gebhart/patrepeval huggingface dataset:
The Role of Exposure History on HIV Acquisition: Insights from Repeated Low-dose Challenge Studies (2012)

To assess the efficacy of HIV vaccine candidates or preventive treatment, many research groups have started to challenge monkeys repeatedly with low doses of the virus. Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection. I developed stochastic models to analyze previously published challenge data. In the mathematical models, I allowed for variation of the animals' susceptibility to infection across challenge repeats, or across animals. In none of the studies I analyzed, I found evidence for an immunizing effect of non-infecting challenges, and in most studies, there is no evidence for variation in the susceptibilities to the challenges across animals. A notable exception was a challenge experiment by Letvin et al. Sci Translat Med (2011) conducted with the strain SIVsmE660. The challenge data of this experiment showed significant susceptibility variation from animal-to-animal, which is consistent with previously established genetic differences between the involved animals. For the studies which did not show significant immunizing effects and susceptibility differences, I conducted a power analysis and could thus exclude a very strong immunization effect for some of the studies. These findings validate the assumption that non-infecting challenges do not immunize an animal - an assumption that is central in the argument that repeated low-dose challenge experiments increase the statistical power of preclinical HIV vaccine trials. They are also relevant for our understanding of the role of exposure history for HIV acquisition and forecasting the epidemiological spread of HIV.
Cellular Localization of the Signaling Components of Arabidopsis His-to-Asp Phosphorelay (2001)

In the higher plant, Arabidopsis thaliana, histidine-to-aspartate (His-to-Asp) phosphorelay signal transduction systems play crucial roles in propagation of environmental stimuli, including plant hormones. This plant has 11 sensor His-kinases, 5 histidine-containing phosphotransfer (HPt) factors (AHPs), and 20 response regulators (ARRs). To gain new insight into the functions of these phosphorelay components, their intracellular localization was examined with use of GFP-fusion proteins, constructed for certain representatives of HPt factors (AHP2) and type-A and type-B ARRs (ARR6/ARR7 and ARR10, respectively). The results showed that AHP2 is mainly located in the cytoplasmic space, while both the types of ARRs have an ability to enter preferentially into the nuclei, if not exclusively. Together with the results from an in vitro phosphorelay assay with AHP2 and ARRs, these results are discussed, in terms of a geneal framework of the Arabidopsis His-to-Asp phosphorelay network.
Pharmacological profile of hypericum extract. Effect on serotonin uptake by postsynaptic receptors. (1995)

In the present study is is reported that the methanolic Hypericum extract LI 160 (Jarsin 300) exerts no protective effect against N-methyl-D-aspartate (NMDA-) or gp120- (from the HIV virus) induced cytotoxicity. Moreover, it is established that Hypericum extract causes no activation of arachidonic acid release from neurons activated by gp120; hence it displays no sensitization effect on the NMDA receptor channel. The main outcome of this study is the finding that Hypericum extract causes a 50% inhibition (IC50 value) of serotonin uptake by rat synaptosomes at a concentration of 6.2 microglml. Therefore it is concluded that the antidepressant activity of Hypericum extract is due to an inhibition of serotonin uptake by postsynaptic receptors. Future studies might focus on the effect of Hypericum extract on serotonin binding to neurons, serotonin storage in granules, the rate of synthesis of serotonin, and on the activity of monoamine oxidase.
Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis (2009)

Existing optical imaging techniques offer us powerful tools to directly visualize the cellular structure at the microscale; however, their capability of nanoscale sensitivity is restricted by the diffraction-limited resolution. We show that the mesoscopic light transport theory analysis of the spectra of partial waves propagating within a weakly disordered medium, such as biological cells [i.e., partial wave spectroscopy (PWS)] quantifies refractive index fluctuations at subdiffractional length scales. We validate this nanoscale sensitivity of PWS using experiments with nanostructured models. We also demonstrate the potential of this technique to detect nanoscale alterations in cells from patients with pancreatic cancer who are otherwise classified as normal by conventional microscopic histopathology.
Prediction of continuous B‐cell epitopes in an antigen using recurrent neural network (2006)

B-cell epitopes play a vital role in the development of peptide vaccines, in diagnosis of diseases, and also for allergy research. Experimental methods used for characterizing epitopes are time consuming and demand large resources. The availability of epitope prediction method(s) can rapidly aid experimenters in simplifying this problem. The standard feed-forward (FNN) and recurrent neural network (RNN) have been used in this study for predicting B-cell epitopes in an antigenic sequence. The networks have been trained and tested on a clean data set, which consists of 700 non-redundant B-cell epitopes obtained from Bcipep database and equal number of non-epitopes obtained randomly from Swiss-Prot database. The networks have been trained and tested at different input window length and hidden units. Maximum accuracy has been obtained using recurrent neural network (Jordan network) with a single hidden layer of 35 hidden units for window length of 16. The final network yields an overall prediction accuracy of 65.93% when tested by fivefold cross-validation. The corresponding sensitivity, specificity, and positive prediction values are 67.14, 64.71, and 65.61%, respectively. It has been observed that RNN (JE) was more successful than FNN in the prediction of B-cell epitopes. The length of the peptide is also important in the prediction of B-cell epitopes from antigenic sequences. The webserver ABCpred is freely available at www.imtech.res.in/raghava/abcpred/.
Clostridium perfringens Type E Animal Enteritis Isolates with Highly Conserved, Silent Enterotoxin Gene Sequences (1998)

Several Clostridium perfringens genotype E isolates, all associated with hemorrhagic enteritis of neonatal calves, were identified by multiplex PCR. These genotype E isolates were demonstrated to express α and ι toxins, but, despite carrying sequences for the gene (cpe) encoding C. perfringens enterotoxin (CPE), were unable to express CPE. These silent cpe sequences were shown to be highly conserved among type E isolates. However, relative to the functionalcpe gene of type A isolates, these silent type Ecpe sequences were found to contain nine nonsense and two frameshift mutations and to lack the initiation codon, promoters, and ribosome binding site. The type E animal enteritis isolates carrying these silent cpe sequences do not appear to be clonally related, and their silent type E cpe sequences are always located, near the ι toxin genes, on episomal DNA. These findings suggest that the highly conserved, silent cpe sequences present in most or all type E isolates may have resulted from the recent horizontal transfer of an episome, which also carries ι toxin genes, to several different type A C. perfringens isolates.
3-Deoxy-d-arabino-Heptulosonate 7-Phosphate Synthase from Carrot Root (Daucus carota) Is a Hysteretic Enzyme (1985)

Roots of carrots (Daucus carota) contain three activities of 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthase, the enzyme that catalyzes the first step of the shikimate pathway. The three activities, enzymes I, II, and III, are separated by chromatography on phosphocellulose. Enzyme III, purified to electrophoretic homogeneity, has a native molecular weight of 103,000 and consists of two identical subunits of 53,000 daltons each. Double reciprocal plots of reaction velocity versus substrate concentration yield K(m) values of 0.03 and 0.07 millimolar for P-enolpyruvate and erythrose-4-P, respectively. Both products, DAHP and orthophosphate, inhibit the enzyme. Enzyme III is a hysteretic enzyme that is activated by physiological concentrations of l-tryptophan and Mn(2+), both of which also partially eliminate the hysteretic lag. Feedback activation of carrot DAHP synthase by tryptophan is interpreted to be an early regulatory signal for polyphenol biosynthesis. The three carrot DAHP synthase isoenzymes share antigenic determinants.
WINNER II Channel Models (2009)

This chapter contains sections titled: Introduction Modelling Considerations Channel-Modelling Approach Channel Models and Parameters Channel Model Usage Conclusion Acknowledgements References
Critical role of host γδ T cells in experimental acute graft-versus-host disease (2005)

Gammadelta T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host gammadelta T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host gammadelta T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) gammadelta monoclonal antibody reduced GVHD, and gammadelta T-cell-deficient (gammadelta-/-) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P < .001). gammadelta T cells were responsible for this difference because reconstitution of gammadelta-/- recipients with gammadelta T cells restored GVHD mortality. gammadelta-/- recipients showed decreased serum levels of tumor necrosis factor alpha (TNF-alpha), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from gammadelta-/- recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with gammadelta T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon gamma (IFN-gamma), TNF-alpha, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host gammadelta T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells.
Functional Debug Techniques for Embedded Systems (2008)

Some problems in a new chip design or its embedded software show up only when a silicon prototype of the chip is placed in its intended target environment and the embedded software is executed. Traditionally, embedded-system debug is very difficult and time-consuming because of the intrinsic lack of internal system observability in the target environment. Design for debug (DFD) is the act of adding debug support to a chip's design in the realization that not every silicon chip or embedded-software application is right the first time. In the past few years, functional debug has made significant progress. This article describes the most common structured approaches available for silicon debug of embedded systems.
Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohnʼs disease and analysis of the IL17F p.His161Arg polymorphism in IBD (2007)

Background: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants.
Continuous localization of cardiac activation sites using a database of multichannel ECG recordings (2000)

Monomorphic ventricular tachycardia and ventricular extrasystoles have a specific exit site that can be localized using the multichannel surface electrocardiogram (ECG) and a database of paced ECG recordings. An algorithm is presented that improves on previous methods by providing a continuous estimate of the coordinates of the exit site instead of selecting one out of 25 predetermined segments. The accuracy improvement is greatest, and most useful, when adjacent pacing sites in individual patients are localized relative to each other. Important advantages of the new method are the objectivity and reproducibility of the localization results.
Optical detection techniques and light delivery with UV LEDs and optical fibres (2007)

Following the recent introduction of AlGaN/GaN based ultraviolet Light Emitting Diodes (UV-LEDs) in the 250 nm to 350 nm wavelength region, a wide range of research activities have begun. For example, using the high levels of power of available UV-light, chemical reactions can be stimulated. However, when optical detection techniques are considered, light intensity and wavelength accuracy are more important to achieve low detection limits. Using LED-based light sources in the ultraviolet instead of the classical deuterium, xenon, mercury or metal halide sources is very attractive due to their high power conversion, relatively simple electronic driving circuitry and low power consumption. For both absorption and fluorescence detection, such LEDs and complete detection systems are powerful tools both traditional and new applications in the field and laboratory. In this work, the electrical and optical properties of these new UV-LEDs will be described. Further, the flexibility of using optical fibres for UV-light delivery will be discussed with respect to the available UV-wavelengths and UV-induced damage. To exemplify the potential of UV LEDs, a self correcting fibre optic detection system over the wavelength range 260 and 280 nm, based on such LEDs will be shown. Further, an overview discussing flexible optical fibre UV-light delivery systems will be given and applications for both will be considered.
Molecular Biology: The Interferon System: A Review with Emphasis on the Role of PKR in Growth Control (1995)

(1995). Molecular Biology: The Interferon System: A Review with Emphasis on the Role of PKR in Growth Control. Cancer Investigation: Vol. 13, No. 3, pp. 327-338.
The Management of Acute Pulmonary Arterial Hypertension (2010)

Acute pulmonary arterial hypertension (PAH), which may complicate the course of many complex disorders, is always underdiagnosed and its treatment frequently begins only after serious complications have developed. Acute PAH is distinctive because they differ in their clinical presentation, diagnostic findings, and response to treatment from chronic PAH. The acute PAH may take either the form of acute onset of chronic PAH or acute PAH or surgery-related PAH. Significant pathophysiologic differences existed between acute and chronic PAH. Therapy of acute PAH should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. There are three classes of drugs targeting the correction of abnormalities in endothelial dysfunction, which have been approved recently for the treatment of PAH: (1) prostanoids; (2) endothelin receptor antagonists; and (3) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH. Intravenous epoprostenol is suggested to serve as the first-line treatment for the most severe patients. In the other situations, the first-line therapy may include bosentan, sildenafil, or a prostacyclin analogue. Recent advances in the management of PAH have markedly improved prognosis.
Femtosecond pulse shaping for synthesis, processing, and time-to-space conversion of ultrafast optical waveforms (1998)

Shaping, signal processing, and time-space conversion of femtosecond pulses can be achieved by linear and nonlinear manipulation of the spatially dispersed optical frequency spectrum within a grating and lens pulse shaper. In this paper, we first review our work on femtosecond pulse shaping and processing, with an emphasis on applications to high-speed communications and information processing. We then present a new concept for generalized time-space processing based on cascaded time-to-space and space-to-time conversions in conjunction with smart pixel optoelectronic arrays and provide a detailed discussion of our recent studies of time-to-space conversion based on second-harmonic generation (SHG) within a femtosecond pulse shaper.
Establishment of a liver metastatic model of human ovarian cancer. (1998)

We have established an in vivo experimental model in which human ovarian cancer grows in the ovary of nude mice and metastasizes to parenchymatous organs. An ovarian cancer cell line was orthotopically injected into the nude mouse ovary together with Matrigel by microsurgical techniques. The cells grew locally in the ovary and metastasized to the peritoneum, colon, omentum, liver, and spleen. When the cells were injected into the intraperitoneal cavity with Matrigel, they formed carcinomatous peritonitis but neither ovarian tumor formation nor the metastasis to parenchymatous organs was detected. Taken together, these findings indicate that the microenvironment of the ovary seems to be essential for metastasis of implanted human ovarian cancer cells. This in vivo experimental model allows us to investigate the mechanism of the metastasis of ovarian cancer, it will be also useful for the establishing a new therapeutic approach to preventing metastasis of human ovarian cancer to parenchymatous organs.
Protein Kinases, Protein Phosphorylation, and the Regulation of Insulin Secretion from Pancreatic β-Cells. (1998)

I. Introduction II. Protein Kinases in -Cells: Expression and Characteristics A. Ca 2 /calmodulin-dependent protein kinases B. Cyclic nucleotide-dependent protein kinases C. Ca 2 /phospholipid-dependent protein kinases D. Mitogen-activated protein kinases E. Protein tyrosine kinases III. Phosphorylation of Endogenous Proteins in -Cells A. Methods for studying protein phosphorylation in -cells B. Endogenous kinase substrates in -cells IV. Protein Kinases and the Regulation of Insulin Secretion A. Ca 2 /calmodulin-dependent protein kinases B. Cyclic nucleotide-dependent protein kinases C. Ca 2 /phospholipid-dependent
Functional Differentiation of Lotus japonicus TT2s, R2R3-MYB Transcription Factors Comprising a Multigene Family (2008)

Leguminous plants have many paralogous genes encoding enzymes involved in the flavonoid biosynthetic pathway. Duplicate genes are predicted to contribute to the production of various flavonoid compounds and to have resulted in a diversity of legume species. We identified gene duplication in the transcription factors regulating flavonoid biosynthesis in the model legume Lotus japonicus. Three copies of a homolog of Arabidopsis thaliana TRANSPARENT TESTA2 (TT2), which is a MYB transcription factor that regulates proanthocyanidin biosynthesis, were present in the L. japonicus genome. The organ specificity and stress responsiveness differed among the three LjTT2s, and correlations between proanthocyanidin accumulation and the expression levels of LjTT2s were observed during seedling development. Moreover, three LjTT2s functionally complemented TT2 in transient expression experiments in A. thaliana leaf cells. The different reporter activity caused by LjTT2a was consistent with the affinity of physical interactions with TT8 and TTG1 in yeast two-hybrid experiments as well as the branching pattern of the phylogenetic tree. These results suggest that LjTT2 factors have diverse functions in the tissues in which they are expressed; in particular, LjTT2a is predicted to have evolved flexibility in interaction with other transcription regulators to resist environmental stresses.
Role of interferon alpha/beta receptor chain 1 in the structure and transmembrane signaling of the interferon alpha/beta receptor complex. (1994)

A previously cloned cDNA encodes one subunit of the human interferon alpha/beta receptor (IFN alpha R), denoted IFN alpha R1. To study the expression and signaling of IFN alpha R1, we used monoclonal antibodies (mAbs) generated against the baculovirus-expressed ectodomain of IFN alpha R1. Immunoprecipitation and immunoblotting of lysates from a variety of human cell lines showed that IFN alpha R1 has an apparent molecular mass of 135 kDa. Binding analysis with 125I-labeled mAb demonstrated high levels of cell surface expression of IFN alpha R1 in human cells and in mouse cells transfected with IFN alpha R1 cDNA, whereas no cross-reactivity was observed in control mouse L929 cells expressing only the endogenous mouse receptor. The subunit was rapidly down-regulated by IFN alpha (80% decrease within 2 hr) and degraded upon internalization. The IFN alpha R1 chain appeared to be constitutively associated with the 115-kDa subunit of the IFN alpha/beta receptor, since the mAbs coprecipitated this protein. IFN alpha/beta treatment induced tyrosine phosphorylation of IFN alpha R1 within 1 min, with kinetics paralleling that of the IFN-activated protein-tyrosine kinases Jak1 and Tyk2. Ligand-induced tyrosine phosphorylation of IFN alpha R1 was blocked by the kinase inhibitors genistein or staurosporine. Although IFN alpha R1 cDNA-transfected mouse cells expressed high levels of this subunit when compared with empty vector-transfected cells the number of binding sites for human IFN alpha (50-75 sites per cell) was not increased. Human IFN alpha induced the expression of a mouse IFN alpha/beta-responsive gene (the 204 gene) in mouse L929 cells transfected with the IFN alpha R1 cDNA, but not in mock-transfected cells. These results suggest that the IFN alpha R1 subunit acts as a species-specific signal transduction component of the IFN alpha/beta receptor complex.
The Tamoxifen Metabolite, Endoxifen, Is a Potent Antiestrogen that Targets Estrogen Receptor α for Degradation in Breast Cancer Cells (2009)

Tamoxifen has been the most important therapeutic agent for the treatment of estrogen receptor (ER)-positive breast cancer for the past three decades. Tamoxifen is extensively metabolized by cytochrome P450 enzymes, and recent in vivo studies have shown that women with genetically impaired cytochrome P450 2D6 have reduced production of endoxifen and a higher risk of breast cancer recurrence. Despite these observations, the contribution of endoxifen to the overall drug effectiveness of tamoxifen remains uncertain. Here, we provide novel evidence that endoxifen is a potent antiestrogen that functions in part by targeting ERalpha for degradation by the proteasome in breast cancer cells. Additionally, we show that endoxifen blocks ERalpha transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation even in the presence of tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxytamoxifen. All of the effects of endoxifen are concentration dependent and do not occur at concentrations observed in human CYP2D6 poor metabolizers. These results support the theory that endoxifen is the primary metabolite responsible for the overall effectiveness of tamoxifen in the treatment of ER-positive breast cancer.