gebhart/patrepeval huggingface dataset:
Mitochondrial DNA damage induces apoptosis in senescent cells (2013)

Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies through their secretion of inflammatory factors that modify the tissue microenvironment and alter the function of nearby normal or transformed cells. Understanding how senescent cells alter the microenvironment would be aided by the ability to induce or eliminate senescent cells at will in vivo. Here, we combine the use of the synthetic nucleoside analog ganciclovir (GCV) with herpes simplex virus thymidine kinase (HSVtk) activity to create or eliminate senescent human cells. We show that low concentrations of GCV induce senescence through the accumulation of nuclear DNA damage while higher concentrations of GCV, similar to those used in vivo, kill non-dividing senescent cells via mitochondrial DNA (mtDNA) damage and caspase-dependent apoptosis. Using this system, we effectively eliminated xenografted normal human senescent fibroblasts or induced senescence in human breast cancer cells in vivo. Thus, cellular senescence and mtDNA damage are outcomes of synthetic nucleoside analog treatment, indicating that the GCV-HSVtk combination can be used effectively to promote the targeted formation or eradication of senescent cells.
Atrial Natriuretic Peptide Induces Mitogen-Activated Protein Kinase Phosphatase-1 in Human Endothelial Cells via Rac1 and NAD(P)H Oxidase/Nox2-Activation (2004)

The cardiovascular hormone atrial natriuretic peptide (ANP) exerts anti-inflammatory effects on tumor necrosis factor-α–activated endothelial cells by inducing mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). The underlying mechanisms are as yet unknown. We aimed to elucidate the signaling pathways leading to an induction of MKP-1 by ANP in primary human endothelial cells. By using antioxidants, generation of reactive oxygen species (ROS) was shown to be crucially involved in MKP-1 upregulation. ANP was found to increase ROS formation in cultured cells as well as in the endothelium of intact rat lung vessels. We applied NAD(P)H oxidase (Nox) inhibitors (apocynin and gp91ds- tat ) and revealed this enzyme complex to be crucial for superoxide generation and MKP-1 expression. Moreover, by performing Nox2/4 antisense experiments, we identified Nox2 as the critically involved Nox homologue. Pull-down assays and confocal microscopy showed that ANP activates the small Rho-GTPase Rac1. Transfection of a dominant-negative (RacN17) and constitutively active Rac1 mutant (RacV12) indicated that ANP-induced superoxide generation and MKP-1 expression are mediated via Rac1 activation. ANP-evoked production of superoxide was found to activate c-Jun N-terminal kinase (JNK). Using specific inhibitors, we linked ANP-induced JNK activation to MKP-1 expression and excluded an involvement of protein kinase C, extracellular signal-regulated kinase, and p38 MAPK. MKP-1 induction was shown to depend on activation of the transcription factor activator protein-1 (AP-1) by using electrophoretic mobility shift assay and AP-1 decoys. In summary, our work provides insights into the mechanisms by which ANP induces MKP-1 and shows that ANP is a novel endogenous activator of endothelial Rac1 and Nox/Nox2.
Intrinsic Interference: a New Type of Viral Interference (1967)

The hemadsorption-negative plaque test has revealed a new type of viral interference, termed intrinsic interference. Several unrelated types of noncytopathic viruses were shown to induce in infected host cells a state of interference unique in being directed solely against superinfection by Newcastle disease virus (NDV). The NDV-refractory state arises only in those individual cells of a population actually infected by the inducing virus, and presumably results from the action of a protein(s) coded for by the viral genome. Thus, intrinsic interference differs fundamentally from that mediated by an extrinsic protein detectable under conditions favoring resistance to a broad spectrum of viruses and characteristic of interference induced by interferon, the latter being coded for by the cell genome. Intrinsic interference is defined as a viral genome-induced cellular state of resistance to challenge by high multiplicities of NDV, coexistent with a state of susceptibility to a broad spectrum of other viruses, similarly tested at high multiplicities. The capacity to induce intrinsic interference was demonstrated with rubella virus, Sindbis virus (arbovirus, group A), West Nile virus (arbovirus, group B), poliovirus (MEF, type 2), the lactic dehydrogenase virus (Riley's agent), and an unidentified nonhemadsorbing, noncytopathic adventitious virus. A state of intrinsic interference was also observed in the V5 line of mouse cells carrying a murine leukemia virus, probably resulting from some heretofore unsuspected contaminating virus. The molecular basis for intrinsic interference is not known, but it appears to involve a step in the NDV growth cycle beyond that of viral attachment, entry, and eclipse.
Programmable current source dedicated to implantable microstimulators (2002)

In this paper, a survey of programmable current-source architectures based on miniaturized digital-to-analog converters (DAC) is elaborated to propose a new design dedicated to a visual microstimulator. The needed current-source constitutes the electronic interface to tissues. A few samples of this current-source will be integrated in an implantable device which is powered and controlled using an electromagnetic coupling technique. The main objective is to select a design that meets as close as possible criteria related to the implant such as reliability, flexibility, energy efficiency and integration area. Consequently, an adequate current source is proposed which is a 5-bit thermometer-code-based DAC architecture. The resulting circuit is simulated using a 0.35 /spl mu/m CMOS technology from PMC-Sierra available through the Canadian Microelectronics Corporation (CMC).
Recent Advances in Chemical Approaches to the Study of Biological Systems (2001)

A number of novel chemical methods for studying biological systems have recently been developed that provide a means of addressing biological questions not easily studied with other techniques. In this review, examples that highlight the development and use of such chemical approaches are discussed. Specifically, strategies for modulating protein activity or protein-protein interactions using small molecules are presented. In addition, methods for generating and utilizing novel biomolecules (proteins, oligonucleotides, oligosaccharides, and second messengers) are examined.
Hydrazines: new charge-transfer physical quenchers of singlet oxygen (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrazines: new charge-transfer physical quenchers of singlet oxygenEdward L. Clennan, L. J. Noe, E. Szneler, and T. WenCite this: J. Am. Chem. Soc. 1990, 112, 13, 5080–5085Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://pubs.acs.org/doi/10.1021/ja00169a013https://doi.org/10.1021/ja00169a013research-articleACS PublicationsRequest reuse permissionsArticle Views382Altmetric-Citations52LEARN 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-Alertsclose Get e-Alerts
2‐Arylamino‐thiophen‐3‐carbonsäurederivate (1984)

2‐Arylamino‐thiophene‐3‐carboxylic Acid Derivatives The title compounds 3 are synthesized by reaction of 2‐amino‐thiophene‐3‐carboxylic acid derivatives 1 with anilines. The nucleophilic 5‐position in 3 allowed the synthesis of 5‐aryliden‐Δ 3 ‐thiolen‐2‐one‐imines 5 , 6 and the oxidative coupling to yield the azo compound 7 . 1‐Aryl‐thieno‐[2,3‐d]pyrimid‐4‐ones 9 , the thieno[2,3‐b]chinolin‐4‐one 10 and the 4‐chloro thieno[2,3‐b]chinolines 10 , 11 can be obtained from 3 .
The microbiology of deep-sea hydrothermal vents (1995)

Geologic Setting and Chemistry of Deep-Sea Hydrothermal Vents, W.E. Seyfried, Jr. and M.J. Mottl Ecology of Free-Living, Hydrothermal Vent Microbial Communities, D.M. Karl Chemoautotrophic and Methanotrophic Endosymbiotic Bacteria at Deep-Sea Vents and Seeps, D.C. Nelson and C.R. Fisher Growth at High Temperatures: Isolation and Taxonomy, Physiology, and Ecology, J.A. Baross and J.W. Deming Microbe-Metal Interactions and Mineral Deposition at Hydrothermal Vents, S.K. Juniper and B.M. Tebo Microbes in Deep-Sea Hydrothermal Plumes, C.D. Winn, J.P. Cowen, and D.M. Karl Stable Isotopes: Clues to Biological Cycling of Elements at Hydrothermal Vents, M.C. Kennicutt II and R.A. Burke, Jr.
Rendering antialiased shadows with depth maps (1987)

We present a solution to the aliasing problem for shadow algorithms that use depth maps. The solution is based on a new filtering technique called percentage closer filtering. In addition to antialiasing, the improved algorithm provides soft shadow boundaries that resemble penumbrae. We describe the new algorithm in detail, demonstrate the effects of its parameters, and analyze its performance.
Using graph theory to analyze biological networks (2011)

Understanding complex systems often requires a bottom-up analysis towards a systems biology approach. The need to investigate a system, not only as individual components but as a whole, emerges. This can be done by examining the elementary constituents individually and then how these are connected. The myriad components of a system and their interactions are best characterized as networks and they are mainly represented as graphs where thousands of nodes are connected with thousands of vertices. In this article we demonstrate approaches, models and methods from the graph theory universe and we discuss ways in which they can be used to reveal hidden properties and features of a network. This network profiling combined with knowledge extraction will help us to better understand the biological significance of the system.
Polyamines and colon cancer (2001)

Colorectal cancer is a major health problem in the western world and is associated with significant morbidity and mortality. Diet makes a significant contribution to the disease, with high fat, low fibre diets correlating positively with a high incidence of colorectal cancer. Intracellular polyamine concentrations and ornithine decarboxylase activity are both increased in colorectal cancer tissue and in premalignant polyps. Measurement of the polyamine content of serum and urine of individuals has been proposed as a diagnostic marker of malignancy but a number of false positives make this idea untenable. There may, however, still be a role for the measurement of urinary polyamine content as a means of monitoring the efficacy of therapy. Inhibition of polyamine metabolism by polyamine analogues or by non-steroidal anti-inflammatory drugs may be useful in the chemotherapy and/or chemoprevention of colorectal cancer. Preliminary results suggest that a low polyamine diet might be helpful as part of a health care plan for cancer patients.
Pituitary Hollow Fiber Units in vivo and in vitro (1981)

A new technique is described for the study of mammalian pituitary cells in vivo and in vitro. The method involves encapsulation of freshly trypsinized rat, sheep or human pituitary cells in XM-50 Amicon hollow fibers followed by their intracranial implantation into hypophysectomized rats. These pituitary fiber units promoted recipient growth for 3 weeks before weight gains plateaued. Body composition analyses showed that significant quantities of protein, fat and ash accounted for the weight gain. Morphological study of the capsule contents 7-39 days postimplantation revealed the presence of intact somatotrophs and corticotrophs. The hollow fibers may provide an immunologically privileged site by virtue of the fact that the 50,000 dalton pores making up the lumen surface permit pituitary hormones to diffuse from the capsule, but theoretically do not permit immunoglobulin molecules to penetrate the capsule. Growth of hypox rats receiving capsules containing allogeneic rat pituitary cells, sheep cells or pieces of human postmortem pituitary support this concept. Furthermore, rats implanted with human PRL adenoma cells had detectable quantities of circulating hPRL 100 days postimplantation. It is suggested that the pituitary hollow fiber units function when they come in contact with a ventricular surface of a hypox animal. With these units, it will be possible to study function of the same group of pituitary cells in vitro and in vivo.
Control of σ factor activity during Bacillus subtilis sporulation (1999)

When starved, Bacillus subtilis undergoes asymmetric division to produce two cell types with different fates. The larger mother cell engulfs the smaller forespore, then nurtures it and, eventually, lyses to release a dormant, environmentally resistant spore. Driving these changes is a programme of transcriptional gene regulation. At the heart of the programme are sigma factors, which become active at different times, some only in one cell type or the other, and each directing RNA polymerase to transcribe a different set of genes. The activity of each sigma factor in the cascade is carefully regulated by multiple mechanisms. In some cases, novel proteins control both sigma factor activity and morphogenesis, co-ordinating the programme of gene expression with morphological change. These bifunctional proteins, as well as other proteins involved in sigma factor activation, and even precursors of sigma factors themselves, are targeted to critical locations, allowing the mother cell and forespore to communicate with each other and to co-ordinate their programmes of gene expression. This signalling can result in proteolytic sigma factor activation. Other mechanisms, such as an anti-sigma factor and, perhaps, proteolytic degradation, prevent sigma factors from becoming active in the wrong cell type. Accessory transcription factors modulate RNA polymerase activity at specific promoters. Negative feedback loops limit sigma factor production and facilitate the transition from one sigma factor to the next. Together, the mechanisms controlling sigma factor activity ensure that genes are expressed at the proper time and level in each cell type.
Human erythrocyte glucose transporter: normal asymmetric orientation and function in liposomes. (1986)

The transport function and orientation of the reconstituted human erythrocyte glucose transporter was studied with liposomes made with bovine brain lipid or Escherichia coli lipid. Reconstitution was achieved by a simple octyl glucoside dilution method. The reconstituted transporters with either lipid showed identical counterflow transport activity, the same response to various inhibitors, and characteristic cytochalasin B (CB) labeling. Functional location and purification of the glucose transporter was performed by using gel-permeation high-performance liquid chromatography with octyl glucoside-containing buffer. The reconstituted transport activity was associated only with band 4.5 protein (preactin) and not with band 3 protein. Both CB binding and transport function of the reconstituted transporters were resistant to trypsin but susceptible to chymotrypsin digestion. However, both trypsin and chymotrypsin treatment of unsealed ghosts completely eliminated the CB labeling and transport function of the glucose transporter. In our reconstitution system the glucose transporters maintained a normal asymmetrical (right-side-out) orientation and good transport function. A specific monoclonal antibody against the glucose transporter inhibited CB labeling of the transporters on unsealed ghosts. This was not found with the reconstituted system; however, after freeze-thawing there was a significant inhibition of CB binding by the antibody. These findings suggest that the CB-binding site of the reconstituted transporter is on the inner side of the proteoliposomes.
Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. (2002)

Adenovirus-mediated suicide gene therapy may hold promise in the treatment of human cancer. We have developed a novel approach that utilizes a lytic, replication-competent adenovirus (Ad5-CD/TKrep) to deliver a cytosine deaminase/herpes simplex virus-1 thymidine kinase fusion gene to tumors. The cytosine deaminase and herpes simplex virus-1 thymidine kinase suicide genes render malignant cells sensitive to specific pharmacological agents and, importantly, sensitize them to radiation. The Phase I study described here represents the first gene therapy trial in which a replication-competent virus was used to deliver a therapeutic gene to humans. The indication is local recurrence of prostate cancer after definitive radiation therapy. An escalating dose (10(10), 10(11), and 10(12) viral particles) of the Ad5-CD/TKrep virus was injected intraprostatically under transrectal ultrasound guidance into 16 patients in four cohorts. Two days later, patients were given 5-fluorocytosine and ganciclovir prodrug therapy for 1 (cohorts 1-3) or 2 (cohort 4) weeks. There were no dose-limiting toxicities, and the maximum tolerated dose of the Ad5-CD/TKrep vector was not defined. Ninety-four percent of the adverse events observed were mild or moderate (grade 1/2) in nature. Seven of 16 (44%) patients demonstrated a >or=25% decrease in serum prostate-specific antigen, and 3 of 16 (19%) patients demonstrated a >or=50% decrease in serum prostate-specific antigen. Transgene expression and tumor destruction at the injection site were confirmed by sextant needle biopsy of the prostate at 2 weeks. Two patients were negative for adenocarcinoma at 1 year follow-up. Although Ad5-CD/TKrep viral DNA could be detected in blood as far out as day 76, no infectious adenovirus was detected in patient serum or urine. Together, the results demonstrate that intraprostatic administration of the replication-competent Ad5-CD/TKrep virus followed by 2 weeks of 5-fluorocytosine and ganciclovir prodrug therapy can be safely applied to humans and is showing signs of biological activity.
Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung (1998)

Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF-1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of <1 min. These findings demonstrate that HIF-1 expression is tightly coupled to O2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.
An object-oriented data model for Intelligent Network services (2002)

A critical issue in achieving flexibility and extendibility in telecommunications networks, where the network data bases are increasingly involved in call processing, is the data model, and the application interface to network services data. The data model should provide application independent data structures and interfaces. The paper presents an object database model of Intelligent Network (IN) services that describes the data as objects and includes dynamicity (operations are associated to objects) and deals with distinctions between persistent and non persistent data. The structure is oriented to Service Independent Building Blocks (SIBs) that are abstract representations of network capabilities existing in an IN. Objects of similar structure and behaviour are grouped together in classes. Classes are organized in a class hierarchy. A service is invoked and activated by request for method (operation) execution connected to the object representing the service.
Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence (2006)

Recent studies have shown that fine structural modifications of Mycobacterium tuberculosis cell envelope lipids mediate host cell immune activation during infection. One such alteration in lipid structure is cis-cyclopropane modification of the mycolic acids on trehalose dimycolate (TDM) mediated by proximal cyclopropane synthase of alpha mycolates (pcaA), a proinflammatory lipid modification during early infection. Here we examine the pathogenetic role and immunomodulatory function of mycolic acid cyclopropane stereochemistry by characterizing an M. tuberculosis cyclopropane-mycolic acid synthase 2 (cmaA2) null mutant (Delta cmaA2) that lacks trans-cyclopropanation of mycolic acids. Although titers of WT and Delta cmaA2 organisms were identical during mouse infection, Delta cmaA2 bacteria were hypervirulent while inducing larger granulomas than WT M. tuberculosis. The hypervirulence of the Delta cmaA2 strain depended on host TNF-alpha and IFN-gamma. Loss of trans-cyclopropanation enhanced M. tuberculosis-induced macrophage inflammatory responses, a phenotype that was transferable with petroleum ether extractable lipids. Finally, purified TDM lacking trans-cyclopropane rings was 5-fold more potent in stimulating macrophages. These results establish cmaA2-dependent trans-cyclopropanation of TDM as a suppressor of M. tuberculosis-induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation.
Constitutively Active TRPC Channels of Adipocytes Confer a Mechanism for Sensing Dietary Fatty Acids and Regulating Adiponectin (2012)

The data suggest that TRPC1 and TRPC5 contribute a constitutively active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which ω-3 fatty acids enhance the anti-inflammatory adipokine, adiponectin.