gebhart/patrepeval huggingface dataset:
Photoactivation-Induced Instability of Rhodopsin Mutants T4K and T17M in Rod Outer Segments Underlies Retinal Degeneration inX. laevisTransgenic Models of Retinitis Pigmentosa (2014)

Retinitis pigmentosa (RP) is an inherited neurodegenerative disease involving progressive vision loss, and is often linked to mutations in the rhodopsin gene. Mutations that abolish N-terminal glycosylation of rhodopsin (T4K and T17M) cause sector RP in which the inferior retina preferentially degenerates, possibly due to greater light exposure of this region. Transgenic animal models expressing rhodopsin glycosylation mutants also exhibit light exacerbated retinal degeneration (RD). In this study, we used transgenic Xenopus laevis to investigate the pathogenic mechanism connecting light exposure and RD in photoreceptors expressing T4K or T17M rhodopsin. We demonstrate that increasing the thermal stability of these rhodopsins via a novel disulfide bond resulted in significantly less RD. Furthermore, T4K or T17M rhodopsins that were constitutively inactive (due to lack of the chromophore-binding site or dietary deprivation of the chromophore precursor vitamin A) induced less toxicity. In contrast, variants in the active conformation accumulated in the ER and caused RD even in the absence of light. In vitro, T4K and T17M rhodopsins showed reduced ability to regenerate pigment after light exposure. Finally, although multiple amino acid substitutions of T4 abolished glycosylation at N2 but were not toxic, similar substitutions of T17 were not tolerated, suggesting that the carbohydrate moiety at N15 is critical for cell viability. Our results identify a novel pathogenic mechanism in which the glycosylation-deficient rhodopsins are destabilized by light activation. These results have important implications for proposed RP therapies, such as vitamin A supplementation, which may be ineffective or even detrimental for certain RP genotypes.
Induced Pluripotent Stem Cells: Progress and Future Perspectives in the Stem Cell World (2012)

Pluripotent stem cells (PSCs) have the potential to differentiate into many cell types and therefore can be a valuable source for cell therapy. Embryonic stem cells (ESCs), which are derived from the inner cell mass (ICM) of the blastocyst, are representative of PSCs. However, use of these cells has some limitations, especially ethical restrictions and immune response. As a result, researchers have been looking for other cell sources or strategies to overcome these limitations. One kind of cellular reprogramming is the process of guiding mature cells into a state of gene expression similar to PSCs. It has been demonstrated that somatic cells can be reprogrammed by various methods, including somatic cell nuclear transfer (SCNT) and cell fusion with ESCs or treatment with their extracts. This implies that some factors in oocytes and ESCs are able to initiate the reprogramming process. Accordingly, induced pluripotent stem cells (iPSCs) have been derived from somatic cells by ectopic expression of some transcription factors. This discovery has resulted in raising several important questions about the mechanisms by which these factors influence the reprogramming and epigenetic status of the cells. iPSCs hold great promise for regenerative medicine, developmental biology, and drug discovery because they circumvent problems associated with both ethical issues and immunological rejection. Here we review the experiments involved in the discovery of iPSCs, important factors in their reprogramming, and their future perspectives in cell therapy.
Quantification of HIV-1 latency reversal in resting CD4 + T cells from patients on suppressive antiretroviral therapy (2014)

Reversal of proviral latency is being pursued as a curative strategy for HIV-1 infection. Recent clinical studies of in vivo administration of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 RNA levels in resting CD4(+) T cells. A critical unknown, however, is the proportion of latent proviruses that can be transcriptionally reactivated by SAHA or T-cell activation. In this study, we quantified the fraction of HIV-1 proviruses in resting CD4(+) T cells from patients on suppressive antiretroviral therapy that were reactivated ex vivo with SAHA or antibodies to CD3/CD28. At concentrations of SAHA achieved clinically, only 0.079% of proviruses in resting CD4(+) T cells were reactivated to produce virions, compared with 1.5% of proviruses in cells treated with anti-CD3/CD28 antibodies after correcting for spontaneous virion production in the medium control. A significant positive correlation (ρ = 0.67, P < 0.001) was found between levels of virions in the supernatant and unspliced cellular HIV-1 RNA following anti-CD3/CD28 treatment, but not following SAHA treatment (ρ = 0.21, P = 0.99). These results reveal that the majority of HIV-1 proviruses are not reactivated by current therapeutic approaches and that more effective means of reversing proviral latency will likely be required to deplete HIV-1 reservoirs.
Leukemic cell targeting and therapy by monoclonal antibody in a mouse model system. (1982)

A monoclonal antibody prepared against the Rauscher virus envelope glycoprotein with a molecular weight of 70,000 targeted to neoplastic cells and cured the Rauscher leukemia virus-induced erythroleukemia in BALB/c mice. This antibody, 103A, specifically reacted with the Rauscher and Friend erythroleukemia viruses and erythroleukemic cells but did not react with other murine ecotropic or xenotropic viruses or feline leukemia virus or with normal spleen cells, thymocytes, or fibroblasts, as measured by radioimmunoassays. P3, a control antibody of the same immunoglobulin G1 subclass, did not bind to any of these cells or viruses. This specificity was maintained in vivo. 125I-Labelled 103A injected into mice targeted to leukemic spleen cells but not to normal cells. Mean uptake ratios of binding to leukemic over normal spleen cells ranged from greater than 70 at 7 hr after injection to less than 10 at 40 hr later. The control antibody showed no binding in vivo. A single small dose of 103A was able to cure leukemic mice as assayed by spleen focus formation on Day 8 or splenomegaly on Day 20. The 50% effective dose was 1.5 micrograms when injected 72 hr after onset of leukemia. The therapeutic potencies of drugs, toxins, and cytotoxic radioisotopes conjugated to antibodies can be quantitatively compared using the established dose-response curve. Such quantitative comparisons showed that 131-labeled 103A immunoglobulin G was no more potent than unlabeled 103A immunoglobulin G in this system.
A Novel Skeletal Rearrangement of 2-Azabicyclo[2.2.1]hept-5-ene-3-carboxylic Acid Derivatives into 2-Oxabicyclo[3.3.0]-oct-7-en-3-ones under Acidic Conditions (1992)

Abstract The reaction of ethyl 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate with aroyl chloride and the subsequent hydrolysis of the ester group provided 2-aroyl-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylic acid derivatives, which underwent a stereospecific rearrangement giving 4-aroylamino-2-oxabicyclo[3.3.0]oct-7-en-3-ones by treatment with trifluoroacetic acid. On the other hand, the reaction of 2-benzoyl-2-azabicyclo[2.2.1]hept-5-ene with trifluoroacetic acid in heated benzene afforded 1-[(benzoylamino)methyl]-1,3-cyclopentadiene which afforded a Diels–Alder cycloadduct with N-phenylmaleimide. A plausible mechanism for the rearrangement is presented.
Acoustic emission and tack of heat-set inks during setting on MWC-papers and fountain solution emulsification (2007)

To investigate the relationship between ink film splitting noise and ink tack, two tack-measuring devices were monitored by a microphone. The first of these was the Deltack® (Prüfbau), to study tack build on paper, and the second was the Hydroscope® (T
Multiple Sclerosis: Levels of Interleukin‐10‐Secreting Blood Mononuclear Cells are Low in Untreated Patients but Augmented During Interferon‐β‐1b Treatment (1999)

The cytokine interleukin (IL)-10 has immune response down-regulatory properties, which include suppression of the synthesis of pro-inflammatory cytokines such as interferon (IFN)-gamma and of major histocompatibility complex (MHC) class II expression on monocytes. To further elucidate the involvement of IL-10 in multiple sclerosis (MS), an enzyme-linked immunospot assay was adopted to enumerate IL-10-secreting mononuclear cells (MNC) in peripheral blood. IFN-gamma secreting MNC were detected in parallel. Levels of IL-10-secreting cells were lower in patients with MS compared with other neurological diseases (OND) and healthy subjects. This difference was seen only in patients with untreated MS, and not in those undergoing treatment with IFN-beta-1b. No differences were observed when subgrouping the patients with MS regarding clinical phase (exacerbation, remission, secondary progression), duration of MS or disability status. Levels of IFN-gamma-secreting blood MNC did not differ in patients with MS, irrespective of treatment with IFN-beta-1b, compared with OND and healthy subjects. Patients with MS, but not the two groups of controls, had elevated numbers of IL-10- and IFN-gamma-secreting cells upon stimulation with MBP compared with culture in the absence of antigen. The data suggest that IL-10 is decreased in MS and that treatment resulting in its up-regulation beneficially influence the disease.
The apparent target size of rat brain benzodiazepine receptor, acetylcholinesterase, and pyruvate kinase is highly influenced by experimental conditions. (1988)

Radiation inactivation is a method to determine the apparent target size of molecules. In this report we examined whether radiation inactivation of various enzymes and brain receptors is influenced by the preparation of samples preceding irradiation. The apparent target sizes of endogenous acetylcholinesterase and pyruvate kinase from rat brain and from rabbit muscle and benzodiazepine receptor from rat brain were investigated in some detail. In addition the target sizes of alcohol dehydrogenase (from yeast and horse liver), beta-galactosidase (from Escherichia coli), lactate dehydrogenase (endogenous from rat brain), and 5-HT2 receptors, acetylcholine muscarine receptors, and [35S] butyl bicyclophosphorothionate tertiary binding sites from rat brain were determined. The results show that apparent target sizes are highly influenced by the procedure applied for sample preparation before irradiation. The data indicate that irradiation of frozen whole tissue as opposed to lyophilized tissue or frozen tissue homogenates will estimate the smallest and most relevant functional target size of a receptor or an enzyme.
Automatic Speech Recognition from Neural Signals: A Focused Review (2016)

Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e., patients suffering from locked-in syndrome). For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people. This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography). As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the <i>Brain-to-text</i> system.
Restricted changes in the adenovirus DNA-binding protein that lead to extended host range or temperature-sensitive phenotypes (1985)

Human adenovirus fails to multiply efficiently in monkey cells owing to a block to late viral gene expression. Ad2hr400 through Ad2hr403 are a set of host range (hr) mutants which were selected for their ability to readily grow in these cells at 37 degrees C. The mutations responsible for this extended host range have previously been mapped to the 5' portion of the gene encoding the 72-kilodalton DNA-binding protein (DBP). DNA sequence analyses indicate that all four hr mutants contain the same alteration at coding triplet 130, which changes a histidine codon to a tyrosine codon. These results extend those of Anderson et al. (J. Virol. 48:31-39, 1983), which suggested that only this change in the DBP amino acid sequence can expand adenovirus host range to monkey cells. The hr phenotype does not appear to require phosphorylation of this tyrosine residue, since no phosphotyrosine was detected in DBP isolated from Ad2hr400-infected monkey cells. The hr mutants Ad2hr400 through Ad2hr403, however, are cold sensitive for growth in monkey cells. The mutant Ad2ts400, which was derived from Ad2hr400, represents a second class of hr mutants which can grow efficiently in monkey cells at 32.5 degrees C. The cold-resistant hr mutation of Ad2ts400 has previously been mapped to the 5' region of the DBP gene (map units 63.6 through 66). DNA sequence analysis of this region shows that this mutant contains the original hr alteration at coding triplet 130 as well as a second alteration at coding triplet 148, which changes an alanine codon to a valine codon. We suspect that the alterations at amino acids 130 and 148 change the structure of the amino-terminal domain of the DBP, allowing it to better interact with monkey cell components required for late viral gene expression. Ad2ts400 also contains a temperature-sensitive mutation which has previously been mapped to the 3' portion of the DBP gene (map units 61.3 through 63.6). Sequence analysis of this region indicates that the DBP coding triplet 413 has been altered. This change from a serine codon to a proline codon is the same alteration reported in the previously sequenced DBP mutants Ad5ts125 (W. Kruijer et al., Nucleic Acids Res. 9:4439-4457, 1981) and Ad5ts107 (W. Kruijer et al., Virology 124:425-433, 1983). Thus it appears that only a very limited number of changes in either the 5' or the 3' portion of the DBP gene can give rise to the hr or temperature-sensitive phenotypes, respectively.
Digital Neural Networks (2005)

Demands for applications requiring massive parallelism in symbolic environments have given rebirth to research in models labeled as neural networks. These models are made up of many simple nodes which are highly interconnected such that computation takes place as data flows amongst the nodes of the network. To present, most models have proposed nodes based on simple analog functions, where inputs are multiplied by weights and summed, the total then optionally being transformed by an arbitrary function at the node. Learning in these systems is accomplished by adjusting the weights on the input lines. This paper discusses the use of digital (boolean) nodes as a primitive building block in connectionist systems. Digital nodes naturally engender new paradigms and mechanisms for learning and processing in connectionist networks. The digital nodes are used as the basic building block of a class of models called ASOCS (Adaptive Self-Organizing Concurrent Systems). These models combine massive parallelism with the ability to adapt in a self-organizing fashion. Basic features of standard neural network learning algorithms and those proposed using digital nodes are compared and contrasted. The latter mechanisms can lead to vastly improved efficiency for many applications.
Delayed fluorescence emitted from light harvesting complex II and photosystem II of higher plants in the 100 ns–5 μs time domain (2000)

This study presents the first report on delayed fluorescence (DF) emitted from spinach thylakoids, D1/D2/Cytb-559 preparations and solubilized light harvesting complex II (LHCII) in the ns time domain after excitation with saturating laser flashes. The use of a new commercially available multichannel plate with rapid gating permitted a sufficient suppression of detector distortions due to the strong prompt fluorescence. The following results were obtained: (a) in dark-adapted thylakoids, the DF amplitudes at 100 ns and 5 micros after each flash of a train of saturating actinic pulses exhibit characteristic period four oscillations of opposite sign: the DF amplitudes at 100 ns oscillate in the same manner as the quantum yield of prompt fluorescence, whereas those at 5 micros resemble the oscillation of the micros kinetics of P680(.) reduction in samples with an intact water oxidizing complex, (b) the quantum yield of total DF emission in the range up to a few micros is estimated to be <10(-4) for thylakoids, (c) the DF of D1/D2/Cytb-559 exhibits a monophasic decay with tau approximately 50 ns, (d) DF emission is also observed in isolated LHCII with biphasic decay kinetics characterized by tau values of 65 ns and about 800 ns, (e) in contrast to thylakoids, the amplitudes of DF in D1/D2/Cytb-559 preparations and solubilized LHCII do not exhibit any oscillation pattern and (f) all spectra of DF from the different sample types are characteristic for emission from the lowest excited singlet state of chlorophyll a. The implications of these findings and problems to be addressed in future research are briefly discussed.
Articular cartilage repair: an update on different clinical repair methods. (2001)

Articular cartilage is a fascinating tissue but due to its poor ability to self repair after injury, its also a troublesome tissue. The treatment of cartilage lesions is difficult and there exist many possible alternate treatments to repair an injured cartilage area. However, still there is a lack of randomized, controlled studies to tell which treatment that could be regarded as the gold cartilage repair standard. This paper gives an update of the different available treatments for local cartilage repair in use over the world and the clinical experience that have been encountered when using those methods.
Novel body tied FinFET cell array transistor DRAM with negative word line operation for sub 60nm technology and beyond (2004)

In this paper, a highly manufacturable 512M FinFET DRAM with novel body tied FinFET cell array transistor on bulk Si substrate has been successfully integrated and the characteristics were compared with RCAT (Recess Channel Array Transistor) and planar cell array transistor DRAM for the first time. We also propose the NWL (Negative Word Line) scheme with low channel doping body tied FinFET for a highly manufacturable FinFET DRAM for sub 60nm technology node.
Synthesis and pharmacological studies of N-[4-[2-hydroxy-3-[[2-[4-(1H-imidazol-1-yl)phenoxy]ethyl]amino]propoxy]phenyl]methanesulfonamide, a novel antiarrhythmic agent with class II and class III activities (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and pharmacological studies of N-[4-[2-hydroxy-3-[[2-[4-(1H-imidazol-1-yl)phenoxy]ethyl]amino]propoxy]phenyl]methanesulfonamide, a novel antiarrhythmic agent with class II and class III activitiesThomas K. Morgan Jr., Randall Lis, William C. Lumma Jr., Ronald A. Wohl, Klaus Nickisch, Gary B. Phillips, Joan M. Lind, John W. Lampe, Susan V. Di Meo, and Cite this: J. Med. Chem. 1990, 33, 4, 1087–1090Publication Date (Print):April 1, 1990Publication History Published online1 May 2002Published inissue 1 April 1990https://pubs.acs.org/doi/10.1021/jm00166a002https://doi.org/10.1021/jm00166a002research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Biological Tyrosine Nitration: A Pathophysiological Function of Nitric Oxide and Reactive Oxygen Species (1998)

Analytical and immunological methodologies and occasionally both methodologies have been applied to detect and quantify 3-nitrotyrosine in almost every major organ system. In certain diseases increased levels of 3-nitrotyrosine have been correlated with elevated levels of other indices of oxidative stress. Numerous reports have established that nitration is a biological process derived from the biochemical interaction of nitric oxide or nitric oxide-derived secondary products with reactive oxygen species. This article addresses critical issues regarding this biological process, namely the biochemical pathways for nitration of tyrosine residuesin vivo,potential protein targets, and pathophysiological consequences of protein tyrosine nitration.
Tiotropium (Spiriva): A Once-Daily Inhaled Anticholinergic Medication for Chronic Obstructive Pulmonary Disease (2004)

Tiotropium represents a new generation of inhaled therapy. No other inhaled product has demonstrated effectiveness with once-daily dosing. Treatment has been associated with improved lung function, decrease in the number of exacerbations, increase in the time to first exacerbation, and improved quality of life. Adverse effects appear to be mild in nature, and the only significant adverse effect is dry mouth. Clinical trials show that tiotropium is more effective than placebo. When compared with current treatment for chronic obstructive pulmonary disease, tiotropium is at least as effective as salmeterol and more effective than ipratropium; moreover, the once-a-day dosing increases the likelihood of patient compliance. The guidelines of the Global Initiative for Chronic Obstructive Lung Disease recommend bronchodilator medications as first-line therapy in the symptomatic management of chronic obstructive pulmonary disease. Tiotropium, an anticholinergic bronchodilator, should be considered a first-line agent for patients with chronic obstructive pulmonary disease.