gebhart/patrepeval huggingface dataset:
Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats (2002)

Acute suppression of dipeptidyl peptidase IV (DPP-IV) activity improves glucose tolerance in the Zucker fatty rat, a rodent model of impaired glucose tolerance, through stabilization of glucagon-like peptide (GLP)-1. This study describes the effects of a new and potent DPP-IV inhibitor, FE 999011, which is able to suppress plasma DPP-IV activity for 12 h after a single oral administration. In the Zucker fatty rat, FE 999011 dose-dependently attenuated glucose excursion during an oral glucose tolerance test and increased GLP-1 (7-36) release in response to intraduodenal glucose. Chronic treatment with FE 999011 (10 mg/kg, twice a day for 7 days) improved glucose tolerance, as suggested by a decrease in the insulin-to-glucose ratio. In the Zucker diabetic fatty (ZDF) rat, a rodent model of type 2 diabetes, chronic treatment with FE 999011 (10 mg/kg per os, once or twice a day) postponed the development of diabetes, with the twice-a-day treatment delaying the onset of hyperglycemia by 21 days. In addition, treatment with FE 999011 stabilized food and water intake to prediabetic levels and reduced hypertriglyceridemia while preventing the rise in circulating free fatty acids. At the end of treatment, basal plasma GLP-1 levels were increased, and pancreatic gene expression for GLP-1 receptor was significantly upregulated. This study demonstrates that DPP-IV inhibitors such as FE 999011 could be of clinical value to delay the progression from impaired glucose tolerance to type 2 diabetes.
Biochemical and functional analyses of a secreted H-2Ld molecule. (1986)

A truncated H-2Ld gene was constructed by deleting the transmembrane and cytoplasmic exons. The truncated H-2Ld gene was introduced into mouse L cells using the thymidine kinase gene as a selectable marker. Transformants were isolated and screened for the presence of truncated H-2Ld antigen. The truncated H-2Ld gene product was present in both the cytoplasm and culture medium, but not on the cell surface. The truncated H-2Ld antigen was stable in culture medium for at least 9 h and was secreted into the medium at a rate similar to the kinetics with which complete H-2 antigens reach the cell surface. Transformants expressing the truncated H-2Ld molecule were not recognized by cytotoxic T lymphocytes specific for the H-2Ld antigen.
Glutamatergic and resting state functional connectivity correlates of severity in major depression - the role of pregenual anterior cingulate cortex and anterior insula (2010)

Glutamatergic mechanisms and resting-state functional connectivity alterations have been recently described as factors contributing to major depressive disorder (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play an important role for major depressive symptoms such as anhedonia and impaired emotion processing. We investigated 22 MDD patients and 22 healthy subjects using a combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) approach. Severity of depression was rated using the 21-item Hamilton depression scale (HAMD) and patients were divided into severely and mildly depressed subgroups according to HAMD scores. Because of their hypothesized role in depression we investigated the functional connectivity between pgACC and left anterior insular cortex (AI). The sum of Glutamate and Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state functional connectivity between the two regions exclusively in depressed patients. Furthermore, functional connectivity between these regions was significantly altered in the subgroup of severely depressed patients (HAMD > 15) compared to healthy subjects and mildly depressed patients. Similarly the Glx ratios, relative to Creatine, in the pgACC were lowest in severely depressed patients. These findings support the involvement of glutamatergic mechanisms in severe MDD which are related to the functional connectivity between pgACC and AI and depression severity.
Essential Role for the Lymphostromal Plasma Membrane Ly-6 Superfamily Molecule Thymic Shared Antigen 1 in Development of the Embryonic Adrenal Gland (2002)

Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system. TSA-1 is also expressed in other nonhematopoietic tissues, in particular, embryonic and adult adrenal glands. To address the function of TSA-1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting. Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities. We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline. We conclude that TSA-1 is required for normal embryonic development but that deletion of its expression does not obviously impair lymphoid development.
A study of reconstruction artifacts in cone beam tomography using filtered backprojection and iterative EM algorithms (1990)

Reconstruction artifacts in cone beam tomography are studied for filtered backprojection (Feldkamp) and iterative EM algorithms. The filtered backprojection algorithm uses a voxel-driven, interpolated backprojection to reconstruct the cone beam data, whereas the iterative EM algorithm performs ray-driven projection and backprojection operations for each iteration. Two weighting schemes for the projection and backprojection operations in the EM algorithm are studied. One weights each voxel by the length of the ray through the voxel and the other equates the value of a voxel to the functional value of the midpoint of the line intersecting the voxel, which is obtained by interpolating between eight neighboring voxels. Cone beam reconstruction artifacts such as rings, bright vertical extremities, and slice-to-slice cross-talk are not found with parallel beam and fan beam geometries. When using filtered backprojection and iterative EM algorithms, the line-length weighting is susceptible to ring artifacts which are improved by using interpolated projector-backprojectors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Microwave-tomographic imaging of the high dielectric-contrast objects using different image-reconstruction approaches (2005)

Microwave tomography is an imaging modality based on differentiation of dielectric properties of an object. The dielectric properties of biological tissues and its functional changes have high medical significance. Biomedical applications of microwave tomography are a very complicated and challenging problem, from both technical and image reconstruction point-of-views. The high contrast in tissue dielectric properties presenting significant advantage for diagnostic purposes possesses a very challenging problem from an image-reconstruction prospective. Different imaging approaches have been developed to attack the problem, such as two-dimensional (2-D) and three-dimensional (3-D), minimization, and iteration schemes. The goal of this research is to study imaging performance of the Newton and the multiplicative regularized contrast source inversion (MR-CSI) methods in 2-D geometry and gradient and MR-CSI methods in 3-D geometry using high-contrast, medium-size phantoms, and biological objects. Experiments were conducted on phantoms and excised segment of a pig hind-leg using a 3-D microwave-tomographic system operating at frequencies of 0.9 and 2.05 GHz. Both objects being of medium size (10-15 cm) possess high dielectric contrasts. Reconstructed images were obtained using all imaging approaches. Different approaches are evaluated and discussed based on its performance and quality of reconstructed images.
Standoff Detection of Chemicals Using Porous Silicon “Smart Dust” Particles (2002)

“Smart dust”—small particles of optically encoded microporous Si—can detect organic vapors by measurement of the intensity of reflected light using a laser probe and a detector stationed 20 m away (see Figure and inside front cover). The porous particles absorb condensable vapors, producing a change in refractive index and consequently a quantitative change in optical reflectivity at the wavelength of the laser.
The Role of Electrospinning in the Emerging Field of Nanomedicine (2006)

The fact that in vivo the extracellular matrix (ECM) or substratum with which cells interact often includes topography at the nanoscale underscores the importance of investigating cell-substrate interactions and performing cell culture at the submicron scale. An important and exciting direction of research in nanomedicine would be to gain an understanding and exploit the cellular response to nanostructures. Electrospinning is a simple and versatile technique that can produce a macroporous scaffold comprising randomly oriented or aligned nanofibers. It can also accommodate the incorporation of drug delivery function into the fibrous scaffold. Endowed with both topographical and biochemical signals such electrospun nanofibrous scaffolds may provide an optimal microenvironment for the seeded cells. This review covers the analysis and control of the electrospinning process, and describes the types of electrospun fibers fabricated for biomedical applications such as drug delivery and tissue engineering.
Abstract PR15: Engineering phagocytic signaling (2016)

Abstract Phagocytosis of specific targets in clinically-relevant settings, including engulfment of tumor cells and removal of cell corpses following aggressive cancer treatment, has been hampered by an incomplete understanding of phagocytic signaling. Therefore, we developed a cellular reconstitution platform amenable to direct, real-time imaging to dissect phagocytic signaling in molecular detail. Our gain-of-function system converts inept phagocytes into efficient ones, enabling us to appreciate the signaling behaviors associated with phagocytic proficiency. We report that 1) phagocytosis receptors form mobile microclusters in response to ligation, 2) microclusters recruit cytosolic collaborators to the plasma membrane and spatially organize actin dynamics at the phagocytic synapse, and 3) the natural ligand-receptor pair can be replaced by an engineered module, indicating that phagocytic signaling can be reprogrammed towards specific targets. Thus, we have discovered that a conserved signaling system required for recognition and removal of altered self bears unexpected mechanistic similarity to adaptive immune responses directed towards pathogens and tumor cells. In addition, our ability to replace the endogenous receptor with a heterologous system indicates that phagocytosis can be programmed in a manner conceptually similar to the Chimeric Antigen Receptor used in the clinic to program cytotoxic T cells to kill tumor cells. Our ability to engineer the process suggests that methods to re-direct phagocytes towards targets of clinical importance are possible, approaches that may enable recognition and removal of tumor cells and boost the anti-tumor immune response. Citation Format: Adam Williamson, Ron Vale. Engineering phagocytic signaling [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR15.
Expression of a Brassica napus Malate Synthase Gene in Transgenic Tomato Plants during the Transition from Late Embryogeny to Germination (1992)

To study gene regulation during the transition from late embryogeny to germination, we have analyzed the expression of a gene encoding the glyoxylate cycle enzyme malate synthase in transgenic tomato (Lycopersicon esculentum) plants. We have shown that although there are at least four classes of malate synthase genes in Brassica napus L., one gene is expressed at a high level during both late embryogeny and postgermination. Analyses of transgenic tomato plants containing the expressed B. napus gene along with 4.7 and 1.0 kilobase pairs of 5' and 3' flanking sequences, respectively, confirmed that a single gene is expressed at both stages of development. Furthermore, localization studies have shown that mRNA encoded by the B. napus gene is distributed throughout the tissues of a mature embryo but is not detected in the vascular cylinder of a seedling. We conclude that the sequences required to qualitatively regulate the gene correctly over the plant life cycle are present within the transferred gene and/or flanking regions. Moreover, the malate synthase gene is regulated differently during late embryogeny and postgermination in the developing vascular cylinder.
Insecticide Toxicology, Mammalian Toxicity of 1-Naphthyl-N-methylcarbamate (Sevin Insecticide) (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInsecticide Toxicology, Mammalian Toxicity of 1-Naphthyl-N-methylcarbamate (Sevin Insecticide)C. P. Carpenter, C. S. Weil, P. E. Palm, M. W. Woodside, J. H. Nair III, and H. F. Smyth Jr.Cite this: J. Agric. Food Chem. 1961, 9, 1, 30–39Publication Date (Print):January 1, 1961Publication History Published online1 May 2002Published inissue 1 January 1961https://pubs.acs.org/doi/10.1021/jf60113a009https://doi.org/10.1021/jf60113a009research-articleACS PublicationsRequest reuse permissionsArticle Views316Altmetric-Citations112LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Helices and Sheets in vacuo (2007)

The structures and properties of unsolvated peptides large enough to possess secondary structure have been examined by experiments and simulations. Some of the factors that stabilize unsolvated helices and sheets have been identified. The charge, in particular, plays a critical role in stabilizing alpha-helices and destabilizing beta-sheets. Some helices are much more stable in vacuum than in aqueous solution. Factors like helix propensity, context, and the incorporation of specific stabilizing interactions have been examined. The helix propensities in vacuum differ from those found in solution. Studies of the hydration of unsolvated peptides can be performed one water molecule at a time. The first few water molecules only bind weakly to unsolvated peptides, and they bind much more strongly to some conformations than to others. The most favorable binding locations are not the protonation sites, but clefts or pockets where a water molecule can establish a network of hydrogen bonds. Non-covalent interactions between secondary structure elements leads to the formation of tertiary structure. Helical peptides assemble into complexes with a variety of intriguing structures. The intramolecular coupling of helices to make antiparallel coiled-coil geometries has also been investigated with model peptides.
Prostate cancer immunotherapy (2007)

Results from several recent clinical trials have suggested that immune-based therapies have clinical benefit in patients with prostate cancer with potentially less toxicity than traditional systemic treatments. We review recent reports of immunotherapies being evaluated in patients with prostate cancer, and highlight the direction for these therapies in combination with other immunotherapies and other traditional therapies.
Induction of Epstein-Barr Virus Kinases To Sensitize Tumor Cells to Nucleoside Analogues (2001)

The presence of Epstein-Barr virus (EBV) in the tumor cells of some EBV-associated malignancies may facilitate selective killing of these tumor cells. We show that treatment of an EBV(+) Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression, including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell line to all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK-expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 microM) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 microM) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected with the EBV TK expression vector than of cells transfected with the control mutant vector (50 microM GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU- or PCV-mediated cell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.
Identification of a naturally processed cyclin D1 T‐helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry (2004)

T-helper (Th) cells play an important role in orchestrating the effector function of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen-presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA-bound peptides and identification of the antigen-derived peptides by mass spectrometric comparison to the non-transfected cells. In vitro-stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy.
The Heterodimeric Sweet Taste Receptor has Multiple Potential Ligand Binding Sites (2006)

The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes.
Purification and Characterization of a Novel Heparinase from Bacteroides stercoris HJ-15 (2000)

A novel type of heparinase (heparin lyase, no EC number) has been purified from Bacteroides stercoris HJ-15, isolated from human intestine, which produces three kinds of heparinases. The enzyme was purified to apparent homogeneity by a combination of QAE-cellulose, DEAE-cellulose, CM-Sephadex C-50, hydroxyapatite, and HiTrap SP chromatographies with a final specific activity of 19.5 mmol/min/mg. It showed optimal activity at pH 7.2 and 45 degrees C and the presence of 300 mM KCl greatly enhanced its activity. The purified enzyme activity was inhibited by Cu(2+), Pb(2+), and some agents that modify histidine and cysteine residues, and activated by reducing agents such as dithiothreitol and 2-mercaptoethanol. This purified Bacteroides heparinase is an eliminase that shows its greatest activity on bovine intestinal heparan sulfate, and to a lesser extent on porcine intestinal heparan sulfate and heparin. This enzyme does not act on acharan sulfate but de-O-sulfated acharan sulfate and N-sulfoacharan sulfate were found to be poor substrates. The substrate specificity of this enzyme is similar to that of Flavobacterial heparinase II. However, an internal amino acid sequence of the purified Bacteroides heparinase shows significant (73%) homology to Flavobacterial heparinase III and only 43% homology to Flavobacterial heparinase II. These findings suggest that the Bacteroidal heparinase is a novel enzyme degrading GAGs.