gebhart/patrepeval huggingface dataset:
Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6 (2006)

Recently, it has been suggested that hepcidin, a peptide involved in iron homeostasis, is regulated by bone morphogenetic proteins (BMPs), apparently by binding to hemojuvelin (Hjv) as a coreceptor and signaling through Smad4. We investigate the role of Hfe, Tfr2 (transferrin receptor 2), and IL-6 in BMP2-, BMP4-, and BMP9-stimulated up-regulation of murine hepcidin, because these molecules, like Hjv, are known to be involved in hepcidin signaling. We show that the BMP signaling pathway acts independently of Hfe, Tfr2, and IL-6: The response to BMP2, BMP4, and BMP9 is similar in isolated hepatocytes of wild-type, Hfe(-/-), IL-6(-/-), and Tfr2(m) mutant mice. The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2. However, in human HepG2 cells, BMP4 and BMP9 are equally potent, whereas BMP2 requires a higher dose to become an effective hepcidin activator. Moreover, all of the tested BMPs are more potent regulators of hepcidin than IL-6 and thus are the most potent known stimulators of hepcidin transcription.
Sputter deposition for semiconductor manufacturing (1999)

Sputter deposition, also known as physical vapor deposition, or PVD, is a widely used technique for depositing thin metal layers on semiconductor wafers. These layers are used as diffusion barriers, adhesion or seed layers, primary conductors, antireflection coatings, and etch stops. With the progression toward finer topographical dimensions on wafers and increasing aspect ratios, the broad angular distribution of depositing, sputtered atoms leads to poor or nonexistent coverage in deep features. This has been partially addressed using directional sputtering techniques such as collimated sputtering or long-throw sputtering. More recently, work originating in IBM has moved toward the deposition of films from metal-rich plasmas fed by sputtering, a technique known as I-PVD (for ionized PVD). This technique, based on fairly minor modifications of existing PVD systems, solves many of the intrinsic problems of PVD and appears headed for widespread manufacturing applications.
Importin β Mediates Nuclear Translocation of Smad 3 (2000)

Smad proteins are intracellular mediators of transforming growth factor-β (TGF-β) and related cytokines. Although ligand-induced nuclear translocation of Smad proteins is clearly established, the pathway mediating this import is yet to be determined. We previously identified a nuclear localization signal (NLS) in the N-terminal region of Smad 3, the major Smad protein involved in TGF-β signal transduction. This basic motif (Lys<sup>40-</sup>Lys-Leu-Lys-Lys<sup>44</sup>), conserved among all the pathway-specific Smad proteins, is required for Smad 3 nuclear import in response to ligand. Here we studied the nuclear import pathway of Smad 3 mediated by this NLS. We demonstrate that the isolated Smad 3 MH1 domain displays significant specific binding to importin β, which is diminished or eliminated by mutations in the NLS. Full-size Smad 3 exhibits weak but specific binding to importin β, which is enhanced after phosphorylation by the type I TGF-β receptor. In contrast, no interaction was observed between importin α and Smad 3 or its MH1 domain, indicating that nuclear translocation of Smad proteins may occur through direct binding to importin β. We propose that activation of all of the pathway-specific Smad proteins (Smads 1, 2, 3, 5, 8, and 9) exposes the conserved NLS motif, which then binds directly to importin β and triggers nuclear translocation.
Finding out about filling-in: A guide to perceptual completion for visual science and the philosophy of perception (1998)

In visual science the term filling-in is used in different ways, which often leads to confusion. This target article presents a taxonomy of perceptual completion phenomena to organize and clarify theoretical and empirical discussion. Examples of boundary completion (illusory contours) and featural completion (color, brightness, motion, texture, and depth) are examined, and single-cell studies relevant to filling-in are reviewed and assessed. Filling-in issues must be understood in relation to theoretical issues about neural-perceptual isomorphism and linking propositions. Six main conclusions are drawn: (1) visual filling-in comprises a multitude of different perceptual completion phenomena; (2) certain forms of visual completion seem to involve spatially propagating neural activity (neural filling-in) and so, contrary to Dennett's (1991; 1992) recent discussion of filling-in, cannot be described as results of the brain's "ignoring an absence" or "jumping to a conclusion"; (3) in certain cases perceptual completion seems to have measurable effects that depend on neural signals representing a presence rather than ignoring an absence; (4) neural filling-in does not imply either "analytic isomorphism" or "Cartesian materialism," and thus the notion of the bridge locus--a particular neural stage that forms the immediate substrate of perceptual experience--is problematic and should be abandoned; (5) to reject the representational conception of vision in favor of an "enactive" or "animate" conception reduces the importance of filling-in as a theoretical category in the explanation of vision; and (6) the evaluation of perceptual content should not be determined by "subpersonal" considerations about internal processing, but rather by considerations about the task of vision at the level of the animal or person interacting with the world.
Proxy Re-Signatures: New Definitions, Algorithms, and Applications. (2005)

In 1998, Blaze, Bleumer, and Strauss (BBS) proposed proxy re-signatures, in which a semitrusted proxy acts as a translator between Alice and Bob. To translate, the proxy converts a signature from Alice into a signature from Bob on the same message. The proxy, however, does not learn any signing key and cannot sign arbitrary messages on behalf of either Alice or Bob.
Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer (2003)

DNA mismatch repair (MMR) is involved in the post-replication correction of errors due to misincorporated nucleotides or DNA slippage during DNA synthesis. We previously reported the reduction or loss of MMR protein expression in human prostate cancer cell lines and some primary tumors. In the present report, we further demonstrate the involvement of defects of MMR in the pathogenesis of prostate cancer. Immunohistochemical analysis of 39 formalin-fixed, paraffin-embedded human prostate tumors, showed reduction or absence of MMR protein expression (MLH1, MSH2, PMS2) in the epithelium of prostate tumor foci compared to normal adjacent prostate tissue. The reduction or absence of the PMS2 and MSH2 (but not MLH1) protein was correlated to the differentiation of the tumor. Poorly differentiated tumors showed greater loss of these two proteins than the well differentiated tumors (P<0.05). We previously reported that microsatellite instability was detectable by a beta-galactosidase restoration mutation assay in the prostate cancer cell lines DU145, PC3, LNCaP, p67SV40T, M2182, and M12. In this study, we detected the insertion or deletion of one nucleotide in the mononucleotide repeats located within the coding regions of BAX gene in DU145, and TGFbetaRII in M12 cells. In addition, we used an in vitro model of defective MMR to demonstrate that microsatellite instability can be induced in an otherwise stable cancer cell line by transfection with a dominant negative fragment of PMS2. These results suggest that defects in MMR may result in MSI in the secondary genes in prostate cancer. From these results, we conclude that loss of MMR function can produce MSI and target some secondary genes containing microsatellites in their coding regions. These series of events may play important roles in the development of human prostate cancer.
Model-Based Framework for Oil Production Forecasting and Optimization: A Case Study in Integrated Asset Management (2006)

Abstract This paper describes the design and implementation of a prototype toolkit that demonstrates Integrated Asset Management (IAM) functionality through an integrated production and forecasting workflow. A graphical modeling environment specially configured for this domain is used to instantiate the asset model. Automatic conversion of legacy data into structured model representations is facilitated through a model synthesis tool. The actual optimization is performed using a commercially available solver. For an oilfield with about 75 wells, the tool requires only a few seconds to read the model information and produce the forecast. The time required to generate the forecast output in the desired format depends on the duration of forecasting, the size of the field, and whether the output is to be produced as a text file or a Microsoft Excel spreadsheet.
Synthesis, Assembly, and Processing of the Env ERVWE1/Syncytin Human Endogenous Retroviral Envelope (2005)

Syncytin is a fusogenic protein involved in the formation of the placental syncytiotrophoblast layer. This protein is encoded by the envelope gene of the ERVWE1 proviral locus belonging to the human endogenous retrovirus W (HERV-W) family. The HERV-W infectious ancestor entered the primate lineage 25 to 40 million years ago. Although the syncytin fusion property has been clearly demonstrated, little is known about this cellular protein maturation process with respect to classical infectious retrovirus envelope proteins. Here we show that the cellular syncytin protein is synthesized as a glycosylated gPr73 precursor cleaved into two mature proteins, a gp50 surface subunit (SU) and a gp24 transmembrane subunit (TM). These SU and TM subunits are found associated as homotrimers. The intracytoplasmic tail is critical to the fusogenic phenotype, although its cleavage requirements seem to have diverged from those of classical retroviral maturation.
The NOX1/4 Inhibitor GKT136901 as Selective and Direct Scavenger of Peroxynitrite (2013)

NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (•O₂⁻) and hydrogen peroxide (H₂O₂), are involved in several pathological conditions, such as stroke, diabetes, atherosclerosis, but also in chronic neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, or multiple sclerosis. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of diabetic nephropathy, stroke, or neurodegeneration. In the present study, we investigated additional pharmacological activities of the compound with respect to direct free radical scavenging. GKT136901 did not interact with nitric oxide (•NO), •O₂⁻, or hydroxyl radicals (•OH), but it acted as selective scavenger of peroxynitrite (PON) already in the submicromolar concentration range. Alpha synuclein (ASYN) is a protein involved in the pathogenesis of Parkinson's disease and a known target for PON-dependent tyrosine nitration. Submicromolar concentrations of GKT136901 prevented tyrosine nitration and di-tyrosine-dependent dimer formation of ASYN by PON as indicated by Western blot and mass spectrometric analysis. GKT136901 itself was degraded when exposed to PON. In a human neuronal cell model, GKT136901 prevented both the depletion of reduced intracellular glutathione, and the degeneration of neurites when present during PON treatment of the cells. When GKT136901 was applied after PON treatment, no protective effect was observed, thus excluding an impact of GKT136901 on cellular death/survival pathways. In summary, selective scavenging of PON is an additional pharmacological property of the NOX-1/4 inhibitor GKT136901, and this may add to the efficiency of the drug in several disease models.
From cardiac repair to cardiac regeneration – ready to translate? (2006)

Cardiovascular disease is a major public health challenge in the western world. Mortality of acute events has improved, but more patients develop HF--a condition affecting up to 22 million people worldwide. Cell transplantation is the first therapy to attempt replacement of lost cardiomyocytes and vasculature to restore lost contractile function. Since the first reported functional repair after injection of autologous skeletal myoblasts into the injured heart in 1998, a variety of cell types have been proposed for transplantation in different stages of cardiovascular disease. Fifteen years of preclinical research and the rapid move into clinical studies have left us with promising results and a better understanding of cells as a potential clinical tool. Cell-based cardiac repair has been the first step, but cardiac regeneration remains the more ambitious goal. Promising new cell types and the rapidly evolving concept of adult stem and progenitor cell fate may enable us to move towards regenerating viable and functional myocardium. Meeting a multidisciplinary consensus will be required to translate these findings into safe and applicable clinical tools.
Induction of Phase 2 Antioxidant Enzymes by Broccoli Sulforaphane: Perspectives in Maintaining the Antioxidant Activity of Vitamins A, C, and E (2012)

Consumption of fruits and vegetables is recognized as an important part of a healthy diet. Increased consumption of cruciferous vegetables in particular has been associated with a decreased risk of several degenerative and chronic diseases, including cardiovascular disease and certain cancers. Members of the cruciferous vegetable family, which includes broccoli, Brussels sprouts, cauliflower, and cabbage, accumulate significant concentrations of glucosinolates, which are metabolized in vivo to biologically active isothiocyanates (ITCs). The ITC sulforaphane, which is derived from glucoraphanin, has garnered particular interest as an indirect antioxidant due to its extraordinary ability to induce expression of several enzymes via the KEAP1/Nrf2/ARE pathway. Nrf2/ARE gene products are typically characterized as Phase II detoxification enzymes and/or antioxidant (AO) enzymes. Over the last decade, human clinical studies have begun to provide in vivo evidence of both Phase II and AO enzyme induction by SF. Many AO enzymes are redox cycling enzymes that maintain redox homeostasis and activity of free radical scavengers such as vitamins A, C, and E. In this review, we present the existing evidence for induction of PII and AO enzymes by SF, the interactions of SF-induced AO enzymes and proposed maintenance of the essential vitamins A, C, and E, and, finally, the current view of genotypic effects on ITC metabolism and AO enzyme induction and function.
The independent effects of oxygen radical scavengers on canine infarct size. Reduction by superoxide dismutase but not catalase. (1985)

Previous studies demonstrated a significant reduction of ultimate infarct size in the canine heart by the combined administration of superoxide dismutase plus catalase. This study was performed to assess the independent effects of each enzyme on ultimate infarct size due to ischemia/reperfusion. Dogs received 2-hour infusions of superoxide dismutase, catalase, or albumin (controls) via the left atrium beginning 15 minutes before and ending 15 minutes after a 90-minute occlusion of the left circumflex coronary artery. The dogs were killed 6 hours after reperfusion. After histochemical staining, infarct and risk area masses were calculated by gravimetric and planimetric analysis. Infarct size expressed as a percentage of the area at risk was: superoxide dismutase, 19 +/- 5; catalase, 30 +/- 5; and controls, 40 +/- 3. Infarct size in the superoxide dismutase group, but not the catalase group, was significantly less than in controls (P less than 0.05). No significant differences in hemodynamics or area at risk were observed that could explain the differences in infarct size. The results indicate that superoxide dismutase alone protects reperfused ischemic myocardium as well as does the combination of superoxide dismutase and catalase. The beneficial effect of superoxide dismutase and insignificant effect of catalase suggest that tissue damage during ischemia and reperfusion may be mediated largely by superoxide anion but not by hydrogen peroxide.
Molecular Biology of Matrix Vesicles (1995)

Matrix vesicles are extracellular 100-nanometer-diameter membrane-invested particles selectively located within the matrix of bone, cartilage, and predentin. They serve as the initial site of calcification in all skeletal tissues. Matrix vesicle biogenesis occurs by polarized budding and pinching off of vesicles from specific regions of the outer plasma membrane of chondrocytes, osteoblasts, and odontoblasts. Seeding of selected areas of matrix with matrix vesicles explains the localized distribution of subsequent zones of mineralization. Matrix vesicle biogenesis in the growth plate is linked to the chondrocyte cell cycle and reflects a stage in programmed cell death (apoptosis). Generation of initial hydroxyapatite mineral crystals occurs within the matrix vesicle membrane during Phase 1 of biologic mineralization. Phase 1 is controlled by phosphatases (including alkaline phosphatase) and Ca-binding molecules with which the matrix vesicles are well endowed. Phase 2 of biologic mineralization begins with breakdown of matrix vesicle membranes, exposing preformed hydroxyapatite to the extracellular fluid after which mineral crystal proliferation is governed by extracellular conditions. Phase 1 and Phase 2 of mineralization are under cellular control. Phase 1 is initiated by cells generating calcifiable matrix vesicles and releasing them into sites of intended calcification. Phase 2 is controlled by cells regulating extracellular ionic conditions and matrix composition.
Classifying Action Items for Semantic Email (2010)

The dihydropyridine receptor purified from rabbit skeletal muscle contains three proteins of 165, 55 and 32 kDa. cAMP kinase and protein kinase C phosphorylate the 165-kDa and the 55-kDa proteins. At identical concentrations of each protein kinase, cAMP kinase phosphorylates the 165-kDa protein faster than the 55-kDa protein. Protein kinase C phosphorylates preferentially the 55-kDa protein. cAMP kinase incorporates up to 1.6 mol phosphate/mol protein into the 165-kDa protein and 1 mol/mol into the 55-kDa protein upon prolonged incubation. At a physiological concentration of cAMP kinase 1 mol phosphate is incorporated/mol 165-kDa protein within 10 min, suggesting a physiological role of this phosphorylation. Protein kinase C incorporates up to 1 mol phosphate/mol into the 55-kDa protein and less than 1 mol/mol into the 165-kDa protein. Tryptic phosphopeptide analysis reveals that cAMP kinase phosphorylates two distinct peptides in the 165-kDa protein, whereas protein kinase C phosphorylates a single peptide in the 165-kDa protein. cAMP kinase and protein kinase C phosphorylate three and two peptides in the 55-kDa protein, respectively. Mixtures of the tryptic phosphopeptides derived from the 165-kDa and 55-kDa proteins elute according to the composite of the two elution profiles. These results suggest that the 165-kDa protein, which contains the binding sites for each class of calcium channel blockers and the basic calcium-conducting structure, is a specific substrate for cAMP kinase. The 55-kDa protein apparently contains sites preferentially phosphorylated by protein kinase C.
Aspartic proteases of Plasmodium vivax are highly conserved in wild isolates (2004)

The plasmepsins are the aspartic proteases of malaria parasites. Treatment of aspartic protease inhibitor inhibits hemoglobin hydrolysis and blocks the parasite development in vitro suggesting that these proteases might be exploited their potentials as antimalarial drug targets. In this study, we determined the genetic variations of the aspartic proteases of Plasmodium vivax (PvPMs) of wild isolates. Two plasmepsins (PvPM4 and PvPM5) were cloned and sequenced from 20 P. vivax Korean isolates and two imported isolates. The sequences of the enzymes were highly conserved except a small number of amino acid substitutions did not modify key residues for the function or the structure of the enzymes. The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics.
An Escherichia coli strain with all chromosomal rRNA operons inactivated: Complete exchange of rRNA genes between bacteria (1999)

Current global phylogenies are built predominantly on rRNA sequences. However, an experimental system for studying the evolution of rRNA is not readily available, mainly because the rRNA genes are highly repeated in most experimental organisms. We have constructed an Escherichia coli strain in which all seven chromosomal rRNA operons are inactivated by deletions spanning the 16S and 23S coding regions. A single E. coli rRNA operon carried by a multicopy plasmid supplies 16S and 23S rRNA to the cell. By using this strain we have succeeded in creating microorganisms that contain only a foreign rRNA operon derived from either Salmonella typhimurium or Proteus vulgaris, microorganisms that have diverged from E. coli about 120-350 million years ago. We also were able to replace the E. coli rRNA operon with an E. coli/yeast hybrid one in which the GTPase center of E. coli 23S rRNA had been substituted by the corresponding domain from Saccharomyces cerevisiae. These results suggest that, contrary to common belief, coevolution of rRNA with many other components in the translational machinery may not completely preclude the horizontal transfer of rRNA genes.
Floating-electrode enhanced constriction dielectrophoresis for biomolecular trapping in physiological media of high conductivity (2012)

We present an electrokinetic framework for designing insulator constriction-based dielectrophoresis devices with enhanced ability to trap nanoscale biomolecules in physiological media of high conductivity, through coupling short-range dielectrophoresis forces with long-range electrothermal flow. While a 500-fold constriction enables field focusing sufficient to trap nanoscale biomolecules by dielectrophoresis, the extent of this high-field region is enhanced through coupling the constriction to an electrically floating sensor electrode at the constriction floor. However, the enhanced localized fields due to the constriction and enhanced current within saline media of high conductivity (1 S/m) cause a rise in temperature due to Joule heating, resulting in a hotspot region midway within the channel depth at the constriction center, with temperatures of ∼8°-10°K above the ambient. While the resulting vortices from electrothermal flow are directed away from the hotspot region to oppose dielectrophoretic trapping, they also cause a downward and inward flow towards the electrode edges at the constriction floor. This assists biomolecular trapping at the sensor electrode through enabling long-range fluid sampling as well as through localized stirring by fluid circulation in its vicinity.