Computer Aided Rating of Large Diameter Rotation Bearings

An interactive computer aided analysis program is developed to assist in the rating of large diameter, special configuration, case hardened, four point contact ball bearings. The rating equations are developed from the results of two models. The finite element method is used for one model. The second model will consist of equations that are developed assuming the bearing race remain rigid when loaded. With dimensional parameters from several bearings, moment, radial, and thrust loads will be applied to both models. As needed, relationships between the two models will be obtained for the rating equations.Mechanical Engineerin

Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases

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Antibody Selection for Cancer Target Validation of FSH-Receptor in Immunohistochemical Settings

Background: The follicle-stimulating hormone (FSH)-receptor (FSHR) has been reported to be an attractive target for antibody therapy in human cancer. However, divergent immunohistochemical (IHC) findings have been reported for FSHR expression in tumor tissues, which could be due to the specificity of the antibodies used. Methods: Three frequently used antibodies (sc-7798, sc-13935, and FSHR323) were validated for their suitability in an immunohistochemical study for FSHR expression in different tissues. As quality control, two potential therapeutic anti-hFSHR Ylanthia® antibodies (Y010913, Y010916) were used. The specificity criteria for selection of antibodies were binding to native hFSHR of different sources, and no binding to non-related proteins. The ability of antibodies to stain the paraffin-embedded Flp-In Chinese hamster ovary (CHO)/FSHR cells was tested after application of different epitope retrieval methods. Results: From the five tested anti-hFSHR antibodies, only Y010913, Y010916, and FSHR323 showed specific binding to native, cell-presented hFSHR. Since Ylanthia® antibodies were selected to specifically recognize native FSHR, as required for a potential therapeutic antibody candidate, FSHR323 was the only antibody to detect the receptor in IHC/histochemical settings on transfected cells, and at markedly lower, physiological concentrations (ex., in Sertoli cells of human testes). The pattern of FSH323 staining noticed for ovarian, prostatic, and renal adenocarcinomas indicated that FSHR was expressed mainly in the peripheral tumor blood vessels. Conclusion: Of all published IHC antibodies tested, only antibody FSHR323 proved suitable for target validation of hFSHR in an IHC setting for cancer. Our studies could not confirm the previously reported FSHR overexpression in ovarian and prostate cancer cells. Instead, specific overexpression in peripheral tumor blood vessels could be confirmed after thorough validation of the antibodies used

Vorausbezahlte Karten: eine Bewertung aus der Sicht der Deutschen Bundesbank

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 378 (36) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Antibody Selection for Cancer Target Validation of FSH-Receptor in Immunohistochemical Settings

Background: The follicle-stimulating hormone (FSH)-receptor (FSHR) has been reported to be an attractive target for antibody therapy in human cancer. However, divergent immunohistochemical (IHC) findings have been reported for FSHR expression in tumor tissues, which could be due to the specificity of the antibodies used. Methods: Three frequently used antibodies (sc-7798, sc-13935, and FSHR323) were validated for their suitability in an immunohistochemical study for FSHR expression in different tissues. As quality control, two potential therapeutic anti-hFSHR Ylanthia® antibodies (Y010913, Y010916) were used. The specificity criteria for selection of antibodies were binding to native hFSHR of different sources, and no binding to non-related proteins. The ability of antibodies to stain the paraffin-embedded Flp-In Chinese hamster ovary (CHO)/FSHR cells was tested after application of different epitope retrieval methods. Results: From the five tested anti-hFSHR antibodies, only Y010913, Y010916, and FSHR323 showed specific binding to native, cell-presented hFSHR. Since Ylanthia® antibodies were selected to specifically recognize native FSHR, as required for a potential therapeutic antibody candidate, FSHR323 was the only antibody to detect the receptor in IHC/histochemical settings on transfected cells, and at markedly lower, physiological concentrations (ex., in Sertoli cells of human testes). The pattern of FSH323 staining noticed for ovarian, prostatic, and renal adenocarcinomas indicated that FSHR was expressed mainly in the peripheral tumor blood vessels. Conclusion: Of all published IHC antibodies tested, only antibody FSHR323 proved suitable for target validation of hFSHR in an IHC setting for cancer. Our studies could not confirm the previously reported FSHR overexpression in ovarian and prostate cancer cells. Instead, specific overexpression in peripheral tumor blood vessels could be confirmed after thorough validation of the antibodies used

Synthesis of Diazirine-Based Photoreactive Saccharin Derivatives for the Photoaffinity Labeling of Gustatory Receptors

Saccharin is one of the most common artificial sweeteners that has a bitter taste at high concentrations. Currently, there are no detailed functional analyses of these gustatory receptors. Therefore, we designed and synthesized photoreactive saccharin derivatives that contain a (trifluoromethyl) diazirinyl moiety at the 5- or 6-position for use as functional analysis tools for photoaffinity labeling

Cyclic Secondary Sulfonamides: Unusually Good Inhibitors of Cancer-Related Carbonic Anhydrase Enzymes

Carbonic anhydrase IX (CA IX) is a target for hypoxic cancer therapies, and the discovery of CA IX selective ligands is imperative for the development of these agents. Primary sulfonamides are broad specificity inhibitors of CA enzymes, while secondary sulfonamides are generally poor CA inhibitors. However, saccharin, a cyclic secondary sulfonamide, has unusually good inhibition of CA IX (<i>K</i>_i = 103 nM). In this study, we demonstrate that the affinity and selectivity of saccharin for CA IX can be further modulated when linked to hydrophobic or hydrophilic substituents. The hydrophilic glyco­conjugate derivative (<b>12</b>) showed improved inhibition of CA IX (<i>K</i>_i = 49.5 nM) and extremely poor inhibition of the predominant off-target CAs (<i>K</i>_i > 50 000 nM) compared to saccharin. This >1000-fold selectivity for CA IX over off-target CAs is unprecedented for classical primary sulfonamide CA inhibitors. Our study highlights the potential of cyclic secondary sulfonamides to be exploited for the discovery of potent, cancer-selective CA inhibitors

Mechanisms of action of carbonic anhydrase inhibitors: compounds that bind “out of the binding site” and compounds with an unknown mechanism of action

So far, the design of human carbonic anhydrase (CA) inhibitors has been easily driven by the introduction of specific Zinc Binding Groups (ZBGs) (primary and secondary sulfonamides and their bioisosteres, dithiocarbamates, phosphonates, hydroxamic acids, and so on), which directly or indirectly block the enzyme-mediated catalytic CO2 hydration. All these inhibitors have been elegantly characterized by X-ray diffraction studies of hCA II-inhibitor adducts. The results led to the discovery of several drug candidates potent and selective for clinical purposes. Conversely, the most exciting innovation was the proposal of an alternative mechanism of inhibition targeting the proton shuttle His64 out of the binding site. Moreover, new chemotypes without the above described moieties are emerging as endowed with an unknown mechanism of interaction. New scenarios could be observed within these scaffold to finely modulate CA activity