin vitronectin receptor. Cell attachment to terminal C complexes could be used for leukocyte adherence and migration during inflammation, and also for attachment of tissue cells during regeneration after disease or traumatic injury.
[Studies on the structure-activity relationship of retinoids--Hansch analysis and 3D-OSAR studies on specific ligands of retinoid x receptor]. (1998)

Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retinoids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitative structure-activity relationships of specific ligands of RXR, we carried out mimesis of environment of ligands interacting with their receptor and, to some extent, mapping the topological and physico-chemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.
Synthesis of an Artificial Cell Surface Receptor that Enables Oligohistidine Affinity Tags to Func-tion as Metal-Dependent Cell-Penetrating Peptides [J. Am. Chem. Soc. 2006, 128, 386−387]. (2006)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionSynthesis of an Artificial Cell Surface Receptor that Enables Oligohistidine Affinity Tags to Func-tion as Metal-Dependent Cell-Penetrating Peptides [J. Am. Chem. Soc.2006, 128, 386−387].Siwarutt Boonyarattanakalin, Sonalee Athavankar, Qi Sun, and Blake R. PetersonCite this: J. Am. Chem. Soc. 2006, 128, 14, 4917Publication Date (Web):March 18, 2006Publication History Published online18 March 2006Published inissue 1 April 2006https://pubs.acs.org/doi/10.1021/ja0612091https://doi.org/10.1021/ja0612091correctionACS PublicationsCopyright © 2006 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views489Altmetric-Citations1LEARN 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 PDF (14 KB) Get e-Alertsclose Get e-Alerts
Selección de elementos mecánicos asistido por software (2017)

The selection of mechanical elements has always been present in any process of design and construction of any machine or component being a very extensive process, this is the importance of computational tools to create through a series of algorithms for the selection of mechanical elements. This article try to harness the information available about the selection processes that have been systematized in software to improve performance of the mechanical parts of information in the context of design, so that it can cope with the increasing complexity in product development related to mechanical systems.
Recent advances in magnetic resonance imaging of the musculoskeletal system. (1994)

Numerous recent technical innovations in magnetic resonance imaging have dramatically improved the imaging evaluation of musculoskeletal disease; however, with the introduction of new techniques comes the risk of inappropriate applications and unanticipated pitfalls in interpretation. Some of the practical and theoretical implications of these recent innovations as well as potential caveats associated with their use are highlighted in the following discussion.