gebhart/patrepeval huggingface dataset:
Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells (2010)

The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs.
A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma (2009)

The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries. Our data suggest that inhibition of the Pim protein kinases may be developed as a therapeutic strategy for the treatment of pre-T-LBL.
A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro. (1989)

An important need in cancer research and treatment is a physiological means in vitro by which to assess the proliferation capacity of human tumors and corresponding normal tissue for comparison. We have recently developed a native-state, three-dimensional, gel-supported primary culture system that allows every type of human cancer to grow in vitro at more than 90% frequency, with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. Here we demonstrate that the native-state culture system allows proliferation indices to be determined for all solid cancer types explanted directly from surgery into long-term culture. Normal tissues also proliferate readily in this system. The degree of resolution of measurement of cell proliferation by histological autoradiography within the cultured tissues is greatly enhanced with the use of epi-illumination polarization microscopy. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas generally have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of cells of mesenchymal organ. Normal tissues can also proliferate at high rates. An image analysis system has been developed to automate proliferation determination. The high-resolution physiological means described here to measure the proliferation capacity of tissues will be important in further understanding of the deregulation of cell proliferation in cancer as well as in cancer prognosis and treatment.
On H&lt;sup&gt;∞&lt;/sup&gt;-optimal sensitivity theory for SISO feedback systems (1984)

This paper deals with the design of feedback controllers which minimize the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H^{\infty}</tex> -norm of the sensitivity function, suitably weighted. This approach to the theory of feedback design was introduced by Zames [1] and developed by Zames and Francis [2]. In this paper the theory of Sarason [3] is applied to the determination of the optimal weighted sensitivity function and an upper bound on its norm. The problem of achieving small sensitivity over a specified frequency band is studied, and the effect of nonminimum phase is elucidated. Finally, a method is introduced for handling plant poles and zeros on the imaginary axis.
Cloning, sequence analysis, and permanent expression of a human α2-adrenergic receptor in Chinese hamster ovary cells (1989)

The gene encoding a human alpha 2-adrenergic receptor was isolated from a human genomic DNA library using a 367-base pair fragment of Drosophila genomic DNA that exhibited 54% identity with the human beta 2-adrenergic receptor and 57% identity with the human alpha 2-adrenergic receptor. The nucleotide sequence of a fragment containing the human alpha 2-receptor gene and 2.076 kilobases of untranslated 5' sequence was determined, and potential upstream regulatory regions were identified. This gene encodes a protein of 450 amino acids and was identified as an alpha 2-adrenergic receptor by homology with published sequences and by pharmacological characterization of the protein expressed in cultured cells. Permanent expression of the alpha 2-receptor was achieved by transfecting Chinese hamster ovary (CHO) cells which lack adrenergic receptors with a 1.5-kilobase NcoI-HindIII fragment of the genomic clone containing the coding region of the gene. The alpha 2-receptor expressed in CHO cells displayed pharmacology characteristic of an alpha 2 A-receptor subtype with a high affinity for yohimbine (Ki = 1 nM) and a low affinity for prazosin (Ki = 10,000 nM). Agonists displayed a rank order of potency in radioligand binding assays of para-aminoclonidine greater than or equal to UK-14304 greater than (-)-epinephrine greater than (-)-norepinephrine greater than (-)-isoproterenol, consistent with the identification of this protein as an alpha 2-receptor. The role of the alpha 2-receptor in modulating intracellular cyclic AMP concentrations was investigated in three transfected cell lines expressing 50, 200, and 1200 fmol of receptor/mg membrane protein. At low concentrations (1-100 nM), (-)-epinephrine attenuated forskolin-stimulated cyclic AMP accumulation by up to 60% in a receptor density-dependent manner. At epinephrine concentrations above 100 nM, cyclic AMP levels were increased up to 140% of the forskolin-stimulated level. Pertussis toxin pretreatment of cells eliminated alpha 2-receptor-mediated attenuation of forskolin-stimulated cyclic AMP levels and enhanced the receptor density-dependent potentiation of forskolin-stimulated cyclic AMP concentrations from 3 to 8-fold. Potentiation of forskolin-stimulated cyclic AMP levels was also elicited by the alpha 2-adrenergic agonists, UK-14304 and para-aminoclonidine, and blocked by the alpha 2-adrenergic antagonist yohimbine, but not by the alpha 1-adrenergic antagonist prazosin or the beta-adrenergic antagonist propranolol.(ABSTRACT TRUNCATED AT 400 WORDS)
Plasma Treatment of Polymers:  The Effects of Energy Transfer from an Argon Plasma on the Surface Chemistry of Polystyrene, and Polypropylene. A High-Energy Resolution X-ray Photoelectron Spectroscopy Study (1998)

Argon plasma treatment and subsequent atmospheric exposure have been used to incorporate new oxygen functionalities at the surface of polystyrene (PS) and polypropylene (PP). High-energy resolution X-ray photoelectron spectroscopy (XPS) has yielded molecular information regarding the site of modification in both polymers. Core level and valence band spectra have been interpreted. We have adopted a simple subtraction process to highlight the changes occurring in the valence band spectra upon treatment. In the case of PS, modification is found to be occurring at ring sites. In PP, modification is thought to be occurring at two sites. We propose that modification at the tertiary carbon site leads to chain scission and subsequent etching, while modification at the methyl side group results in functionalities being incorporated at the polymer surface. These data help to substantiate mechanisms that were previously proposed, based on the accepted mechanisms of cross-linking vs chain scission for these polymers.
Androgen deprivation causes truncation of the C‐terminal region of androgen receptor in human prostate cancer LNCaP cells (2012)

The androgen receptor (AR) acts as a ligand-dependent transcription factor, whereas mutant AR lacking the C-terminal ligand-binding domain functions in a ligand-independent manner. In the present study we report that the C-terminal truncated AR, which we named AR-NH1 (the N-terminal fragment of AR cleaved in the neighborhood of helix 1 of the ligand-binding domain), is produced in LNCaP prostatic carcinoma cells. The AR-NH1 of ~90 kDa was observed in an androgen-independent LNCaP subline and was further accumulated by the proteasome inhibitor MG132. MG132 treatment caused the accumulation of AR-NH1 even in parent LNCaP cells. AR-NH1 was produced in the absence of ligand or in the presence of the AR antagonist bicalutamide, whereas AR agonists suppressed its production. AR-NH1 was detected with different AR antibodies recognizing amino acid residues 1-20 and 300-316 and was also generated from exogenous AR. Both siRNA-mediated AR knockdown and treatment with a serine protease inhibitor (4-(2-aminoethyl)-benzenesulfonyl fluoride) reduced AR-NH1 levels. According to the predicted cleavage site (between amino acid residues 660-685) and its nuclear localization, it is assumed that AR-NH1 functions as a constitutively active transcription factor. These data suggest that AR-NH1 is produced under hormone therapy and contributes to the development of castration-resistant prostate cancer due to its ligand-independent transcriptional activity.
Swine Influenza Virus Vaccination in Patients with Multiple Sclerosis (1977)

A double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of inactivated influenza virus vaccines in patients with multiple sclerosis. The vaccine used contained 200 chick cell-agglutinating (CCA) units of influenza A/New Jersey/76 and 200 CCA units of influenza A/Victoria/75 whole viruses (Merrell-National Laboratories, Cincinnati, Ohio). The frequency of clinical relapses of multiple sclerosis was the same in the vaccine-treated (four of 33 patients) and placebo-treated (four of 33) groups. An untreated control group had a slightly higher rate of relapses (four of 22). Toxic reactions to the vaccine were not a significant problem. The efficacy of the vaccination as measured by titers of hemagglutination-inhibiting antibody was comparable to that reported for the general population. However, patients with preexisting antibody were less responsive to the vaccine than normal controls studied previously. The patients who did not respond to the vaccine tended to be older and more disabled. There were no changes in titers of antibody to rubeola or rubella virus after vaccination or in relation to change in clinical course. It is concluded that the vaccine is safe and effective in patients with multiple sclerosis.
Recent Developments in Anti-Cancer Agents Targeting the Ras/Raf/ MEK/ERK Pathway (2008)

The Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) pathway mediates cellular responses to different growth signals and is frequently deregulated in cancer. There are three Raf kinases-A-Raf, B-Raf, and C-Raf; however, only B-Raf is frequently mutated in various cancers. The most common B-Raf mutation involves a substitution of a glutamic acid residue to a valine moiety at codon 600. Subsequently, the MAPK pathway is constitutively activated, even in the absence of any growth signals. Although early attempts to target Ras have not yielded any viable drug candidates, many novel compounds inhibiting the activities of Raf and MEK have been developed and investigated in clinical trials in recent years. The first MEK inhibitor (CI-1040) lacked efficacy in clinical trials, but its low toxicity has encouraged the search for novel compounds with enhanced target potency to inhibit MAPK activation at low nanomolar concentrations. In this review, we will discuss new patents or patent applications related to inhibitors of the Ras/Raf/MEK/ERK pathway.
Mechanism of D-Xylose Transport in Human Small Intestine (1986)

The transport mechanism of D-xylose across the mucosal border of small intestine was investigated in humans both in vitro and in vivo. A comparative study was also made between infants and adults. We investigated the Na+ dependence of D-xylose influx from the mucosal solution into the epithelial cells, the phlorizin sensitivity of the influx, transport kinetics and electrogenic property of the D-xylose transport. The results of kinetic study indicated that the transport of D-xylose was completely diffusional. The influx of D-xylose across the mucosal border of human small intestine was Na+ independent and phlorizin insensitive. The electrical property of D-xylose transport could not be observed. There was no difference in the characteristics of D-xylose transport between small intestines of infants or adults. These results in the present study suggest that D-xylose does not share a common transport mechanism of D-glucose, and xylose tolerance test does not give any information about the absorptive capacity of D-glucose.
Assessing the Structure of Communication on the World Wide Web (2006)

This paper examines closely the nature of the hypertext link as a communication tool for Web designers and authors. The strategic nature of the link raises important questions for the representation and interpretation of Web structure. Network analysis is suggested as a methodology that can be used by researchers investigating the World Wide Web from a communication perspective.
Exhaustive analysis of the P53 gene coding sequence by denaturing gradient gel electrophoresis: Application to the detection of point mutations in acute leukemias (1994)

We report the set-up of a denaturant gradient gel electrophoresis (DGGE) assay to screen for mutations in the whole coding sequence of the p53 gene. These DGGE experimental conditions were applied to the analysis of the p53 gene in acute leukemias. Forty adults with acute myelogenous leukemia (AML) and 21 with acute lymphoid leukemia (ALL) were investigated. Eleven of the AML patients were investigated at the time of the initial diagnosis and at relapse. In contrast with most reports based on amplified fragments analyzed by single-strand conformation electrophoresis and focusing on exons 5 to 8, we analyzed the whole coding sequence of the gene. Two of the 40 AML patients displayed a point mutation in exon 7; it was either an A to G substitution that converted Tyr-234 to Cys, or a G to A change that converted Arg-248 to Gln. The screening procedure led to the discovery of several intronic and exonic polymorphisms. These results confirm the low incidence of p53 mutations in acute leukemias and suggest a limited role of the p53 protein in leukemogenesis. The computerized modeling and electrophoresis parameters presented here provide a powerful tool for the exhaustive characterization of p53 mutants in all kinds of malignancies.
Bioactive Glass for Bone Replacement in Craniomaxillofacial Reconstruction (2004)

Gosain, Arun K. M.D. the Plastic Surgery Educational Foundation DATA Committee Author Information
Perturbation theory and discrete Hamiltonian dynamics (2006)

Abstract. In this paper we discuss a weak version of KAM theory for symplectic maps which arise from the discretization of the minimal action principle. These maps have certain invariant sets, the Mather sets, which are the generalization of KAM tori in the non-differentible case. These sets support invariant measures, the Mather measures, which are action minimizing measures. We generalize viscosity solution methods to study discrete systems. In particular, we show that, under non-resonance conditions, the Mather sets can be approximated uniformly, up to any arbitrary order, by finite perturbative expansions. We also present new results concerning the approximation of Mather measures. Departamento de Matemática
A 3D-IC Technology with Integrated Microchannel Cooling (2008)

A 3D-IC technology with integrated microchannel cooling is demonstrated in this paper. Fluidic interconnect network fabrication proceeds at the wafer-level, is compatible with CMOS processing and flip-chip assembly and requires four lithography steps. Measurements for single chips prior to 3D stacking reveal that each die in a two chip 3D stack may potentially exhibit a junction-to-ambient thermal resistance of 0.24°C/W. The demonstrated silicon die contain a through-silicon copper via density of 2500/cm2 integrated within the microchannel heat sink.
Intelligent camera control for graphical environments (1994)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Program in Media Arts & Sciences, 1994.
On the Precision of Adjectives Which Denote Fuzzy Sets (1974)

Abstract The characteristic function of a fuzzy set denoted by a phrase “much larger than 5,” or “heavy,” is investigated experimentally. The S-shaped curve for the characteristic function is derived from some plausible assumptions involving a differential equation, and its parameters are estimated statistically. It was found that the precision of the fuzzy set–measured by the maximum slope of the characteristic function–denoted by “much greater than 5” is less than that denoted by “very much greater than 5.” When the subject is allowed to be fuzzy in his response about grade of membership, there is greater consistency in the response. Anchoring was also found to make an adjective denoting fuzzy set more precise.
Anti-aliased line drawing using brush extrusion (1983)

This algorithm draws lines on a gray-scale raster display by dragging a “brush” along the path of the line. The style of the line is determined by the properties of the brush. An anti-aliasing calculation is performed once for the brush itself and thereafter only a trivial additional operation is needed for each pixel through which the brush is dragged to yield an anti-aliased line.
Purification, cDNA Cloning, and Expression of UDP-Gal: Glucosylceramide β-1,4-Galactosyltransferase from Rat Brain (1998)

Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide, and thus participates in the biosynthesis of most glycosphingolipids in mammals. We purified this enzyme over 61,000-fold to near homogeneity with a 29. 7% yield from rat brain membrane fractions. The isolation procedure included solubilization with Triton X-100, affinity chromatography on wheat germ agglutinin-agarose and UDP-hexanolamine-agarose, and hydroxylapatite column chromatography, followed by ion exchange chromatography. The final preparation migrated as a broad band with an apparent molecular mass of 61 kDa on SDS-polyacrylamide gel electrophoresis. This apparent molecular mass was reduced to 51 kDa by N-glycanase digestion, suggesting that the enzyme has a glycoprotein nature. The enzyme required Mn2+ for its activity, and glucosylceramide was its preferred substrate. The cDNA for the enzyme was cloned from a rat brain cDNA library. The cDNA insert encoded a polypeptide of 382 amino acid residues, with a molecular weight of 44,776. The polypeptide contained eight putative glycosylation sites and a 20-amino acid residue transmembrane domain at its N terminus. Amino acid sequence homology analysis revealed that this enzyme shared 39% homology with mouse beta-1, 4-galactosyltransferase (EC 2.4.1.38), which catalyzes the transfer of Gal to beta-1,4-GlcNAc in glycoproteins.
Embossed Optical Waveguides (1972)

Dielectric optical waveguides have been made by embossing grooves in a thermoplastic substrate and filling them with a liquid which is then solidified. Grooves (7 μm wide and 3.5 μm deep) in poly(methyl methacrylate) (n=1.49) were filled with cyclohexyl methacrylate which was photopolymerized to produce a permanent guide (n=1.505). The attenuation was 2–4 dB/cm at λ=0.633 μm.
GaInP/GaAs/GaInAs Monolithic Tandem Cells for High-Performance Solar Concentrators (2005)

We present a new approach for ultra-high-performance tandem solar cells that involves inverted epitaxial growth and ultra-thin device processing. The additional degree of freedom afforded by the inverted design allows the monolithic integration of high-, and medium-bandgap, lattice-matched (LM) subcell materials with lower-bandgap, lattice-mismatched (LMM) materials in a tandem structure through the use of transparent compositionally graded layers. The current work concerns an inverted, series-connected, triple-bandgap, GaInP (LM, 1.87 eV)/GaAs (LM, 1.42 eV)/GaInAs (LMM, {approx}1 eV) device structure grown on a GaAs substrate. Ultra-thin tandem devices are fabricated by mounting the epiwafers to pre-metallized Si wafer handles and selectively removing the parent GaAs substrate. The resulting handle-mounted, ultra-thin tandem cells have a number of important advantages, including improved performance and potential reclamation/reuse of the parent substrate for epitaxial growth. Additionally, realistic performance modeling calculations suggest that terrestrial concentrator efficiencies in the range of 40-45% are possible with this new tandem cell approach. A laboratory-scale (0.24 cm2), prototype GaInP/GaAs/GaInAs tandem cell with a terrestrial concentrator efficiency of 37.9% at a low concentration ratio (10.1 suns) is described, which surpasses the previous world efficiency record of 37.3%.