gebhart/patrepeval huggingface dataset:
Imaging Methods in Gene Therapy of Cancer (2001)

Clinical gene therapy needs non invasive tools to evaluate the efficiency of gene transfer. This includes the evaluation of infection efficiency as well as the verification of successful gene transfer in terms of gene transcription. These informations can be used for therapy planning, follow up studies in treated tumors and as an indicator of prognosis. Therapy planning is performed by the assessment of gene expression for example using radiolabeled specific substrates to determine the activity of suicide enzymes as the Herpes Simplex Virus thymidine kinase or cytosine deaminase. Furthermore, other in vivo reporter genes as receptors, antigens or transport proteins may be used in bicistronic vector systems for the evaluation of gene transduction and expression. This is done using radiolabeled ligands, antigens or substrates. Follow up studies with magnetic resonance imaging, single photon emission tomography or positron emission tomography may be done to evaluate early or late effects of gene therapy on tumor volume, metabolism or proliferation. Finally, enhancement of radioactive isotope accumulation in tumors by transfer of the appropriate genes may be used for the treatment of malignant tumors.
Identification of the subunits of GTP-binding proteins coupled to somatostatin receptors. (1991)

Somatostatin (SRIF) induces its biological effects by interacting with membrane-bound receptors that are linked to cellular effector systems via G proteins. We have studied SRIF receptor-G protein associations by solubilizing the SRIF receptor from rat brain and AtT-20 cells and immunoprecipitating the receptor-G protein complex with peptide-directed antisera against the different subunits of the G protein heterotrimer. Antiserum 8730, which selectively interacts with all Gi alpha subtypes, maximally and specifically immunoprecipitated SRIF receptor-Gi alpha complexes. To identify the subtypes of Gi alpha that are coupled to SRIF receptors, the subtype-selective antisera 3646, 1521, and 1518, which specifically interact with Gi alpha 1, Gi alpha 2, and Gi alpha 3, respectively, were used to immunoprecipitate SRIF receptor-Gi alpha complexes. Antiserum 3646 immunoprecipitated SRIF receptor-Gi alpha 1 complexes from both brain and AtT-20 cells. Antiserum 1521 immunoprecipitated Gi alpha 2 from both brain and AtT-20 cells but did not immunoprecipitate SRIF receptors from these tissues. Antiserum 1518 immunoprecipitated AtT-20 cell SRIF receptors but uncoupled brain SRIF receptor-G protein complexes. This result was confirmed with another peptide-selective antiserum, SQ, directed against Gi alpha 3. The findings from these studies indicate that Gi alpha 1 and Gi alpha 3 are coupled to SRIF receptors, whereas Gi alpha 2 is not. Even though brain and AtT-20 cell SRIF receptors were both coupled to Gi alpha, the receptors from these tissues differed in their coupling to Go alpha. Antiserum 2353, which is directed against Go alpha, immunoprecipitated SRIF receptors from AtT-20 cells, but did not immunoprecipitate or uncouple SRIF receptor-G protein complexes from rat brain. To determine the beta subunits associated with the SRIF receptor, antisera directed against G beta 36 and G beta 35 were used to immunoprecipitate SRIF receptor-G protein complexes from brain. Peptide-directed antiserum against G beta 36 selectively immunoprecipitated solubilized brain SRIF receptors. However, antiserum directed against the G beta 35 subunit did not immunoprecipitate brain SRIF receptors, suggesting that brain SRIF receptors may preferentially associate with G beta 36. In addition to coimmunoprecipitating with Gi alpha and G beta, brain SRIF receptors coimmunoprecipitated the G protein gamma subunits, G gamma 2 and G gamma 3. These results provide the first evidence that SRIF receptors are coupled to different subunits of G proteins and suggest that selectivity exists in the association of different G protein subunits with the SRIF receptor.
Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria (2007)

Small changes in tumor size or density on CT are sensitive and specific methods of assessing the response of GISTs. If the prognostic value of our proposed CT response criteria can be confirmed prospectively, the criteria should be employed in future studies of patients with GIST.
Example‐based Multiple Local Color Transfer by Strokes (2008)

Abstract This paper investigates a new approach for color transfer. Rather than transferring color from one image to another globally, we propose a system with a stroke‐based user interface to provide a direct indication mechanism. We further present a multiple local color transfer method. Through our system the user can easily enhance a defect (source) photo by referring to some other good quality (target) images by simply drawing some strokes. Then, the system will perform the multiple local color transfer automatically. The system consists of two major steps. First, the user draws some strokes on the source and target images to indicate corresponding regions and also the regions he or she wants to preserve. The regions to be preserved which will be masked out based on an improved graph cuts algorithm. Second, a multiple local color transfer method is presented to transfer the color from the target image(s) to the source image through gradient‐guided pixel‐wise color transfer functions. Finally, the defect (source) image can be enhanced seamlessly by multiple local color transfer based on some good quality (target) examples through an interactive and intuitive stroke‐based user interface.
Nerve fibre regeneration after traumatic lesions of the CNS; progress and problems (1991)

Abstract Four distinct phases can be distinguished in the regenerative response of a lesioned CNS axon: sprouting of the proximal axon stump, elongation, target recognition, and formation of appropriate synapses. These processes can be observed in such a way only in lower vertebrates, in particular, in the optic system. In these species and systems, both, the guidance mechanisms leading regenerating fibres to their former target areas, and the mechanisms responsible for specific synapse formation are retained throughout life. As during development, guidance crucially depends on the presence of favourable substrate molecules, and on chemotropic signals (Dodd &amp; Jessel 1989; Tessier-Lavigne et al.1988; Harris 1989). The cell biological mechanisms responsible for target recognition including the arrest of long-distance growth, the initiation of side branch formation and terminal arborization, and the selection of specific post-synaptic partners (cell type; soma, proximal or distal dendrite, spines, axons) remain unknown up to now.
Drug Delivery to the Inner Ear: Strategies and Their Therapeutic Implications for Sensorineural Hearing Loss (2012)

Hearing aids or cochlear implants constitute almost exclusively the treatment options currently available to patients suffering from sensorineural hearing loss and related conditions, such as noise-induced hearing loss, ototoxicity or autoimmune inner ear disease. While some systemic treatments exist, they generally exert adverse secondary effects and their efficacy is hampered by the blood-cochlear barrier that limits drug access to the inner ear. Hence, the new therapies that are being developed for hearing loss focus on strategies for direct drug delivery to the inner ear. The passive and active methods for local delivery can be categorized into two general groups: intratympanic or intracochlear. The intratympanic approach is a non-invasive method that preserves hearing and takes advantage of the permeability of the round window to gain access to the cochlea. However, this technique is limited by not knowing the dose of the drug that reaches the cochlea, (a handicap which might be overcome by the use of tagged drugs). While direct access to the inner ear by intracochlear administration avoids this problem, this method requires surgery. Currently, laboratory animals are being used to explore which therapeutic approaches are best suited to address this problem. These include cochleostomy and the insertion of devices that pump drugs into the inner ear without inducing cochlear damage. In this article, we review the different techniques under evaluation in animal models of deafness, and their potential use for drug delivery and treatment of human inner ear diseases.
Organic Synthesis in the Solid State via Hydrogen-Bond-Driven Self-Assembly (2008)

This Perspective describes how chemists can control intermolecular [2 + 2] photodimerizations in the solid state using small molecules as linear templates. The templates assemble olefins into positions for the reaction via hydrogen-bond-driven self-assembly. We attach functional groups to the olefins that complement hydrogen bond donor and acceptor groups of the templates. The resulting cyclobutane-based products form stereospecifically, quantitatively, and in gram amounts. The templates are used to direct the formation of a [2.2]paracyclophane and ladderanes. The organic solid state is an exciting medium within which to control chemical reactivity since it is possible to synthesize, or construct, molecules that may be, otherwise, unobtainable from solution. The products form with a high degree of stereocontrol provided by a crystal lattice. The critical covalent-bond-forming process also occurs in a solvent-free environment. That molecules are virtually frozen in position in a solid also means that this methodology enables chemists to employ principles of molecular recognition and self-assembly to direct and conduct organic synthesis.
Cooperative activation of human factor IX by the human extrinsic pathway of blood coagulation (1991)

The activation of human coagulation factor IX by human tissue factor.factor VIIa.PCPS.Ca2+ (TF.VIIa.PCPS.Ca2+) and factor Xa.PCPS.Ca2+ enzyme complexes was investigated. Reactions were performed in a highly purified system consisting of isolated human plasma proteins and recombinant human tissue factor with synthetic phospholipid vesicles (PCPS: 75% phosphatidylcholine (PC), 25% phosphatidylserine (PS)). Factor IX activation was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, [3H]factor IX activation peptide assay, colorimetric substrate thiobenzyl benzyloxycarbonyl-L-lysinate (Z-Lys-SBzl) hydrolysis, and specific incorporation of a fluorescent peptidyl chloromethyl ketone. Factor IX activation by the TF.VIIa.PCPS.Ca2+ enzyme complex was observed to proceed through the obligate non-enzymatic intermediate species factor IX alpha. The simultaneous activation of human coagulation factors IX and X by the TF.VIIa.PCPS.Ca2+ enzyme complex were investigated. When factors IX and X were presented to the TF.VIIa complex, at equal concentrations, it was observed that the rate of factor IX activation remained unchanged while the rate of factor X activation slowed by 45%. When the proteolytic cleavage products of this reaction were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was observed that the intermediate species factor IX alpha was generated more rapidly when factor X was present in the reaction mixture. When factor IX was treated with factor Xa.PCPS in the presence of Ca2+, it was observed that factor IX was rapidly converted to factor IX alpha. The activation of factor IX alpha by the TF.VIIa.PCPS.Ca2+ complex was evaluated, and it was observed that factor IX alpha was activated more rapidly by the TF.VIIa.PCPS.Ca2+ complex than was factor IX itself. These data suggest that factors IX and X, when presented to the TF.VIIa.PCPS.Ca2+ enzyme complex, are both rapidly activated and that factor Xa, which is generated in the initial stages of the extrinsic pathway, participates in the first proteolytic step in the activation of factor IX, the generation of factor IX alpha.
Requirement of IFN-γ–Mediated Indoleamine 2,3-Dioxygenase Expression in the Modulation of Lymphocyte Proliferation by Human Adipose–Derived Stem Cells (2009)

Human adipose-derived mesenchymal stem cells (hASCs) are mesenchymal stem cells (MSCs) with reduced immunogenicity and capability to modulate immune responses. Whereas the immunosuppressive activity of bone marrow-MSCs has received considerable attention during the last few years, the specific mechanisms underlying hASC-mediated immunosuppression have been poorly studied. Recent studies comparing both cell types have reported differences at transcriptional and proteomic levels, suggesting that hASCs and bone marrow-MSCs, while having similarities, are quite different. This suggests that different mechanisms of immunosuppression may apply. Here, we report that hASCs inhibit peripheral blood mononuclear cells (PBMCs), and CD4(+) and CD8(+) T cell proliferation in both cell-cell contact and transwell conditions, which is accompanied by a reduction of proinflammatory cytokines. We demonstrate that hASCs do not constitutively express immunomodulatory factors. Conditioned supernatants from hASCs stimulated by IFN-gamma, PBMCs, or activated PBMCs highly inhibited PBMC proliferation, indicating that inhibitory factors are released upon hASC activation. Many factors have been involved in MSC-mediated immunosuppression, including IFN-gamma, IL-10, hepatocyte growth factor, prostaglandin E2, transforming growth factor-beta1, indoleamine 2,3-dioxygenase (IDO), nitric oxide, and IL-10. Using pharmacological inhibitors, neutralizing antibodies, and genetically modified hASCs that constitutively express or silence IDO enzyme, we demonstrate that, in the case of hASCs, the IFN-gamma/IDO axis is essential. Taken together, our data support the key role of IDO in the therapeutic use of hASC on immunomediated diseases.
INTERSPECIFIC HYBRIDIZATION IN CUCURBITA: II C. moschata Poir × Xerophytic Species of Cucurbita (1963)

Journal Article INTERSPECIFIC HYBRIDIZATION IN CUCURBITA: II C. moschata Poir × Xerophytic Species of Cucurbita Get access W. P. BEMIS W. P. BEMIS Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 54, Issue 6, November 1963, Pages 285–289, https://doi.org/10.1093/oxfordjournals.jhered.a107269 Published: 01 November 1963
The Viviparous-1 gene and abscisic acid activate the C1 regulatory gene for anthocyanin biosynthesis during seed maturation in maize. (1992)

The Viviparous-1 (Vp1) gene is required for expression of the C1 regulatory gene of the anthocyanin pathway in the developing maize seed. We show that VP1 overexpression and the hormone, abscisic acid (ABA), activate a reporter gene driven by the C1 promoter in maize protoplasts. Cis-acting sequences essential for these responses were localized. Mutation of a conserved sequence in the C1 promoter abolishes both ABA regulation and VP1 trans-activation. An adjacent 5-bp deletion blocks ABA regulation but not VP1 trans-activation. The latter mutant reconstructs the promoter of c1-p, an allele that is expressed during seed germination but not during seed maturation. We suggest that VP1 activates C1 specifically during maturation by interacting with one or more ABA-regulated transcription factors.
Recombinant Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake and Improves Left Ventricular Performance in Conscious Dogs With Pacing-Induced Dilated Cardiomyopathy (2004)

rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.
Improved methods for building protein models in electron density maps and the location of errors in these models (1991)

Map interpretation remains a critical step in solving the structure of a macromolecule. Errors introduced at this early stage may persist throughout crystallographic refinement and result in an incorrect structure. The normally quoted crystallographic residual is often a poor description for the quality of the model. Strategies and tools are described that help to alleviate this problem. These simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
BaSi2 and thin film alkaline earth silicides on silicon (1993)

The epitaxial structural development and surface reactions of the alkaline earth metals with silicon have been studied as a function of surface coverage. The barium reaction has been characterized in detail from submonolayer structures to the thick film orthorhombic phase, BaSi2. From 0 to 1 monolayer a series of ordered surface structures develops that suggests a cubic Ba-Si compound. We have also shown that strontium, calcium, and magnesium develop these highly ordered submonolayer silicides. These submonolayer structures are the templates for the heteroepitaxial transition to alkaline earth containing oxides on silicon.
Controlled Alternate Layer-by-Layer Assembly of Lectins and Glycopolymers Using QCM-D (2011)

Layer-by-layer (LBL) assembly of concanavalin A (Con A), peanut agglutinin (PNA) plant lectins, and well-defined synthetic glycopolymers via their biological affinities have been prepared using a quartz crystal microbalance with dissipation monitoring (QCM-D). We demonstrate the use of mannose/galactose glycopolymers as lectin binders due to their selective binding to Con A/PNA, respectively. A detailed analysis of the adsorption processes and the adsorbed layer are provided and tuning the composition of multilayers using a series of well-defined glycopolymers differing only in the pendant sugar ratio is discussed.
Structure and evolution of genes encoding polyubiquitin and ubiquitin-like proteins in Arabidopsis thaliana ecotype Columbia. (1995)

The Arabidopsis thaliana ecotype Columbia ubiquitin gene family consists of 14 members that can be divided into three types of ubiquitin genes; polyubiquitin genes, ubiquitin-like genes and ubiquitin extension genes. The isolation and characterization of eight ubiquitin sequences, consisting of four polyubiquitin genes and four ubiquitin-like genes, are described here, and their relationships to each other and to previously identified Arabidopsis ubiquitin genes were analyzed. The polyubiquitin genes, UBQ3, UBQ10, UBQ11 and UBQ14, contain tandem repeats of the 228-bp ubiquitin coding region. Together with a previously described polyubiquitin gene, UBQ4, they differ in synonymous substitutions, number of ubiquitin coding regions, number and nature of nonubiquitin C-terminal amino acid(s) and chromosomal location, dividing into two subtypes; the UBQ3/UBQ4 and UBQ10/UBQ11/UBQ14 subtypes. Ubiquitin-like genes, UBQ7, UBQ8, UBQ9 and UBQ12, also contain tandem repeats of the ubiquitin coding region, but at least one repeat per gene encodes a protein with amino acid substitutions. Nucleotide comparisons, Ks value determinations and neighbor-joining analyses were employed to determine intra- and intergenic relationships. In general, the rate of synonymous substitution is too high to discern related repeats. Specific exceptions provide insight into gene relationships. The observed nucleotide relationships are consistent with previously described models involving gene duplications followed by both unequal crossing-over and gene conversion events.
SARCOSYL-PAGE: A New Electrophoretic Method for the Separation and Immunological Detection of PEGylated Proteins (2012)

PEGylation of recombinant proteins and synthetic peptides aims to generate biopharmaceuticals with altered physical properties. The modification may lead to a prolonged serum half-life caused by a decreased receptor-mediated endocytosis and/or a delay in renal clearance caused by the increased hydrodynamic volume of the pharmaceutical. MIRCERA, a PEGylated recombinant erythropoietin (rhEpo) frequently used in the treatment of anemia due to chronic kidney disease, has been also abused by athletes as a performance-enhancing drug. While it can be detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting, the sensitivity of the test is significantly lower compared to other epoetins. By replacing SDS with sarcosyl in the sample and running buffers, the interaction between SDS and the PEG group of the protein no longer reduces the affinity of the monoclonal anti-Epo antibody (clone AE7A5) to the protein chain. Contrary to SDS, sarcosyl only binds to the amino acid chain of the PEGylated protein, thus leading to enhanced antibody binding and a sharper electrophoretic band. While the method was originally developed for anti-doping purposes, it may be also useful for other PEGylated proteins and their electrophoretic separation and immunological detection.
Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. (1990)

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2(+)-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2(+)-ATPase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P less than 0.01 and -47%, P less than 0.05, respectively). The LV ratio of Ca2(+)-ATPase mRNA to 18S RNA positively correlated with cardiac index (P less than 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P less than 0.02, P less than 0.02, and P less than 0.01, respectively). We suggest that a decrease of the SR Ca2(+)-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.
Successful Antimanic Treatment and Mood Stabilization with Lamotrigine, Clozapine, and Valproate in a Bipolar Patient after Lithium-induced Cerebellar Deterioration (2003)

We report the case of a 56-year-old male with an 18-year history of a bipolar I affective disorder (DSM-IV criteria), who has been successfully treated with lithium for 8 years. When lithium was discontinued due to a lithium-induced persistent cerebellar syndrome at therapeutic lithium levels, the combination of valproate and clozapine was less effective to achieve mood stabilization. A re-challenge with lithium failed due to impairment of neurological symptoms. When lamotrigine at a daily dose of 50 mg was co-administered to valproate and clozapine, the patient’s condition improved rapidly and remained stable over a follow-up period of 12 months. Concomitant administration of lamotrigine increased the serum levels of both valproate and clozapine. We conclude that