gebhart/patrepeval huggingface dataset:
Antisense Drug Technology (2010)

Basic Principles of Antisense Technology Stanley T. Crooke Medicinal Chemistry of Antisense Oligonucleotides P. Dan Cook Analytical Methods for Antisense Drugs Janet M. Leeds and Lendell L. Cummins A Role for Antisense Technology in the Discovery of Highly Specific and Versatile Signal Transduction Inhibitors Brett P. Monia, Erich Koller, and William A. Gaarde Methods of Selecting Sites in RNA for Antisense Targeting Susan M. Freier Properties of Phosphorothioate Oligonucleotides Pharmacokinetic Properties in Animals Richard S. Geary, Rosie Z. Yu, Janet M. Leeds, Michael V. Templin, Tanya A. Watanabe, Scott P. Henry, and Arthur A. Levin Suborgan Pharmacokinetics Rosanne M. Crooke and Mark J. Graham Pharmacokinetic Properties in Humans Rosie Z. Yu, Steven L. Schoenfeld, Richard S. Geary, Tanya A. Watanabe, and Arthur A. Levin Toxicity of Antisense Oligonucleotides Arthur A. Levin, Scott P. Henry, David Monteith, and Michael V. Templin Clinical Safety of Phosphorothioate Oligodeoxynucleotides F. Andrew Dorr, Josephine M. Glover, and T. Jesse Kwoh General Pharmacology of Phosphorothioate Oligodeoxynucleotides C. Frank Bennett Properties of Advanced Novel Clinical Classes of Oligonucleotides Pharmacology of 2'-0-(2-Methoxy)ethyl Modified Antisense Oligonucleotides Nicholas M. Dean, Madeline Butler, Brett P. Monia, and Muthiah Manoharan Locked Nucleic Acid Jesper Wengel Antisense Properties of Peptide Nucleic Acid (PNA) Uffe Koppelhus and Peter J. Nielsen Phosphorodiamidate Morpholino Oligomers Patrick Iversen Oligonucleotide Conjugates in Antisense Technology Muthiah Manoharan Immune Stimulation by Oligonucleotides Arthur M. Krieg Pre-mRNA Splicing as a Target for Antisense Oligonucleotides Ryszard Kole and Danielle Mercatante Application of Antisense Oligonucleotides to the Study of CNS Protein Function Siew Peng Ho Antisense Approach to Isoform-Specific Blockade of Acetylcholinesterase Hermona E. Soreq and Shlomo Seidman Serine/Threonine Protein Phosphates Richard E. Honkanen Pharmacological Activities of Antisense Drugs: Inflammatory Diseases James G. Karras, Kathleen J. Myers, and Brenda F. Baker Respirable Antisense Oligonucleotides (RASONs) Jonathan W. Nyce Combined Antisense Therapy and Chemotherapy in Animal Models Dan Mercola Antisense Oligodesoxynucleotide Strategies in Renal and Cardiovascular Disease Hermann Haller, Christian Maasch, Duska Dragun, Maren Wellner, and Friedrich C. Luft The Development of Antisense Oligonucleotides as Antivirals Lisa R. Grillone Clinical Activities in Patients with Solid Tumors or Lymphoma Jon T. Holmlund Nucleic Acid Therapeutics for the Treatment of Human Leukemia Alan M. Gewirtz ISIS 2302, an Antisense Inhibitor of Intercellular Adhesion Molecule 1 (ICAM-1) William R. Shanahan, Jr. New Routes and Novel Formulations for Delivery of Antisense Oligonucleotides Gregory E. Hardee, Susan P. Weinbach, and Lloyd G. Tillman DNA-Binding Molecules Roland W. Burli and Heinz E. Moser Targeted Genome Modification via Triple Helix Formation Margaret A. Macris and Peter M. Glazer Intracellular Ribozyme Applications John J. Rossi
Construction of an integrative shuttle vector for Zymomonas mobilis (1995)

An integrative shuttle vector, pZMOCPI, was constructed by ligating EcoRV digests of the plasmid cloning vector pBluescript and pZMPI, a cryptic plasmid of Zymomonas mobilis PROM Al. The 7.2-kb plasmid pZMOCPI replicated in Escherichia coli and could also be transferred from this host by electroporation to Z. mobilis ATCC 29191. The transformants were selected by ampicillin resistance. The integrative characteristic was detected by hybridization in situ. The vector was stably maintained in Z. mobilis after 200 generations without selective pressure.
Mechanisms of Protein Sorting in Mitochondria (2012)

A protein's function is intimately linked to its correct subcellular location, yet the machinery required for protein synthesis is predominately cytosolic. How proteins are trafficked through the confines of the cell and integrated into the appropriate cellular compartments has puzzled and intrigued researchers for decades. Indeed, studies exploring this premise revealed elaborate cellular protein translocation and sorting systems, which ensure that all proteins are shuttled to the appropriate cellular destination, where they fulfill their specific functions. This holds true for mitochondria, where sophisticated molecular machines serve to recognize incoming precursor proteins and integrate them into the functional framework of the organelle. We summarize the recent progress in our understanding of mitochondrial protein sorting and the machineries and mechanisms that mediate and regulate this highly dynamic cellular process essential for survival of virtually all eukaryotic cells.
CLINICAL APPLICATION OF 4‐HYDROXYBUTYRATE SODIUM AND 4‐BUTYROLACTONE IN NEUROPSYCHIATRIC PATIENTS (1966)

S ummary 4‐hydroxybutyrate sodium (HB) and/or 4‐butyrolactone (BL) were applied orally or intravenously to 288 neuropsychiatric patients and 9 normal adults. The results obtained were as follows: 1. In 9 normal adults to whom 1 to 8 gm of the drugs were administered, no serious changes were observed in respiration, heart rate, blood pressure and temperature. However, when more than 5 gm were given, there were somniferous, muscle relaxing and sedative effects. 2. These compounds showed remarkable sedative, somniferous, muscle relaxing, anesthetic effects and had a regulating effect on psychosis in neuropsychiatric patients. 3. The relationship between the somniferous effect and dosage was studied in patients aged from 1.5 to 71 years. 4. A wide spectrum of their clinical application was emphasized and future clinical application was suggested. The side‐effects of these compounds were also discussed.
Bergmann Glial AMPA Receptors Are Required for Fine Motor Coordination (2012)

The impact of glial neurotransmitter receptors in vivo is still elusive. In the cerebellum, Bergmann glial (BG) cells express α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) composed exclusively of GluA1 and/or GluA4 subunits. With the use of conditional gene inactivation, we found that the majority of cerebellar GluA1/A4-type AMPARs are expressed in BG cells. In young mice, deletion of BG AMPARs resulted in retraction of glial appendages from Purkinje cell (PC) synapses, increased amplitude and duration of evoked PC currents, and a delayed formation of glutamatergic synapses. In adult mice, AMPAR inactivation also caused retraction of glial processes. The physiological and structural changes were accompanied by behavioral impairments in fine motor coordination. Thus, BG AMPARs are essential to optimize synaptic integration and cerebellar output function throughout life.
Approximating Catmull-Clark subdivision surfaces with bicubic patches (2008)

We present a simple and computationally efficient algorithm for approximating Catmull-Clark subdivision surfaces using a minimal set of bicubic patches. For each quadrilateral face of the control mesh, we construct a geometry patch and a pair of tangent patches. The geometry patches approximate the shape and silhouette of the Catmull-Clark surface and are smooth everywhere except along patch edges containing an extraordinary vertex where the patches are C 0 . To make the patch surface appear smooth, we provide a pair of tangent patches that approximate the tangent fields of the Catmull-Clark surface. These tangent patches are used to construct a continuous normal field (through their cross-product) for shading and displacement mapping. Using this bifurcated representation, we are able to define an accurate proxy for Catmull-Clark surfaces that is efficient to evaluate on next-generation GPU architectures that expose a programmable tessellation unit.
The Relation Between Psychometric Test Performance and Physical Performance in Older Adults (1999)

Cognitive processing speed is a significant component of physical frailty in this population, although it accounts for a small percentage of variance on a standardized physical performance test.
Branch Flow Model: Relaxations and Convexification—Part I (2013)

We propose a branch flow model for the analysis and optimization of mesh as well as radial networks. The model leads to a new approach to solving optimal power flow (OPF) that consists of two relaxation steps. The first step eliminates the voltage and current angles and the second step approximates the resulting problem by a conic program that can be solved efficiently. For radial networks, we prove that both relaxation steps are always exact, provided there are no upper bounds on loads. For mesh networks, the conic relaxation is always exact but the angle relaxation may not be exact, and we provide a simple way to determine if a relaxed solution is globally optimal. We propose convexification of mesh networks using phase shifters so that OPF for the convexified network can always be solved efficiently for an optimal solution. We prove that convexification requires phase shifters only outside a spanning tree of the network and their placement depends only on network topology, not on power flows, generation, loads, or operating constraints. Part I introduces our branch flow model, explains the two relaxation steps, and proves the conditions for exact relaxation. Part II describes convexification of mesh networks, and presents simulation results.
Effect of Decompression Craniotomy on Increase of Contusion Volume and Functional Outcome after Controlled Cortical Impact in Mice (2003)

If, how, and when decompressive craniotomy should be used for the treatment of increased intracranial pressure after traumatic brain injury are widely discussed clinical subjects. Despite the large number of clinical studies addressing this issue, experimental evidence of a beneficial or detrimental role of decompressive craniotomy after brain trauma is sparse. Therefore, we investigated the influence of craniotomy on intracranial pressure, contusion volume, and functional outcome in a model of traumatic brain injury in mice. Male C57/Bl6 mice were craniotomized above the right parietal cortex and were subjected to controlled cortical impact injury. In control mice, the craniotomy was closed immediately after trauma, whereas in treated animals the craniotomy was left open. In control mice intracranial pressure (ICP) increased to a maximum of 23.7 +/- 3.1 mm Hg 6 h after trauma (p < 0.001), while in craniotomized animals, no ICP increase was observed. Twenty-four hours after trauma, the point in time of maximal lesion expansion, contusion volume in craniotomized mice was 40% smaller as compared to controls (18.3 +/- 2.0 vs. 30.2 +/- 3.5 mm(3), p < 0.04). Furthermore, craniotomized mice showed significantly improved motor function in a beam walking task (p < 0.04) and faster recovery of body weight after trauma (p < 0.02). Our results demonstrate that craniotomy blunts post-traumatic ICP increase, significantly reduces secondary brain damage and improves functional outcome after experimental TBI. Careful clinical evaluation of craniotomy as a therapeutic option after TBI in man may therefore be indicated.
Infant epidermal skin physiology: adaptation after birth (2011)

Functional and structural skin adaptation is a dynamic process which starts immediately after birth in humans and in mammalian skin in general. This adjustment to the extrauterine dry environment is accomplished in the first year of postnatal life of humans.To assess the dynamic changes in vivo after birth in the molecular composition and skin physiology parameters compared with older children and adults.The molecular composition of the stratum corneum (SC) and the water profile were investigated noninvasively by in vivo Raman confocal microscopy as a function of depth. Functional parameters including transepidermal water loss (characterizing epidermal permeability barrier), capacitance (as an indirect parameter for SC hydration) and skin surface pH were assessed noninvasively. The measurements were performed in 108 subjects divided into six age groups: full-term newborns (1-15 days), babies aged 5-6 weeks, babies aged 6±1 months, children aged 1-2 years, children aged 4-5 years and adults aged 20-35 years.We showed that skin acidification is still under development during the first weeks of life. While the basal epidermal barrier is competent immediately after birth, the SC is less hydrated in the first 2 weeks of postnatal life. Similar continuous decreasing water content towards the surface for all age groups was observed, whereas this gradient was lower for the newborns. Dynamic changes in the amounts of the natural moisturizing factor constituents were revealed in the period of infancy.We demonstrated the relation of formation of an acidic pH as well as underlying mechanisms in the induction of a fully hydrated SC over the first weeks of human life as a dynamic functional adaptation.
Human placenta and fetal membranes contain peptide YY1-36 and peptide YY3-36 (1998)

Extracts of human term amniotic, placental, and chorion/decidua tissue contained, respectively, 4.36 +/- 2.79 (pmol/g wet wt; mean +/- S.E.M.: n = 5). 2.78 +/- 0.5 (n = 5) and 0.68 +/- 0.68 (n = 5) peptide YY (PYY)-like immunoreactivity. Using a specific PYY antiserum, gel filtration chromatography and reverse-phase high performance liquid chromatography (HLPC), amniotic, placental and fetal intestinal tissue extracts were demonstrated to contain PYY-like immunoreactivity consisting of equal amounts of PYY1-36 and PYY3-36. The presence of pancreatic polypeptide was not detected in any of the extracts. Positive immunohistochemical staining for PYY was seen in extravillous trophoblasts in the decidual septa and fetal membranes, the syncytiotrophoblast and cytotrophoblasts, amniotic epithelial cells and in maternal decidual stromal cells. Positive staining for PYY was found at the earliest date examined (9.5 weeks) and remained present throughout pregnancy to term. PYY1-36 and PYY3-36 may play important roles in human pregnancy, acting via endocrine or paracrine mechanisms.
Inventing new medicines: The FGF21 story (2014)

Since the discovery of insulin in 1921, protein therapeutics have become vital tools in the treatment of diabetes mellitus. This heritage has been extended with the comparatively recent introduction of recombinant and re-engineered insulins, in addition to the advent of GLP1 agonists. FGF21 represents an example of a novel experimental protein therapy which is able to induce favorable metabolic effects in various species ranging from rodents to man. The aim of this review is to communicate the story of the FGF21 drug discovery path from identification in a functional in vitro screen, to the eventual evaluation of its utility in patients. Given that the development of FGF21 advanced hand-in-hand with rapidly evolving scientific research around this target, we have also attempted to describe our view of recent developments regarding the mechanistic understanding of FGF21 biology.
Sesquiterpenoid stress metabolites of capsicums (1983)

Conference Article| October 01 1983 Sesquiterpenoid stress metabolites of capsicums DAVID G. WATSON; DAVID G. WATSON Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar FRED C. BAKER; FRED C. BAKER * Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar CHARLES J. W. BROOKS CHARLES J. W. BROOKS Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1983) 11 (5): 589–590. https://doi.org/10.1042/bst0110589 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation DAVID G. WATSON, FRED C. BAKER, CHARLES J. W. BROOKS; Sesquiterpenoid stress metabolites of capsicums. Biochem Soc Trans 1 October 1983; 11 (5): 589–590. doi: https://doi.org/10.1042/bst0110589 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1983 Biochemical Society1983 Article PDF first page preview Close Modal You do not currently have access to this content.
Spectral determination of the amplitude and the phase of intense ultrashort optical pulses (1996)

We present the results of the spectral analysis of intense ultrashort laser pulses propagating through nonlinear transparent media. We discuss the spectral features characteristic of the self-phase-modulation process, which is the most prominent process during nonguided propagation in the weakly nonlinear regime. We describe an application of automatic pulse phase retrieval based on the Kerr-like nonlinearity.
Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters (2005)

Abstract New analogues of 2′‐deoxynucleotides and ribonucleotides incorporating a unique squaramide structure were synthesized. Because of the strong acidity of this moiety (p K a = 2.3), these nucleotide analogues exist in a monoanionic form, which can be regarded as an electronic isoster of 5′‐nucleotides under physiological conditions. The synthesis of the nucleotide analogues was achieved through the condensation of 5′‐ or 3′‐aminonucleosides with dimethyl squarate, whilst the selective removal of the methyl group was effectively accomplished by treatment with sodium bromide. In addition, we also synthesized 3′,5′‐cyclic nucleotide analogues from the 3′,5′‐diazidonucleoside derivatives. NMR analysis revealed that their ribose puckering was of an N‐type form, identical to that in cAMP and cGMP. Because of the unique structural, electronic, and conformational properties of squaramide‐type nucleotide analogues, these analogues should be quite interesting as potential biologically active compounds such as antiviral and anticancer agents. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Deterministic edge-preserving regularization in computed imaging (1997)

Many image processing problems are ill-posed and must be regularized. Usually, a roughness penalty is imposed on the solution. The difficulty is to avoid the smoothing of edges, which are very important attributes of the image. In this paper, we first give conditions for the design of such an edge-preserving regularization. Under these conditions, we show that it is possible to introduce an auxiliary variable whose role is twofold. First, it marks the discontinuities and ensures their preservation from smoothing. Second, it makes the criterion half-quadratic. The optimization is then easier. We propose a deterministic strategy, based on alternate minimizations on the image and the auxiliary variable. This leads to the definition of an original reconstruction algorithm, called ARTUR. Some theoretical properties of ARTUR are discussed. Experimental results illustrate the behavior of the algorithm. These results are shown in the field of 2D single photon emission tomography, but this method can be applied in a large number of applications in image processing.
Reduced tissue macrophage population in the lung by anticancer agent cyclophosphamide: restoration by local granulocyte macrophage–colony-stimulating factor gene transfer (2002)

Granulocytopenia is thought to be the sole mechanism underlying the increased susceptibility to bacterial infection in hosts with anticancer chemotherapy. Little is known about the functional state of tissue macrophage populations in such hosts. Using a model of chemotherapy-induced leukopenia, the number and function of alveolar macrophages (AMS) were examined during and after multiple injections of an anticancer agent, cyclophosphamide (CP). Although CP quickly reduced peripheral blood leukocytes, the number of these cells rebounded quickly 3 to 4 days after the withdrawal of CP. Accompanying blood leukopenia was a profound reduction in the number of AMs. Contrary to the rapid onset of blood leukopenia, tissue macrophage deficiency was a more chronic process that worsened gradually as the CP regimen continued. Of importance, in contrast to blood leukopenia, which restored itself shortly after CP withdrawal, tissue macrophage deficiency was not immediately self-recoverable in spite of a restored number of circulating leukocytes. Although AMS had a decreased ability to proliferate during, but not after, the CP regimen, these cells retained a normal ability to release tumor necrosis factor-alpha and nitric oxide. To identify the potential therapeutics for recovering macrophages, a gene vector expressing granulocyte macrophage-colony-stimulating factor (GM-CSF) was delivered either systemically or locally. GM-CSF transgene was able to expand macrophage populations only when delivered to the lung after, but not during, the CP regimen. This study thus identifies tissue macrophage deficiency as a mechanism of weakened innate immunity by chemotherapy and suggests the usefulness of topical GM-CSF transgene expression for restoring innate immunity in the lung.
Restricted reassociation of heavy and light chains from hapten-specific monoclonal antibodies. (1981)

Six murine monoclonal antifluorescyl antibody clones encompassing a defined range of affinities and containing kappa light chains with IgG1 or IgG2 heavy chains were examined. As the fluorescence of the ligand is quenched greater than 90% when fluorescein is bound by antifluorescyl antibodies, fluorescence quenching was assayed to monitor polypeptide reconstitution and active site formation on mixing of resolved heavy (H) and light (L) chains. Of 36 possible experimental combinations of H- and L-chain reaction mixtures, only homologous H and L chains (derived from the same parental immunoglobulin molecule) bound fluorescein. Results from fluorescence polarization studies, conducted independently of fluorescence quenching, confirmed the findings. Competitive inhibition and molecular sieve experiments showed that, despite preferential association of homologous H and L chains, several heterologous H and L chains associated to form intact 7S molecules, although no active site was constituted. Thus, polypeptide recombination and formation of functional antigen binding sites are two processes that immunocytes must regulate during cell differentiation and generation of diversity. A mechanism and underlying the observed preferential reassociation of specific H and L chains and a means of generating affinity maturation, as exhibited by the antifluorescein system, is proposed.