gebhart/patrepeval huggingface dataset:
Dyad : a system for using physically secure coprocessors (2018)

Abstract: "The Dyad project at Carnegie Mellon University is using physically secure coprocessor [sic] to achieve new protocols and systemsaddressing a number of perplexing security problems. These coprocessors can be produced as boards or integrated circuit chips and can be directly inserted in standard workstation or PC-style computers. This paper presents a set of security problems and easily implementable solutions that exploit the power of physically secure coprocessors: (1) protecting the integrity of publicly accessible workstations (2) tamper-proof accounting/audit trails (3) copy protection (4) electronic currency without centralized servers [sic] We outline the architectural requirements for the use of secure coprocessors."
Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B (2006)

To assess the prognostic impact of cytogenetics in elderly patients with acute myeloid leukemia (AML) receiving intensive induction and consolidation treatment according to a single protocol specifically designed for patients above age 60, pretreatment samples from 361 patients registered for the AML HD98-B trial of the German-Austrian AML Study Group were analyzed by chromosome banding and fluorescence in situ hybridization, and cytogenetic findings were correlated with outcome. Using a proportional hazards model with backward selection, 3 prognostic subgroups were identified based on the influence of cytogenetic abnormalities on overall survival (OS): low-risk, t(15;17), and inv(16) in 25 of 361 patients (7%); standard-risk, normal karyotype, t(8;21), t(11q23), +8 within a noncomplex karyotype, and +11 within a noncomplex karyotype in 208 of 361 patients (58%); high-risk, all other aberrations in 128 of 361 patients (35%). On multivariate analysis, high-risk cytogenetics (hazard ratio [HR], 2.24) and age above 70 years (HR, 2.34) were independent prognostic factors affecting OS, and stratification according to these parameters demonstrated that a large subgroup of patients (55%), characterized by age 70 or older or high-risk cytogenetics, or both, had very unfavorable treatment results despite intensive chemotherapy. Thus, karyotype and age are major determinants of outcome in elderly patients with AML.
A rapid method for isolation of total DNA from pathogenic filamentous plant fungi (2010)

DNA isolation from some fungal organisms of agronomic importance is difficult because they have cell walls or capsules that are relatively unsusceptible to lysis. We have developed a fast DNA isolation protocol for Fusarium oxysporum, which causes fusarium wilt disease in more than 100 plant species, and for Pyrenochaeta terrestris, which causes pink root in onions. This protocol was based on the sodium dodecyl sulfate/phenol method, without beta-mercaptoethanol and without maceration in liquid nitrogen; it uses phenol/chloroform extraction to remove proteins and co-precipitated polysaccharides. The A(260/280) absorbance ratios of isolated DNA were around 1.9, suggesting that the DNA fraction was pure and may be used for further analysis. Additionally, the A(260/230) values were higher than 1.8, suggesting negligible contamination by polysaccharides. The DNA isolated by this protocol is of sufficient quality for molecular applications; this technique could be applied to other organisms that have similar substances that hinder DNA extraction.
Therapeutic Targeting of Transcription in Acute Promyelocytic Leukemia by Use of an Inhibitor of Histone Deacetylase (1998)

Clinical treatment with an inhibitor of histone deacetylase induces histone hyperacetylation in target cells and may restore sensitivity to the anti-leukemic effects of all-trans-retinoic acid in acute promyelocytic leukemia. Similar therapy may prove useful in other neoplastic diseases that are associated with oncogenic repression of gene transcription due to recruitment of histone deacetylases.
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors (2015)

Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL.
RNA Interference as A Gene-Specific Approach for Molecular Medicine (2005)

The discovery of RNA interference (RNAi) in eukaryotic cells has been the major recent breakthrough in molecular and cell biology. RNAi machineries exert biological functions in gene regulation, genome defense and chromatin architecture and dynamics. The potential of RNAi to silence any gene of interest in a highly specific and efficient manner via double-stranded RNA (dsRNA) has literally revolutionized modern genetics. RNAi-based functional genomics now permits, for the first time, to evaluate the cellular role of individual gene products on a genome-wide scale in higher organisms like mammals, presenting an alternative to the generation of animal knockouts often doomed to failure because of a lethal phenotype. RNAi has had an enormous impact on the development of novel disease models in animals, and it is likely that small interfering RNAs (siRNAs), which are the trigger molecules for RNA silencing, will become an invaluable tool for the treatment of genetic diseases. First clinical trials, using siRNAs directed against the vascular endothelial growth factor (VEGF) or one of its receptors, have been initiated recently for the treatment of age-related macular degeneration. Improving guidelines for the rational design of siRNAs, based on recent progress in understanding the mechanisms underlying RNAi, as well as the introduction of chemical modifications into siRNAs are expected to improve their pharmacokinetic and pharmacodynamic properties for in vivo applications. Finally, successful therapeutic application of RNAi will depend on the development of improved siRNA delivery strategies that combine high specificity and efficiency with a low immunostimulatory and tumorigenic potential.
Prourokinase-Annexin V Chimeras (1995)

Annexin V is a human protein that binds with high affinity to the abundant phosphatidylserine molecules exposed on activated platelets and accumulates selectively in thrombi after intravenous administration in animal models of arterial thrombosis. We designed two chimeras that use annexin V as a means to target thrombolytic agents to platelet-containing thrombi: prourokinase (1-411)-annexin V (1-320); and prourokinase (144-411)-annexin V (1-320) (amino acid numbers of parent proteins given in parentheses). Chimeras were produced by cytoplasmic expression in Escherichia coli, refolded, and purified in single-chain form. Both chimeras had the same specific activity as annexin V in binding to cell membranes containing exposed phosphatidylserine. After activation with plasmin, both chimeras had specific amidolytic activity similar to that of urokinase. Both chimeras activated plasminogen in vitro with kinetic parameters similar to those for urokinase, and both showed full activity compared to urokinase in an assay of clot lysis in vitro. This study shows the feasibility of producing chimeric plasminogen activators in which annexin V provides the thrombus-targeting component; although not yet tested in vivo, such chimeras may have advantages over antibody-based targeting agents.
Detection of Deoxyribonucleic Acid Fragmentation in Human Sperm: Correlation with Fertilization in Vitro1 (1997)

The objective of this study was to determine the incidence of DNA fragmentation in human sperm, and to correlate any detected DNA damage with semen analysis parameters and fertilization rates in in vitro fertilization (IVF). A total of 298 semen samples were collected from men in the infertility program at The Toronto Hospital. For each sample, the percentage of sperm with DNA fragmentation was determined using the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling (TUNEL) and fluorescence-activated cell sorting. The percentage of sperm with fragmented DNA was less than 4% in the majority of samples but ranged from 5% to 40% in approximately 27% of the samples. A negative correlation was found between the percentage of DNA fragmentation and the motility, morphology, and concentration of the ejaculated sperm. In 143 IVF samples, a significant negative association was also found between the percentage of sperm with DNA fragmentation and fertilization rate (p = 0.008) and embryo cleavage rate (p = 0.01). In addition, 35 men who smoked demonstrated an increased percentage of sperm with fragmented DNA (4.7 +/- 1.2%) as compared to 78 nonsmokers (1.1 +/- 0.2%; p = 0.01). These results demonstrate a negative association between semen analysis parameters and sperm with fragmented DNA. Since extremely poor semen samples are the indication for intracytoplasmic sperm injection, there is a high likelihood that sperm with fragmented DNA may be selected by chance and used for oocyte injection, resulting in poor fertilization and/or cleavage rates.
Storage of intestinal bacteria in samples frozen with glycerol (1999)

For clinical studies, it would be useful to store faecal samples before bacteriological analyses.However, information is needed on the effect of freezing on the survival of micro-organisms.In this study, faecal samples were stored in glycerol at -80C for four months.Although the concentrations of predominant anaerobic bacterial populations ( \ 8 log(cfu g -1 ), total anaerobes and bifidobacteria, decreased significantly (pB 0.05) after freezing, this decrease did not exceed interindividual variation.The facultative anaerobes, enterobacteria, enterococci and lactobacilli, were not significantly affected by freezing.Furthermore, the magnitude of individual variability was similar before and after freezing.These results confirm the relevance of our freezing technique for studying the intestinal microflora which involves numerous samples that cannot be analysed simultaneously for practical reasons.
Reversal of cognitive decline: A novel therapeutic program (2014)

This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.
Synthesis, hybridization properties and antiviral activity of lipid-oligodeoxynucleotide conjugates (1990)

Triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (2) was coupled to the 5' terminus of oligodeoxynucleotides via hydrogen phosphonate solid support DNA synthesis methodology. Duplex DNA oligomers with a single 5'-phospholipid melted at lower temperatures than the corresponding unmodified duplex, but duplexes bearing lipids at each 5' end had higher Tms. In uptake experiments with L929 cells, 8-10 times more lipid-DNA became cell-associated than did unmodified DNA. Unmodified antisense diesters were inactive in a VSV antiviral assay in L929 cells (at up to 200 microM). Attachment of a lipid to the oligomer, however, led to a greater than 90% at 150 microM (greater than 80% at 100 microM) reduction in viral protein synthesis. The antiviral activity depended on the sequence of the oligodeoxynucleotide, but some compounds having little or no base complementarity to the viral target were also effective. Phosphorothioate derivatives reduced viral protein synthesis by 20-30% at 100 microM in the VSV assay. The lipid-DNA compounds were not toxic to the cells at up to 100 microM.
Central Memory CD4+ T Cells Are Responsible for the Recombinant Bacillus Calmette-Guérin ΔureC::hly Vaccine's Superior Protection Against Tuberculosis (2014)

Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4(+) T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4(+) T cells than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.
Eradication of human non-Hodgkin's lymphoma in SCID mice by BCL-2 antisense oligonucleotides combined with low-dose cyclophosphamide. (2000)

Cancers overexpressing Bcl-2 protein, which prevents programmed cell death (apoptosis), are less sensitive to stresses that produce cellular damage, including chemotherapy. If the level of Bcl-2 protein can be reduced sufficiently using antisense oligonucleotides (ASOs) targeting the gene message, then cytotoxic agents may be rendered more effective in eliminating disease and increasing cure rate. Preclinical studies in SCID mice bearing Bcl-2 overexpressing systemic human B-cell lymphoma (DoHH2) were undertaken to support development of a clinical trial. These data confirm that a combination of an ASO (5 mg/kg) targeting bcl-2 and a low dose of cyclophosphamide (35 mg/kg) was an effective strategy, leading to the eradication of the DoHH2 cells in vivo and cure of the animals. When mice deficient in natural killer cell activity were treated with an ASO, similar results were observed, suggesting that ASO stimulation of the host immune system was not a significant factor in elimination of lymphoma cells. These studies indicate that therapeutic strategies involving the use of an ASO targeting bcl-2 in combination with a cytotoxic agent may improve clinical outcomes.
Fluorescent Probes for Hydrogen Peroxide Based on a Non‐Oxidative Mechanism (2004)

Highly selective detection of H2O2 through a non-oxidative mechanism has been achieved by desulfonylation of 1 to the corresponding fluorescein. This approach has been used for the intracellular formation of H2O2 in algal cells by using the acetyl derivatives of 1 as fluorescent probes. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z52381_s.pdf or from the author. 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.
A single-inductor dual-output switching converter with average current mode control (2009)

An integrated single-inductor dual-output (SIDO) switching DC–DC converter is presented. The outputs are specified with 1.2 V/400 mA and 1.8 V/200 mA. A decoupling small signal model is proposed to analyze the multi-loop system and to design the on-chip compensators. An average current control mode is introduced with lossless, continuous current detection. The converter has been fabricated in a 0.25 μm 2P4M CMOS process. The power efficiency is 86% at a total output power of 840 mW while the output ripples are about 40 mV at an oscillator frequency of 600 kHz.
Phenotype of Frailty: Characterization in the Women's Health and Aging Studies (2006)

The findings of this study are consistent with the widely held theory that conceptualizes frailty as a syndrome. The frailty definition developed in the CHS is applicable across diverse population samples and identifies a profile of high risk of multiple adverse outcomes.
TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-α-inhibitor and exerts a strong anti-inflammatory effect in vivo (1996)

TNF-stimulated gene 6 (tsg6), encoding a 35-kDa secretory glycoprotein (TSG-6), is induced in fibroblasts, chondrocytes, synovial cells, and mononuclear cells by the proinflammatory cytokines TNF-alpha and IL-1, or by LPS. Large amounts of TSG-6 protein were found in synovial fluids of patients with rheumatoid arthritis. TSG-6 protein forms a stable complex with components of the serine protease inhibitor, inter-alpha-inhibitor (I alpha I). In this work, we show that TSG-6 potentiates the inhibitory effect of l alpha l on the protease activity of plasmin. The plasmin/plasminogen activator system is important in the protease network associated with inflammation. To test the hypothesis that through their cooperative inhibitory effect on plasmin TSG-6 and l alpha l can modulate the protease network and thus inhibit inflammation, we examined the effect of TSG-6 on experimentally induced inflammation. Human recombinant TSG-6 protein showed a potent anti-inflammatory activity in the murine air pouch model of carrageenan- or IL-1-induced acute inflammation. The inhibitory effect of locally administered TSG-6 on the IL-1-induced cellular infiltration was comparable with that of systemic dexamethasone treatment. Two mutant TSG-6 proteins with single amino acid substitutions close to the N terminus showed a complete or partial loss of anti-inflammatory activity. The anti-inflammatory effect of the TNF/IL-1-inducible TSG-6 protein, along with its ability to inhibit protease action through interaction with l alpha l, suggests that TSG-6 production during inflammation is part of a negative feedback loop operating through the protease network.
Ultrasonic Exposure Thresholds for Changes in Cells and Tissues (1972)

The first part of this paper reports an experimental investigation of some parameters that control the occurrence of biologically effective cavitation-type phenomena in the frequency region 0.25 4 MHz. The experimental criterion by which “cavitation” is recognized here is the simultaneous occurrence of degradation of DNA in aqueous solution, liberation of free I2 from KI solution, and generation of half-order subharmonic. The intensity threshold for cavitation rises with frequency from 0.14 to 17.5 W cm−2 (spatial peak) in the above frequency range. Pulse duration and duty factor are also found to be determining parameters, with cavitation activity reducing to zero when values of both parameters are sufficiently low. A strong positive correlation between ambient pressure and intensity threshold has also been determined. On the basis of observations of the levels of scattered half-order subharmonic signals from various media, no evidence could be found for cavitation activity in sonicated mammalian tissues, although such activity could be detected in a wide range of liquids. The second part of the paper consists of a review, conducted in the light of the above results, of published experimental data relating to the existence and values of exposure thresholds for possible nonthermal, noncavitational mechanisms of action of ultrasound in living cells and tissues.
Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer (2005)

The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time- and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell line, UM-UC-3(LUC). PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.
Stability of 2-chloro-2'-deoxyadenosine at various pH and temperature. (1994)

In this paper data concerning the stability of 2-chloro-2'-deoxyadenosine (2-CdA) solutions at various pH and temperature conditions are presented. Decomposition of 2-CdA was measured as content of its hydrolysis product--2-chloroadenine, using the HPLC method. We found that 2-CdA is stable at basic and neutral pH and temperatures between 37 and 80 degrees C. At acidic pH, decomposition markedly increased with time, even in physiological temperatures. At pH 2 and 37 degrees, after 6 h, only 13% of 2-CdA remained in solution. At pH 1--after 2 h of heating to 37 degrees 2-CdA content was as low as 2%. Calculated half time T 1/2 was equal to 1.6 h (pH 2, temperature = 37 degrees) and 0.37 h (pH 1, temperature = 37 degrees).
Inscription of optical waveguides in crystalline silicon by mid-infrared femtosecond laser pulses (2005)

For the first time to the authors' knowledge, optical waveguides have been inscribed in bulk crystalline silicon by ultrafast laser radiation. Femtosecond laser pulses of 40-nm spectral bandwidth, 1-kHz repetition rate, and 1.7-microJ on-target energy were applied at a mid-infrared wavelength of 2.4 microm to induce nonlinear absorption in the focal volume of the beam. By scanning the laser beam with respect to the sample, buried optical waveguides have been created that were single mode at 1550 and 1320 nm and guided light only with its polarization perpendicular to the sample's surface. Propagation losses with an upper limit of 1.2 dB/cm or less were observed throughout the optical telecommunications band.
Optimizing the Readout Bias for the Capacitorless 1T Bulk FinFET RAM Cell (2009)

In this letter, we demonstrate a one-transistor capacitorless DRAM on standard bulk FinFET, using no additional processing. It is shown that, due to the use of the ground-plane doping and optimization of the READ bias conditions, no special process adjustment is required to obtain wide programming windows and long retention times, even for fin widths down to 20 nm.