gebhart/patrepeval huggingface dataset:
Antiviral Activity of Emetine Dihydrochloride Against Dengue Virus Infection (2009)

Dengue fever has become a global concern as dengue infections are prevalent in the tropics and the subtropics, and can lead to a severe life-threatening illness. Currently, there is a widespread interest to search for vaccine or antiviral therapy to combat DENV infection. In this study, we have identified emetine dihydrochloride with potent antiviral activity against DENV infection. Emetine was also shown to inhibit DENV replication consistently in all the dengue serotypes. Experiments were designed to define the stage of viral replication cycle at which emetine blocked DENV infection. Emetine did not target the entry process of DENV into cells as inhibitory effect of emetine on DENV infectivity remained when naked dengue viral RNA were transfected directly into the cells. Thus, we further investigated the inhibitory effect of emetine through timecourse studies and emetine was shown to strongly inhibit DENV infection at early stage of viral replication cycle by either affecting the synthesis viral RNA pathway or viral protein translation pathway.Quantitative RT-PCR assay indicated that emetine strongly reduced the production of positive-strand and negative-strand of DENV RNA. Ultrastructural analysis of emetine-treated cells further revealed that the formations of membranous replication complexes of DENV within cells were aborted in the presence of emetine. Together, these results suggest that emetine can inhibit DENV infection by impeding viral RNA synthesis therefore emetine could be further assessed and developed as a potential antiviral therapeutic agent against DENV infection.
Synthesis of insulinlike growth factor binding proteins and of the acid-labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: Regulation by insulin, insulinlike growth factor, and growth hormone (1996)

The adult liver is the main source of circulating insulinlike growth factors (IGFs) and their serum binding proteins (IGFBPs) including the acid-labile subunit (ALS), a component of the ternary binding protein complex. Within the liver, the biosynthesis of individual proteins has been attributed to different cell populations, e.g., that of ALS to hepatocytes and that of IGFBP-3 to nonparenchymal cells. Ligand and immunoblotting as well as Northern blotting analyses were used to study synthesis of IGFBPs and their hormonal regulation in cultured adult rat hepatocytes, Kupffer cells (KCs), and cocultures. In hepatocytes, synthesis of IGFBP-1, -2, and -4 was observed; insulin and IGF-I decreased that of IGFBP-1, and -2 while increasing that of IGFBP-4. KCs synthesized IGFBP-2, and -3, insulin and IGF-I showing no effect. In cocultures, however, synthesis of IGFBP-3 was stimulated by insulin and IGF-I. By immunocytochemistry IGFBP-3 biosynthesis was localized to KCs exclusively. When pore membranes were used for separation of hepatocytes and KCs in coculture, this insulin-stimulatory action on IGFBP-3 synthesis was preserved. Growth hormone (GH) did not affect biosynthesis of IGFBPs. Expression of ALS was localized in hepatocytes only. Insulin, IGF-I, and GH increased ALS expression. It can be concluded that biosynthesis of individual IGFBPs and of ALS are compartmentalized in adult rat liver and are distinctly regulated by insulin, IGF-I, and GH. The insulin-dependent stimulation of IGFBP-3 synthesis in KCs appears to require a diffusable mediator derived from hepatocytes.
Development of Matrix Metalloproteinase Inhibitors in Cancer Therapy (2001)

The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of the extracellular matrix. The MMPs have been implicated in the processes of tumor growth, invasion, and metastasis; are frequently overexpressed in malignant tumors; and have been associated with an aggressive malignant phenotype and adverse prognosis in patients with cancer. A number of MMP inhibitors are being developed for the treatment of cancer. The most extensively studied class of MMP inhibitors includes collagen peptidomimetics and nonpeptidomimetic inhibitors of the MMP active site, tetracycline derivatives, and bisphosphonates. The hydroxamate peptidomimetic inhibitor batimastat and its orally bioavailable analogue marimastat, which bind covalently to the zinc atom at the MMP-active site, were the first MMP inhibitors to be studied in detail. Marimastat is currently being studied in randomized clinical trials. The nonpeptidic MMP inhibitors were synthesized in an attempt to improve the oral bioavailability and pharmaceutical properties of the peptidic inhibitors. Several members of this class of compounds are undergoing evaluation in phase III clinical trials. The tetracyclines and, particularly, the nonantibiotic chemically modified tetracyclines, interfere with several aspects of MMP expression and activation and inhibit tumor growth and metastases in preclinical models. A representative agent of this class, Col-3, is currently undergoing phase I clinical trials. The development of the MMP inhibitors, like that of other targeted and predominantly antiproliferative compounds, poses a challenge because the paradigms that have governed the design of clinical oncology trials may not be relevant to this new class of agents. The anticipated need for long-term administration of these drugs, together with their cytostatic mechanism of action, will require novel clinical trial design strategies.
Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox (1994)

A protein molecule is a covalent chain of amino acid residues. Although it is topologically linear, in physiological conditions it folds into a unique (though flexible) three-dimensional structure. This structure, which has been determined by x-ray crystallography and nuclear magnetic resonance for many proteins (Bernstein et al., 1977; Abola et al., 1987), is referred to as the native structure. As demonstrated by the experiments of Anfinsen and co-workers (Anfinsen et al., 1961; Anfinsen, 1973), at least some protein molecules, when denatured (unfolded) by disrupting conditions in their environment (such as acidity or high temperature) can spontaneously refold to their native structures when proper physiological conditions are restored. Thus, all of the information necessary to determine the native structure can be contained in the amino acid sequence.
Regulation of integrated adenovirus sequences during adenovirus infection of transformed cells (1980)

A human cell line (293) transformed by adenovirus type 5 encodes mRNA's and proteins from the early region 1 (E1) of the viral genome. These products correspond to those synthesized early after adenovirus infection of normal cells. This pattern of expression is different from that observed at later times in the lytic cycle. We have determined whether integrated sequences can undergo the early-late transition during infection of transformed cells. Cultures of 293 cells were infected with mutants of adenovirus type 5 that have deletions in EI genes. In such infections, the integrated sequence complements the deletion mutants so that viral DNA replication, late mRNA and protein synthesis, and viral assembly occur. Because the infecting genomes lack EI sequences, the products synthesized from the integrated DNA could be analyzed. In contrast to the early-late transition that occurs with EI DNA in free viral genomes, the pattern of mRNAs and proteins made from the integrated sequences was restricted to the early pattern. Assuming that the viral sequences in 293 cells have not become altered during the history of the cells, our results suggest that regulation of integrated adenovirus genes may not be determined exclusively by nucleotide sequence recognition. Apparently, during infection certain factors prevent the integrated viral genes from responding to the regulatory signals which control late expression from free EI DNA. The distinction between integrated and free viral sequences might reflect the different fates of viral and host transcripts during the lytic cycle of adenovirus.
Getting out of the Iraq trap (2003)

The Iraq crisis has been variously defined as a problem of local leadership, regional security, culture clash, arms control, neo—imperialism, transatlantic relations and international legitimacy. The competing definitions reflect the worldviews of different actors with a stake in the outcome of the crisis. Each perspective has validity for its proponent and none of them can be expected to triumph to the exclusion of the others. Consequently, it is argued here, whatever the goals of UN and/or military intervention in Iraq, at the receiving end, the experience will be at odds with what is meant or sought by such intervention. A way to understand the problem and thence to address it is ventured which combines local, regional and international perspectives and calls for a multitiered, multilateral approach to rethinking Iraq and the region. The intention is to take on ‘the hawks’ who claim that the United States can deliver democracy to client states, challenge their logic and propose an alternative vision that would require all parties, international and local, to take shared responsibility not only for Iraq but for Palestine too.
Voice puppetry (1999)

Article Voice puppetry Share on Author: Matthew Brand MERL -- a Mitsubishi Electric Research Laboratory, 201 Broadway, Cambridge, MA MERL -- a Mitsubishi Electric Research Laboratory, 201 Broadway, Cambridge, MAView Profile Authors Info & Claims SIGGRAPH '99: Proceedings of the 26th annual conference on Computer graphics and interactive techniquesJuly 1999 Pages 21–28https://doi.org/10.1145/311535.311537Online:01 July 1999Publication History 249citation1,623DownloadsMetricsTotal Citations249Total Downloads1,623Last 12 Months60Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Microwave Biomedical Data Inversion Using the Finite-Difference Contrast Source Inversion Method (2009)

We present a contrast source inversion (CSI) technique which is based on a finite-difference (FD) solver for use in microwave biomedical imaging. The algorithm is capable of inverting complex-permittivity biomedical data sets without the explicit use of a forward solver at each iteration. The FD solver is based in the frequency domain, utilizes perfectly matched layer (PML) boundary conditions, and the stiffness matrix is solved via an LU decomposition and Gaussian elimination. An important feature of the FD-CSI algorithm is that the stiffness matrix associated with the FD solver depends only upon the background medium and frequency, and thus the LU decomposition is only performed once, before the iterative inversion process. Unlike the usual integral equation (IE) based inversion techniques, the FD-CSI algorithm is readily capable of utilizing an arbitrary backarbitrary backgroundground medium for the inversion process.
In vitro T cell responses to a candidate Epstein‐Barr virus vaccine: human CD4+ T cell clones specific for the major envelope glycoprotein gp340 (1988)

Specific T cell proliferation was observed in short-term blood mononuclear cell cultures set up from Epstein-Barr virus (EBV)-immune individuals and challenged either with UV-irradiated EB virions or with a candidate subunit vaccine preparation, the purified envelope glycoprotein gp340 incorporated into immune stimulating complexes (gp340 iscoms). Limiting dilution culture of the activated T lymphoblasts in interleukin 2-containing medium generated stable CD3+CD4+CD8- T cell clones. Particular clones showing virus-specific proliferation in preliminary screening assays were selected for more detailed study. Three gp340 iscoms-induced clones from EBV-immune donor CG responded specifically to restimulation either with UV-EBV or with purified gp340 iscoms in the presence of autologous antigen-presenting cells (APC). Both T cell-depleted blood mononuclear cells and the EBV-transformed B cell line (treated with Acyclovir to block endogenous gp340 production) could be used for presentation, the latter being the more efficient when gp340 iscoms was the source of antigen. Blocking studies with monoclonal antibodies to HLA class II antigens and experiments using HLA-typed allogeneic APC indicated that all three gp340-specific CG clones were restricted through the HLA-DR2 antigen. One gp340 iscoms-induced clone from another EBV-immune donor, MR, likewise showed gp340-specific proliferation, in this case restricted through a HLA-DR4 antigen. Using HLA-DR-homozygous B cell lines representing the five known DR4 subtypes, efficient presentation of gp340 to this T cell clone was observed with both DR4 Dw4 and DR4 Dw14 antigens. Parallel experiments on one UV-EBV-induced T cell clone from donor MR gave a different pattern of results; these cells appeared to be specific for a virus structural component other than gp340 and to be restricted through an HLA-DP determinant.
Expression and Cellular Provenance of Thymic Stromal Lymphopoietin and Chemokines in Patients with Severe Asthma and Chronic Obstructive Pulmonary Disease (2008)

Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer (2005)

Activation in transformed cells of normal stem cells' self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene-driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell-resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell-like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1-driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.
Sodium-Dependent Norepinephrine-Induced Currents in Norepinephrine-Transporter-Transfected Hek-293 Cells Blocked by Cocaine and Antidepressants (1995)

Transport of norepinephrine (NE+) by cocaine- and antidepressant-sensitive transporters in presynaptic terminals is predicted to involve the cotransport of Na+ and Cl-, resulting in a net movement of charge per transport cycle. To explore the relationship between catecholamine transport and ion permeation through the NE transporter, we established a human norepinephrine transporter (hNET) cell line suitable for biochemical analysis and patch-clamp recording. Stable transfection of hNET cDNA into HEK-293 (human embryonic kidney) cells results in lines exhibiting (1) a high number of transporter copies per cell (10(6)), as detected by radioligand binding and hNET-specific antibodies, (2) high-affinity, Na(+)-dependent transport of NE, and (3) inhibitor sensitivities similar to those of native membranes. Whole-cell voltage-clamp of hNET-293 cells reveals NE-induced, Na(+)-dependent currents blocked by antidepressants and cocaine that are absent in parental cells. In addition to NE-dependent currents, transfected cells posses an NE-independent mode of charge movement mediated by hNET. hNET antagonists without effect in non-transfected cells abolish both NE-dependent and NE-independent modes of charge movement in transfected cells. The magnitude of NE-dependent currents in these cells exceeds the expectations of simple carrier models using previous estimates of transport rates. To explain our observations, we propose that hNETs function as ion-gated ligand channels with an indefinite stoichiometry relating ion flux to NE transport. In this view, external Na+ and NE bind to the transporter with finite affinities in a cooperative fashion. However, coupled transport may not predict the magnitude or the kinetics of the total current through the transporter. We propose instead that Na+ gates NE transport and also the parallel inward flux of an indeterminate number of ions through a channel-like pore.
Online CBT in patients with multiple sclerosis and depression (2015)

1Depression in these patients is associated with decreased quality of life, impaired functioning, and lower adherence rates and might thus have direct consequences for overall health outcome. 1 Up to 50% of patients with multiple sclerosis, a chronic infl ammatory and demyelinating disease of the CNS, will have a major depressive episode during the course of their illness. 2 Eff ective and safe treatment options for depression are urgently needed in this group of patients. Although fi ndings from a Cochrane review showed some benefi t of anti depressant drugs in patients with depression and multiple sclerosis, a higher risk for adverse side-eff ects from such treatment exists in this population. 3 Moreover, multiple sclerosis often causes motor impairment and decreased mobility, posing an additional barrier to adequate diagnosis and treatment. The potential eff ectiveness of cognitive behavioural therapy (CBT) in these patients in a group or individual settings is lent support by fi ndings from a
Tissue Characterization of Myocardial Cells by Use of High-Frequency Acoustic Microscopy: Differential Myocyte Sound Speed and Its Transmural Variation in Normal, Pressure-Overload Hypertrophic, and Amyloid Myocardium (1999)

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.
An Integrated System for Wireless Capsule Endoscopy in a Liquid-Distended Stomach (2013)

The design and development of a functional integrated system for gastroscopy is reported in this paper. The device takes advantage of four propellers enabling locomotion in a liquid environment and generating a maximum propulsive force of 25.5 mN. The capsule has been equipped with a miniaturized wireless vision system that acquires images with a frame rate of 30 fps (frames per second). The overall size of the capsule is 32 mm in length and 22 mm in diameter, with the possibility of decreasing the diameter to swallowable dimensions. The capsule is remotely controlled by the user who can intuitively drive the device by looking at the video streaming on the graphical interface. The average speed of the device is 1.5 cm/s that allows for a fine control of the capsule motion as demonstrated in experimental tasks consisting of passing through circular targets. The video system performances have been characterized by evaluating the contrast, the focus, and the capability of acquiring and perceiving different colors. The usability of the device has been tested on bench and on explanted tissues by three users in real time target-identification tasks, in order to assess the success of the integration process. The lifetime of the capsule with active motors and vision system is 13 min, that is, a timeframe consistent with traditional gastroscopic examinations.