gebhart/patrepeval huggingface dataset:
Ouabain induces cell proliferation through calcium-dependent phosphorylation of Akt (protein kinase B) in opossum kidney proximal tubule cells (2006)

Cardiotonic glycosides, like ouabain, inhibit Na(+)-K(+)-ATPase. Recent evidence suggests that low molar concentrations of ouabain alter cell growth. Studies were conducted to examine the effect of ouabain on Akt phosphorylation and rate of cell proliferation in opossum kidney (OK) proximal tubule cells. Cells exposed to 10 nM ouabain displayed increased Akt Ser(473) phosphorylation, as evidenced by an increase in phospho-Akt Ser(473) band density. Ouabain-stimulated Akt Ser(473) phosphorylation was inhibited by pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 and wortmannin), a PLC inhibitor (edelfosine), and an Akt inhibitor. Moreover, ouabain-mediated Akt Ser(473) phosphorylation was suppressed by reduction of extracellular calcium (EGTA) or when intracellular calcium was buffered by BAPTA-AM. An inhibitor of calcium store release (TMB-8) and an inhibitor of calcium entry via store-operated calcium channels (SKF96365) also suppressed ouabain-mediated Akt Ser(473) phosphorylation. In fura-2 AM-loaded cells, 10 nM ouabain increased capacitative calcium entry (CCE). Ouabain at 10 nM did not significantly alter baseline cytoplasmic calcium concentration in control cells. However, treatment with 10 nM ouabain caused a significantly higher ATP-mediated calcium store release. After 24 h, 10 nM ouabain increased the rate of cell proliferation. The Akt inhibitor, BAPTA-AM, SKF96365, and cyclopiazonic acid suppressed the increase in the rate of cell proliferation caused by 10 nM ouabain. Ouabain at 10 nM caused a detectable increase in (86)Rb uptake but did not significantly alter Na(+)-K(+)-ATPase (ouabain-sensitive pNPPase) activity in crude membranes or cell sodium content. Taken together, the results point to a role for CCE and Akt phosphorylation, in response to low concentrations of ouabain, that increase the rate of cell proliferation without inhibiting Na(+)-K(+)-ATPase-mediated ion transport.
Competing Fracture in Kinetically Controlled Transfer Printing (2007)

Transfer printing by kinetically switchable adhesion to an elastomeric stamp shows promise as a powerful micromanufacturing method to pickup microstructures and microdevices from the donor substrate and to print them to the receiving substrate. This can be viewed as the competing fracture of two interfaces. This paper examines the mechanics of competing fracture in a model transfer printing system composed of three laminates: an elastic substrate, an elastic thin film, and a viscoelastic member (stamp). As the system is peeled apart, either the interface between the substrate and thin film fails or the interface between the thin film and the stamp fails. The speed-dependent nature of the film/stamp interface leads to the prediction of a critical separation velocity above which separation occurs between the film and the substrate (i.e., pickup) and below which separation occurs between the film and the stamp (i.e., printing). Experiments verify this prediction using films of gold adhered to glass, and the theoretical treatment extends to consider the competing fracture as it applies to discrete micro-objects. Temperature plays an important role in kinetically controlled transfer printing with its influences, making it advantageous to pickup printable objects at the reduced temperatures and to print them at the elevated ones.
A Wide-View Parallax-Free Eye-Mark Recorder with a Hyperboloidal Half-Silvered Mirror and Appearance-Based Gaze Estimation (2010)

In this paper, we propose a wide-view parallax-free eye-mark recorder with a hyperboloidal half-silvered mirror and a gaze estimation method suitable for the device. Our eye-mark recorder provides a wide field-of-view video recording of the user's exact view by positioning the focal point of the mirror at the user's viewpoint. The vertical angle of view of the prototype is 122 degree (elevation and depression angles are 38 and 84 degree, respectively) and its horizontal view angle is 116 degree (nasal and temporal view angles are 38 and 78 degree, respectively). We implemented and evaluated a gaze estimation method for our eye-mark recorder. We use an appearance-based approach for our eye-mark recorder to support a wide field-of-view. We apply principal component analysis (PCA) and multiple regression analysis (MRA) to determine the relationship between the captured images and their corresponding gaze points. Experimental results verify that our eye-mark recorder successfully captures a wide field-of-view of a user and estimates gaze direction with an angular accuracy of around 2 to 4 degree.
Separation and Characterization of Late Endosomal Membrane Domains (2002)

Very little is known about the biophysical properties and the lipid or protein composition of membrane domains presumably present in endocytic and biosynthetic organelles. Here we analyzed the membrane composition of late endosomes by suborganellar fractionation in the absence of detergent. We found that the internal membranes of this multivesicular organelle can be separated from the limiting membrane and that each membrane population exhibited a defined composition. Our data also indicated that internal membranes may consist of at least two populations, containing primarily phosphatidylcholine or lysobisphosphatidic acid as major phospholipid, arguing for the existence of significant microheterogeneity within late endosomal membranes. We also found that lysobisphosphatidic acid exhibited unique pH-dependent fusogenic properties, and we speculated that this lipid is an ideal candidate to regulate the dynamic properties of this internal membrane mosaic.
Expression of Transgenic APP mRNA Is the Key Determinant for Beta-Amyloid Deposition in PS2APP Transgenic Mice (2008)

Our results demonstrate that a 2-fold reduction in APP expression can result in a profound decrease in brain pathology.
Autotaxin and lysophospholipids in rheumatoid arthritis. (2010)

Autotaxin (ATX) is an autocrine motility-stimulating factor and an extracellular enzyme that catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA). Although ATX can also hydrolyze sphingosylphosphorylcholine (SPC) to sphingosine-1-phosphate (S1P), the major source of extracellular S1P originates from the intracellular phosphorylation of sphingosine by sphingosine kinases (SphKs). LPA and S1P are well-characterized bioactive lysophospholipid mediators, which have critical roles in multiple cellular processes through binding and activating GPCRs. These two lipids have been implicated in various physiological (eg, cell growth, differentiation, migration and survival) and pathological (eg, angiogenesis, metastasis and autoimmunity) processes. The roles of LPA and S1P in autoimmune diseases, including rheumatoid arthritis (RA), have recently emerged. This review discusses recent findings suggesting that the LPA- and S1P-induced cellular functions of synoviocytes from patients with RA may contribute to the pathophysiology of the disease by exacerbating the disease process. ATX and the lysophospholipid mediators are potential targets for the treatment of patients with RA.
A comparison of some properties of C=O and C=S bonds (2010)

The properties of compounds with carbonyl and thiocarbonyl groups have been examined theoretically, and the results have been compared with the available experimental data. The properties include the bond dissociation energies, the vibrational force constants, the n* transitions and the charge distributions. The origin of the differences in properties are discussed
Pharmacologic Rescue of Conformationally‐Defective Proteins: Implications for the Treatment of Human Disease (2004)

The process of quality control in the endoplasmic reticulum involves a variety of mechanisms which ensure that only correctly folded proteins enter the secretory pathway. Among these are conformation-screening mechanisms performed by molecular chaperones that assist in protein folding and prevent non-native (or misfolded) proteins from interacting with other misfolded proteins. Chaperones play a central role in the triage of newly formed proteins prior to their entry into the secretion, retention, and degradation pathways. Despite this stringent quality control mechanism, gain- or loss-of-function mutations that affect protein folding in the endoplasmic reticulum can manifest themselves as profound effects on the health of an organism. Understanding the molecular, cellular, and energetic mechanisms of protein routing could prevent or correct the structural abnormalities associated with disease-causing misfolded proteins. Rescue of misfolded, "trafficking-defective", but otherwise functional, proteins is achieved by a variety of physical, chemical, genetic, and pharmacological approaches. Pharmacologic chaperones (or "pharmacoperones") are template molecules that may potentially arrest or reverse diseases by inducing mutant proteins to adopt native-type-like conformations instead of improperly folded ones. Such restructuring leads to a normal pattern of cellular localization and function. This review focuses on protein misfolding and misrouting related to various disease states and describes promising approaches to overcoming such defects. Special attention is paid to the gonadotropin-releasing hormone receptor, since there is a great deal of information about this receptor, which has recently emerged as a particularly instructive model.
Novel prime-boost combinations of PSMA-based vaccines for prostate cancer (2005)

2572 Background and Methods The development of vaccination strategies targeted to tumor antigens holds great promise for cancer therapy. Prostate-specific membrane antigen (PSMA) is an attractive candidate self-antigen for vaccination based on its expression signature. PSMA is abundantly expressed on the surface of prostate cancer cells and on the neovasculature of a wide array of other tumors, but PSMA has limited expression in normal extraprostatic tissues. In prostate cancer, PSMA expression increases with disease progression, becoming highest in high-grade, metastatic, hormone-refractory disease. Our main goals are to overcome tolerance to PSMA by active immunization and to induce recognition and rejection of tumor cells expressing PSMA. We are investigating non-replicating vaccine replicon particles (VRP) based on the alphavirus, Venezuelan equine encephalitis virus. VRP have demonstrated potency in animal models, and infect cells in the lymph nodes where the replicon drives production of large quantities of the heterologous antigen. Robust immune responses can be further amplified by VRP-induced cell apoptosis leading to cross-priming. We are also evaluating a complementary purified protein vaccine based on a novel recombinant soluble PSMA (rsPMSA) immunogen both alone and with VRP in prime-boost regimens. Results When used as single immunogens, VRP encoding full-length human PSMA elicited vigorous, durable Th1-biased cellular and humoral responses in normal BALB/c mice, whereas rsPSMA vaccines induced high levels of Th2-biased antibodies. We have now extended this analysis to human HLA-A2 transgenic mice, a more pertinent model for quantification of human Class I-restricted cellular responses, and to prime-boost regimens. Mice were immunized with VRP alone or in combination with rsPSMA boosts. PSMA-specific immune responses were measured with a panel of cellular and humoral immunoassays, including ELISPOT and intracellular cytokine staining for IFN-γ and IL-4 in T cell subsets. Conclusions Based on these translational findings, the rsPSMA protein vaccine has been advanced into a dose-escalating Phase I clinical trial in advanced prostate cancer, while the VRP-PSMA vaccine is in late-stage preclinical testing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AlphaVax, PSMA Development Company, LLC
Pigs expressing the human inhibitory ligand PD‐L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties (2018)

These data indicate a low immunogenic, immune-protected status of cells from hPD-L1 transgenic pigs. The integration of the hPD-L1 concept into existing multi-transgenic pigs is promising to achieve long-term survival of porcine xenografts in non-human primate recipients.
Fourteenth Annual Pezcoller Symposium: the novel dichotomy of immune interactions with tumors. (2003)

The main focus of the Symposium was the fact that cell types of the innate and adaptive immune systems can have tumor-favoring as well as tumor antagonistic effects, both in a preventive and therapeutic mode. It was shown that macrophages (Mphi) and dendritic cells within a tumor exert tumor-favoring effects through the action of certain cytokines. Inflammatory reactions could favor the onset and growth of tumors. Dual immune functions were shown with CD4+ T cells and certain matrix metalloproteinase (MMP) activities favoring tumor progression and CD8+ T cells and certain heat shock proteins having antitumor action. Lack of antitumor action despite positive immune stimulation was also shown to depend on the existence of barriers to tumor infiltration by lymphocytes; remodeling of vasculature, e.g., by IFNgamma-induced cytokines like MIG and IPIO, reversed this type of impediment. Certain CXC cytokines increased tumor progression, whereas others, particularly those induced by IFNgamma, had the opposite effect; stromal-derived factor-1 and its receptor CXCR4 affected tumor propensity to metastasize in certain organs. Stromal-derived factor-1 induced MMP9, which in turn regulated the bioavailability of vascular endothelial growth factor and the cascade of its tumor-favoring effects, whereas granulocyte colony-stimulating factor decreased MMP9 and the consequences of its action. The effects of certain proinflammatory cytokines and vascular endothelial growth factor functions in angiogenesis and lymphoangiogenesis were also discussed. The favoring effects of fever-like thermal stress on the function of molecules instrumental in lymphoid cell adhesion to vessels and infiltration into sites of immune actions were described. The mechanisms involved in the development of immune memory and those conditioning Type I and CTL responses were also discussed. A number of presentations were concerned with laboratory studies aimed at developing clinical regimens with potential activity in the prevention or treatment of cancer. Prevention of Her2/neu breast cancer in transgenic mice was achieved by suitable regimens with IL12 combined with vaccines, including DNA-based vaccines administered in conjunction with electroporation. Vaccination with shared tumor antigen MUCI or cyclin B was discussed, and its clinical translation was described. The prevention of TRAMP prostate tumor in transgenic mice by anti-CTLA4 antibody plus vaccine was described, as was the translation of these regimens to the clinics. Clinical successes in melanoma patients using antimelanoma antigen antibodies in a therapeutic mode and precautions to be exerted in evaluating in vivo immune responses based on in vitro assays were emphasized. The symposium was concluded with an overall discussion focused on basic questions related to the capability of immunity to exert tumor-favoring or antitumor effects depending on conditions determined by both tumor and host functions.
Differentiation and Transdifferentiation of the Retinal Pigment Epithelium (1997)

The retinal pigment epithelium (RPE) lies between the retina and the choroid of the eye and plays a vital role in ocular metabolism. The RPE develops from the same sheet of neuroepithelium as the retina and the two derivatives become distinguished by different expression patterns of a number of transcription factors during embryonic development. As the RPE layer differentiates it expresses a set of unique molecules, many of which are restricted to certain regions of the cell. PRE cells undergo both a loss of polarity and a loss of expression of many of these cell type-specific molecules when placed in monolayer culture. The RPE of many species, including mammals, can be induced to transdifferentiate by growth factors such as basic fibroblast growth factor. Under the influence of such factors the RPE is triggered to alter expression of a wide array of molecules and to take on a retinal epithelium fate, from which differentiated retinal cell types including rod photoreceptors can be produced.
Purification of a multipotential colony-stimulating factor from pokeweed mitogen-stimulated mouse spleen cell conditioned medium. (1985)

A factor able to stimulate the proliferation and differentiation of multipotential stem cells and progenitor cells of the granulocyte-macrophage, eosinophil, and erythroid lineages as well as being able to maintain factor-dependent cell lines in culture has been purified from pokeweed mitogen-stimulated mouse spleen cell-conditioned medium. The factor was purified over 2 million-fold by sequential fractionation using salting out chromatography, chromatography on phenyl-Sepharose, gel filtration on Sephadex G-75, ion exchange chromatography on DEAE-Sepharose, reverse-phase high performance liquid chromatography on a phenyl-silica column, and gel permeation high performance liquid chromatography. All of the biological activities ascribed to the multipotential colony-stimulating factor co-fractionated through all steps, and the other known mouse-active hemopoietic regulator in pokeweed mitogen-stimulated mouse spleen cell-conditioned medium, granulocyte-macrophage colony-stimulating factor, was separated at the ion exchange step. Two protein species having Mr = 24,000 and 19,000 were visualized by silver-staining of sodium dodecyl sulfate-polyacrylamide gels of the purified factor. Both species migrated coincidently with the biological activities. The factor was active at a half-maximal concentration of 1 X 10(-13) M when assayed on a factor-dependent cell line.
Obscurin is required for the lateral alignment of striated myofibrils in zebrafish (2006)

Obscurin/obscurin-MLCK is a giant sarcomere-associated protein with multiple isoforms whose interactions with titin and small ankyrin-1 suggest that it has an important role in myofibril assembly, structural support, and the sarcomeric alignment of the sarcoplasmic reticulum. In this study, we characterized the zebrafish orthologue of obscurin and examined its role in striated myofibril assembly. Zebrafish obscurin was expressed in the somites and central nervous system by 24 hours post-fertilization (hpf) and in the heart by 48 hpf. Depletion of obscurin using two independent morpholino antisense oligonucleotides resulted in diminished numbers and marked disarray of skeletal myofibrils, impaired lateral alignment of adjacent myofibrils, disorganization of the sarcoplasmic reticulum, somite segmentation defects, and abnormalities of cardiac structure and function. This is the first demonstration that obscurin is required for vertebrate cardiac and skeletal muscle development. The diminished capacity to generate and organize new myofibrils in response to obscurin depletion suggests that it may have a vital role in the causation of or adaptation to cardiac and skeletal myopathies.
Tailored fatty acid synthesis via dynamic control of fatty acid elongation (2013)

Medium-chain fatty acids (MCFAs, 4-12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even- and odd-chain-length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired.
Extending temporal logic to support high-level simulations (1995)

A high-level simulation language based on temporal logic is described. The language combines a large set of temporal tenses and a rich class of high-level modeling primitives. Also an implementation of the language interpreter is presented. Finally, a real-world case study is described that shows how a programmer can develop structured, reliable, and well-maintainable simulation programs using the language.
Isolation and characterization of the human uracil DNA glycosylase gene. (1989)

A series of anti-human placental uracil DNA glycosylase monoclonal antibodies was used to screen a human placental cDNA library in phage lambda gt11. Twenty-seven immunopositive plaques were detected and purified. One clone containing a 1.2-kilobase (kb) human cDNA insert was chosen for further study by insertion into pUC8. The resultant recombinant plasmid selected by hybridization a human placental mRNA that encoded a 37-kDa polypeptide. This protein was immunoprecipitated specifically by an anti-human placental uracil DNA glycosylase monoclonal antibody. RNA blot-hybridization (Northern) analysis using placental poly(A)+ RNA or total RNA from four different human fibroblast cell strains revealed a single 1.6-kb transcript. Genomic blots using DNA from each cell strain digested with either EcoRI or Pst I revealed a complex pattern of cDNA-hybridizing restriction fragments. The genomic analysis for each enzyme was highly similar in all four human cell strains. In contrast, a single band was observed when genomic analysis was performed with the identical DNA digests with an actin gene probe. During cell proliferation there was an increase in the level of glycosylase mRNA that paralleled the increase in uracil DNA glycosylase enzyme activity. The isolation of the human uracil DNA glycosylase gene permits an examination of the structure, organization, and expression of a human DNA repair gene.
Efficient Expression of the Tumor-Associated Antigen MAGE-3 in Human Dendritic Cells, Using an Avian Influenza Virus Vector (2000)

Dendritic cells (DCs) are the most potent inducers of immune reactions. Genetically modified DCs, which express tumor-associated antigens (TAA), can efficiently induce antitumor immunity and thus have a high potential as tools in cancer therapy. The gene delivery is most efficiently achieved by viral vectors. Here, we explored the capacity of influenza virus vectors to transduce TAA genes. These viruses abortively infect DCs without interfering with their antigen-presenting capacity. In contrast to other viruses used for DC transduction, influenza viruses can be efficiently controlled by antiviral pharmaceuticals, lack the ability to integrate into host chromosomes, and fail to establish persistent infections. Genes encoding a melanoma-derived TAA (MAGE-3), or the green fluorescence protein (GFP), were introduced into a high-expression avian influenza virus vector. Monocyte-derived mature DCs infected by these recombinants efficiently produced GFP or MAGE-3. More than 90% of the infected DCs can express a transduced gene. Importantly, these transduced DCs retained their characteristic phenotype and their potent allogeneic T cell stimulatory capacity, and were able to stimulate MAGE-3-specific CD8(+) cytotoxic T cells. Thus influenza virus vectors provide a highly efficient gene delivery system in order to transduce human DCs with TAA, which consequently stimulate TAA-specific T cells.
Porous SiC Preparation, Characterization and Morphology (2008)

This chapter contains sections titled: Introduction Triangular Porous Morphology in n-type 4H-SiC Nano-columnar Pore Formation in 6H-SiC Summary Acknowledgements References