gebhart/patrepeval huggingface dataset:
Intrahepatic Induction of Alpha/Beta Interferon Eliminates Viral RNA-Containing Capsids in Hepatitis B Virus Transgenic Mice (2000)

We have previously shown that hepatitis B virus (HBV) replication is abolished in the liver of HBV transgenic mice by stimuli that induce alpha/beta interferon (IFN-alpha/beta) in the liver. The present study was done to identify the step(s) in HBV replication that is affected by this cytokine in transgenic mice treated with the IFN-alpha/beta inducer polyinosinic-polycytidylic acid [poly(I-C)]. Here we show that the pool of cytoplasmic HBV pregenomic RNA (pgRNA)-containing capsids is reduced 10-fold within 9 h after poly(I-C) administration, while there is no change in the abundance of HBV mRNA or in the translational status of cytoplasmic HBV transcripts. In addition, we show that the pool of HBV DNA-containing capsids is not reduced to the same degree until at least 15 h posttreatment, and we show that virus export is not accelerated and the half-life of virions in the serum is unchanged. These results indicate that IFN-alpha/beta triggers intracellular events that either inhibit the assembly of pgRNA-containing capsids or accelerate their degradation, and that maturation and secretion of virus is responsible for clearance of HBV capsids and their cargo of replicative intermediates from the cytoplasm of the hepatocyte.
Molecular cloning, sequence analysis, and expression of the yeast alcohol acetyltransferase gene (1994)

The ATF1 gene, which encodes alcohol acetyltransferase (AATase), was cloned from Saccharomyces cerevisiae and brewery lager yeast (Saccharomyces uvarum). The nucleotide sequence of the ATF1 gene isolated from S. cerevisiae was determined. The structural gene consists of a 1,575-bp open reading frame that encodes 525 amino acids with a calculated molecular weight of 61,059. Although the yeast AATase is considered a membrane-bound enzyme, the results of a hydrophobicity analysis suggested that this gene product does not have a membrane-spanning region that is significantly hydrophobic. A Southern analysis of the yeast genomes in which the ATF1 gene was used as a probe revealed that S. cerevisiae has one ATF1 gene, while brewery lager yeast has one ATF1 gene and another, homologous gene (Lg-ATF1). Transformants carrying multiple copies of the ATF1 gene or the Lg-ATF1 gene exhibited high AATase activity in static cultures and produced greater concentrations of acetate esters than the control.
Diverse Solid Tumors Expressing a Restricted Epitope of L1-CAM Can Be Targeted by Chimeric Antigen Receptor Redirected T Lymphocytes (2014)

Adhesion molecule L1-CAM (CD171) was originally reported to be overexpressed on neuroblastoma and to play an important role during tumor progression. More recently, it has been shown to be overexpressed on many other solid tumors such as melanoma and carcinomas of the cervix, ovary, bladder, and others. Thus, there has been a growing interest in using this cell-surface molecule as a target for both antibody-based and cellular-based therapy-our group has previously examined the clinical utility of chimeric antigen receptor (CAR)-redirected cytolytic T cells that specifically target the CE7 epitope of L1-CAM on neuroblastoma patients. Here, we sought to determine whether this CE7 epitope is present on other recently identified L1-CAM tumors and whether it too can be targeted by CAR T cells. Our studies demonstrate that a diverse array of human tumor cell lines and primary solid tumors (ovarian, lung, and renal carcinoma, glioblastoma and neuroblastoma) do express the CE7 epitope and can efficiently stimulate CE7-specific CAR-redirected (CE7R) T-cell lytic activity and secretion of proinflamatory cytokines. L1-CAM was also detected on a limited number of normal tissues; however, L1-CAM expressed on normal human monocytes was not bound by the CE7 mAb nor was it targeted by CE7R T cells, suggesting that the CE7 epitope is more tumor restricted and not expressed on all L1-CAM tissues. Overall, the CE7 epitope of L1-CAM on a variety of tumors may be amenable to targeting by CE7R T cells, making it a promising target for adoptive immunotherapy.
High Resolution Diffraction Imaging of Small Scale Fractures in Shale and Carbonate Reservoirs (2015)

Summary Current research in the field of seismic depth imaging has identified a new approach to image with super-resolution fractured zones, fault edges, small scale faults, pinch-outs, reef edges, channel edges, salt flanks, reflector unconformities, injectites, fluid fronts, caves and karst, and in general any small scattering objects, by using Diffraction Imaging as a complement to the structural images produced by reflection imaging. Diffraction Imaging is the imaging of discontinuities in the earth. Diffractions are the seismic response of small elements (or diffractors) in the subsurface of the earth, such as small scale faults, fractures, near surface scattering objects and in general all objects which are small compared to the wavelength of seismic waves. We show results in different areas of the world, in fractured carbonates and unconventional shale reservoirs. Using Diffraction Imaging to identify areas with increased natural fracture density, which correlate with increased production, the reservoir engineers can design an optimal well placement program that targets the sweet spots and minimizes the total number of wells used for a prospective area.
A Neural Network Approach to Context-Sensitive Generation of Conversational Responses (2015)

Alessandro Sordoni, Michel Galley, Michael Auli, Chris Brockett, Yangfeng Ji, Margaret Mitchell, Jian-Yun Nie, Jianfeng Gao, Bill Dolan. Proceedings of the 2015 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2015.
Mutations in the FMN Domain Modulate MCD Spectra of the Heme Site in the Oxygenase Domain of Inducible Nitric Oxide Synthase (2009)

The nitric oxide synthase (NOS) output state for NO production is a complex of the flavin mononucleotide (FMN)-binding domain and the heme domain, and thereby it facilitates the interdomain electron transfer from the FMN to the catalytic heme site. Emerging evidence suggests that interdomain FMN-heme interactions are important in the formation of the output state because they guide the docking of the FMN domain to the heme domain. In this study, notable effects of mutations in the adjacent FMN domain on the heme structure in a human iNOS bidomain oxygenase/FMN construct have been observed by using low-temperature magnetic circular dichroism (MCD) spectroscopy. The comparative MCD study of wild-type and mutant proteins clearly indicates that a properly docked FMN domain contributes to the observed L-Arg perturbation of the heme MCD spectrum in the wild-type protein and that the conserved surface residues in the FMN domain (E546 and E603) play key roles in facilitating a productive alignment of the FMN and heme domains in iNOS.
Electroporation of cells and tissues (2000)

Electrical pulses that cause the transmembrane voltage of fluid lipid bilayer membranes to reach at least U/sub m//spl ap/0.2 V, usually 0.5-1 V, are hypothesized to create primary membrane "pores" with a minimum radius of -1 nm. Transport of small ions such as Na/sup +/ and Cl/sup -/ through a dynamic pore population discharges the membrane even while an external pulse tends to increase U/sub m/, leading to dramatic electrical behavior. Molecular transport through primary pores and pores enlarged by secondary processes provides the basis for transporting molecules into and out of biological cells. Cell electroporation in vitro is used mainly for transfection by DNA introduction, but many other interventions are possible, including microbial killing. Ex vivo electroporation provides manipulation of cells that are reintroduced into the body to provide therapy. In vivo electroporation of tissues enhances molecular transport through tissues and into their constitutive cells. Tissue electroporation, by longer, large pulses, is involved in electrocution injury. Tissue electroporation by shorter, smaller pulses is under investigation for biomedical engineering applications of medical therapy aimed at cancer treatment, gene therapy, and transdermal drug delivery. The latter involves a complex barrier containing both high electrical resistance, multilamellar lipid bilayer membranes and a tough, electrically invisible protein matrix.
ACTION SPECTRUM FOR ERYTHEMA IN HUMANS INVESTIGATED WITH DYE LASERS (1995)

Erythema reactions of human skin were reevaluated with improved experimental methods: a tunable, highly monochromatic irradiation source as well as an instrumental measurement of skin reactions were used. The irradiation system consisted of an excimer laser pumped dye laser and a UV fiber optic system. The skin color after irradiation was determined with a colorimeter in the three-dimensional norm system of the Commission Internationale d'Eclairage (CIE). The wavelength dependence for delayed erythema was investigated in the UVB and UVA region from 294 nm to 374 nm in skin type II and III individuals. The maximum of the action spectrum in the UVB range was measured at 298.5 nm and an additional maximum was found at 362 nm in the UVA range. The action spectrum is compared with previous spectra from the literature and with the current standard erythema curve of the CIE as well as with other photobiological action spectra. Our results suggest a UVA/UVB boundary at 330 nm.
Two-photon absorption and optical-limiting properties of novel organic compounds (1995)

The optical-limiting behavior and two-photon absorption properties of four novel organic compound solutions in tetrahydrofuran have been investigated. An ultrashort laser source with 0.5-ps pulse width and 602-nm wavelength was employed. The transmissivities of the various 1-cm-thick solution samples have been measured as a function of the beam intensity as well as of the solute concentration. The measured results can be fitted on the assumption that two-photon absorption is the only predominant mechanism causing the observed opticallimiting behavior. Based on the intensity-dependent transmissivity measurements, the molecular two-photon absorption coefficients for the four compounds are presented.
Immobilization of Protein on Micropatterns by the Use of Photoremovable Activated Ester (1995)

Abstract 3-Nitrophenoxycarbonyl group was introduced to a silylated glass surface with 3-mercaptopropyltrimethoxysilane (MPS) through the Michael addition of corresponding acrylic acid ester to the mercapto group of the MPS. The nature of this ester group, reactivity to amino group giving amide bond (activated ester) under dark and to water giving a corresponding carboxylic acid upon UV-irradiation, was utilized to prepare micropatterns of protein on the glass surface.
The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. (1990)

Functional studies demonstrate that T cell activation often requires not only occupancy of the TCR but costimulatory interactions of other molecules, which remain largely undefined. We have tested the hypothesis that LFA-1 interaction with its ligand intercellular adhesion molecule 1 (CD54) (ICAM-1) is such a costimulatory interaction in a model system using biochemically purified ICAM-1 and TCR cross-linking by anti-CD3 mAb OKT3 immobilized on plastic. Resting T cells do not respond to OKT3 mAb immobilized on plastic. However ICAM-1 deposited on plastic together with the nonmitogenic immobilized OKT3 results in a potent activating stimulus. This costimulation cannot be readily accounted for by ICAM-1-mediated adhesion but is consistent with a role in signaling, which is observed in ICAM-1-mediated augmentation of activation induced by PMA/ionomycin. The ability of ICAM-1 to costimulate with immobilized CD3 contrasts with minimal costimulatory activity of cytokines IL-1 beta, IL-2, and IL-6. The proliferative response to co-immobilized OKT3 and ICAM-1 is dependent on the IL-2R, which is induced only in the presence of both OKT3 and ICAM-1. The present data demonstrate that LFA-1/ICAM-1 interaction is a potent costimulus for TCR-mediated activation; this observation, interpreted in light of previous reports, suggests that LFA-1/ICAM-1 is of major physiologic importance as a costimulatory signal.
Bone cancer pain (2014)

There is both a nociceptive and neuropathic component of bone cancer pain. In bone cancer pain, there is frequently a continual afferent drive of sensory nerve fibers that induces a peripheral and central sensitization. These mechanistic insights have begun to lead to advances in not only how we understand bone cancer pain but to the development of new therapies to treat bone cancer pain.
Development of mammalian artificial chromosomes for the treatment of genetic diseases: Sandhoff and Krabbe diseases (2005)

Mammalian artificial chromosomes (MACs) are being developed as alternatives to viral vectors for gene therapy applications, as they allow for the introduction of large payloads of genetic information in a non-integrating, autonomously replicating format. One class of MACs, the satellite DNA-based artificial chromosome expression vehicle (ACE), is uniquely suited for gene therapy applications, in that it can be generated denovo in cells, along with being easily purified and readily transferred into a variety of recipient cell lines and primary cells. To facilitate the rapid engineering of ACEs, the ACE System was developed, permitting the efficient and reproducible loading of pre-existing ACEs with DNA sequences and/or target gene(s). As a result, the ACE System and ACEs are unique and versatile platforms for ex vivo gene therapy strategies that circumvent and alleviate existing safety and delivery limitations surrounding conventional gene therapy vectors. This review will focus on the status of MAC technologies and, in particular, the application of the ACE System towards an ex vivo gene therapy treatment of lysosomal storage diseases, specifically Sandhoff (MIM #268800) and Krabbe (MIM #245200) diseases.
Methodology of magnetic resonance imaging (1987)

Abstract A survey of magnetic resonance imaging techniques is presented. Emphasis is put on the basic types of measurement procedures rather than, discussing all variants proposed so far. The general experimental procedure consists of two phases, the preconditioning period and the image formation period. While the preconditioning period determines the image contrast, the image formation process is responsible for image resolution. Means to improve sensitivity and to minimize measurement time are discussed.
Joint Optimization of Cascaded Classifiers for Computer Aided Detection (2007)

The existing methods for offline training of cascade classifiers take a greedy search to optimize individual classifiers in the cascade, leading inefficient overall performance. We propose a new design of the cascaded classifier where all classifiers are optimized for the final objective function. The key contribution of this paper is the AND-OR framework for learning the classifiers in the cascade. In earlier work each classifier is trained independently using the examples labeled as positive by the previous classifiers in the cascade, and optimized to have the best performance for that specific local stage. The proposed approach takes into account the fact that an example is classified as positive by the cascade if it is labeled as positive by all the stages and it is classified as negative if it is rejected at any stage in the cascade. An offline training scheme is introduced based on the joint optimization of the classifiers in the cascade to minimize an overall objective function. We apply the proposed approach to the problem of automatically detecting polyps from multi-slice CT images. Our approach significantly speeds up the execution of the computer aided detection (CAD) system while yielding comparable performance with the current state-of-the-art, and also demonstrates favorable results over cascade AdaBoost both in terms of performance and online execution speed.
Immunologic approaches to the management of pancreatic cancer. (2002)

Pancreatic cancer remains one of the most difficult cancers to treat; very few effective therapies are available, with surgery being the sole chance for cure-yet surgery is not a viable option for most pancreatic cancer patients. Immunotherapy has the potential to provide a non-cross-resistant mechanism of antitumor activity that can be integrated with surgery, radiation therapy, and chemotherapy. However, the inherent instability of the tumorgenome as well as tumor tolerance mechanisms are significant practical obstacles that must be overcome if immune-based approaches for pancreatic cancer can achieve its promise. Recent advances in both tumor immunology and vaccine design have already resulted in promising preliminary data from phase I studies, and additional trials are already in progress. This article summarizes some of the progress and challenges in immunotherapy research.
The Effect of Chloroquine on Lysosomal Prolactin Receptors in Rat Liver* (1984)

PRL receptors have been previously identified in purified rat liver plasma membrane and Golgi vesicle preparations. In this study, we report on PRL receptors located in highly purified lysosome preparations. These lysosomal PRL receptors were characterized using Scatchard analysis and compared to other intracellular and cell surface receptors. We have identified two classes of lysosomes. Lighter lysosome-like vesicles, which are greatly enriched in acid phosphatase activity (the marker enzyme of lysosomes), contain a great deal of binding activity. This PRL binding was only slightly increased by pretreatment of animals with the lysosomotropic agent chloroquine. In contrast, mature lysosomes showed very little binding activity in control animals, but chloroquine treatment increased binding 7- to 8-fold in these mature lysosomes. We suggest that the lysosome-like structures are immature lysosomes (namely prelysosomes) toward which the hormone-receptor complex is internalized: they appear to bear little proteolytic activity. These structures could play a role in PRL receptor recycling. Lysosomal PRL receptors showed curvilinear Scatchard plots, in contrast to plasma membrane and Golgi counterparts, which were linear over the same range of hormone concentrations. The high affinity site in lysosomes had a Kd comparable to the cell surface and Golgi receptors. The number of binding sites per mg protein in prelysosomes and lysosomes was 3 times greater than that in the homogenate, but Golgi preparations were 3 times as rich as lysosomes. The great number of PRL receptors in prelysosomes could be attributed, in large part, to the low affinity sites. The internalization of PRL into rat liver was examined after in vivo injection of [125I]iodoovine PRL. The labeled hormone was found initially in the plasma membrane fraction, after which it localized preferentially in the Golgi fraction, with maximum incorporation 15 min postinjection. Substantial radioactivity was observed in both classes of lysosomes (L-1 and L-2). In contrast to the Golgi fraction, maximum incorporation of [125I]iodoovine PRL in lysosomes occurred at 30 min. This suggests either that during internalization, PRL first reaches Golgi elements and is then transferred to the lysosomal compartment, or that there are two independent pathways of internalization, one rapid toward the Golgi complex (may be a path of receptor recycling) and the other toward lysosomes (probably leading to receptor degradation).
Pattern recognition engineering (1993)

Deux systemes predominent dans la Reconnaissance des formes : Reconnaissance des formes statistique et reconnaissance des formes syntaxique (structurale). Le livre propose une etude comparative des avantages et desavantages des 2 methodes ; il decrit une methode qui les combine (approche statistico-structurale) et peut ainsi resoudre de nombreux problemes difficiles et augmenter le nombre d'applications possibles ; les aspects materiels et logiciels sont etudies pour l'implantation d'un systeme de reconnaissance des formes ; exposes des methodes les plus utilisees aujourd'hui : - Methode de detection des bords (edge detection.) - Methode destate machinepour la conception de systemes ; apprentissage. - Methode de plus proche voisin Methode iterative pour l'apprentissage des regles statistiques.
EXPLOSIVE FORMING OF METALS (1964)

Abstract : In view of the current high level of interest in explosive metal- working processes this report has been prepared to review the status of forming materials with high explosives. The information presented has been obtained from the open literature and from firms active in this work. Explosives and their characteristics are described along with discussions of general explosive- forming techniques. More detailed treatment is given to descriptions and requirements of facilities, die designs and materials, and current applications and practice in the forming of sheet, plate, and tubular products. In addition, the response of materials to high velocity forming is described in terms of effects on microstructures, formability, and mechanical properties. Methods of determining peak pressures and energy requirements are presented in an appendix along with appropriate nomographs.
Fracture of the vertebral endplates, but not equienergetic impact load, promotes disc degeneration in vitro (2011)

Vertebral endplate damage is associated with intervertebral disc (IVD) degeneration (DD) in vivo as confirmed by in-vitro investigations. Our aims were to further characterize the process of DD using an in vitro full-organ culture model and to elucidate whether significant endplate damage or impact loading alone is pivotal for the initiation of DD. Rabbit spinal segments (n = 80) were harvested, subjected to pure axial impact loading (n = 40) using a custom-made device, and cultured for 28 days. The applied threshold energy (0.76 J) induced endplate fractures in 21 specimens (group A); 19 remained intact (group B). Markers for DD (cell viability, apoptosis, necrosis, matrix remodeling, and inflammation) were monitored for 28 days post-trauma in the annulus fibrosus (AF) and nucleus pulposus and compared to non-impacted control discs. Cell viability in both groups stayed at a control level. Group A compared to group B showed enhanced lactate dehydrogenase (LDH) and caspase-3/7 activity, reduced glycosaminoglycan content, reduced aggrecan mRNA, but elevated mRNA for collagen-2, catabolic enzymes (MMP-1/-3/-13), and pro-inflammatory (TNFα, IL-6, IL-8, MCP-1) and pro-apoptotic (fas ligand, caspase-3) proteins. Group B compared to control only showed small changes in mRNA levels. Our findings demonstrate that burst endplates, but not equienergetic loading, promotes DD.
Virus-specific CD4+ T cells: ready for direct attack (2006)

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CD4+ T cells.
Valgrind (2003)

Valgrind is a programmable framework for creating program supervision tools such as bug detectors and profilers. It executes supervised programs using dynamic binary translation, giving it total control over their every part without requiring source code, and without the need for recompilation or relinking prior to execution. New supervision tools can be easily created by writing skins that plug into Valgrind's core. As an example, we describe one skin that performs Purify-style memory checks for C and C++ programs.