gebhart/patrepeval huggingface dataset:
In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus (2002)

In vitro-assembled core-like particles produced from alphavirus capsid protein and nucleic acid were studied by cryoelectron microscopy. These particles were found to have a diameter of 420 A with 240 copies of the capsid protein arranged in a T=4 icosahedral surface lattice, similar to the nucleocapsid core in mature virions. However, when the particles were subjected to gentle purification procedures, they were damaged, preventing generation of reliable structural information. Similarly, purified nucleocapsid cores isolated from virus-infected cells or from mature virus particles were also of poor quality. This suggested that in the absence of membrane and glycoproteins, nucleocapsid core particles are fragile, lacking accurate icosahedral symmetry.
Quantitation of Tumor Cell Removal from Bone Marrow: A Preclinical Model (1992)

We have developed a multiassay system consisting of fluorescence microscopy, immunocytology and tumor colony assay to monitor the removal of tumor cells from bone marrow. This system was tested in preclinical purging experiments in which neuroblastoma cells were seeded into bovine marrow and purged by treatment with monoclonal antibodies and immunomagnetic beads. Eight experiments were performed on two different neuroblastoma cell lines seeded at 2% and/or 5% contamination. We consistently demonstrated greater than a 3 log removal with one cycle of antibody/bead treatment and greater than a 1 log further reduction by addition of a second cycle. We also demonstrated removal of all detectable tumor stem cells by this purging method. We feel that this system will prove valuable for monitoring ex vivo tumor removal in future clinical studies and should be considered for use in other purging trials.
Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent newcastle disease virus (1990)

Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T-lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity.
A Pilot Study Examining Associations between DYRK1A and α-Synuclein Dementias (2012)

DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia.
Inhibition of mutant p53 expression and growth of DMS-153 small cell lung carcinoma by antagonists of growth hormone-releasing hormone and bombesin (2003)

We investigated the effects of growth hormone-releasing hormone (GHRH) antagonists, JV-1-65 and JV-1-63, and bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC-3940-II on DMS-153 human small cell lung carcinoma xenografted into nude mice. Treatment with 10 microg/day JV-1-65 or RC-3940-II decreased tumor volume by 28% (P < 0.05) and 77% (P < 0.01), respectively, after 42 days compared with controls. Combination of JV-1-65 and RC-3940-II induced the greatest inhibition of tumor proliferation (95%; P < 0.01), suggesting a synergism. Western blotting showed that the antitumor effects of these antagonists were associated with inhibition of the expression of the mutant tumor suppressor protein p53 (Tp53). Mutation was detected by sequence analysis of the p53 gene at codon 155: ACC [Thr] --> CCC [Pro]. Combination of JV-1-65 and RC-3940-II decreased the levels of mutant p53 protein by 42% (P < 0.01) compared with controls. JV-1-65, JV-1-63, and RC-3940-II, given singly, reduced mutant p53 protein expression by 18-24% (P < 0.05). Serum insulin-like growth factor (IGF)-I levels were diminished in animals receiving GHRH antagonists. mRNA levels for IGF-II, IGF receptor-I, GRP receptor, and EGF receptor in tumors were significantly decreased by combined treatment with JV-1-65 and RC-3940-II. DMS-153 tumors expressed mRNAs for GHRH and GHRH receptor splice variants 1 and 2, suggesting that GHRH could be an autocrine growth factor. Proliferation of DMS-153 cells in vitro was stimulated by GRP and IGF-II and inhibited by JV-1-65. This study indicates that GHRH antagonists and BN/GRP antagonist inhibit the growth of DMS-153 small cell lung carcinoma concomitantly with the expression of mutant Tp53, which might uncouple the signal transduction pathways for cell growth stimulation.
Two maternal genes, apx-1 and pie-1, are required to distinguish the fates of equivalent blastomeres in the early Caenorhabditis elegans embryo (1994)

In a 4-cell Caenorhabditis elegans embryo, two sister blastomeres called ABa and ABp are born with equivalent developmental potential, but eventually produce distinct patterns of cell fate. The different fates of ABa and ABp are specified at least in part by inductive interactions with neighboring blastomeres. Previous studies indicate that, at the 4-cell stage, a signal from the posterior-most blastomere, P2, is required for ABp to produce at least one of its unique cell types. This P2/ABp interaction depends on glp-1, a putative receptor for intercellular interactions. To investigate this early induction further, we isolated mutants in which ABp developed abnormally. We describe the effects of recessive mutations in apx-1, a maternal gene that appears to be required for P2 to signal ABp. In embryos from mothers homozygous for mutations in apx-1 (apx-1 embryos), ABp fails to produce its characteristic cell types. Instead, ABp from apx-1 embryos develops more like its sister ABa: it produces ABa-like pharyngeal cells and it recapitulates ABa-like cell lineages. Because mutations in apx-1 affect the development of only the ABp blastomere, we suggest that the wild-type gene encodes a component of the P2/ABp signalling pathway. To explain the observation that ABp in apx-1 embryos adopts an ABa-like fate, we propose a model in which the P2 signal is required to break the initial equivalence of ABa and ABp. We performed two independent tests of this model. First, we examined ABp development in pie-1 mutant embryos, in which P2 adopts the identity of another blastomere. We find that, in pie-1 embryos, APp fails to produce its characteristic cell types and instead adopts a fate similar to that of ABa. We conclude that the changed identity of P2 in pie-1 embryos prevents the P2/ABp interaction. As a second test, we examined ABp development in wild-type embryos after physically removing P2. These operated embryos produce extra pharyngeal cells, consistent with out proposal that a signal from P2 breaks the initially equivalent developmental state of ABa and ABp. We discuss the possibility that apx-1 acts as a ligand in this glp-1-dependent signalling pathway.
Direct method for restoration of motion-blurred images (1998)

We deal with the problem of restoration of images blurred by relative motion between the camera and the object of interest. This problem is common when the imaging system is in moving vehicles or held by human hands, and in robot vision. For correct restoration of the degraded image, it is useful to know the point-spread function (PSF) of the blurring system. We propose a straightforward method to restore motion-blurred images given only the blurred image itself. The method first identifies the PSF of the blur and then uses it to restore the blurred image. The blur identification here is based on the concept that image characteristics along the direction of motion are affected mostly by the blur and are different from the characteristics in other directions. By filtering the blurred image, we emphasize the PSF correlation properties at the expense of those of the original image. Experimental results for image restoration are presented for both synthetic and real motion blur.
Crystal Structure of Thrombin Bound to Heparin (2004)

Thrombin is the final protease in the blood coagulation cascade and serves both pro- and anticoagulant functions through the cleavage of several targets. The ability of thrombin to specifically recognize a wide range of substrates derives from interactions that occur outside of the active site of thrombin. Thrombin possesses two anion binding exosites, which mediate many of its interactions with cofactors and substrates, and although many structures of thrombin have been solved, few such interactions have been described in molecular detail. Glycosaminoglycan binding to exosite II of thrombin plays a major role in switching off the procoagulant functions of thrombin by mediating its irreversible inhibition by circulating serpins and by its binding to the endothelial cell surface receptor thrombomodulin. Here we report the 1.85-A structure of human alpha-thrombin bound to a heparin fragment of eight monosaccharide units in length. The asymmetric unit is composed of two thrombin dimers, each sharing a single heparin octasaccharide chain. The observed interactions are fully consistent with previous mutagenesis studies and illustrate on a molecular level the cofactor interaction that is critical for the restriction of clotting to the site of blood vessel injury.
Evidence for Genetic Modifiers of Ovarian Follicular Endowment and Development from Studies of Five Inbred Mouse Strains (2002)

The laboratory mouse is the model of choice for genetic studies in mammals due to the availability of many genetically defined inbred strains and inbred congenic strains, as well as the ability to study the effects of over-expression (transgenics) or inactivation (knockouts) of a given gene on cells or tissues. During our studies using these technologies to uncover the importance of various genes to apoptosis in the ovary, we observed that the size of the primordial oocyte reserve was affected by mouse strain in the absence of any other genetic manipulation. To determine if genetic modifiers of oocyte endowment truly exist, herein we examined follicle numbers in one outbred (CD-1) and several inbred (129/Sv, DBA/2, C57BL/6, FVB, AKR/J) strains of mice at day 4 (neonatal) and day 42 (young adult) postpartum. In neonatal life, ovaries of AKR/J females had the lowest total number of follicles, whereas 129/Sv females possessed the highest total number of follicles (P < 0.05 for AKR/J versus 129/Sv). There were more primordial follicles in 129/Sv compared with DBA/2 (P < 0.05), C57BL/6 (P < 0.05), FVB (P < 0.05) or AKR/J (P < 0.05) females, and in CD-1 compared with AKR/J (P < 0.05) females. Although no significant strain-dependent differences in primary follicle numbers were noted, C57BL/6 females had the fewest number of small preantral follicles (P < 0.05 versus all other strains). Evaluation of ovaries at 42 days of age revealed the persistence of strain-dependent differences in early follicle growth patterns, although the total numbers of follicles were comparable. Of interest, marked strain-dependent differences in the rate of primordial follicle growth activation, as well as in the rate of follicle loss (atresia), between days 4 and 42 were observed. These results indicate that genetic modifiers play a major role in follicle endowment, development and atresia in the mouse ovary.
Gene Therapy for Coronary Restenosis: A Promising Strategy for the New Millennium? (2000)

Gene therapy is an attractive alternative for reducing restenosis after percutaneous coronary interventions. Several approaches, using genes encoding antiproliferative, antimigratory, cytostatic, or cytotoxic proteins have been successfully tested in relevant animal models. Antiproliferative, gene-based strategies also appear to be good candidates for the highly proliferative lesion responsible for in-stent restenosis. However, several key issues, including vector safety and delivery mechanisms, still have to be resolved before percutaneous gene therapy can be widely applied in the clinic. The amount of experimental research in this field indicates a medical evolution that can (and should) not be ignored by cardiologists.
Evaluation of intracoronary stenting by intravascular optical coherence tomography (2003)

Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.
Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. (1995)

We report a phase I trial to determine the feasibility of collection, ex vivo culture-expansion and intravneous infusion of human bone marrow-derived progenitor stromal cells (mesenchymal progenitor cells (MPCs)). Ten milliliter bone marrow samples were obtained from 23 patients with hematologic malignancies in complete remission. Bone marrow mononuclear cells were separated and adherent cells were culture-expanded in vitro for 4-7 weeks. Autologous MPCs were reinfused intravenously and a bone marrow examination repeated 2 weeks later for histologic assessment and in vitro hematopoietic cultures. Patient age ranged from 18 to 68 years and 12 subjects previously had undergone an autologous or syngeneic bone marrow transplant 4-52 months prior to collection of MPCs. A median of 364 x 10(6) nucleated bone marrow cells (range: 103 to 1004 x 10(6)) were used for ex vivo expansion. Median number of MPCs which were obtained after ex vivo culture expansion was 59.0 (range: 1.1 to 347 x 10(6)) representing a median cell doubling of 16,000-fold (13 doublings). Fifteen of 23 patients completed the ex vivo expansion and underwent MPC infusion. Time to infusion of MPCs after collection ranged from 28 to 49 days. Five patients in each of three groups were given 1, 10 and 50 x 10(6) MPCs. No adverse reactions were observed with the infusion of the MPCs. MPCs obtained from cancer patients can be collected, expanded in vitro and infused intravenously without toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Glycan Arrays on Aluminum‐Coated Glass Slides (2008)

We have developed a novel method of immobilizing glycans onto aluminum-coated glass (ACG) slides for potential use in disease diagnosis and drug discovery. The quality of these sugar chips can be assessed by mass spectrometry and fluorescence measurements with high sensitivity. The unique properties of ACG slides include: 1) the metal oxide layer on the surface can be activated for grafting organic compounds such as modified oligosaccharides; 2) the surface remains electrically conductive, and the grafted oligosaccharides can be simultaneously characterized by mass spectrometry and carbohydrate-binding assay; and 3) the slides are more sensitive than transparent glass slides in binding analysis. To demonstrate this, we synthesized a model compound of mannose with a built-in photocleavable linker bound to the ACG slide surface. The molecular weight of the grafted mannose was identified by mass spectrometry, and the slide was subjected to biotinylated ConA binding followed by Cy3-tagged streptavidin detection. This method was further extended to the preparation of glycan arrays containing lactose and the cancer antigen Globo H.
Human Apolipoprotein E Is Required for Infectivity and Production of Hepatitis C Virus in Cell Culture (2007)

Recent advances in reverse genetics of hepatitis C virus (HCV) made it possible to determine the properties and biochemical compositions of HCV virions. Sedimentation analysis and characterization of HCV RNA-containing particles produced in the cultured cells revealed that HCV virions cover a large range of heterogeneous densities in sucrose gradient. The fractions of low densities are infectious, while the higher-density fractions containing the majority of HCV virion RNA are not. HCV core protein and apolipoprotein B and apolipoprotein E (apoE) were detected in the infectious HCV virions. The level of apoE correlates very well with HCV infectivity. Both apoE- and HCV E2-specific monoclonal antibodies precipitated HCV, demonstrating that HCV virions contain apoE and E2 proteins. apoE-specific monoclonal antibodies efficiently neutralized HCV infectivity in a dose-dependent manner, resulting in a reduction of infectious HCV by nearly 4 orders of magnitude. The knockdown of apoE expression by specific small interfering RNAs (siRNAs) remarkably reduced the levels of intracellular as well as secreted HCV virions. The apoE siRNA suppressed HCV production by more than 100-fold at 50 nM. These findings demonstrate that apoE is required for HCV virion infectivity and production, suggesting that HCV virions are assembled as apoE-enriched lipoprotein particles. Our findings also identified apoE as a novel target for discovery and development of antiviral drugs and monoclonal antibodies to suppress HCV virion formation and infection.
The rat brain delta opioid receptor studied with anti-idiotypic antibodies to anti-leucine enkephalin. (1993)

Anti-idiotypic antibodies to anti-leucine enkephalin raised in rabbits immunized with leucine enkephalin conjugated to BSA, were purified and characterized for their ability to mimic leucine enkephalin in binding to the rat brain delta opioid receptor. An ELISA was standardized to assay the delta opioid receptor using these antibodies. The rat brain receptor was purified to 308 fold with a yield of 1.5% using these antibodies for assay. The receptor, probed with these anti-idiotypic antibodies, was characterized with respect to binding parameters, molecular weight and effect of divalent cations.
Ultra-thin gate dielectrics: they break down, but do they fail? (2002)

We study breakdown in high-quality 2-7 nm gate dielectrics, and find that soft breakdown becomes more likely for thinner oxides and for oxides stressed at lower voltages. For 2 nm oxides, an increase in gate noise is the only precise indication of soft breakdown. For many applications, devices should remain functional with the level of gate noise we have observed, after soft breakdown.
CAMP-disk test for presumptive identification of group B streptococci (1977)

The modification of the CAMP test for goup B streptococci involved substituting a paper disk impregnated with partially purified beta-hemolysin for the staphylococcal culture that was the source of beta-hemolysin in the original test. The disk is placed onto a sheep blood agar plate beside the streak of Streptococcus being tested. The plate is then incubated aerobically at 35 degrees C. A positive reaction consists of a lunar-shaped clear zone that appears within 24 h in the dark beta-hemolysin zone surrounding the disk. A double-blind study of 135 randomly coded streptococcal isolates showed complete agreement between the CAMP-disk test and the standard Lancefield precipitin test. All group B streptococci tested had positive reactions, and all strains tested from streptococcal groups A, C, D, and G were negative. The CAMP-disk test is a simple and convenient way to identify presumptively group B streptococci.
Arrays of complementary oligonucleotides for analysing the hybridisation behaviour of nucleic acids (1994)

Arrays of oligonucleotides corresponding to a full set of complements of a known sequence can be made in a single series of base couplings in which each base in the complement is added in turn. Coupling is carried out on the surface of a solid support such as a glass plate, using a device which applies reagents in a defined area. The device is displaced by a fixed movement after each coupling reaction so that consecutive couplings overlap only a portion of previous ones. The shape and size of the device and the amount by which it is displaced at each step determines the length of the oligonucleotides. Certain shapes create arrays of oligonucleotides from mononucleotides up to a given length in a single series of couplings. The array is used in a hybridisation reaction to a labelled target sequence, and shows the hybridisation behaviour of every oligonucleotide in the target sequence with its complement in the array. Applications include sequence comparison to test for mutation, analysis of secondary structure, and optimisation of PCR primer and antisense oligonucleotide design.
Chebyshev and Fourier Spectral Methods (2001)

Completely revised text focuses on use of spectral methods to solve boundary value, eigenvalue, and time-dependent problems, but also covers Hermite, Laguerre, rational Chebyshev, sinc, and spherical harmonic functions, as well as cardinal functions, linear eigenvalue problems, matrix-solving methods, coordinate transformations, methods for unbounded intervals, spherical and cylindrical geometry, and much more. 7 Appendices. Glossary. Bibliography. Index. Over 160 text figures.
Serum tumour markers in patients with chronic kidney disease (2007)

The increase in the serum levels of CA19-9, CA125 (in males), CYFRA 21-1, NSE and SCC-Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag.
Optimizing Stimulation of Coalbed Methane Reservoirs Using an Integrated Fracture Modeling Approach (2005)

Abstract Conventional methodologies have failed to address the difficulties involved in the design and execution of fracture treatments of reservoirs with complex geology and stress conditions such as coal bed methane (CBM) reservoirs. This paper presents an innovative technique to optimize and design hydraulic fracture treatments in naturally fractured CBM reservoirs. This methodology integrates (1) a three dimensional (3D), finite element based numerical design tool to predict the fracture geometry for given reservoir and operating conditions, (2) a production model to estimate fluid flow in the CBM reservoir, and (3) cost analysis to optimize the design parameters against different field scenarios using a hybrid genetic-evolutionary optimization tool. The technique has been used to design fracture treatments in a coal bed methane reservoir to illustrate its potential benefits in improving the reservoir's productivity. Results of this study have shown that the use of a 3D geometry model enabled realistic post-frac productivity analysis. This provided reliable conservative estimates on the revenue derived from the stimulation program. Furthermore, the optimization approach allowed operators to incorporate operating constraints based on sound industry practice and company guidelines for a cost-effective exploitation of CBM reservoirs.