gebhart/patrepeval huggingface dataset:
Therapeutic and Diagnostic Agents for Parkinson's Disease (2003)

Abstract This chapter considers the biology and medical chemistry‐based treatment of Parkinson's disease, the second most common of the major neurodegenerative neuropsychiatric disorders. It surveys basic clinical features, neuropathology, and etiological theories based on genetics, maturational and oxidative‐metabolic degenerative processes, and environmental neurotoxins including MPTP. Treatments reviewed include L ‐dopa as a replacement therapy, direct dopaminergic agonists and their structure‐activity relationships, and agents that potentiate dopamine by preventing the metabolism of dopa or dopamine by peripheral aromatic amino acid decarboxylase, catechol‐ O ‐methyltransferase, or monoamineoxidase. Drugs acting on nondopaminergic systems considered include anticholinergic, adenosine agonist, glutamate antagonist, and serotonin agonist agents. Agents useful for the diagnosis of Parkinson's disease and monitoring progression of the disease include radioactive dopa and dopamine transporter labeling agents for use in brain imaging. Finally, future directions of efforts to improve the treatment of Parkinson's disease are considered, with an emphasis on the continued central importance of medicinal chemistry.
Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3 pathway (2008)

These data provide the first direct evidence that tissue kallikrein protects against acute-phase MI by promoting neovascularization, restoring regional blood flow and improving cardiac function through the kinin B2 receptor-Akt-GSK-3beta and VEGF signalling pathways.
CD28 Costimulation Overcomes Transforming Growth Factor-β–Mediated Repression of Proliferation of Redirected Human CD4+ and CD8+ T Cells in an Antitumor Cell Attack (2007)

The T-cell-mediated antitumor immune response is frequently repressed in the tumor environment by an immunologic barrier, the predominant mediators of which are thought to be interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). We explored the effect of these cytokines on the individual T-cell effector functions on antigen engagement during an antitumor cell attack. Isolated CD4+ and CD8+ T cells were antigen-specifically redirected toward carcinoembryonic antigen (CEA)-positive tumor cells by expression of a recombinant T-cell receptor (immunoreceptor), which triggers T-cell activation via CD3zeta on binding to CEA. Immunoreceptor-activated T cells secrete IFN-gamma, proliferate, and lyse CEA+ but not CEA- tumor cells. Whereas IL-10 has no direct effect on immunoreceptor-triggered effector functions, TGF-beta represses proliferation of both CD4+ and CD8+ T cells but neither IFN-gamma secretion nor specific cytolytic activities. CD28 costimulation, however, overcomes TGF-beta-mediated repression in T-cell proliferation. Consequently, T cells redirected by a combined CD28-CD3zeta signaling immunoreceptor are largely resistant to TGF-beta-mediated repression. This is reflected in vivo by a more pronounced antitumor activity of T cells against TGF-beta-secreting tumors when redirected by a costimulatory CD28-CD3zeta than by a CD3zeta signaling immunoreceptor.
Diuretic Therapy in Heart Failure – Current Approaches (2015)

The use of diuretics is common in patients with heart failure (HF), to relieve the congestive symptoms of HF. Although they are widely used, there are limited data on their ability to modulate HF-related morbidity and mortality. Diuretic efficacy may be limited by adverse neurohormonal activation and by 'congestion-like' symptoms. Diuretics are an extremely useful and varied class of agent for the management of hypervolaemic states. This review summarises the basic features of diuretics, including their mechanism of action, indications and adverse effects in heart failure.
Effects of surface passivation on breakdown of AlGaN/GaN high-electron-mobility transistors (2004)

The effect of Si3N4 surface passivation on breakdown of AlGaN/GaN high-electron-mobility transistors was studied in detail by investigating dependences of the off-state breakdown voltage on temperature and gate reverse current, and by measuring electroluminescence distribution. Impact ionization in the channel which was triggered by the gate reverse current was responsible for the off-state breakdown. Surface passivation by Si3N4 film was effective to improve the off-state breakdown voltage. This has been explained by a change in the potential distribution due to suppression of electron trapping at the surface states, based on results of electroluminescence measurements.
TAL Effector-Nucleotide Targeter (TALE-NT) 2.0: tools for TAL effector design and target prediction (2012)

Transcription activator-like (TAL) effectors are repeat-containing proteins used by plant pathogenic bacteria to manipulate host gene expression. Repeats are polymorphic and individually specify single nucleotides in the DNA target, with some degeneracy. A TAL effector-nucleotide binding code that links repeat type to specified nucleotide enables prediction of genomic binding sites for TAL effectors and customization of TAL effectors for use in DNA targeting, in particular as custom transcription factors for engineered gene regulation and as site-specific nucleases for genome editing. We have developed a suite of web-based tools called TAL Effector-Nucleotide Targeter 2.0 (TALE-NT 2.0; https://boglab.plp.iastate.edu/) that enables design of custom TAL effector repeat arrays for desired targets and prediction of TAL effector binding sites, ranked by likelihood, in a genome, promoterome or other sequence of interest. Search parameters can be set by the user to work with any TAL effector or TAL effector nuclease architecture. Applications range from designing highly specific DNA targeting tools and identifying potential off-target sites to predicting effector targets important in plant disease.
Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood (1994)

The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to T cells and monocytes. We show that it is also expressed in the B cell and in the granulocytic lineage, the levels of expression being related to distinct maturational stages. CD34+ cells of BM were found to express the antigen at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2 densities appeared progressively reduced with a considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages showed lower MIC2 expression levels, with a remarkable reduction concomitant with loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a subsequent slight upregulation along with maturation to CD10-CD20high surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by the most immature thymic T-lineage cells characterized by the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes stained slightly less intense with 12E7, whereas all subsequent stages of T-lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2. In the CD4+ population, the distinct MIC2 levels were related to the well-studied functional subdivision by differential expression of CD45 isoforms, the helper-inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or intermediate expression, and granulocytes exhibited no or only dim expression. These results document that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is differentially expressed during T- and B-lymphoid, as well as granulocytic maturation; (3) shows highest expression in the most immature lymphocytic and granulocytic developmental stages; and (4) is also differentially expressed on functional T-cell subsets. We speculate that these observations imply a functional significance of MIC2 in the network of hematopoietic adhesion pathways.
Adjustable- Versus Fixed-Rate Mortgage Choice: The Role of Initial Rate Discounts (1991)

This paper investigates relative pricing determinants of the fixed-rate mortgage (FRM) versus adjustable-rate mortgage (ARM) decision. A probit model is estimated using data from a national sample of residential housing transactions for the 1986 to 1988 period. The results suggest that the probability of ARM choice is highly sensitive to ARM initial rate (“teaser”) discounts and differences in the ratio of FRM to ARM points. In addition, the findings indicate that the level of local housing prices is an important determinant of ARM choice.
OFDM-CPM signals (2002)

A class of orthogonal frequency division multiplexing–continuous phase modulation (OFDM-CPM) signals is introduced in which binary data sequence is mapped to complex symbols using the concept of correlated phase states of a CPM signal. Various types of signals are defined as a function of parameter h and pulse duration. An investigation of bit error rate and peak-to-average-power ratio performance of these signals is also presented.
Autonomous pleiotropy in Drosophilia. (1968)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Uptake and transient expression of chimeric genes in seed-derived embryos. (1989)

Uptake of DNA in dry and viable embryos of wheat by imbibition in DNA solution was detected by monitoring the transient expression of chimeric genes. Gene expression vectors used in this study contained a neomycin phosphotransferase (NPT) II reporter gene fused to various promoters. Some of the chimeric "neo" genes were shown to yield reproducibly NPT II activity in germinating embryos. This NPT II activity was increased markedly when the neo genes were carried by a vector capable of autonomous replication. Dimers of wheat dwarf virus, a monopartite gemini virus, were thus shown to be effective in amplifying the transient expressed NPT II activity in embryos of several cereals. These and other observations indicate that the observed transient expression really results from DNA uptake and expression in plant embryo cells and is not due to contaminating microorganisms.
A functional protein pore with a “retro” transmembrane domain (1999)

Extended retro (reversed) peptide sequences have not previously been accommodated within functional proteins. Here, we show that the entire transmembrane portion of the beta-barrel of the pore-forming protein alpha-hemolysin can be formed by retrosequences comprising a total of 175 amino acid residues, 25 contributed by the central sequence of each subunit of the heptameric pore. The properties of wild-type and retro heptamers in planar bilayers are similar. The single-channel conductance of the retro pore is 15% less than that of the wild-type heptamer and its current-voltage relationship denotes close to ohmic behavior, while the wild-type pore is weakly rectifying. Both wild-type and retro pores are very weakly anion selective. These results and the examination of molecular models suggest that beta-barrels may be especially accepting of retro sequences compared to other protein folds. Indeed, the ability to form a retro domain could be diagnostic of a beta-barrel, explaining, for example, the activity of the retro forms of many membrane-permeabilizing peptides. By contrast with the wild-type subunits, monomeric retro subunits undergo premature assembly in the absence of membranes, most likely because the altered central sequence fails to interact with the remainder of the subunit, thereby initiating assembly. Despite this difficulty, a technique was devised for obtaining heteromeric pores containing both wild-type and retro subunits. Most probably as a consequence of unfavorable interstrand side-chain interactions, the heteromeric pores are less stable than either the wild-type or retro homoheptamers, as judged by the presence of subconductance states in single-channel recordings. Knowledge about the extraordinary plasticity of the transmembrane beta-barrel of alpha-hemolysin will be very useful in the de novo design of functional membrane proteins based on the beta-barrel motif.
Cloning of a Type I TGF-β Receptor and Its Effect on TGF-β Binding to the Type II Receptor (1993)

Transforming growth factor-beta (TGF-beta) affects cellular proliferation, differentiation, and interaction with the extracellular matrix primarily through interaction with the type I and type II TGF-beta receptors. The type II receptors for TGF-beta and activin contain putative serine-threonine kinase domains. A murine serine-threonine kinase receptor, Tsk 7L, was cloned that shared a conserved extracellular domain with the type II TGF-beta receptor. Overexpression of Tsk 7L alone did not increase cell surface binding of TGF-beta, but coexpression with the type II TGF-beta receptor caused TGF-beta to bind to Tsk 7L, which had the size of the type I TGF-beta receptor. Overexpression of Tsk 7L inhibited binding of TGF-beta to the type II receptor in a dominant negative fashion. Combinatorial interactions and stoichiometric ratios between the type I and II receptors may therefore determine the extent of TGF-beta binding and the resulting biological activities.
A class of DFT polyphase filter banks for orthogonal multiple carrier data transmission (2003)

Based on a polyphase IFFT filter bank in the transmitter and a polyphase FFT filter bank in the receiver, orthogonal multiple carrier (OMC) data transmission with high computational efficiency and high bandwidth efficiency can be achieved. The orthogonality is conditioned by an ideal sampling of the receive vector at proper time instants. The authors discuss the effect of the filter transfer function characteristic on the amount of signal distortion due to nonideal timing recovery (timing synchronization) in the receiver. A special class of Nyquist systems is introduced, and an optimum low-pass filter transfer function for the polyphase filter bank of the OMC data transmission system is given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Hepcidin-Ferroportin System as a Therapeutic Target in Anemias and Iron Overload Disorders (2011)

The review summarizes the current understanding of the role of hepcidin and ferroportin in normal iron homeostasis and its disorders. The various approaches to therapeutic targeting of hepcidin and ferroportin in iron-overload disorders (mainly hereditary hemochromatosis and β-thalassemia) and iron-restrictive anemias (anemias associated with infections, inflammatory disorders, and certain malignancies, anemia of chronic kidney diseases, and iron-refractory iron-deficiency anemia) are also discussed.
Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression. (1992)

Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta 1 transforming growth factor (TGF-beta 1) in human monocytes. TGF-beta 1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-beta are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-beta 1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.
Stable load control with load prediction in multipath packet forwarding (2002)

With the invention of multiprotocol label switching (MPLS), complex traffic engineering and multipath packet forwarding has become a reality. To use multipath packet forwarding, efficient load control between paths is necessary. Furthermore, dynamic load control is needed to optimize load mapping between paths depending on the network state. Unfortunately, distributed dynamic load control algorithms, if not carefully designed, can make the load mapping unstable, thus making many packets dropped due to unbalanced mapping. We propose a dynamic load control scheme which makes the network efficient while keeping load mapping stable.
In vitro evaluation of DNA-DNA hybridization as a two-step approach in radioimmunotherapy of cancer. (1994)

The specific delivery of radioisotopes to a tumor at minimal radiation of normal tissue is the ultimate aim of radioimmunotherapy. In this respect a two-step pretargeting regimen generally leads to an improved tumor to normal tissue uptake ratio compared to direct administration of radioimmunoconjugates. In this paper, in vitro studies are described in which the specific hybridization of complementary DNA fragments is the recognition mechanism in a pretargeting regimen comprising tumor cell saturation with a monoclonal antibody (MoAb)-oligonucleotide conjugate, followed by administration of the radiolabeled complementary oligonucleotide. Complementary oligodeoxynucleotides (15-mers; melting temperature, 68 degrees C) were prepared on a DNA synthesizer. The 5'-end was derivatized with a functional group for labeling with iodine, and the 3'-end was substituted with an amino function suitable for conjugation to an antibody (or attachment of a biotin residue). Both terminal modifications ensure stability of the oligonucleotides against exonucleases because the unconjugated form is stable for 24 h and the conjugated form is stable for several days when incubated in human plasma at 37 degrees C. Antibody-DNA conjugates were prepared by introduction of sulfhydryl groups into the oligonucleotide, followed by conjugation to maleimide-substituted MoAbs. Typically, 3 oligonucleotides were conjugated to an IgG, and 4-6 were conjugated to an IgM with preservation of immunoreactivity. Histochemistry on fresh frozen sections of breast cancer tissue demonstrated qualitatively the specificity of our two-step procedure. In vitro experiments with human tumor cell lines and tumor-specific MoAbs showed that, after saturation with tumor-specific MoAb-DNA conjugates, quantitative hybridization of the tumor cell-bound oligonucleotides occurred at a 30-fold excess of the labeled complementary oligonucleotide: hybridization was complete after 30 min of incubation. No reaction was observed with an irrelevant MoAb-DNA conjugate. The oligonucleotide was neither taken up by tumor cells or endothelial cells nor hybridized to a significant extent with human genomic DNA. These data indicate the feasibility of this two-step approach in radioimmunotherapy.
Fast shadows and lighting effects using texture mapping (1992)

article Free Access Share on Fast shadows and lighting effects using texture mapping Authors: Mark Segal Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CA Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CAView Profile , Carl Korobkin Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CA Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CAView Profile , Rolf van Widenfelt Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CA Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CAView Profile , Jim Foran Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CA Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CAView Profile , Paul Haeberli Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CA Silicon Graphics Computer Systems, 2011 N. Shoreline Blvd., Mountain View, CAView Profile Authors Info & Claims ACM SIGGRAPH Computer GraphicsVolume 26Issue 2July 1992 pp 249–252https://doi.org/10.1145/142920.134071Online:01 July 1992Publication History 266citation2,979DownloadsMetricsTotal Citations266Total Downloads2,979Last 12 Months78Last 6 weeks13 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF