gebhart/patrepeval huggingface dataset:
Antisense oligonucleotides are effective inhibitors of hepatitis B virus replication in vitro (1995)

Antisense oligonucleotides are currently being used in numerous laboratories as potential anticancer and antiviral agents. The unique replication cycle of hepatitis B virus (HBV) contains several different steps which are potentially amenable to modulation by these molecules. We have examined the ability of 56 different single-stranded, oligodeoxyribonucleotides (14-23 nucleotides in length), which target several HBV-specific functions, to inhibit HBV replication in the human hepatoblastoma cell line, 2.2.15. None of the oligonucleotides examined were toxic at concentrations up to 500 microM. Oligonucleotides directed against the HBV surface antigen (HBsAg) gene (S gene), the preS1 open reading frame, and the HBV core antigen (HBcAg) gene (C gene) were effective at depressing virus production, while molecules targeting the HBV e antigen (HBeAg) open reading frame and the HBV polymerase (POL) gene were ineffective. Oligonucleotides directed against the HBV encapsidation signal/structure (epsilon) comprised some of the most effective antiviral molecules against HBV. None of 5 oligonucleotides complementary (i.e., 'sense' orientation) to the antisense oligonucleotides targeting HBsAg, HBcAg, HBeAg, preS1 and POL had any measurable effect on HBV production. The relative effectiveness of oligonucleotides targeting the S and C genes on HBV replication was highly correlated with an effect on HBsAg or HBcAg levels, respectively. None of the antisense oligonucleotides examined affected either the levels or the sizes of HBV-specific RNA transcripts. Since antisense oligonucleotides can exert biologic effects on HBV in 2.2.15 cell cultures in a sequence-specific manner which are consistent with predicted modes of action, such molecules may have practical applications in the therapy of chronic HBV infection.
Binding and entry of respiratory syncytial virus into host cells and initiation of the innate immune response (2003)

Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection in infants and the elderly. There is currently no effective antiviral treatment for the infection, but advances in our understanding of RSV uptake, especially the role of surfactant proteins, the attachment protein G and the fusion protein F, as well as the post-binding events, have revealed potential targets for new therapies and vaccine development. RSV infection triggers an intense inflammatory response, mediated initially by the infected airway epithelial cells and antigen-presenting cells. Humoral and cell-mediated immune responses are important in controlling the extent of infection and promoting viral clearance. The initial innate immune response may play a critical role by influencing the subsequent adaptive response generated. This review summarizes our current understanding of RSV binding and uptake in mammalian cells and how these initial interactions influence the subsequent innate immune response generated.
The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. (1994)

The replication of human immunodeficiency virus type 1 (HIV-1) in nondividing host cells such as those of macrophage lineage is an important feature of AIDS pathogenesis. The pattern of HIV-1 replication is dictated, in part, by the nucleophilic property of the viral gag matrix (MA) protein, a component of the viral preintegration complex that facilitates nuclear localization of viral nucleic acids in the absence of mitosis. We now identify the accessory viral protein Vpr, as a second nucleophilic component that influences nuclear localization of viral nucleic acids in nondividing cells. Reverse transcription and nuclear localization of viral nucleic acids following infection of cells by viruses lacking Vpr or viruses containing mutations in a gag MA nuclear localization sequence were indistinguishable from the pattern observed in cells infected by wild-type HIV-1. These viruses retained the ability to replicate in both dividing and nondividing host cells including monocyte-derived macrophages. In contrast, introduction of both gag MA and Vpr mutations in HIV-1 attenuated nuclear localization of viral nucleic acids in nondividing cells and virus replication in monocyte-derived macrophages. These studies demonstrate redundant nucleophilic determinants of HIV-1 that independently permit nuclear localization of viral nucleic acids and virus replication in nondividing cells such as monocyte-derived macrophages. In addition, these studies provide a defined function for an accessory gene product of HIV-1.
Energy-efficient polymeric gas separation membranes for a sustainable future: A review (2013)

Over the past three decades, polymeric gas separation membranes have become widely used for a variety of industrial gas separations applications. This review presents the fundamental scientific principles underpinning the operation of polymers for gas separations, including the solution-diffusion model and various structure/property relations, describes membrane fabrication technology, describes polymers believed to be used commercially for gas separations, and discusses some challenges associated with membrane materials development. A description of new classes of polymers being considered for gas separations, largely to overcome existing challenges or access applications that are not yet practiced commercially, is also provided. Some classes of polymers discussed in this review that have been the focus of much recent work include thermally rearranged (TR) polymers, polymers of intrinsic microporosity (PIMs), room-temperature ionic liquids (RTILs), perfluoropolymers, and high-performance polyimides.
Sum Capacity of Multiuser MIMO Broadcast Channels with Block Diagonalization (2006)

The sum capacity of a Gaussian broadcast MIMO channel can be achieved with Dirty Paper Coding (DPC). Deploying DPC in real-time systems is, however, impractical. Block Diagonalization (BD) is an alternative precoding technique for downlink multiuser MIMO systems, which can eliminate inter-user interference at each receiver, at the expense of suboptimal sum capacity vs. DPC. In this paper, we study the sum capacity loss of BD for a fixed channel. We show that 1) if the user channels are orthogonal to each other, then BD achieves the complete sum capacity; and 2) if the user channels lie in a common row vector space, then the gain of DPC over BD can be bounded by the minimum of the number of transmit and receive antennas and the number of users. We also compare the ergodic sum capacity of DPC with that of BD in a Rayleigh fading channel. Simulations show that BD can achieve a significant part of the total throughput of DPC. An upper bound on the ergodic sum capacity gain of DPC over BD is derived, which can be evaluated with a few numerical integrations. With this bound, we can easily estimate how far away BD is from being optimal in terms of ergodic sum capacity, which is useful in directing practical system designs.
A comparative study of sensitivity of sputum microscopy by direct method versus sodium hypochlorite concentration method at RNTCP Centre (2017)

In revised national tuberculosis control program (RNTCP), microscopic examination of sputum for AFB plays an important role in the initial diagnosis of tuberculosis. Decontamination and liquefaction with by 5% sodium hypochlorite increases sensitivity and safety for handling specimen. In this prospective hospital based cross sectional analytical study, patients of all ages and either sex coming to RNTCP centre were included according to RNTCP criteria. From each patient, two samples of sputum were collected one spot and one morning. One set of smears was prepared by RNTCP guidelines and remaining samples were concentrated by using 5% NaOCl, followed by centrifugation and staining with ZN stain. Both set of smears were observed by two observers to remove observer’s bias. A total of 882 patients were included in the study with 577 (65%) males and 305 (35%) females. A total of 172(19.5%) patients were positive by RNTCP method whereas 201(22.79%) patients were positive by concentration method diagnosing 29 additional patients. This constitutes a rise of 3.29%. This constitute 16.86% rise in case detection over RNTCP method. There is a rise in smear positive cases after concentration with 5% sodium hypochlorite solution. The bleach method has advantage over routine RNTCP method as it is simple, does not require any additional expertise, is safe, reagents are also affordable and easily available and could diagnose additional cases.
PTEN and Cancer (2003)

Genetic evidence strongly suggested that a tumor suppressor was located on chromosome 10. During the development of glioblastoma, one copy of chromosome 10 was typically lost (). Cytogenetic and molecular analysis revealed partial or complete loss of chromosome 10 in bladder, endometrial, and prostate cancer (,). These studies implicated 10q23 as a chromosomal region likely to contain one or more important tumor suppressor genes. When wild-type chromosome 10 was reintroduced into glioblastoma cell lines, it reduced the ability of these cell lines to form tumors in nude mice, in part due to inhibition of angiogensis (). During the same year (1996), a linkage analysis report of a cancer predisposition syndrome, Cowden disease (CD), determined that a CD locus was present on chromosome10q23 (). These findings greatly bolstered the idea that chromosome 10q23 contained a novel tumor suppressor gene whose loss was key in the formation of several types of cancer.
Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification (2004)

Polyethylene glycol (PEG)-conjugated therapeutic peptides/proteins have been shown to exhibit clinical properties superior to those of their corresponding unmodified parent molecules. However, the desirable pharmacological features gained by protein PEGylation become irrelevant if conjugates are inactivated or cannot reach their target tissues. Here we describe the design and synthesis of MAL-FMS-OSU. This bifunctional agent enables PEG chains to be linked to peptides and proteins through a slowly hydrolysable chemical bond. PEG-FMS-peptide/protein conjugates thus formed undergo spontaneous hydrolysis at a slow rate upon incubation at pH 8.5, 37 degrees C with a t(1/2) value of 8-14 +/- 2 h, generating the unmodified parent molecule. The validity of this approach was studied with exendin-4 and human growth hormone. A single subcutaneous administration of PEG(40,000)-FMS-exendin-4 facilitated a prolonged and stable reduction in glucose levels in mice (t(1/2) = 30 +/- 2 h) and exceeded the effect obtained by the same dose of the native hormone by 7-8 times.
Abstract 12433: Plasma Galectin-3 Levels in Patients with Structural and Clinical Manifestations of Hypertensive Heart Disease: Relationship to Determinants of Matrix Composition (2010)

Background: The β-galactoside binding protein galectin-3 (Gal-3) has been demonstrated to regulate both cellular and extracellular structure and function in tissue remodeling processes such as inflammation and cancer. Gal-3 binds to a number of extracellular matrix (ECM) ligands including fibrillar collagens, basement membrane proteins and integrins. The development of LV hypertrophy (LVH) and progression to diastolic heart failure (DHF) are accompanied by significant changes in the ECM, but whether plasma Gal-3 levels are altered in these processes and related to other determinants of ECM remodeling is unknown. Methods/Results: Plasma profiles for Gal-3 and determinants of ECM remodeling such as matrix metalloproteinases (MMPs-2,-9,-3,-7,-8), tissue inhibitors of MMPs (TIMPs-1,-2,-3,-4), and collagen peptides (PIIINP, CITP) were measured by high sensitivity immunoassays in control subjects (n=19 CTL); patients with LVH but no DHF (n=21, LVH), and patients with LVH and DHF (n=21, DHF). Echocardiography and 6 minute hall walk (6MHW) showed that DHF patients had shorter 6MHW and increased pulmonary wedge pressures vs. CTL or LVH. Plasma MMP-2, TIMP-1, TIMP-4, NT-proBNP, and Gal-3 were increased in the DHF group vs. CTL and LVH, (Table). Gal-3 values were significantly correlated with changes in MMP-2, TIMP-1, TIMP-4, and NT-proBNP (all r ≥0.3, p Conclusions: Plasma profiles of the bioactive molecule Gal-3, which regulates ECM composition and structure, were significantly increased in patients with DHF; Gal-3 was associated with changes in other determinants of ECM remodeling. Thus, biomarker profiling of the ECM remodeling process holds potential diagnostic and prognostic utility in identifying patients transitioning from LVH to DHF.
Prions and prion proteins 1 (1991)

Neurodegenerative diseases of animals and humans including scrapie, bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease are caused by unusual infectious pathogens called prions. There is no evidence for a nucleic acid in the prion, but diverse experimental results indicate that a host-derived protein called PrPSc is a component of the infectious particle. Experiments with scrapie-infected cultured cells show that PrPSc is derived from a normal cellular protein called PrPC through an unknown posttranslational process. We have analyzed the amino acid sequence and posttranslational modifications of PrPSc and its proteolytically truncated core PrP 27-30 to identify potential candidate modifications that could distinguish PrPSc from PrPC. The amino acid sequence of PrP 27-30 corresponds to that predicted from the gene and cDNA. Mass spectrometry of peptides derived from PrPSc has revealed numerous modifications including two N-linked carbohydrate moieties, removal of an amino-terminal signal sequence, and alternative COOH termini. Most molecules contain a glycosylinositol phospholipid (GPI) attached at Ser-231 that results in removal of 23 amino acids from the COOH terminus, whereas 15% of the protein molecules are truncated to end at Gly-228. The structure of the GPI from PrPSc has been analyzed and found to be novel, including the presence of sialic acid. Other experiments suggest that the N-linked oligosaccharides are not necessary for PrPSc formation. Although detailed comparison of PrPSc with PrPC is required, there is no obvious way in which any of the modifications might confer upon PrPSc its unusual physical properties and allow it to act as a component of the prion. If no chemical difference is found between PrPC and PrPSc, then the two isoforms of the prion protein may differ only in their conformations or by the presence of bound cellular components.
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders (2010)

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.
Lipoprotein(a) and LDL Particle Size Are Related to the Severity of Coronary Artery Disease (2007)

The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD.
Oxidation of docosahexaenoic acid by rat liver microsomes. (1984)

[1-14C]Docosahexaenoic acid (n-3) was incubated at 37 degrees C for 30 min in the presence of rat liver microsomes and 1 mM NADPH. The products were isolated using organic solvent extractions, reverse phase, and normal phase high performance liquid chromatography. Isolates were identified using ultraviolet spectroscopy, capillary gas-liquid chromatography, and gas chromatography-mass spectrometry. The major metabolites were: 19,20-, 16,17-, 13,14-, 10,11-, and 7,8-dihydroxydocosapentaenoic acids, 22-hydroxydocosahexaenoic acid, and 21-hydroxydocosahexaenoic acid. The minor metabolites were 17-hydroxy-4,7,10,13,15,19-, 16-hydroxy-4,7,10,17,19-, 14-hydroxy-4,7,10,12,-16,19-, 13-hydroxy-4,7,10,14,16,19-, 11-hydroxy-4,7,9,13,16,19-, 10-hydroxy-4,7, 11,13,16,19-, 8-hydroxy-4,6,10,13,16,19-, and 7-hydroxy-4,8,10,13,16,19 -docosahexaenoic acids. These metabolites of docosahexaenoic acid resulted from four distinct classes of oxidation, omega-hydroxylations, (omega-1)-hydroxylations, epoxidations, and lipoxygenase-like hydroxylations. The similarity of these product profiles to those reported for comparable microsomal incubations with other essential fatty acids suggest that microsome cytochrome P-450 monooxygenases were involved.
Identification of highly transformable wheat genotypes for mass production of fertile transgenic plants (2002)

The efficiency of wheat biolistic transformation systems strongly depends on the bombardment parameters, the condition of the donor plant, and the plant genotype chosen for the transformation process. This paper analyzes the transformation efficiency of the 129 wheat sister lines generically called 'Bobwhite', originally obtained from the cross 'Aurora'//'Kalyan'/'Bluebird 3'/'Woodpecker'. A number of factors influencing the transformation were examined, such as the ability to produce embryogenic callus, regeneration in selection medium, and overall transformation performance. Of the 129 genotypes evaluated, eight demonstrated transformation efficiencies above 60% (60 independent transgenic events per 100 immature embryos bombarded). Among the eight genotypes identified, we studied agronomic characteristics such as earliness to identify the most adaptable line(s) for different lab conditions. 'Bobwhite' SH 98 26 was identified as a super-transformable wheat line.
Electrochemistry of Room Temperature Protic Ionic Liquids (2008)

Eighteen protic ionic liquids containing different combinations of cations and anions, hydrophobicity, viscosity, and conductivity have been synthesized and their physicochemical properties determined. In one series, the diethanolammonium cations were combined with acetate, formate, hydrogen sulfate, chloride, sulfamate, and mesylate anions. In the second series, acetate and formate anions were combined with amine bases, triethylamine, diethylamine, triethanolamine, di-n-propylamine, and di-n-butylamine. The electrochemical characteristics of the eight protic ionic liquids that are liquid at room temperature (RTPILs) have been determined using cyclic, microelectrode, and rotating disk electrode voltammetries. Potential windows of the RTPILs have been compared at glassy carbon, platinum, gold, and boron-doped diamond electrodes and generally found to be the largest in the case of glassy carbon. The voltammetry of IUPAC recommended potential scale reference systems, ferrocene/ferrocenium and cobaltocenium/cobaltocene, have been evaluated and found to be ideal in the case of the less viscous RTPILs but involve adsorption in the highly viscous ones. Other properties such as diffusion coefficients, ionic conductivity, and double layer capacitance also have been measured. The influence of water on the potential windows, viscosity, and diffusion has been studied systematically by deliberate addition of water to the dried ionic liquids. The survey highlights the problems with voltammetric studies in highly viscous room temperature protic ionic liquids and also suggests the way forward with respect to their possible industrial use.
Hand-held robotic device for laparoscopic surgery and training (2014)

Laparoscopic surgery (LS) has revolutionized traditional surgical techniques introducing minimally invasive procedures for diagnosis and local therapies. LSs have undeniable advantages, such as small patient incisions, reduced postoperative pain and faster recovery. On the other hand, restricted vision of the anatomical target, difficult handling of the surgical instruments, restricted mobility inside the human body, need of dexterity to hand-eye coordination and inadequate and non-ergonomic surgical instruments may restrict LS only to more specialized surgeons. To overcome the referred limitations, this work presents a new robotic surgical handheld system - the EndoRobot. The EndoRobot was designed to be used in clinical practice or even as a surgical simulator. It integrates an electromechanical system with 3 degrees of freedom. Each degree can be manipulated independently and combined with different levels of sensitivity allowing fast and slow movements. As other features, the EndoRobot has battery power or external power supply, enables the use of bipolar radiofrequency to prevent bleeding while cutting and allows plug-and-play of the laparoscopic forceps for rapid exchange. As a surgical simulator, the system was also instrumented to measure and transmit, in real time, its position and orientation for a training software able to monitor and assist the trainee's surgical movements.
Plasticity-Associated Molecular and Structural Events in the Injured Brain (2002)

Injury to the brain appears to create a fertile ground for functional and structural plasticity that is, at least partly, responsible for functional recovery. Increases in dendritic arborization, spine density, and synaptogenesis in both peri-injury and intact cortical areas are the potential morphological strategies that enable the brain to reorganize its neuronal circuits. These injury-initiated alterations are time-dependent and frequently proceed in interaction with behavior-related signals. A complex concert of a variety of genes/proteins is required to tightly control these changes. Two broad categories of molecules appear to be involved. First, regulatory molecules or effector molecules with regulatory function, such as immediate early genes/transcription factors, kinase network proteins, growth factors, and neurotransmitter receptors, and second, structural proteins, such as adhesion molecules and compounds of synapses, growth cones, and cytoskeleton. A better understanding of the processes contributing to postinjury plasticity may be an advantage for developing new and more effective therapeutic approaches. This knowledge might also shed light on other forms of brain plasticity, such as those involved in learning processes or ontogeny.