gebhart/patrepeval huggingface dataset:
A development that may evolve into a revolution in medicine: mRNA as the basis for novel, nucleotide-based vaccines and drugs (2013)

Recent advances strongly suggest that mRNA rather than DNA will be the nucleotide basis for a new class of vaccines and drugs. Therapeutic cancer vaccines against a variety of targets have been developed on this basis and initial clinical experience suggests that preclinical activity can be successfully translated to human application. Likewise, prophylactic vaccines against viral pathogens and allergens have demonstrated their activity in animal models. These successes could be extended preclinically to mRNA protein and gene replacement therapy as well as the induction of pluripotent stem cells by mRNA encoded transcription factors. The production of mRNA-based vaccines and drugs is highly flexible, scalable and cost competitive, and eliminates the requirement of a cold chain. mRNA-based drugs and vaccines offer all the advantages of a nucleotide-based approach at reduced costs and represent a truly disruptive technology that may start a revolution in medicine.
Nedd2 Is Required for Apoptosis after Trophic Factor Withdrawal, But Not Superoxide Dismutase (SOD1) Downregulation, in Sympathetic Neurons and PC12 Cells (1997)

Activation of cysteine aspartases (caspases) seems to be a required element of apoptotic death in many paradigms. We have shown previously that general inhibitors of cysteine aspartases block apoptosis of PC12 cells and sympathetic neurons evoked by either trophic factor (nerve growth factor and/or serum) deprivation or superoxide dismutase (SOD1) downregulation. Moreover, activation of a caspase family member similar or equivalent to the interleukin-1beta-converting enzyme (ICE) was implicated for death caused by SOD1 downregulation, but not withdrawal of trophic support. The experiments presented here demonstrate that diminished expression of the cysteine aspartase Nedd2 in PC12 cells and sympathetic neurons induced by an appropriate vector peptide-linked antisense oligonucleotide rescues them from death caused by trophic factor deprivation without inhibiting apoptosis in the same cell types evoked by SOD1 downregulation. Neither the level (as revealed by Western immunoblotting) nor the cellular distribution (as revealed immunohistochemically) of Nedd2 was altered demonstrably by trophic factor deprivation. However, evidence for proteolytic processing of Nedd2 (consistent with commencement of activation) was observed in PC12 cells after withdrawal of trophic support. These findings indicate that neuronal death triggered by different initial causes may be mediated by distinct members of the cysteine aspartase family.
Smart sensing technology: opportunities and challenges (2004)

‘Smart’ sensors with embedded microprocessors and wireless communication links have the potential to change fundamentally the way civil infrastructure systems are monitored, controlled, and maintained. Indeed, a 2002 National Research Council report noted that the use of networked systems of embedded computers and sensors throughout society could well dwarf all previous milestones in the information revolution. However, a framework does not yet exist that can allow the distributed computing paradigm offered by smart sensors to be employed for structural health monitoring and control systems; current algorithms assume that all data is centrally collected and processed. Such an approach does not scale to systems with densely instrumented arrays of sensors that will be required for the next generation of structural health monitoring and control systems. This paper provides a brief introduction to smart sensing technology and identifies some of the opportunities and associated challenges. Copyright © 2004 John Wiley & Sons, Ltd.
Inhibition of Caspases Increases the Sensitivity of L929 Cells to Necrosis Mediated by Tumor Necrosis Factor (1998)

Murine L929 fibrosarcoma cells treated with tumor necrosis factor (TNF) rapidly die in a necrotic way, due to excessive formation of reactive oxygen intermediates. We investigated the role of caspases in the necrotic cell death pathway. When the cytokine response modifier A (CrmA), a serpin-like caspase inhibitor of viral origin, was stably overexpressed in L929 cells, the latter became 1,000-fold more sensitive to TNF-mediated cell death. In addition, TNF sensitization was also observed when the cells were pretreated with Ac-YVAD-cmk or zDEVD-fmk, which inhibits caspase-1- and caspase-3-like proteases, respectively. zVAD-fmk and zD-fmk, two broad-spectrum inhibitors of caspases, also rendered the cells more sensitive, since the half-maximal dose for TNF-mediated necrosis decreased by a factor of 1,000. The presence of zVAD-fmk also resulted in a more rapid increase of TNF-mediated production of oxygen radicals. zVAD-fmk-dependent sensitization of TNF cytotoxicity could be completely inhibited by the oxygen radical scavenger butylated hydroxyanisole. These results indicate an involvement of caspases in protection against TNF-induced formation of oxygen radicals and necrosis.
Mars Reconnaissance Orbiter's High Resolution Imaging Science Experiment (HiRISE) (2007)

The HiRISE camera features a 0.5 m diameter primary mirror, 12 m effective focal length, and a focal plane system that can acquire images containing up to 28 Gb (gigabits) of data in as little as 6 seconds. HiRISE will provide detailed images (0.25 to 1.3 m/pixel) covering ∼1% of the Martian surface during the 2‐year Primary Science Phase (PSP) beginning November 2006. Most images will include color data covering 20% of the potential field of view. A top priority is to acquire ∼1000 stereo pairs and apply precision geometric corrections to enable topographic measurements to better than 25 cm vertical precision. We expect to return more than 12 Tb of HiRISE data during the 2‐year PSP, and use pixel binning, conversion from 14 to 8 bit values, and a lossless compression system to increase coverage. HiRISE images are acquired via 14 CCD detectors, each with 2 output channels, and with multiple choices for pixel binning and number of Time Delay and Integration lines. HiRISE will support Mars exploration by locating and characterizing past, present, and future landing sites, unsuccessful landing sites, and past and potentially future rover traverses. We will investigate cratering, volcanism, tectonism, hydrology, sedimentary processes, stratigraphy, aeolian processes, mass wasting, landscape evolution, seasonal processes, climate change, spectrophotometry, glacial and periglacial processes, polar geology, and regolith properties. An Internet Web site (HiWeb) will enable anyone in the world to suggest HiRISE targets on Mars and to easily locate, view, and download HiRISE data products.
Involvement of Heparanase in Early Pregnancy Losses (2008)

Abstract Heparanase activity is implicated in cell invasion, tumor metastasis and angiogenesis. Recently, we have reported that heparanase stimulates tissue factor (TF) expression in endothelial and cancer cells, resulting in elevation of coagulation activity (Nadir et al. JTH, 2006). We also found that heparanase releases tissue factor pathway inhibitor (TFPI) from endothelial and tumor cells, contributing to the local procoagulant balance (Nadir et al. TH, 2008). Heparanase was cloned from and is abundant in the placenta. We investigated the role of heparanase in the placenta, focusing on its effect on TF, TFPI, TFPI-2, and vascular endothelial growth factor-A (VEGF-A). Twenty formalin embedded samples of early pregnancy losses (weeks 5–10) were studied. Ten cases were miscarriages of women with thrombophilia and recurrent fetal losses, and ten control cases were pregnancy terminations. Applying real time RT-PCR and immunostaining for heparanase, TF, TFPI, TFPI-2, and VEGF-A it was found that in fetal losses related to thrombophilia the levels of heparanase, VEGF-A and TFPI-2 were significantly increased (2–3 fold) compared to placentas from controls. Next, JAR (human choriocarcinoma throphoblast) cells were transfected to overexpress the full length (65 kDa) heparanase or incubated with active (50+8 kDa) recombinant heparanase. Immunoblotting and real time RT-PCR showed that throphoblasts overexpressing or incubated with exogenous heparanase exhibited a 2–3 fold increase in TFPI and TFPI-2 in cell lysates both at the protein and mRNA levels, with no detectable effect on VEGF-A and TF. Accumulation of TFPI and TFPI-2 in the cell culture medium was increased 5–6 fold, exceeding the observed induction of TFPI and TFPI-2 gene transcription. Extracellular accumulation of TFPI and TFPI-2 was already evident 60 min following heparanase addition, prior to protein induction, indicating an active release of preformed proteins. These results indicate a regulatory effect of heparanase on TFPI and TFPI-2 in throphoblasts, suggesting a potential involvement in early miscarriages.
Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex (2004)

The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for the cellular response to DNA double-strand breaks, integrating DNA repair with the activation of checkpoint signaling through the protein kinase ATM (ataxia telangiectasia mutated). We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX. MRN makes multiple contacts with ATM and appears to stimulate ATM activity by facilitating the stable binding of substrates. Phosphorylation of Nbs1 is critical for MRN stimulation of ATM activity toward Chk2, but not p53. Kinase-deficient ATM inhibits wild-type ATM phosphorylation of Chk2, consistent with the dominant-negative effect of kinase-deficient ATM in vivo.
Pancreatic stem cells: building blocks for a better surrogate islet to treat type 1 diabetes (2001)

Type 1, insulin-dependent, diabetes is one of the more costly chronic diseases of children, adolescents and adults in Europe and North America. While routine insulin injections currently provide diabetic patients with their daily insulin requirements, blood glucose excursions are common, leading eventually to microvascular and macrovascular complications and early death. A 'cure' for Type 1 diabetes relies on replacement of the beta-cell mass which, today, is accomplished by pancreas transplants or islets of Langerhans implants. Recent advances in the isolation of stem cells that possess the capacity to differentiate to functional endocrine pancreas provide new opportunities to produce large numbers of islets, even autologous islets, that can be used as implants. We discuss briefly this new technology and its meaning for diabetes.
Insulin demand regulates β cell number via the unfolded protein response (2015)

Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown. Here, we identified the β cell unfolded protein response (UPR), which senses insulin production, as a regulator of β cell proliferation. Using genetic and physiologic models, we determined that among the population of β cells, those with an active UPR are more likely to proliferate. Moreover, subthreshold endoplasmic reticulum stress (ER stress) drove insulin demand-induced β cell proliferation, through activation of ATF6. We also confirmed that the UPR regulates proliferation of human β cells, suggesting that therapeutic UPR modulation has potential to expand β cell mass in people at risk for diabetes. Together, this work defines a stem cell-independent model of tissue homeostasis, in which differentiated secretory cells use the UPR sensor to adapt organ size to meet demand.
Sulfated Galactocerebrosides as Potential Antiinflammatory Agents (1997)

Native sulfatides, as well as many sulfated glycolipids, have been shown to avidly bind to the selectin receptors. In vivo, native sulfatides significantly block activity in selectin-dependent inflammatory responses. The fact that nonsulfated galactocerebrosides did not inhibit selectin-mediated adhesion identified a critical role for the anionic sulfate residue. We therefore initiated a program to evaluate the activity of position isomers. This study showed a binding selectivity for the positions 2 and 3 of the sulfate group on the carbohydrate ring as well as enhanced activity for the disulfated analogs. Furthermore, it was discovered that the attachment of lipophilic substituents on the carbohydrate ring was tolerated, consistent with the presence of a lipophilic pocket in the binding activity. This resulted in compounds with a 6-fold increased potency.
Increased efficiency in selective elimination of leukemia cells by a combination of a stable derivative of cyclophosphamide and a human B-cell-specific immunotoxin containing pokeweed antiviral protein. (1985)

Leukemia cells were mixed with normal human bone marrow cells to simulate bone marrow from leukemia patients; the mixture was then treated with a combination of stabilized derivative of cyclophosphamide [Mafosfamide (ASTA Z 7557)] and pokeweed antiviral protein-containing immunotoxin. The ability of this protocol for selective elimination of B-ALL cells was evaluated by clonogenic assay. The monoclonal antibody (B43) portion of the immunotoxin was directed against human B-cells and was linked to pokeweed antiviral protein by a disulfide bond. The combination of ASTA Z 7557 and immunotoxin was superior to either ASTA Z 7557 or the immunotoxin alone and produced nearly 7 logs of elimination of leukemia cells from the cell mixtures. About 5 logs of contaminating tumor cells were eliminated from a 200-fold excess of normal marrow under conditions where fewer than 50% of pluripotent stem cells were lost. Moreover, this manipulation did not inhibit subsequent production of pluripotent stem cells in long-term bone marrow cultures, indicating that the more primitive progenitors were not harmed.
Four functionally distinct C-type natriuretic peptides found in fish reveal evolutionary history of the natriuretic peptide system (2003)

Natriuretic peptides (NPs) are major cardiovascular and osmoregulatory hormones in vertebrates. Although tetrapods generally have three subtypes, atrial NP (ANP), B-type NP (BNP), and C-type NP (CNP), some teleosts lack BNP, and sharks and hagfish have only one NP. Thus, NPs have diverged during fish evolution, possibly reflecting changes in osmoregulatory systems. In this study, we found, by cDNA cloning, four distinct CNPs (1 through 4) in the medaka (Oryzias latipes) and puffer fish (Takifugu rubripes), although to our knowledge no more than two CNPs have been isolated from a vertebrate species. Predicted mature CNP-1 was most similar, and CNP-4 was most dissimilar, to mammalian CNPs. However, synthetic CNP-4 most potently activated OlGC1, a medaka CNP-specific receptor (NPR-B) expressed in cultured cells, whereas CNP-1 and CNP-3 most activated OlGC7 and OlGC2, two medaka homologues of the ANP/BNP receptor (NPR-A), respectively. Linkage mapping in medaka followed by comparative genomic analyses among fishes and humans located four CNP genes in separate medaka chromosomes corresponding to human chromosomes 1, 2, 12, and 17. From conserved synteny, the following evolutionary history of NPs was evoked: (i) four CNP genes were generated by chromosomal duplications before the divergence of elasmobranchs; (ii) the CNP-3 gene generated ANP and BNP genes through tandem duplication before the divergence of tetrapods and teleosts; (iii) CNP-1 and -2 genes were retained in the teleost lineage but not in the tetrapod lineage; (iv) the CNP-3 gene disappeared from the tetrapod lineage after divergence of amphibians; and (v) the CNP-4 gene is retained in humans as CNP.
Induction of cytochrome P-450 by glucocorticoids in rat liver. II. Evidence that glucocorticoids regulate induction of cytochrome P-450 by a nonclassical receptor mechanism. (1984)

In the companion report we used primary cultures of adult rat hepatocytes to demonstrate that glucocorticoids comprise a "class" of compounds that stimulate de novo synthesis of a form of cytochrome P-450 (P450PCN) indistinguishable from that induced by the nonhormonal steroid pregnenolone 16 alpha-carbonitrile (PCN). Because induction of P450PCN is stereospecific for glucocorticoids and is dependent on the concentration of and the length of exposure to steroids it seemed possible that P450PCN represented another of the many genes whose expression is coordinately regulated by glucocorticoids bound to their specific cytoplasmic receptor and translocated into the nucleus. However, in cultured hepatocytes treated with glucocorticoids, synthesis of P450PCN failed to parallel synthesis of a typical glucocorticoid-responsive liver function, tyrosine aminotransferase, in the time course of induction, in the concentrations of glucocorticoids required for half-maximal induction, and in the order of effective steroids ranked by potency. Indeed, two moderately potent inducers of P450PCN either failed to induce tyrosine aminotransferase (spironolactone) or actually antagonized induction of tyrosine aminotransferase synthesis by glucocorticoids (PCN). Moreover, in the same cultures in which glucocorticoid induction of tyrosine aminotransferase was blocked by the presence of PCN or other previously identified antiglucocorticoids, synthesis of P450PCN was actually enhanced. We conclude that synthesis of P450PCN is a specific glucocorticoid-responsive liver function evoked by a novel mechanism readily distinguishable from the classic glucocorticoid receptor pathway.
Activation of the Radiosensitive EGR-1 Promoter Induces Expression of the Herpes Simplex Virus Thymidine Kinase Gene and Sensitivity of Human Glioma Cells to Ganciclovir (1995)

Herein we describe experiments showing that the early growth response gene 1 (EGR-1) promoter is sufficient to confer selective expression of the luciferase gene (Luc) in glioma cell lines exposed to ionizing radiation. Activity of the EGR-1 promoter was investigated in human glioblastoma cells using the plasmid vector, pEGR-Luc. The EGR-1 promoter gene directed radiosensitive expression of luciferase. This promoter showed high levels of activity (10-fold) in irradiated glioma cell lines as compared to basal levels of activity in nonirradiated cell lines. Maximum activation was detectable at 1-3 hr after stimulation with 20 Gy. The results also demonstrate that cells modified to contain the herpes simplex virus-thymidine kinase (HSV-tk) gene under control of the EGR-1 promoter become sensitive to treatment with the antiviral agent ganciclovir (GCV), whereas nonirradiated cells and nontransfected cells were unaffected by this agent. This results suggest that therapeutic genes can be expressed selectively in irradiated glioma cells. The results also indicate that the EGR-1 promoter can be used to induce exogenous genes selectively in radiation fields used for the treatment of malignant brain tumors.
Identification of a novel growth factor with transforming activity secreted by individual chick embryos (1990)

Previously we have developed a microassay for anchorage independent growth (AIG) of fibroblasts in soft agar, which can detect very small quantities of transforming growth factors (TGFs). Using this assay, we have shown that small pieces of dissected chick embryo tissue will stimulate AIG of both NR6 and NRK 49f cells, and that this property can be used to map production of growth factors with transforming activity in individual early embryos. We now show that this activity can be transferred to conditioned medium (CM) prepared using chick embryo tissue. Using two cell lines with differential responsiveness to TGFs, and by coincubating normal and heat-treated CM with trypsin, Con-A and neutralising antibodies, we show that CM contains at least two different growth factors with transforming activity. One of these is heat-stable, and stimulates colony formation in NRK 49f cells in the presence of EGF, but not in its absence. This activity corresponds to a TGF beta-like molecule. The other component is a heat-labile glycoprotein, which has TGF alpha-like properties, but does not appear to behave like known TGFs with these properties. It therefore appears to be a novel growth factor. Both activities are present from the intermediate primitive streak stage of development.
Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas (2014)

We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified.
582: P-AKT Pathway Activation and Inhibition Depends on N-Cadherin or P-EGFR Expression in Invasive Human Bladder Cancer Cell Lines (2005)

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00 am - 12:00 pm1 Apr 2005582: P-AKT Pathway Activation and Inhibition Depends on N-Cadherin or P-EGFR Expression in Invasive Human Bladder Cancer Cell Lines Hervé Wallerand, Ying Cai, Gaëlle Nicole, Dominique K. Chopin, and Robert E. Reiter Hervé WallerandHervé Wallerand More articles by this author , Ying CaiYing Cai More articles by this author , Gaëlle NicoleGaëlle Nicole More articles by this author , Dominique K. ChopinDominique K. Chopin More articles by this author , and Robert E. ReiterRobert E. Reiter More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34822-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "582: P-AKT Pathway Activation and Inhibition Depends on N-Cadherin or P-EGFR Expression in Invasive Human Bladder Cancer Cell Lines." The Journal of Urology, 173(4S), p. 159 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 159 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Hervé Wallerand More articles by this author Ying Cai More articles by this author Gaëlle Nicole More articles by this author Dominique K. Chopin More articles by this author Robert E. Reiter More articles by this author Expand All Advertisement PDF downloadLoading ...
DNA sequence, structure and gene expression of mycobacteriophage L5: a phage system for mycobacterial genetics (1993)

Genetic studies of Mycobacterium tuberculosis and other mycobacterial pathogens have suffered from the lack of a sophisticated genetic system. To address this issue we have developed a viral system through a detailed characterization of mycobacteriophage L5, a temperate phage that infects both fast- and slow-growing mycobacteria. We describe here the complete DNA sequence of the L5 genome and initial characterization of L5 virion structure and gene expression. In addition to providing a genetic 'tool-box' for the mycobacteria we find that L5 offers a new paradigm for dsDNA phages, being phenotypically temperate but employing genetic strategies for phage growth usually associated with lytic bacteriophages.
Interventional radiology of trauma. (1992)

Percutaneous transcatheter embolization has become an integral part of the trauma team's armamentarium. Still, it is probably underused in many centers because of lack of familiarity on the part of both the trauma team and the radiologists. Recognition of the role of interventional radiology in vascular trauma can have a significant impact in decreasing the morbidity and mortality associated with this ever-growing problem in our society.