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Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

Cellular & Molecular Immunology 2007年第2期4卷 127-133页

作者： Ludmila Okruhlicova Rosemarie Morwinski Wolfgang Schulze Sabine Bartel Peter Weismann Narcisa Tribulova gerd Wallukat Institute for Heart Research Slovak Academy of Sciences Dubravska cesta 9 PO Box 45 840 05 Bratislava 45 Slovak Republic Max-Delbruck-Center for Molecular Medicine Robert Rssle Str. 10 D-13125 Berlin Germany Max-Delbruck-Center for Molecular Medicine Robert Rssle Str. 10 D-13125 Berlin Germany Medical Faculty Comenius University Institute of Anatomy Sasinkova 2 813 72 Bratislava Slovak Republic Institute for Heart Research Slovak Academy of Sciences Dubravska cesta 9 PO Box 45 840 05 Bratislava 45 Slovak Republic

Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α-adrenoceptor and angiotensin Ⅱ ATl-receptor, agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence （p 〈 0.05） and their enlarged diameters of the mast cells when compared to age-matched ones. In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls （p 〈 0.01）. In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones （p 〈 0.001）. Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

关键词： mast cell autoantibody rat heart cell culture immunofluorescence

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MRI versus 64-row MDCT for diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2009年第48期15卷 6044-6051页

作者： Michael Bernhard Pitton Roman Kloeckner Sascha Herber gerd Otto Karl Friedrich Kreitner Christoph Dueber Department of Diagnostic and Interventional Radiology Johannes Gutenberg-University Department of Transplantation and Hepatobili-opancreatic Surgery University of Mainz

AIM： To compare the diagnostic capability of multidetector computed tomography （MDCT） and magnetic resonance imaging （MRI） for the detection of hepatocellular carcinoma （HCC） tumour nodules and their effect on patient management. METHODS： A total of 28 patients （25 male, 3 female, mean age 67 ± 10.8 years） with biopsy-proven HCC were investigated with 64-row MDCT （slice 3 mm native, arterial and portal-venous phase, 120 mL Iomeprol, 4 mL/s, delay by bolus trigger） and MRI （Tlfs fl2d TE/ TR 2.72/129 ms, T2tse TE/TR 102/4000 ms, 5-phase dynamic contrast-enhanced Tlfs fl3d TE/TR 1.56/4.6, Gadolinium-DTPA, slice 4 mm）. Consensus reading of both modalities was used as reference. Tumour nodules were analyzed with respect to number, size, and location. RESULTS： In total, 162 tumour nodules were detected by consensus reading. MRI detected significantly more tumour nodules （159 vs 123, P 〈 0.001） compared to MDCT, with the best sensitivity for early arterial phase MRI. False-negative CT findings included nodules ≤ 5 mm （n = 5）, ≤ 10 mm （n = 17）, ≤ 15 mm （n= 12）,≤20mm（n=4）,andlnodule〉*** missed 2 nodules ≤ 10 mm and 1 nodule ≤ 15 mm. On MRI, nodule diameters were greater than on CT （29.2 ≤25.1 mm, range 5-140 mm vs 24.1 ± 22.7 mm, range 4-129 mm, P 〈 0.005）. In 2 patients, MDCT showed only unilobar tumour spread, whereas MRI revealed additional nodules in the contralateral lobe. Detection of these nodules could have changed the therapeutic strategy. CONCLUSION： Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC nodules. Patients should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.

关键词： American Association for the Study of Liver Diseases European Association for the Study of the Liver Hepatocellular carcinoma Multidetector computed tomography Magnetic resonance imaging

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Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis

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World Journal of Gastroenterology 2007年第11期13卷 1687-1695页

作者： Alexandra Zahn Christoph Moehle Thomas Langmann Robert Ehehalt Frank Autschbach Wolfgang Stremmel gerd Schmitz Department of Gastroenterology University Hospital Heidelberg Heidelberg 69120 Germany Institute of Clinical Chemistry University of Regensburg Regensburg 93042 Germany Institute of Pathology University of Heidelberg Heidelberg 69120 Germany

AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis （UC） and Crohn＇s disease （CD） compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS： We could show that aquaporin-8 （AQP8） mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQPS, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION： Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflao mmation and ulceration.

关键词： Aquaporin-8 Colonic mucus barrier DNA microarrays Expression profiling Ulcerative colitis

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Facile synthesis of ( β -chlorodifluoroethyl)phosphonates via chlorination reaction of difluoroalkyl diazo derivatives with HCl

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Chinese Chemical Letters 2022年第5期33卷 2429-2432页

作者： Jiang Liu Romana Pajkert Li Wang Haibo Mei gerd-Volker Röschenthaler Jianlin Han Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and MaterialsCollege of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China Department of Life Sciences and Chemistry Jacobs University Bremen gGmbHCampus Ring 1Bremen 28759Germany

An efficient chlorination reaction of in situ generated(β-diazo-α,α-difluoroethyl)phosphonates has been achieved with hydrochloric acid as a chlorine source under mild and operationally convenient *** reaction does not need any catalyst and tolerates a wide scope of substrates,which affords the(β-chlorodifluoroethyl)phosphonate products in good to excellent *** reaction represents the first example of the halogenation of difluoroalkyl diazo compounds,and also provides an easy way for the synthesis of difluoromethylenephosphonate-containing compounds.

关键词： Difluorodiazoethane (β-Diazo-α,α-difluoroethyl)phosphonates Halogenation reaction Difluoroalkyl diazo Hydrochloric acid Masked carbene

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Real and Fitted Spherical Indentations

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Advances in Materials Physics and Chemistry 2020年第10期10卷 207-229页

作者： gerd Kaupp University of Oldenburg Oldenburg Germany

Spherical indentations that rely on original date are analyzed with the physically correct mathematical formula and its integration that take into account the radius over depth changes upon penetration. Linear plots, phase-transition onsets, energies, and pressures are algebraically obtained for germanium, zinc-oxide and gallium-nitride. There are low pressure phase-transitions that correspond to, or are not resolved by hydrostatic anvil onset pressures. This enables the attribution of polymorph structures, by comparing with known structures from pulsed laser deposition or molecular beam epitaxy and twinning. The spherical indentation is the easiest way for the synthesis and further characterization of polymorphs, now available in pure form under diamond calotte and in contact with their corresponding less dense polymorph. The unprecedented results and new possibilities require loading curves from experimental data. These are now easily distinguished from data that are “fitted” to make them concur with widely used unphysical Johnson’s formula for spheres (“P = (4/3)h3/2R1/2E∗”) not taking care of the R/h variation. Its challenge is indispensable, because its use involves “fitting equations” for making the data concur. These faked reports (no “experimental” data) provide dangerous false moduli and theories. The fitted spherical indentation reports with radii ranging from 4 to 250 μm are identified for PDMS, GaAs, Al, Si, SiC, MgO, and Steel. The detailed analysis reveals characteristic features.

关键词： Spherical Indentations Correct Formula Phase-Transition Onset Pressure False Johnson Formula Detection of Data Fittings

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Laboratory evaluation of higher-order aberrations and light scattering in explanted opacified intraocular lenses

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Eye and Vision 2021年第1期8卷 124-134页

作者： GrzegorzŁabuz Timur M.Yildirim gerd U.Auffarth Hyeck-Soo Son Ramin Khoramnia David J Apple Center for Vision Research Department of OphthalmologyUniversity of HeidelbergIm Neuenheimer Feld 40069120 HeidelbergGermany

Background:Intraocular lens(IOL)calcification is a serious condition that can only be treated by removing the clouded *** explantation bears the risk of complications,it is often deferred until the patient finds the symptoms ***,as the IOL opacifies,visual acuity is minimally affected early *** this study,we assessed the impact of IOL opacification on optical ***:We analyzed ten opacified explanted IOLs(Oculentis GmbH).Wavefront aberrations were obtained with a SHSOphthalmic device(Optocraft GmbH),which features a Hartmann-Shack *** root mean square(RMS)of higher-order aberrations(HOAs)was *** effect of calcification on image quality was assessed through the Strehl ratio(SR).We detected light scattering with a C-Quant(Oculus GmbH)and expressed it as a straylight ***:At 2 mm,3mm and 4 mm,the mean RMS(±standard deviation)was 0.033μm(±0.026μm),0.044μm(±0.027),and 0.087μm(±0.049),*** mean SR value was 0.81±0.15 at 3 mm,with four IOLs showing a nearly diffraction-limited performance,but in two explants,opacification precluded reliable *** straylight was found in all opacified IOLs with a mean value of 150.2±56.3 deg^(2)/sr at 3 ***:We demonstrated that IOL opacification induces ***,the RMS remained low,which resulted only in a slight reduction of the SR-derived optical *** the other hand,we found a severe straylight elevation in the opacified lenses,which may result in dysphotopsia,such as glare,and subjective complaints,despite good visual acuity.

关键词： Higher-order aberrations Intraocular lens Straylight IOL opacification

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The Non-Equivalence of Pyramids and Their Pseudo-Cones: Important New Insights

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Journal of Applied Mathematics and Physics 2022年第4期10卷 1158-1166页

作者： gerd Kaupp University of Oldenburg Oldenburg Germany

The simulation of indentations with so called “equivalent” pseudo-cones for decreasing computer time is challenged. The mimicry of pseudo-cones having equal basal surface and depth with pyramidal indenters is excluded by basic arithmetic and trigonometric calculations. The commonly accepted angles of so called “equivalent” pseudo-cones must not also claim equal depth. Such bias (answers put into the questions to be solved) in the historical values of the generally used half-opening angles of pseudo-cones is revealed. It falsifies all simulations or conclusions on that basis. The enormous errors in the resulting hardness HISO and elastic modulus Er-ISO values are disastrous not only for the artificial intelligence. The straightforward deduction for possibly ψ-cones (ψ for pseudo) without biased depths’ errors for equal basal surface and equal volume is reported. These ψ-cones would of course penetrate much more deeply than the three-sided Berkovich and cube corner pyramids (r a/2), and their half-opening angles would be smaller than those of the respective pyramids (reverse with r > a/2 for four-sided Vickers). Also the unlike forces’ direction angles are reported for the more sideward and the resulting downward directions. They are reflected by the diameter of the parallelograms with length and off-angle from the vertical axis. Experimental loading curves before and after the phase-transition onsets are indispensable. Mimicry of ψ-cones and pyramids is also quantitatively excluded. All simulations on their bases would also be dangerously invalid for industrial and solid pharmaceutical materials.

关键词： Basic Mathematics Extreme Errors False Cone Angles Indentation Unphysical Cone Models for Pyramids Undue Simulations

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Exciting News from Indentations onto Silicon, Copper, and Tungsten

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Journal of Applied Mathematics and Physics 2023年第12期11卷 4042-4078页

作者： gerd Kaupp Department of Chemistry University of Oldenburg Oldenburg Germany

Indentations onto crystalline silicon and copper with various indenter geometries, loading forces at room temperature belong to the widest interests in the field, because of the physical detection of structural phase transitions. By using the mathematically deduced FNh3/2 relation for conical and pyramidal indentations we have a toolbox for deciding between faked and experimental loading curves. Four printed silicon indentation loading curves (labelled with 292 K, 260 K, 240 K and 210 K) proved to be faked and not experimental. This is problematic for the AI (artificial intelligence) that will probably not be able to sort faked data out by itself but must be told to do so. High risks arise, when published faked indentation reports remain unidentified and unreported for the mechanics engineers by reading, or via AI. For example, when AI recommends a faked quality such as “no phase changes” of a technical material that is therefore used, it might break down due to an actually present low force, low transition energy phase-change. This paper thus installed a tool box for the distinction of experimental and faked loading curves of indentations. We found experimental and faked loading curves of the same research group with overall 14 authoring co-workers in three publications where valid and faked ones were next to each other and I can thus only report on the experimental ones. The comparison of Si and Cu with W at 20-fold higher physical hardness shows its enormous influence to the energies of phase transition and of their transition energies. Thus, the commonly preferred ISO14577-ASTM hardness values HISO (these violate the energy law and are simulated!) leads to almost blind characterization and use of mechanically stressed technical materials (e.g. airplanes, windmills, bridges, etc). The reasons are carefully detected and reported to disprove that the coincidence or very close coincidence of all of the published loading curves from 150 K to 298

关键词： Phase-Transition-Onset and -Energy Indentation of Silicone Copper Copper Nanoparticles Tungsten with Polymorphs Low-Temperature Indentations Detection of Faked Loading Curves Protection of AI from False Advices Risk of Catastrophic Crashes Physical Hardness Exothermic Copper-Transitions Algebraic Calculations Negative-Standard-Energy Polymorphs

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Undue Hardness/Modulus Ratio Claims instead of Physical Penetration Resistance and Applications with Mollusk Shells

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Advances in Materials Physics and Chemistry 2021年第2期11卷 45-57页

作者： gerd Kaupp University of Oldenburg Oldenburg Germany

The Nanoindentation is a precise technique for the elucidation of mechanical properties. But such elucidation requires physically based interpretation of the loading curves that is widely still not practiced. The use of indentation hardness H and indentation modulus Er is unphysical and cannot detect the most important phase-transitions under load that very often occur. The claim that H versus E plots relate linearly for all different materials is neither empirically found nor correctly deduced. It is most dangerous by producing incorrect materials properties and misleading. The use of H/E (that is also called “elasticity index”) in complicated formulas for brittle parameter, yield strength, toughness, and so-called “true hardness” is also in error. The use of H/E cannot reveal the true qualities of materials without considering phase-transitions under load that require the correct exponent 3/2 on h for the loading curves (instead of disproved 2). This is exemplified with the physical data of different mollusk shells that experience phase-transitions, a new bionics model, and different contributions for their strengthening. The data are compared to the ones of aragonite and calcite and vaterite.

关键词： Nanoindentation H/E Ratio Challenge Phase-Transitions Penetration Resistance Mollusk Shells Aragonite Calcite Bionics

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Phase-Transitions at High, Very High, and Very Low Temperatures upon Nano-Indentations: Onset Forces and Transition Energies

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Advances in Materials Physics and Chemistry 2023年第6期13卷 101-120页

作者： gerd Kaupp Chemistry Department University of Oldenburg Oldenburg Germany

This paper describes the phase-transition energies from published loading curves on the basis of the physically deduced FN = k-h3/2 law that does not violate the energy law by assuming h2 instead, as still do ISO-ASTM 14,577 standards. This law is valid for all materials and all “one-point indentation” temperatures. It detects initial surface effects and phase-transition kink-unsteadiness. Why is that important? The mechanically induced phase-transitions form polymorph interfaces with increased risk of crash nucleation for example at the pickle forks of airliners. After our published crashing risk, as nucleated within microscopic polymorph-interfaces via pre-cracks, had finally appeared (we presented microscopic images (5000×) from a model system), 550 airliners were all at once grounded for 18 months due to such microscopic pre-cracks at their pickle forks (connection device for wing to body). These pre-cracks at phase-transition interfaces were previously not complained at the (semi)yearlycheckups of all airliners. But materials with higher compliance against phase- transitions must be developed for everybody’s safety, most easily by checking with nanoindentations, using their physically correct analyses. Unfortunately, non-physical analyses, as based on the after all incredible exponent 2 on h for the FN versus h loading curve are still enforced by ISO-ASTM standards that cannot detect phase-transitions. These standards propagate that all of the force, as applied to the penetrating cone or pyramid shall be used for the depth formation, but not also in part for the pressure to the indenter environment. However, the remaining part of pressure (that was not consumed for migrations, etc.) is always used for the elastic modulus detection routine. That severely violates the energy-law! Furthermore, the now physically analyzed published loading curves contain the phase-transition onsets and energies information, because these

关键词： Aluminum Alloy Aviation Cosmology Epochal News High and Liquid Nitrogen Temperature Indentations Negative-Energy-Content Polymorph Molybdenum Phase-Transition-Energy

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