gebhart/patrepeval huggingface dataset:
Turning the 10–23 DNAzyme On and Off with Light (2010)

Spaced out. DNAzymes incorporating photocleavable spacers were switched “on” or “off” with light. A DNAzyme (left) with two photocleavable spacers, in a binding arm and the catalytic core, lost the ability to hydrolyze RNA upon UV photolysis. Conversely, a circular DNAzyme (right) attached to a self-complementary strand via two photocleavable spacers remained “off” until UV irradiation restored activity. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Stat5 constitutive activation rescues defects in spinal muscular atrophy (2007)

Proximal spinal muscular atrophy (SMA) is a motor neuron degeneration disorder for which there is currently no effective treatment. Here, we report three compounds (sodium vanadate, trichostatin A and aclarubicin) that effectively enhance SMN2 expression by inducing Stat5 activation in SMA-like mouse embryonic fibroblasts and human SMN2-transfected NSC34 cells. We found that Stat5 activation enhanced SMN2 promoter activity with increase in both full-length and deletion exon 7 SMN transcripts in SMN2-NSC34 cells. Knockdown of Stat5 expression disrupted the effects of sodium vanadate on SMN2 activation but did not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2 transcriptional regulation. In addition, constitutive activation of Stat5 mutant (Stat5A1*6) profoundly increased the number of nuclear gems in SMA-patient lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. These results demonstrate that Stat5 signaling could be a possible pharmacological target for treating SMA.
Narrow Optical Homogeneous Linewidths in Rare Earth Doped Nanocrystals (2013)

A homogeneous linewidth of 85.6±4.4 kHz is reported in 60 nm Eu3+ doped Y2O3 nanocrystals at 1.3 K. This linewidth was measured by two-pulse photon echoes on highly scattering powders using heterodyne detection. Spectral diffusion was also investigated by three-pulse photon echoes and resulted in a limited broadening of the homogenous linewidth of about 250 kHz over 120 μs. Compared to achievable Rabi frequencies, in the range of several MHz, these values show that rare earth doped nanocrystals can be useful for applications in optical quantum information processing.
Peptide Fine Specificity of Anti-Glycoprotein 100 CTL Is Preserved Following Transfer of Engineered TCRαβ Genes Into Primary Human T Lymphocytes (2003)

TCR with known antitumor reactivity can be genetically introduced into primary human T lymphocytes and provide promising tools for immunogene therapy of tumors. We molecularly characterized two distinct TCRs specific for the same HLA-A2-restricted peptide derived from the melanocyte differentiation Ag gp100, yet exhibiting different stringencies in peptide requirements. The existence of these two distinct gp100-specific TCRs allowed us to study the preservation of peptide fine specificity of native TCRalphabeta when engineered for TCR gene transfer into human T lymphocytes. Retroviral transduction of primary human T lymphocytes with either one of the two sets of TCRalphabeta constructs enabled T lymphocytes to specifically kill and produce TNF-alpha when triggered by native gp100(pos)/HLA-A2(pos) tumor target cells as well as gp100 peptide-loaded HLA-A2(pos) tumor cells. Peptide titration studies revealed that the cytolytic efficiencies of the T lymphocyte transductants were in the same range as those of the parental CTL clones. Moreover, primary human T lymphocytes expressing either one of the two engineered gp100-specific TCRs show cytolytic activities in response to a large panel of peptide mutants that are identical with those of the parental CTL. The finding that two gp100-specific TCR, derived from two different CTL, can be functionally introduced into primary human T lymphocytes without loss of the Ag reactivity and peptide fine specificity, holds great promise for the application of TCR gene transfer in cancer immunotherapy.
Brother Felix Fabri's Evagatorium: From Travel Wanderings to Narrative Wanderings (2008)

There are only a few literary studies on the monumental Evagatorium written by the Dominican Felix Fabri (ca. 1440–1502), who travelled to the East on two occasions. The Evagatorium cannot just be reduced to a collection of data; it is also a piece written with particular care. The work has three objectives: To instruct by faithfully describing the places visited, holy places in particular; to entertain; and to make the reader imagine the experience of the grand journey with all its dangers and exoticism. Felix Fabri was aware of the heterogeneous quality of his book, which is an account neither of a journey, nor of a pilgrimage, nor of an expedition, and this explains the choice of the neologism evagatorium to describe it. This article would therefore like to demonstrate that this evagatory was conceived not only to reflect the author's own wanderings of body and spirit, but also to lead the reader into wandering.
Method of artificial DNA spling by directed ligation(SDL) (1991)

An approach to directed genetic recombination in vitro has been devised, which allows for joining together, in a predetermined way, a series of DNA segments to give a precisely spliced polynucleotide sequence (DNA splicing by directed ligation, SDL). The approach makes use of amplification, by means of several polymerase chain reactions (PCR), of a chosen set of DNA segments. Primers for the amplifications contain recognition sites of the class IIS restriction endonucleases, which transform blunt ends of the amplification products into protruding ends of unique primary structures, the ends to be used for joining segments together being mutually complementary. Ligation of the mixture of the segments so synthesized gives the desired sequence in an unambiguous way. The suggested approach has been exemplified by the synthesis of a totally processed (intronless) gene encoding human mature interleukin-1 alpha.
Pulsed dielectric breakdown of pressurized water and salt solutions (1995)

The dielectric breakdown of pressurized water and salt solutions subjected to high amplitude electric fields of submicrosecond duration has been investigated. Well-defined pulses (80 kV, 3 ns rise time, 100 ns duration) have been applied to a gap (0.04–0.21 cm), between Rogowski profile electrodes, containing de-ionized, nondistilled water; de-ionized, distilled water; sodium chloride solutions (0.001–1.0 M); or magnesium sulfate solutions (0.01–0.1 M). Breakdown in these liquids has been studied at pressures up to 400 atm. Calibrated voltage dividers situated on the source and load sides of the test gap permitted measurement of the interelectrode potential and the current response. From these measurements, the time lag to breakdown, breakdown voltage, power input to the liquid, and temporal characteristics of the breakdown process have been determined. The breakdown time lag increases with increasing pressure and gap width, and decreases with increasing field. Moreover, it is weakly dependent on the conductivity of the liquid. A dynamical model has been developed to explain these results. In this model, field emission currents heat the liquid and create a region with density below the critical density for the formation of electron avalanches. An ionizing wave front subsequently develops and propagates via a sequence of processes occurring in the region ahead of the front; namely, heating by electron injection, lowering of the liquid density, and avalanche growth and retardation. The time for nucleation of the low density region has been experimentally determined and is in good agreement with theory.
Atomic Layer Deposition of Platinum Thin Films (2003)

Platinum thin films were grown at 300 °C by atomic layer deposition (ALD) using (methylcyclopentadienyl)trimethylplatinum (MeCpPtMe3) and oxygen as precursors. The films had excellent uniformity, low resistivity, and low-impurity contents. Structural studies by X-ray diffraction showed that the films were strongly (111) oriented. Growth rates of 0.45 Å cycle-1 were obtained with 4 s total cycle times. The film thickness was found to linearly depend on the number of the reaction cycles. Also, the possible reaction mechanism is discussed.
Insulin Resistance and Insulin Sensitizers (2001)

Insulin resistance is a key factor in the pathogenesis of type 2 diabetes mellitus and a co-factor in the development of dyslipidaemia, hypertension and atherosclerosis. The causes of insulin resistance include factors such as obesity and physical inactivity, and there may also be genetic factors. The mechanism of obesity-related insulin resistance involves the release of factors from adipocytes which exert a negative effect on glucose metabolism: free fatty acids, tumour necrosis factor-alpha and the recently discovered hormone, resistin. The two resulting abnormalities observed consistently in glucose-intolerant states are impaired suppression of endogenous glucose production, and impaired stimulation of glucose uptake. Among the genetic factors, a polymorphism (Pro12Ala) in the peroxisome proliferator-activated receptor (PPAR) gamma is associated with a reduced risk of type 2 diabetes mellitus and increased insulin sensitivity, primarily that of lipolysis. On the other hand, the association with insulin resistance of a common polymorphism (Gly972Arg) in the insulin receptor substrate 1, long believed to be a plausible candidate gene, is weak at best. This polymorphism may instead be associated with reduced insulin secretion, which, in view of the recent recognition of the insulin signalling system in beta-cells, results in the development of a novel pathogenic concept. Finally, fine-mapping and positional cloning of the susceptibility locus on chromosome 2 resulted in the identification of a polymorphism (UCSNP-43 G/A) in the calpain-10 gene. In non-diabetic Pima Indians, this polymorphism was associated with insulin resistance of glucose disposal. The pharmacological treatment of insulin resistance has recently acquired a novel class of agents: the thiazolidinediones. They act through regulation of PPARgamma-dependent genes and probably interfere favourably with factors released from adipocytes which mediate obesity-associated insulin resistance.
Synergistic Cytotoxicity and Pharmacogenetics of Gemcitabine and Pemetrexed Combination in Pancreatic Cancer Cell Lines (2004)

Abstract Purpose: Gemcitabine is an inhibitor of ribonucleotide reductase (RR) and DNA synthesis and is an effective agent in the treatment of pancreas cancer. The present study investigates whether the multitargeted antifolate pemetrexed would be synergistic with gemcitabine against MIA PaCa-2, PANC-1, and Capan-1 pancreatic cancer cell lines. Experimental Design: Cells were treated with gemcitabine and pemetrexed, and the type of drug interaction was assessed using the combination index. Cytotoxicity of gemcitabine was examined with inhibitors of (a) deoxycytidine kinase (dCK), which activates gemcitabine by phosphorylation, and (b) 5′-nucleotidase (drug dephosphorylation) and cytidine deaminase (drug deamination), the main inactivating enzymes. The effects of gemcitabine and pemetrexed on cell cycle were analyzed by flow cytometry, and apoptosis was examined by fluorescence microscopy. Finally, quantitative, real-time PCR was used to study the pharmacogenetics of the drug combination. Results: Synergistic cytotoxicity and enhancement of apoptosis was demonstrated, mostly with the sequence pemetrexed→gemcitabine. Pemetrexed increased cells in S phase, the most sensitive to gemcitabine, and a positive correlation was found between the expression ratio of dCK:RR and gemcitabine sensitivity. Indeed, pemetrexed significantly enhanced dCK gene expression (+227.9, +86.0, and +135.5% in MIA PaCa-2, PANC-1, and Capan-1 cells, respectively), and the crucial role of this enzyme was confirmed by impairment of gemcitabine cytotoxicity after dCK saturation with 2′-deoxycytidine. Conclusions: These data demonstrate that the gemcitabine and pemetrexed combination displays schedule-dependent synergistic cytotoxic activity, favorably modulates cell cycle, induces apoptosis, and enhances dCK expression in pancreatic cancer cells.
Investigating the Relationship Between Stroke and Obstructive Sleep Apnea (1996)

Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.
A randomized phase II study of elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. (2012)

8020 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting CS1, a cell surface glycoprotein. CS1 is highly expressed on &gt;95% of multiple myeloma (MM) cells, with lower expression on natural killer cells and little to no expression on normal tissues. A phase 1 trial of Elo plus lenalidomide and low-dose dexamethasone (Elo/Len/Dex) demonstrated an 82% objective response rate (ORR) in patients (pts) with relapsed/refractory (RR) MM (Lonial et al. J Clin Oncol, in press). Methods: In this phase 2 study, previously treated pts with MM were randomized to Elo 10 or 20 mg/kg IV (days 1, 8, 15, and 22 every 28-days in first 2 cycles and days 1 and 15 of subsequent cycles), Len 25 mg PO (days 1-21) and Dex 40 mg PO weekly. Prophylaxis for infusion-related reactions (IRs) was administered prior to each Elo infusion. Treatment continued until disease progression or unacceptable toxicity. The primary objective was to assess efficacy (ORR ≥partial response [PR]) according to IMWG criteria. Results: Among73 pts (median age 63 years; range, 39-82), 55% had received ≥2 prior therapies, 60% had received prior bortezomib, and 62% prior thalidomide. ORR was 82% for all pts including 48% ≥ very good PR (VGPR). The ORRs were 92% in the 10 mg/kg group (n=36) and 73% in the 20 mg/kg group (n=37). Median time to best response was 2.2 months (range, 0.7-17.5). After a median follow-up of 14.1 months, median progression-free survival (PFS) has not been reached, with PFS rates of 75% (10 mg/kg) and 65% (20 mg/kg). Elo/Len/Dex also showed encouraging activity in pts with high-risk cytogenetics (ORR 80%) and/or Stage 2-3 MM (ORR 81%). The most common grade 3/4 toxicities were neutropenia (16%), lymphopenia (16%), and thrombocytopenia (16%). Investigator-designated IRs were reported in 12% of pts (all grades); 1 pt (1.4%) had grade 3 IR (rash). Conclusions: Elo/Len/Dex was generally well tolerated and resulted in a high ORR, and PFS not reached after 14.1 months of median follow-up in pts with RR MM. Updated results will be presented at the meeting. Two phase 3 trials of 10 mg/kg Elo/Len/Dex are ongoing in newly diagnosed MM (ELOQUENT1; CA204-006; NCT01335399) and RR MM (ELOQUENT2; CA204-004; NCT01239797).
Growth inhibition of human lung cancer cell lines by interleukin 6 in vitro: a possible role in tumor growth via an autocrine mechanism. (1993)

It has been considered that growth of human lung cancer cells, like other malignant cells, is positively and negatively regulated by a variety of growth factors via autocrine as well as paracrine mechanisms. The autocrine mechanism is considered to be important in the autonomy of proliferation of cancer cells. Recently, the role of autocrine growth-inhibiting factors such as transforming growth factor beta attracts special attention for better understanding of growth regulation of malignant cells. Here, we have demonstrated that a multifunctional cytokine interleukin 6 (IL-6) had an inhibitory effect on the proliferation of human non-small cell lung cancer cell lines, as shown by the growth accelerating effect of the specific anti-IL-6 antibody as well as the effect of exogenously added IL-6. Moreover, IL-6 can be expressed and released by human lung cancer cells, and these cells had specific IL-6 receptors on their cell surfaces, suggesting an autocrine mechanism. The growth-inhibitory effect of IL-6 was additive to that of transforming growth factor beta, and could not be neutralized by the addition of anti-transforming growth factor beta antibody. These results suggested that IL-6 may function as another class of autocrine growth-inhibiting factor in the growth regulation of human lung cancer. Relatively lower IL-6 sensitivity of these cells than noncarcinogenic human bronchial epithelial cells also suggested that escape from growth regulation by inhibitory factors such as IL-6 could be involved in lung cancer oncogenesis.
Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen (2016)

Antibody-drug conjugates (ADC), combining the specificity of tumor recognition by monoclonal antibodies (mAb) and the powerful cytotoxicity of anticancer drugs, are currently under growing interest and development. Here, we studied the potential of Chi-Tn, a mAb directed to a glyco-peptidic tumor-associated antigen, to be used as an ADC for cancer treatment. First, we demonstrated that Chi-Tn specifically targeted tumor cells in vivo. Also, using flow cytometry and deconvolution microscopy, we showed that the Chi-Tn mAb is rapidly internalized - condition necessary to ensure the delivery of conjugated cytotoxic drugs in an active form, and targeted to early and recycling endosomes. When conjugated to saporin (SAP) or to auristatin F, the Chi-Tn ADC exhibited effective cytotoxicity to Tn-positive tumor cells in vitro, which correlated with the level of tumoral Tn expression. Furthermore, the Chi-Tn mAb conjugated to auristatin F also exhibited efficient antitumor activity in vivo, validating for the first time the use of an anti-Tn antibody as an effective ADC.
Computer analysis of user interfaces based on repetition in transcripts of user sessions (1991)

article Free Access Share on Computer analysis of user interfaces based on repetition in transcripts of user sessions Authors: Antonio C. Siochi Christopher Newport College, Newport News, VA Christopher Newport College, Newport News, VAView Profile , Roger W. Ehrich Virginia Polytechnic Institute and State Univ., Blacksburg Virginia Polytechnic Institute and State Univ., BlacksburgView Profile Authors Info & Claims ACM Transactions on Information SystemsVolume 9Issue 4pp 309–335https://doi.org/10.1145/119311.119312Published:01 October 1991Publication History 44citation699DownloadsMetricsTotal Citations44Total Downloads699Last 12 Months30Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Skriba■o!El Kie? (1994)

Nekredeble,mi sukcesis,li pensis.La laboro estis pli malfaeila ol enerale,kaj en lia nuna situacio…Pot sukcese starigikaj funkciigi la rnainaron,kiel li jus faris,necesas povi pensi,zorge rigardi ion vidindan,
Levels of Circulating Cell-Free Nuclear and Mitochondrial DNA in Benign and Malignant Ovarian Tumors (2008)

Elevated levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in epithelial ovarian cancer may have diagnostic value. Our finding suggests that the circulating molecules might be potential biomarkers in the disease.
Immunofluorescent detection of Histoplasma capsulatum in primate experimental ocular histoplasmosis (1986)

We have developed a polyclonal anti-Histoplasma capsulatum antibody to detect H. capsulatum antigens in ocular tissue. Antibodies were specific for H. capsulatum as determined by enzyme linked immunosorbent assay and immunoprecipitation. A total of 21 choroidal histoplasmic lesions in 4 primate eyes (Macaca speciosa and Macaca mulatta), taken at various times from 14 to 60 days after the internal carotid artery injection of yeast phase organisms, were evaluated. Using an indirect immunofluorescent technique, these antibodies stained yeast phase organisms within acute choroidal lesions at 14 days after infection. By 60 days intact organisms were no longer detected; occasional cells, however, contained intracellular inclusions that stained with these antibodies. Although yeast phase organisms are rapidly cleared from the primate choroid, these data indicate that residual H. capsulatum antigens may remain in choroidal lesions after the acute infectious stage. These findings are consistent with the hypothesis that H. capsulatum antigens play a role in the immunologic reactivation of atrophic choroidal scars in ocular histoplasmosis.
High-Performance Flexible Graphene Field Effect Transistors with Ion Gel Gate Dielectrics (2010)

A high-performance low-voltage graphene field-effect transistor (FET) array was fabricated on a flexible polymer substrate using solution-processable, high-capacitance ion gel gate dielectrics. The high capacitance of the ion gel, which originated from the formation of an electric double layer under the application of a gate voltage, yielded a high on-current and low voltage operation below 3 V. The graphene FETs fabricated on the plastic substrates showed a hole and electron mobility of 203 +/- 57 and 91 +/- 50 cm(2)/(V x s), respectively, at a drain bias of -1 V. Moreover, ion gel gated graphene FETs on the plastic substrates exhibited remarkably good mechanical flexibility. This method represents a significant step in the application of graphene to flexible and stretchable electronics.
Synthesis and Characterization of Diblock Copolymers Containing Oligothiophenes with Defined Regiospecificity and Molecular Weights (1996)

A series of regiospecific, alkyl-substituted oligothiophenes were synthesized and their structure/property relationships were studied. The formylation of the oligothiophenes introduced an aldehyde functionality into one of the terminals which can be used to couple with living anionic polystyrene species to generate diblock copolymers. Three diblock copolymers were synthesized by coupling the oligothiophene aldehyde with living polystyrenes of different chain lengths. These copolymers were stable at temperature up to 380 °C and have similar glass transition temperatures to the corresponding polystyrene homopolymers.