gebhart/patrepeval huggingface dataset:
Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model (2008)

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC(50) 3 nmol/L) than pancreatic tumor cells (IC(50) 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment.
Inhibition of Adhesion of Type 1 Fimbriated Escherichia coli to Highly Mannosylated Ligands (2002)

The inhibitory potencies of a number of mannosides, di- and trivalent mannosides, a set of mannose-terminating dendrimers, and five types of mannose-bearing neoglycoproteins were determined by using a binding assay that measures the binding of (125)I-labeled, highly mannosylated neoglycoprotein to a type 1 fimbriated Escherichia coli (K12) strain in suspension. The IC(50) values (the concentration of inhibitor that causes 50 % reduction in the bound (125)I-ligand to E. coli) obtained by this method were much lower than the equivalent values obtained by hemagglutination or in assays that involve microplate immobilization. Two important factors that strongly influence the affinity to E. coli adhesin are: 1) the presence of an alpha-oriented aglycon that has a long aliphatic chain or an aromatic group immediately next to the glycosyl oxygen, and 2) the presence of multiple mannosyl residues that can span a distance of 20 nm or longer on a relatively inflexible structure. The two best inhibitors, which are a highly mannosylated neoglycoprotein with the longest linking arm between a mannose and protein amino group and the largest mannosylated dendrimer (fourth generation), exhibited sub-nM IC(50) values.
Photochemistry of the furan-side 8-methoxypsoralen-thymidine monoadduct inside the DNA helix. Conversion to diadduct and to pyrone-side monoadduct (1985)

We have studied the photochemical reactions of 8-methoxypsoralen (8-MOP) with calf thymus DNA. Analysis of the photoproducts formed was carried out by enzymatic digestion of the 8-MOP-modified DNA, followed by HPLC separation of photoadducts by high-pressure liquid chromatography (HPLC). The 4',5' (furan-side) monoadduct of 8-MOP bound to thymidine is converted to cross-linked thymidine-8-MOP-thymidine diadduct by 341.5 nm light with a quantum yield of 0.028 +/- 0.004. This is 4 times greater than the quantum yield for initial adduct formation (0.0065 +/- 0.0004). When low levels of 8-MOP are covalently bound to DNA by using 397.9 nm light, less than 10% of the adducts formed are diadducts yet nearly 70% are in 5'-TpA cross-linkable sites. The furan-side monoadducts in these sites can subsequently be converted to diadduct or to a lesser extent 3,4 (pyrone-side) monoadduct.
Chemical Modifications at a Single Site Can Induce Significant Shifts in the pH Profiles of a Serine Protease† (1998)

Developing the ability to vary the pH−activity profile of an enzyme in a controlled manner has been a long sought-after goal. Such tailoring provides important insights into mechanism and permits optimization of enzyme performance in organic synthesis applications. The most successful approaches to date toward altering pH−activity profiles of enzymes have employed either site-directed mutagenesis or chemical modification to alter enzyme surface charge. We now report that, by combining these two methodologies, dramatic pKa changes can be induced in the serine protease subtilisin B. lentus. In particular, site specific incorporation of unnatural amino acid side chains by the following strategy, WT → Asn62Cysmutant + H3C−SO2−S−R → Asn62Cys-S−R, where R may be infinitely variable, has demonstrated that pKa shifts of up to 0.72 unit are achievable and are accompanied by significant activity enhancements. The most dramatic pKa shifts are caused by chemical modification with hydrophobic aliphatic moieties. A linear correlation between the hydrophobicity indicator log P for the side chain of the modification and the observed pKa demonstrates that the hydrophobicity in the vicinity of the catalytic triad modulates the pKa of the catalytic residue His64. Molecular modeling analysis reveals that the side chain R of Asn62Cys-S−R, where R is a hydrophobic modification such as decyl or cyclohexyl, positions itself over the imidazole moiety of His64 in the minimized structure.
Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes (2005)

Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.
HIV-1 Reverse Transcriptase Is a Target for Cytotoxic T Lymphocytes in Infected Individuals (1988)

Characterization of the host immune response to human immunodeficiency virus type 1 (HIV-1) is critical to the rational design of an effective AIDS vaccine. In this study, cytotoxic T lymphocytes (CTL) specific for HIV-1 reverse transcriptase (RNA-dependent DNA polymerase) were found in blood samples from HIV-1-infected individuals. CTL targets were prepared by immortalizing B cells from ten seropositive and six seronegative individuals, and then infecting these cells with recombinant vaccinia viruses containing HIV-1 genes. CTL directed against autologous B lymphoblasts expressing HIV-1 reverse transcriptase were detected in fresh blood samples from eight HIV-1 seropositive subjects, but in no seronegative controls. The effector cells were identified as major histocompatibility complex-restricted CD3+CD8+ lymphocytes. Because the HIV-1 pol gene is highly conserved among different isolates and generates both humoral and cellular immune responses, it bears consideration for inclusion in a candidate AIDS vaccine.
128 &#215; 128 deformable mirror device (1983)

The deformable mirror device (DMD) is an <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X-Y</tex> array of deformable mirror elements addressed by an underlying array of MOS transistors. Applications include optical information processing and projection displays. The architecture, operation, and experimental results are presented for a 128 × 128 DMD.
Genetic polymorphisms of matrix metalloproteinase 12 and 13 genes are implicated in endometriosis progression (2008)

These data show a potential role for MMP12 -82 A/G and MMP13 -77 A/G combined polymorphisms in superficial endometriosis. As no association was found with deep infiltrating endometriosis, this combination of polymorphisms might protect from a more in-depth penetration of tissues.
Mechanism of iron toxicity and its possible role in red cell membrane damage. (1989)

The purpose of this review is to explore the role of iron in membrane lipid peroxidation in general; to define the variables that may modify the severity of iron toxicity; to identify the primary targets of iron toxicity; and to examine critically the available evidence supporting the role of iron stress in the pathogenesis of red blood cell (RBC) membrane damage in thalassemia
Continuous Production of Interferon in Normal Mice: Effect of Anti-interferon Globulin, Sex, Age, Strain and Environment on the Levels of 2-5A Synthetase and p67K Kinase (1985)

Two interferon-mediated enzymes, a 2-5A synthetase and a kinase that phosphorylates a 67 000 mol. wt. (p67K) protein were found at variable levels in different organs of mice. Among the different strains of mice included in this study, germ-free mice had the lowest levels of these enzymes. The levels of 2-5A synthetase and p67K kinase were enhanced significantly in all mice following treatment with mouse (alpha + beta) interferon. Here, we show that the presence of 2-5A synthetase and p67K kinase in different organs of normal mice (untreated) was due, at least in part, to a constant production of interferon under different physiological conditions. Accordingly, injection of normal mice with anti-mouse interferon (alpha + beta) globulin led to a significant decrease in the level of 2-5A synthetase and p67K kinase. In conventional mice (C3H/He), the level of both of these enzymes was higher in female than in male animals and was decreased with age or when such animals were reared isolated in a pathogen-free protected unit. The levels of 2-5A synthetase and p67K kinase were also decreased in normal mice following injection with a powerful antibiotic against a very wide spectrum of Gram-positive and Gram-negative bacteria. These results suggest that the production of interferon was induced continuously in normal mice. Such induction was mediated by both internal and external agents.
Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis (1998)

Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of enzymatic digestion of subendothelial basement membrane and other components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9 is increased around multiple sclerosis plaques and in brain tissue in experimental allergic encephalomyelitis. To measure quantitatively the expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2), we analysed samples from 52 patients with relapsing-remitting and primary progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay) and substrate-gel electrophoresis (zymography). MMP-9 was increased over controls in 100% of relapsing-remitting multiple sclerosis cases, with similar levels detected in relapses and clinically stable phases of disease. In primary progressive multiple sclerosis, MMP-9 was increased in 57% of CSF samples, but concentrations were below those encountered in the relapsing-remitting form. The selective upregulation of MMP-9 suggests that T-cells and macrophages invading the brain parenchyma and the CSF space are the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs (MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of patients with relapsing-remitting and primary progressive multiple sclerosis. The sustained increase of MMP-9 in clinically stable multiple sclerosis supports the concept that multiple sclerosis is associated with ongoing proteolysis that may result in progressive tissue damage. The selective inhibition of MMP-9 could be a useful approach for the prevention of disease progression in multiple sclerosis.
Sequence analysis of the human major histocompatibility gene SX alpha. (1985)

The DP subregion of the human major histocompatibility complex contains two closely linked gene pairs, DP alpha, DP beta and SX alpha, SX beta. The exon-intron organization and the complete DNA sequence of the SX alpha gene are reported here. There are several mutations within the SX alpha gene which strongly suggest that it is a pseudogene. These include two frameshift mutations, one in the alpha 1 domain and the other in the cytoplasmic domain. A 5' splice site mutation at the end of the alpha 1 exon also exists. DNA sequence homology between DP alpha and SX alpha suggests that these genes arose through a gene duplication event.
Photoreactive Polymers: The Science and Technology of Resists (1989)

A brief history of resists negative photoresists aspects of photophysics and photochemistry in solid polymers photoinitiated polymerization positive resists based on diazonaphthoquinones the rudiments of imaging science deep-UV lithography electron beam lithography X-ray and ion beam lithographies multilayer techniques and plasma processing.
Analysis of the repertoire of anti‐NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response (1978)

Abstract Spleen cells from C57BL/6 mice sensitized to the hapten (4‐hydroxy‐3‐nitrophenyl)acetyl (NP) were hybridized with myeloma cells, and a variety of hybrid cell lines was isolated which secreted homogeneous anti‐NP antibodies. The antibodies were purified by affinity chromatography and their chain composition, affinity and fine specificity were determined. All antibodies recovered from the primary immune response carried λ light and μ or γ 1 heavy chains. Their variable portions were nonidentical but similar in terms of hapten‐binding specificity with a higher affinity for the cross‐reacting haptens (4‐hydroxy‐3,5‐dinitro‐phenyl)acetyl (NNP) and (4‐hydroxy‐5‐iodo‐3‐nitro‐phenyl)acetyl (NIP) than for the homologous hapten NP. This heteroclitic property as well as the presence of λ, μ and γ 1 chains are characteristic for primary anti‐NP sera of C57BL/6 mice. In contrast, four families of anti‐NP antibodies, each with a characteristic fine specificity pattern, were found among the hybrid cell antibodies derived from the hyperimmune anti‐NP response. The antibodies of one of these families were related to the antibodies recovered from the primary immune response in that they were heteroclitic and carried λ light chains. All members of the other groups expressed k chains and were nonheteroclitic. The finding of well‐defined antibody families in this system and the isolation of their members enable us to approach the problem of V gene expression and diversification in a new way.
Covalent attachment of synthetic DNA to self-assembled monolayer films (1996)

The covalent attachment of thiol-modified DNA oligomers; to self-assembled monolayer silane films on fused silica and oxidized silicon substrates is described. A heterobifunctional crosslinking molecule bearing both thiol- and amino-reactive moieties was used to tether a DNA oligomer (modified at its terminus with a thiol group) to an aminosilane film formed on silica surfaces. A variety of aminosilanes, crosslinkers and treatment conditions have been tested to identify optimal conditions for DNA immobilization using this approach. The DNA films which result have been characterized using UV spectroscopy, water contact angle measurement, radiolabeling and hybridization methods.
Evolution of the Sabin Vaccine into Pathogenic Derivatives without Appreciable Changes in Antigenic Properties: Need for Improvement of Current Poliovirus Surveillance (2009)

The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with "Sabin-like" properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV.
Defects in the Acquisition of CD8 T Cell Effector Function after Priming with Tumor or Soluble Antigen Can Be Overcome by the Addition of an OX40 Agonist (2007)

Several members of the TNFR superfamily, including OX40 (CD134), 4-1BB (CD137), and CD27 provide critical costimulatory signals that promote T cell survival and differentiation in vivo. Although several studies have demonstrated that OX40 engagement can enhance CD4 T cell responses, the mechanisms by which OX40-mediated signals augment CD8 T cell responses are still unclear. Previously, we and others have shown that OX40 engagement on Ag-specific CD8 T cells led to increased CD8 T cell expansion, survival, and the generation of greater numbers of long-lived memory cells. Currently, we demonstrate that provision of an OX40 agonist during the activation of naive CD8 T cells primed in vivo with either soluble or tumor-associated Ag significantly augments granzyme B expression and CD8 T cell cytolytic function through an IL-2-dependent mechanism. Furthermore, augmented CTL function required direct engagement of OX40 on the responding CD8 T cells and was associated with increased antitumor activity against established prostate tumors and enhanced the survival of tumor-bearing hosts. Thus, in the absence of danger signals, as is often the case in a tumor-bearing host, provision of an OX40 agonist can overcome defective CD8 T cell priming and lead to a functional antitumor response in vivo.
YIN, a fundamental frequency estimator for speech and music (2002)

An algorithm is presented for the estimation of the fundamental frequency (F0) of speech or musical sounds. It is based on the well-known autocorrelation method with a number of modifications that combine to prevent errors. The algorithm has several desirable features. Error rates are about three times lower than the best competing methods, as evaluated over a database of speech recorded together with a laryngograph signal. There is no upper limit on the frequency search range, so the algorithm is suited for high-pitched voices and music. The algorithm is relatively simple and may be implemented efficiently and with low latency, and it involves few parameters that must be tuned. It is based on a signal model (periodic signal) that may be extended in several ways to handle various forms of aperiodicity that occur in particular applications. Finally, interesting parallels may be drawn with models of auditory processing.
A new DRAM cell with a transistor on a lateral epitaxial silicon layer (TOLE cell) (1990)

A new dynamic RAM (DRAM) cell structure and its fabrication technology are proposed. The proposed DRAM cell consists of a transistor on a lateral epitaxial silicon layer (TOLE) and a stacked capacitor formed in a trench. It can achieve high immunity to alpha-particle-induced noise and a low parasitic bit-line capacitance. The TOLE structure is produced by a silicon-on-insulator fabrication technology newly developed by combining epitaxial lateral overgrowth and preferential polishing. Reasonable electrical characteristics for the TOLE and high immunity against alpha-particle disturbance for the TOLE cell were confirmed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
13C nuclear magnetic resonance study of some phosphinolipids: Assignments and conformational studies (1989)

Abstract 13 C chemical shifts and 31 P, 13 C spin‐spin coupling constants are reported for six model phosphinates and eight synthetic phosphinolipids. The complex spectra of the synthetic phosphinolipids could be assigned from increments and couplings derived from the model compounds. Based on these investigations the 3 J (PC) couplings of 7–15 Hz indicate a preferential trans orientation of the respective head‐group carbon relative to the phosphorus. This behaviour is similar to that of natural phosphatidylcholine lipids.
Fast subsequence matching in time-series databases (1994)

We present an efficient indexing method to locate 1-dimensional subsequences within a collection of sequences, such that the subsequences match a given (query) pattern within a specified tolerance. The idea is to map each data sequences into a small set of multidimensional rectangles in feature space. Then, these rectangles can be readily indexed using traditional spatial access methods, like the R*-tree [9]. In more detail, we use a sliding window over the data sequence and extract its features; the result is a trail in feature space. We propose an efficient and effective algorithm to divide such trails into sub-trails, which are subsequently represented by their Minimum Bounding Rectangles (MBRs). We also examine queries of varying lengths, and we show how to handle each case efficiently. We implemented our method and carried out experiments on synthetic and real data (stock price movements). We compared the method to sequential scanning, which is the only obvious competitor. The results were excellent: our method accelerated the search time from 3 times up to 100 times.
Calculation of Absorbed Dose for Immersion in Semi-Infinite Radioactive Cloud...(1) (1985)

In general, dose rates for a monoenergetic gamma emitter uniformly distributed in an infinite cloud have been calulated by using the monoenergetic point-isotorpic source kernel technique. The most serious limitation on use of the kernel technique is subjected to the fact that it estimates the dose only at the surface of body. As a result, an alternative method is presented in which estimates of dose rate for immersion in a radioactive cloud are resulted from the scattered photon spectra incident on the surface of body. The results are in excellent agreement with other's. Work is currently in progress to apply these results to immersion dose problems associated with absorbed dose distribution in the MIRD phatom.
Electrophoretic drawing of continuous fibers of single-walled carbon nanotubes (2005)

Control over the current during electrophoretic drawing of continuous fibers of single-walled carbon nanotubes (SWCNTs) is shown to be critical in producing long fibers with specific diameters. In the process, as-produced SWCNTs are first dispersed in N,N-dimethylformamide (DMF) by sonication. A tungsten probe tip is then immersed in the SWCNT∕DMF solution, and a dc bias is applied between the tip and another electrode at the bottom of the beaker containing the solution. After a dark cloud several millimeters in diameter develops around the tip, the electrode is withdrawn to form continuous macroscopic fibers of SWCNTs. The resulting fiber length and diameter are found to be principally determined by the magnitude of the current. Under constant voltage conditions where the current is allowed to vary, the fibers are short (several millimeters long) and their diameters vary drastically along their lengths. Of significance is the fact that when the current is maintained at constant values, fibers several centimeters in length with uniform diameters ranging from 26to42μm are obtained at a withdrawal rate of 0.85μm∕s. For this withdrawal rate, long fibers (∼3cm and greater) are obtained at an optimum value of the current (400nA) using hybrid conditions where the voltage is maintained constant earlier in the process while the current is maintained constant later in the process. Control of the total current at low values during this process has the potential to produce long fibers with uniform submicron diameters.
Google Street View: Capturing the World at Street Level (2010)

Street View serves millions of Google users daily with panoramic imagery captured in hundreds of cities in 20 countries across four continents. A team of Google researchers describes the technical challenges involved in capturing, processing, and serving street-level imagery on a global scale.