Structural behaviour of tapered steel plate girders subjected to shear

Tapered plate girders often form part of large-scale structures such as long continuous bridges or industrial buildings where due to considerable loads the higher resistance is required. There are several important reasons choosing non-prismatic girders. First of all, their tapered shape with gradually changing inertia allows for more effective stress distribution inside the web-panel and contributes to steel reduction and thereby to decrease the overall cost of the structure. Trapezoidal shape of such panels also may be desirable in structures with non-standard shape for example where pre-formed service openings are needed. Although rectangular plate girders were studied in many occasions in last few decades, the latest investigations have shown that the structural behaviour of tapered panels is more complex and different distribution of the internal forces takes place. Due to a lack of design rules for assessment of ultimate shear resistance of tapered plate structures with considerable angle of a slope (> 10 degrees), this research is focused on searching for a solution of the problem. The main body of the thesis is composed of four independent publications where each of them summarizes different phase of the research. The most relevant issues related to tapered panels discussed in the papers were: the critical shear load in tapered simple-supported plates, the influence of geometrical and structural imperfections, the optimal position of the longitudinal stiffener, the Resal effect, and finally the ultimate shear resistance of stiffened and unstiffened tapered plate girders. Nevertheless, the main objective of this work was the development of a reliable design tool to assess of the ultimate shear resistance of non-prismatic plate girders. The methodology applied in the research consists of the following stages: study of the bibliography and initial theoretical research, development of a numerical model, execution of two experimental programs, development of a wide parametric study, analysis of the experimental and numerical results, comparing them with those obtained according to EN 1993-1-5, and finally - development of a new design proposal for the assessment of the ultimate shear resistance for tapered steel plate girders. The PhD research was supported by two experimental programs focused on the structural behaviour of tapered plate girders. In the first program, transversally stiffened members subjected to shear and shear-bending interaction were tested. The second experimental program was focused on longitudinally stiffened tapered plate girders under shear. Results obtained from the experimental tests were used for the verification of the numerical model. Plate girders reveal tendency to possess a significant post-buckling resistance. This phenomenon can be observed as a diagonal tension field developing within the web-panel. In both experimental tests and numerical analyses, this characteristic behaviour was observed. Using verified the numerical model, a wide parametric study for a large number of tapered plate girders was carried out. All numerical results presented in this research were compared with those obtained according to EN 1993-1-5 and discussed. Finally, a new design method for the assessment of the ultimate shear resistance of tapered steel plate girders was presented. The new design proposal is based on the currently valid - Rotated Stress Field Method. The procedure maintains its simplicity and improves considerably results obtained for non-prismatic panels. This new reliable design tool, valid for any geometry and any typology of tapered steel plate girders, provides a solution of the main objective defined in this researc

Propuesta de cálculo de la resistencia a cortante de vigas armadas de acero de canto variable

Numerous experimental and numerical studies on prismatic plate girders subjected to shear can be found in the literature. However, the real structures are frequently designed as non-uniform structural elements. The main objective of the research is the development of a new proposal for the calculation of the ultimate shear resistance of tapered steel plate girders taking into account the specific behaviour of such members. A new mechanical model is presented in the paper and it is used to show the differences between the behaviour of uniform and tapered web panels subjected to shear. EN 1993-1-5 design specifications for the determination of the shear strength for rectangular plates are improved in order to assess the shear strength of tapered elements. Numerical studies carried out on tapered steel plate girders subjected to shear lead to confirm the suitability of the mechanical model and the proposed design expression.En la literatura pueden encontrarse numerosos estudios experimentales y numéricos sobre vigas armadas de acero de canto constante sometidas a cortante. Sin embargo, muchas estructuras de acero se proyectan, frecuentemente, con elementos de canto variable. El objetivo del artículo es ofrecer una formulación para el cálculo de la resistencia última a cortante de paneles de alma de canto variable, basada en un nuevo modelo mecánico, que es utilizado para mostrar las diferencias de comportamiento entre paneles de alma de canto constante y variable, sometidos a cortante. Las reglas de cálculo de EN 1993-1-5 para determinar la resistencia a cortante de paneles de alma de canto constante se mejoran para poder evaluar la resistencia a cortante de paneles de canto variable. Los numerosos estudios numéricos llevados a cabo sobre vigas armadas de acero de canto variable confirman la idoneidad del modelo mecánico y de la nueva expresión propuesta para el cálculo

Intestinal DMBT1 Expression Is Modulated by Crohn’s Disease-Associated IL23R Variants and by a DMBT1 Variant Which Influences Binding of the Transcription Factors CREB1 and ATF-2

Objectives: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Methods: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn’s disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. Results: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0×10−7, OR 1.42; 95% CI 1.24–1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1×10−18). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. Conclusion: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis

a randomized, double-blind, placebo-controlled, multi-centric clinical trial phase II

Nach erfolgreicher Erstinfektion des Wirtes besitzt das Herpes-Simplex-Virus die Fähigkeit sich der immunologischen Kontrolle zu entziehen, und es kommt zu einer „latenten Persistenz“ die lebenslang dauert. Durch verschiedene Provokationsfaktoren kann es zu einer endogenen Reaktivierung der in den Ganglien latent vorhandenen Herpes-Simplex-Viren kommen. Die Viren wandern auf neuralem Weg vom Ganglion zentrifugal in die Haut oder die Schleimhäute wo in Epidermis- bzw. Epithelzellen wieder eine Replikation stattfindet Eine HSV bedingte Infektion der Sakralganglien ruft das Klinische Bild eines Herpes genitalis hervor. Dabei kommt es in unterschiedlicher Häufigkeit zum rezidivierenden Befall der Haut und der Schleimhäute an und um die Geschlechtsorgane herum - mit den typischen Effloreszenzen: gruppierte Bläschen auf gerötetem Grund. Bei immunkompetenten Patienten heilt der Herpes genitalis für gewöhnlich komplikationslos binnen 7-10 Tage narbenfrei ab. Bei immunsupprimierten Patienten können disseminierte und fulminante Krankheitsverläufe mit lebensbedrohlichen Erkrankungen der innerer Organe und des ZNS auftreten. Durch mangelnde Aufklärung steigt das Risiko einer Übertragung. Die Zahl der Infizierten ist höher als zunächst vermutet werden kann. Der Leidensdruck der Betroffenen ist oft groß. Die wiederkehrenden Infekte mindern die Lebensqualität. Das effektivste Mittel mit dem man gegen die große Durchseuchung mit HSV kämpfen könnte, wäre eine Vakzinierung. Doch bis lang gibt es keinen Impfstoff, der einen sicheren Schutz vor einer HSV Infektion ermöglicht. So bleibt die Behandlung von HSV Infektion symptomorientiert. Es besteht nach wie vor die Notwendigkeit, nach einem wirksamen topischen Medikament zu forschen. Cyclodextrine sind cycklische Kohlenwasserstoffe und haben die besondere Fähigkeit Komplexe zu bilden mit in Wasser gelösten Molekülen, wie z.B. dem Cholesterin. Cholesterin ist einer der Bausteine von Lipid Rafts, welche wiederum einen wichtigen Bestandteil von Plasmamebranen und Virushüllen bilden. Diverse Studien haben belegt, dass eine Cholesterinextraktion in vielen Fällen zu einem Riß der Lipid Rafts oder zu einer herabgesetzten Infektiosität eines Virus führte. Der Einfluß von Cyclodextrinen auf die Heilung von genitalen HSV Infektionen ist bis jetzt nicht untersucht worden. Diese Arbeit legt die Ergebnisse über die klinische Erprobung eines Cyclodextrin Gels mit dem Wirkstoff 2-Hydroxypropyl ß-Cyclodextrin (2-HP-BCD) an Patienten mit einem rezidivierenden Herpes genitalis in der Prodromalphase dar. Diese multizentrische und doppelblinde Studie untersuchte dabei das Cyclodextrin Gel im Vergleich zu einem Placebo Gel. Insgesamt nahmen 218 Patienten an dieser Studie teil. Das topisch applizierte Cyclodextrin Gel erwies sich effektiver als das Placebo und gut verträglich für die Behandlung der Läsion einer genitalen Herpes Simplex Infektion. Bezüglich der Wirksamkeit vom Cyclodextrin Gel zeigte sich eine kürzere Dauer bis zur Verkrustung mit einer schnelleren Heilung und weniger Rötung sowie eine etwas kürzere Schmerzepisode im Vergleich zum Placebo. Das Medikament kann als sicher und unbedenklich erachtet werden. Aber obwohl die Überlegenheit des Cyclodextrin Gel im Vergleich zum Placebo signifikant ist sind die Unterschiede in der Wirkung nicht sehr groß. Sie stimmen jedoch optimistisch, weitere Untersuchung bezüglich Dosisfindung und Konzentrationsstärke zu machen.After the initial infection of the host, the herpes-simplex-virus (HSV) has the capability of eluding the immunological control and it results in a life- long latent persistence. The latent existing herpes-simplex-virus in the ganglia can be reactivated through various provocation factors. The virus travels centrifugally through the neural system from ganglion to the mucosa or epidermis and is replicated in the epithelial layer. A HSV resulted infection of the sacral ganglia induces the clinical symptoms of herpes genitalis. This generates, in various frequency, a recurrent affection of the cutis and mucosa on and around the genitals with the typical efflorescence grouped vesicle on reddened skin. In the cases of immunocompetent patients, the herpes genitalis virus generaly heals without complications, within 7-10 days, scar-free. Immunocompromised patients, can suffer from disseminated and fulminant etiopathology. Lack of education leads to higher risk of transmission. The number of infected persons is higher than assumed. The suffering of the infected is often high and reduces their quality of life. A vaccination would be the most effective method to avoid the large prevalence. Presently there is no vaccination available and the method of treatment is limited to its symptoms. There is still the need for an effective topically applied anti- viral medication. Cyclodextrins are cyclic hydrocarbons and have the ability to bind water solvent molecules into complexes, for example Cholesterol. Cholesterol is one of the components of lipid rafts, which are an important part of the plasma membrane of the viral coat. Various studies proved that an extraction of cholesterol leads to a tear in lipid rafts and decreases the risk of infection. The impact of cholesterol extraction with cyclodextrins to advance the healing of genital HSV has not been investigated. This work presents the results of the clinical trial with 2-Hydroxypropyl Beta- Cyclodextrin (2-HP-BCD) on patients with a recurring herpes genitalis in the prodromal stage. This multi-centric and double-blind trial, investigated the 2 -HP-BCD in comparison to a placebo gel. In total 218 patients took part in this study. The topically applied 2-HP-BCD proved to be more effective than the placebo and well tolerated. In comparison to the placebo, the 2-HP-BCD showed a shorter period to incrustation with a quicker healing and less reddening, as well as, a somewhat shorter period of pain. The medication proved to be safe and uncritical. Although the 2-HP-BCD showed a significant advantage over the placebo, the results of the differences were not immense. The results were however, optimistic enough to make further studies regarding dosage and concentration

Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia

Kinetics of apo B and apo AI were assessed in 8 patients with mixed hyperlipidemia at baseline and after 8 weeks of atorvastatin 80 mg q.d. and micronised fenofibrate 200 mg q.d. in a cross-over study. Both increased hepatic production and decreased catabolism of VLDL accounted for elevated cholesterol and triglyceride concentrations at baseline. Atorvastatin significantly decreased triglyceride, total, VLDL and LDL cholesterol and apo B concentrations (-65%, -36%, -57%, -40% and -33%, respectively, Ptextless0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL1 and decreased VLDL1 production. Fenofibrate lowered triglycerides and VLDL cholesterol (-57% and -64%, respectively, Ptextless0.05) due to enhanced delipidation of VLDL1 and VLDL2 and increased VLDL1 catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, Ptextless0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, Ptextless0.05). We conclude that atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity. Fenofibrate but not atorvastatin increases apo AI production and plasma turnover

Numerical and experimental research in tapered steel plate girders subjected to shear

Postprint (published version

Design proposal for ultimate shear strength of tapered steel plate girders

Numerous experimental and numerical studies on prismatic plate girders subjected to shear can be found in the literature. However, the real structures are frequently designed as non-uniform structural elements. The main objective of the research is the development of a new proposal for the calculation of the ultimate shear resistance of tapered steel plate girders taking into account the specific behaviour of such members. A new mechanical model is presented in the paper and it is used to show the differences between the behaviour of uniform and tapered web panels subjected to shear. EN 1993-1-5 design specifications for the determination of the shear strength for rectangular plates are improved in order to assess the shear strength of tapered elements. Numerical studies carried out on tapered steel plate girders subjected to shear lead to confirm the suitability of the mechanical model and the proposed design expression.Peer Reviewe