gebhart/patrepeval huggingface dataset:
Purification and partial amino acid sequence of asialo murine granulocyte-macrophage colony stimulating factor. (1985)

A procedure utilizing reversed-phase high-performance liquid chromatography is described for the purification of asialo granulocyte-macrophage colony stimulating factor (asialo-GM-CSF) from mouse lung-conditioned medium. In the purification, the partially purified factor was treated with neuraminidase to reduce charge heterogeneity due to variable degrees of sialation. Three active forms of the asialo factor were separated by the final reversed-phase liquid chromatography step. These each gave a single major band and several minor bands on polyacrylamide gel electrophoresis and had similar amino acid compositions. The specific activity of purified murine asialo-GM-CSF was approximately 8 X 10(9) colonies per mg of protein. Amino acid sequence determination of the major form gave a single amino-terminal sequence, which has been used to develop oligonucleotide probes for the isolation of two cDNA clones encoding GM-CSF. The nucleotide sequence of these two clones gave a deduced amino acid sequence almost identical with that determined for the amino terminus of asialo-GM-CSF and an amino acid composition very similar to that for asialo-GM-CSF.
The apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme is elevated in premalignant and malignant cervical cancer. (1998)

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease (APE) is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA-binding capability of JUN and FOS, HeLa AP-1, and numerous other transcription factors, including Myb, members of the CREB family and nuclear factor-kappa B. Although previously presumed to be ubiquitously expressed at comparable levels in all tissues and cell types, recent evidence has shown APE to vary significantly in its expression between tissues and even within tissues. To further characterize APE expression at various stages of cervical neoplasia, we investigated the levels of APE protein expression using immunohistochemistry in normal cervix, pre-invasive and invasive squamous lesions of the cervix, as well as in cervical cancer cell lines. We report here that the APE protein is predominantly expressed in the nuclei of cells from both primary tumors and cervical cell lines, but the level of APE protein is significantly and dramatically elevated in cervical cancer tissue. These results implicate the use of anti-APE antibodies as an effective reagent in the early detection of premalignant and malignant cancer of the cervix. These findings are suggestive that the increase of a DNA repair enzyme in cancerous cells may allow these cells to be refractive to chemotherapy.
Fast and low-complexity LSF quantization using algebraic vector quantizer (2002)

This paper presents an algebraic vector-quantization scheme for encoding the LSF parameters used in describing the time-varying short-term spectrum of speech in many modern vocoders. The quantizer achieves an average spectral distortion of 1 dB at 28 bits/frame for the telephone bandwidth. The scheme is based on low-dimensionality regular-point lattices. The properties of lattices are taken advantage of in both the design and the search of the quantizer codebook. Namely, this algebraic codebook need not be stored in memory and the optimum vector is found through simple rounding of the input variables instead of the usual exhaustive search. Thus, the scheme results in significant savings of memory and reduced computational complexity when compared to traditional vector-quantizer solutions.
Mutagenesis of the yellow fever virus NS2B/3 cleavage site: determinants of cleavage site specificity and effects on polyprotein processing and viral replication (1995)

The determinants of cleavage site specificity of the yellow fever virus (YF) NS3 proteinase for its 2B/3 cleavage site have been studied by using site-directed mutagenesis. Mutations at residues within the GARR decreases S sequence were tested for effects on cis cleavage of an NS2B-3(181) polyprotein during cell-free translation. At the P1 position, only the conservative substitution R-->K exhibited significant levels of cleavage. Conservative and nonconservative substitutions were tolerated at the P1' and P2 positions, resulting in intermediate levels of cleavage. Substitutions at the P3 and P4 positions had no effects on cleavage efficiency in the cell-free assay. Processing at other dibasic sites was studied by using transient expression of a sig2A-5(356) polyprotein. Cleavage at the 2B/3 site was not required for processing at downstream sites. However, increased accumulation of high-molecular-weight viral polyproteins was generally observed for mutations which reduced cleavage efficiency at the 2B/3 site. Several mutations were also tested for their effects on viral replication. Virus was not recovered from substitutions which blocked or substantially reduced cleavage in the cell-free assay, suggesting that efficient cleavage at the 2B/3 site is required for flavivirus replication.
A compact PIFA suitable for dual-frequency 900/1800-MHz operation (1998)

Planar inverted F antennas (PIFA) have been proposed as possible candidates for mobile telephone handsets. We describe the design of a compact PIFA suitable for operation at 900 MHz. In addition, we provide modifications to this design that allow it to operate in dual-frequency bands at 300 and 1800 MHz. Finite-difference time-domain (FDTD) and experimental results are provided.
The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaP-Pro5 prostate cancer cells. (2003)

Advanced prostate cancer is resistant to current therapeutic strategies. Bortezomib (Velcade; previously called PS-341) is a potent and specific inhibitor of the 26S proteasome that is currently in clinical trials for treatment of various malignancies, including prostate cancer. We investigated the effects of bortezomib on p53 in the LNCaP-Pro5 prostate cancer cell line. Bortezomib induced strong stabilization of p53, but it did not promote phosphorylation on serines 15 and 20, and p53 remained bound to its inhibitor, mdm2. Nonetheless, bortezomib stimulated p53 translocation to the nucleus (not mitochondria) and enhanced p53 DNA binding, accumulation of p53-dependent transcripts, and activation of a p53-responsive reporter gene. Furthermore, stable LNCaP-Pro5 transfectants of LNCaP-Pro5 expressing the p53 inhibitor human papillomavirus-E6 displayed reduced bortezomib-induced p53 activation and cell death. Together, our data demonstrate that bortezomib stimulates p53 activation via a novel mechanism.
Integrating segmentation and paging protection for safe, efficient and transparent software extensions (1999)

The trend towards extensible software architectures and component-based software development demands safe, efficient, and easy-to-use extension mechanisms to enforce protection boundaries among software modules residing in the same address space. This paper describes the design, implementation, and evaluation of a novel intra-address space protection mechanism called Palladium, which exploits the segmentation and paging hardware in the Intel X86 architecture and efficiently supports safe kernel-level and user-level extensions in a way that is largely transparent to programmers and existing programming tools. Based on the considerations on ease of extension programming and systems implementation complexity, Palladium uses different approaches to support user-level and kernel-level extension mechanisms. To demonstrate the effectiveness of the Palladium architecture, we built a Web server that exploits the user-level extension mechanism to invoke CGI scripts as local function calls in a safe way, and we constructed a compiled network packet filter that exploits the kernel-level extension mechanism to run packet-filtering binaries safely inside the kernel at native speed. The current Palladium prototype implementation demonstrates that a protected procedure call and return costs 142 CPU cycles on a Pentium 200MHz machine running Linux.
Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate (2001)

Epigallocatechin-3-gallate is a potent inhibitor of gelatinases and an orally available pharmacologic agent that may confer the antiangiogenic and antimetastatic activity associated with green tea.
Reoxidation of the NADPH produced by the pentose phosphate pathway is necessary for the utilization of glucose by Kluyveromyces lactis rag2 mutants (1996)

Kluyveromyces lactis mutants defective in the glycolytic enzyme phosphoglucose isomerase are able to grow in glucose media and to produce ethanol, but they depend on a functional respiratory chain and do not grow in glucose-antimycin media. We postulate that this is due to the necessity of reoxidizing, in the mitochondria, the NADPH produced by the pentose phosphate pathway, which may be highly active in these mutants in order to bypass the blockade in the phosphoglucose isomerase step. This oxidation would be mediated by a cytoplasmic-side mitochondrial NAD(P)H dehydrogenase that would pass the electrons to ubiquinone. Data supporting this hypothesis are provided.
High-efficiency organic electrophosphorescent devices (2001)

We have fabricated saturated red, orange, yellow and green OLEDs, utilizing phosphorescent dopants. Using phosphorescence based emitters we have eliminated the inherent 25% upper limit on emission observed for traditional fluorescence based systems. The quantum efficiencies of these devices are quite good, with measured external efficiencies &gt; 15% and &gt; 40 lum/W (green) in the best devices. The phosphorescent dopants in these devices are heavy metal containing molecules (i.e. Pt, and Ir), prepared as both metalloporphyrins and organometallic complexes. The high level of spin orbit coupling in these metal complexes gives efficient emission from triplet states. In addition to emission from the heavy metal dopant, it is possible to transfer the exciton energy to a fluorescent dye, by Forster energy transfer. The heavy metal dopant in this case acts as a sensitizer, utilizing both singlet and triplet excitons to efficiently pump a fluorescent dye. We discuss the important parameters in designing electrophosphorescent OLEDs as well as their strengths and limitations. Accelerated aging studies, on packaged devices, have shown that phosphorescence based OLEDs can have very long device lifetimes.
Suitability of N-ON recessed implanted gate vertical-channel SiC JFETs for optically triggered 1200 V solid-state-circuit-breakers (2015)

A requirement for the commercialization of power SiC transistors is their long term reliable operation under the hard switching conditions and high temperatures encountered in the field. Normally-ON 1200 V vertical-channel implanted-gate SiC JFETs, designed for high-power bidirectional (four quadrant) solid-state-circuit-breaker applications, were repetitively pulse hard switched at 150 °C from a 1200 V blocking state to an on-state current of 115 A, which is in excess of 13 times the JFET's 250-W/cm2 rated current at 150 °C. The JFETs were fabricated in seven photolithographic levels with a single masked ion-implantation forming the p+ gates and guard rings, and with no epitaxial regrowth. The pulsed testing was performed using a low inductance RLC circuit. In this circuit, energy initially stored in a capacitor is discharged in a load resistor through the JFET under test. The JFET hard-switch stressing included over 2.4 million 1200-V/115-A hard-switch events at 150 °C and at a repetition rate of 10 Hz. The peak energies and powers dissipated by the JFET at each hard-switch event were 73.2 mJ and 68.2 kW, respectively. The current rise rate was 166 A/μs and the pulse FWHM was 1.8 μs. After over 2.4 million hard-switch events at 150 °C, the JFET blocking voltage characteristics remained unchanged while the on-state conduction slightly improved, which indicate reliable operation. An optically triggered solid-state-circuit-breaker, based on these rugged JFET, is proposed.
An in-vitro evaluation of the cellular uptake and infraphagocytic bioactivity of clarithromycin (A-56268, TE-031), a new macrolide antimicrobial agent (1988)

Erythromycin base and its 6-0-methyl derivative clarithromycin were actively accumulated 7.3 +/- 1.2-fold and 9.2 +/- 2-fold respectively by human neutrophils in vitro. The intraphagocytic bioactivities of the antimicrobial agents were investigated using the combination of a radioassay, colony counting method and a fluorescence microassay which facilitates the distinction between intracellular bacteriostatic and bactericidal mechanisms. Staphylococcus aureus, Listeria monocytogenes and Legionella micdadei were used as the test intraphagocytic microbial pathogens. Both agents were found to possess intracellular bioactivity for all three species of bacteria with clarithromycin being consistently more active than erythromycin. Under the assay conditions used both agents were bacteriostatic (intracellularly) for S. aureus and Leg. micdadei and bactericidal for List. monocytogenes. Clarithromycin is clearly a potent intraphagocytic antibiotic and potentially superior in this respect to erythromycin.
Detection of Volatile Compounds with Mass-Sensitive Sensor Arrays in the Presence of Variable Ambient Humidity (1999)

Mass-sensitive sensor arrays were established for the detection of isomeric or highly analogue analyte mixtures, which show similar physical and morphological properties. Supramolecular host-guest chemistry and arrays of four mass-sensitive quartz crystal microbalances have been successfully combined with multivariate calibration techniques in the presence of variable air moisture. This system enabled even the separation of xylene isomers [Formula: see text] a task that might be crucial even by gas chromatography. The data of the sensor arrays were analyzed with partial least squares and artificial neural networks. The xylene isomers could be detected with an accuracy of ∼1% in the range of 0-200 ppm, nearly eliminating the residual water cross-sensitivity of the sensor coatings, which allows effective work place or environmental monitoring of toxic compounds with fast response levels.
A combined computational-experimental approach predicts human microRNA targets (2004)

A new paradigm of gene expression regulation has emerged recently with the discovery of microRNAs (miRNAs). Most, if not all, miRNAs are thought to control gene expression, mostly by base pairing with miRNA-recognition elements (MREs) found in their messenger RNA (mRNA) targets. Although a large number of human miRNAs have been reported, many of their mRNA targets remain unknown. Here we used a combined bioinformatics and experimental approach to identify important rules governing miRNA-MRE recognition that allow prediction of human miRNA targets. We describe a computational program, "DIANA-microT", that identifies mRNA targets for animal miRNAs and predicts mRNA targets, bearing single MREs, for human and mouse miRNAs.
Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling (2001)

Nitroxyl anion (NO(-)) is the one-electron reduction product of nitric oxide (NO( small middle dot)) and is enzymatically generated by NO synthase in vitro. The physiologic activity and mechanism of action of NO(-) in vivo remains unknown. The NO(-) generator Angeli's salt (AS, Na(2)N(2)O(3)) was administered to conscious chronically instrumented dogs, and pressure-dimension analysis was used to discriminate contractile from peripheral vascular responses. AS rapidly enhanced left ventricular contractility and concomitantly lowered cardiac preload volume and diastolic pressure (venodilation) without a change in arterial resistance. There were no associated changes in arterial or venous plasma cGMP. The inotropic response was similar despite reflex blockade with hexamethonium or volume reexpansion, indicating its independence from baroreflex stimulation. However, reflex activation did play a major role in the selective venodilation observed under basal conditions. These data contrasted with the pure NO donor diethylamine/NO, which induced a negligible inotropic response and a more balanced veno/arterial dilation. AS-induced positive inotropy, but not systemic vasodilatation, was highly redox-sensitive, being virtually inhibited by coinfusion of N-acetyl-l-cysteine. Cardiac inotropic signaling by NO(-) was mediated by calcitonin gene-related peptide (CGRP), as treatment with the selective CGRP-receptor antagonist CGRP(8-37) prevented this effect but not systemic vasodilation. Thus, NO(-) is a redox-sensitive positive inotrope with selective venodilator action, whose cardiac effects are mediated by CGRP-receptor stimulation. This fact is evidence linking NO(-) to redox-sensitive cardiac contractile modulation by nonadrenergic/noncholinergic peptide signaling. Given its cardiac and vascular properties, NO(-) may prove useful for the treatment of cardiovascular diseases characterized by cardiac depression and elevated venous filling pressures.
Technical Advance: Cytometric analysis of an epitope‐tagged transit peptide bound to the chloroplast translocation apparatus (2001)

Chloroplast transit peptides are necessary and sufficient for the targeting and translocation of precursor proteins across the chloroplast envelope. However, the mechanism by which transit peptides engage the translocation apparatus has not been investigated. To analyse this interaction, we have developed a novel epitope-tagged transit peptide derived from the precursor of the small subunit of pea Rubisco. The recombinant transit peptide, His-S-SStp, contains a removable dual-epitope tag, His-S, at its N-terminus that permits both rapid purification via immobilized metal affinity chromatography and detection by blotting, flow cytometry and laser-scanning confocal microscopy. Unlike other chimeric precursors, which place the passenger protein C-terminal to the transit peptide, His-S-SStp bound to the translocation apparatus yet did not translocate across the chloroplast envelope. This early translocation intermediate allowed non-radioactive detection using fluorescent and chemiluminescent reporters. The physiological relevance of this interaction was confirmed by protein import competitions, sensitivity to pre- and post-import thermolysin treatment, photochemical cross-linking and organelle fractionation. The interaction was specific for the transit peptide since His-S alone did not engage the chloroplast translocation apparatus. Quantitation of the bound transit peptide was determined by flow cytometry, showing saturation of binding yet only slight ATP-dependence. The addition of GTP showed inhibition of the binding of His-S-SStp to the chloroplasts indicating an involvement of GTP in the formation of this early translocation intermediate. In addition, direct visualization of His-S-SStp and Toc75 by confocal microscopy revealed a patch-like labeling, suggesting a co-ordinate localization to discrete regions on the chloroplast envelope. These findings represent the first direct visualization of a transit peptide interacting with the chloroplast translocation apparatus. Furthermore, identification of a chloroplast-binding intermediate may provide a novel tool to dissect interactions between a transit peptide and the chloroplast translocation apparatus.
Bijels formed by direct mixing (2017)

By combining interfacial nanoparticles and molecular surfactants together with immiscible liquids of high viscosity, we develop an alternative strategy for creating bicontinuous interfacially jammed emulsion gels (bijels). These bijels are prepared from common ingredients which are widely used in industry: glycerol, silicone oil, silica nanoparticles together with cetyltrimethylammonium bromide (CTAB) surfactant. We tune the sample composition and develop a multi-step mixing protocol to achieve a tortuous arrangement of liquid domains. We show that the nanoparticle location changes from one of the phases to the interface during mixing. The changes in both the microscopic and macroscopic sample configuration after a waiting time of months were assessed. In order for the structure to have long-term stability we find that the densities of the two phases must be similar which we achieved by filling one of the phases with nanoparticle-stabilised droplets of the other. This work paves the way to the production of bijels using fully immiscible liquids and hence their exploitation in many application areas.
Therapeutic Vaccination against Metastatic Carcinoma by Expression-Modulated and Immunomodified Autologous Tumor Cells: A First Clinical Phase I/II Trial (2001)

Therapeutic vaccination of tumor patients with cytokine gene-transfected tumor cells leads to tumor regression in animal models but has so far not resulted in significant clinical benefit. We and others demonstrated that tumor cells transfected to mediate overexpression of a cytokine gene activate immunologic effector cells for an improved proliferation rate and significantly higher antitumoral cytotoxic activity. Here, we performed a pilot study of therapeutic vaccination in patients with metastatic disease. Autologous tumor cells were simultaneously transfected with novel minimalistic, immunogenically defined, gene expression constructs (MIDGE) for overexpression of the two cytokines interleukin 7 (IL-7) and GM-CSF and newly designed double stem-loop immunomodulating oligodeoxyribonucleotides (d-SLIM) as a Th1-promoting and NK cell-stimulating adjuvant. Transfection was performed ex vivo by ballistomagnetic gene transfer. Patients received four subcutaneous injections of at least 1 x 10(6) of their expression-modulated and immunomodified autologous tumor cells. Ten patients have been enrolled in the study protocol. In all patients no adverse effects could be detected. IL-7 and interferon gamma levels were elevated in the serum of the patients after treatment. Interestingly, cytotoxicity of patient-derived PBLs increased significantly during treatment. All 10 patients had progressive disease when entering our protocol. One complete, one partial, and one mixed response with progression of abdominal metastases and regression of lung metastases were observed. Two patients showed a stable disease after treatment and five patients remained in progressive disease. Our observations confirm the capability of autologous expression-modified and immunomodulated tumor cell vaccines to stimulate a strong immune response in patients with metastatic cancer even in the presence of a large tumor burden.
Design of a Novel Class of Peptide Inhibitors of Cyclin-dependent Kinase/Cyclin Activation (2005)

Cyclin dependent kinases (CDKs) are key regulators of the cell cycle progression and therefore constitute excellent targets for the design of anticancer agents. Most of the inhibitors identified to date inhibit kinase activity by interfering with the ATP-binding site of CDKs. We recently proposed that the protein/protein interface and conformational changes required in the molecular mechanism of CDK2-cyclin A activation were potential targets for the design of specific inhibitors of cell cycle progression. To this aim, we have designed and characterized a small peptide, termed C4, derived from amino acids 285-306 in the alpha5 helix of cyclin A. We demonstrate that this peptide does not interfere with complex formation but forms stable complexes with CDK2-cyclin A. The C4 peptide significantly inhibits kinase activity of complexes harboring CDK2 in a competitive fashion with respect to substrates but does not behave as an ATP antagonist. Moreover, when coupled with the protein transduction domain of Tat, the C4 peptide blocks the proliferation of tumor cell lines, thereby constituting a potent lead for the development of specific CDK-cyclin inhibitors.