An efficient method for the static deflection analysis of an infinite beam on a nonlinear elastic foundation of one-way spring model

An efficient numerical iterative method is constructed for the static deflection of an infinite beam on a nonlinear elastic foundation. The proposed iterative scheme consists of quasilinear method (QLM) and Green’s function technique. The QLM translates the nonlinear ordinary differential equation into iterative linear ordinary differential equation. The successive iterations of quasilinear form of ordinary differential equation (ODE) show the quadratic convergence if an initial guess is chosen in the neighbourhood of true solution. The Green’s function technique converts the differential operator into an integral operator and the integral operator is approximated by discrete summation which finally gives us an iterative formula for the resulting set of algebraic equations.The numerical validity and efficiency are proved by simulating some nonlinear problems.Peer ReviewedPostprint (published version

Structure-based drug design approach to target toll-like receptor signaling pathways for disease treatment

Toll-like receptor (TLR) signaling pathways are the first line of defence against many microbial organisms. The question of how TLRs recognize endogenous ligands remains controversial. Several studies have shown that TLRs are implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Therefore, in structure-based drug design, TLRs are now viewed as potential therapeutic targets in the treatment of autoimmune diseases. This review shows how proteins, specifically TLRs, are used as therapeutic targets to design inhibitors (drugs) using the structure-based drug design approach for disease treatment.Keywords: Structure-based drug design, Toll-like receptors, Autoimmune diseases, Endogenous ligands, X-ray crystallography, Homology modelin

Motivation and leader-member-exchange theories applied to the General Authority of Civil Aviation in Saudi Arabia and their effect on employees' job performance

Motivation and its effect on employees’ performance is a broad, interesting, and important issue particularly for Human Resources Management (HRM). Motivation is the power behind individuals’ actions. For organisations’ high performance and maximum productivity motivation, programmes should be efficiently utilized. Leader Member Exchange (LMX) which is employed as a mediator in this empirical study between employees' motivation and job performance has also its influence on employees' job performance. Researchers have investigated motivation and its effect on job performance and developed theories which indicate and reflect the importance of these topics to organisations. The General Authority of Civil Aviation (GACA) is the organization of concern in this study. GACA is a public sector organisation which is located in Saudi Arabia. It has about 2500 employees. A quantitative methodology was employed to collect data from GACA's employees where 480 questionnaires were administered to all sectors of GACA in the headquarters in Jeddah, of which 319 were usable to be analysed. Exploratory factor analysis was employed to purify the refine factors of the main constructs, followed by confirmatory factor analysis to verify the factors and determine the constructs' psychometric properties. The hypothesised relationships were tested by employing structural equation modelling based on partial least square procedures. Mediation effects were examined using the Sobel test.The findings indicate that factors were reliable, valid and consistent with the employed motivation and LMX theories. Details of the nineteen factors produced from the five constructs and four dimensions of the conceptual model Figure 3.2 are presented in chapters five and six. All but two hypotheses of this study were supported, the exceptions being (H4: Job security and LMX are positively related, and H8, Work environment and LMX are positively related) which were rejected, as the relationships were not significant. This implies that employees' motivation in its all different forms has strong influence on employees' job performance when properly implemented and utilized. However in regard to GACA, which is a public sector organisation, the respondents' responses suggest that employees are not influenced by the motivation system as there is strong concern about, for example, the opportunities for training and development courses, rewards, incentives, allowances, promotion, HRM practices, etc., which imply that reform is needed and consequently job performance is not high. In reform of the motivation system, the administration or top management should take a strategic approach that is factual, effective and efficient, which would reflect on HRM practices, human resource development, LMX and all related parties. This would structure and constitute a much better and more constructive work environment, conductive to high job performance

Haar Wavelet Method for the System of Integral Equations

We employed the Haar wavelet method to find numerical solution of the system of Fredholm integral equations (SFIEs) and the system of Volterra integral equations (SVIEs). Five test problems, for which the exact solution is known, are considered. Comparison of the results is obtained by the Haar wavelet method with the exact solution

The role of IL-17 in CD95L-driven nonapoptotic pathology during respiratory disease

CD95L can induce a pathological nonapoptotic pathway and promote Th17 migration when cleaved from the cell surface by proteases. The targeted inhibition of this nonapoptotic pathway by blocking the calcium-inducing domain to impede IL-17 migration could be of therapeutic benefit in inflammation, as seen in a murine lupus model. We aimed to investigate the CD95L nonapoptotic pathway and factors involved in the cleavage of CD95L in the context of SARS-CoV-2 infection and pulmonary fibrosis. Three approaches were used: in vitro studies, in vivo murine models and human clinical sample-based studies. In vitro, the Jurkat cell line was stimulated with PHA, LPS, recombinant MMP9 and mouse sera to optimise conditions for the expression and cleavage of CD95L. MMP9 was investigated as a putative cleavage factor of CD95L and was found at higher levels in naïve lung supernatant than in serum. In a SARS-CoV-2 murine model, the effect of inhibitory peptide treatment on mice intranasally infected with 104 PFU SARS-CoV-2 was assessed. IL-17 serum levels in the peptide-treated group were significantly lower than in the control group, yet this difference did not translate to disease progression, measured by viral load, weight loss, histopathology and survival. IL-17 and sCD95L levels were tested in SARS-CoV-2 patient samples from a biobank cohort and healthy control samples. There was no difference between the groups, and sCD95L was undetectable in the SARS-CoV-2 patient group. Our hypothesis on pulmonary fibrosis was tested through a model of bleomycin-induced fibrosis in BALB/c mice across 36 days. Animals were challenged with 4x105 of murine gammaherpesvirus (MHV) intranasally to aid fibrosis development on day 0. Bleomycin was administered twice at 40 mg/kg on day 8 and day 17. Inhibitory peptide treatment, control peptide treatment or mock treatment was given the day after bleomycin administration. Post-mortem, cardiac bleeds and lung and liver tissue were collected. IL-17, MMP9 and sCD95L were measured by ELISA. Right lungs were processed using Trizol for qPCR, and left lungs, along with livers, were prepared for histopathology. No difference was found between groups in terms of IL-17, MMP9 or sCD95L serum levels, gene expression of il-17 or ccr6, fibrosis scores based on Masson’s trichrome staining, and weight loss or survival rate. However, a significant correlation was seen between weight loss and the fibrosis score. In human pulmonary fibrosis serum samples, IL-17 levels were barely detectable and did not differ from those in healthy controls. Interestingly, sCD95L levels were significantly higher and MMP9 levels were significantly lower than in healthy controls. In summary, blocking the calcium-inducing domain could reduce IL-17 levels but did not affect disease progression in a SARS-CoV-2 model. Moreover, these findings could not be translated to other respiratory diseases, like pulmonary fibrosis

Crystallization and X-ray diffraction analysis of the N-terminal domain of the Toll-like receptor signalling adaptor protein TRIF/TICAM-1

As part of the mammalian innate immune response, Toll-like receptors 3 and 4 can signal via the adaptor protein TRIF/TICAM-1 to elicit the production of type-I interferons and cytokines. Recent studies have suggested an auto-inhibitory role for the N-terminal domain (NTD) of TRIF. This domain has no significant sequence similarity to proteins of known structure. In this paper, the crystallization and X-ray diffraction analysis of TRIF-NTD and its selenomethionine-labelled mutant TRIF-NTDA66M/L113M are reported. Thin plate-like crystals of native TRIF-NTD obtained using polyethylene glycol 3350 as precipitant diffracted X-rays to 1.9 Å resolution. To facilitate phase determination, two additional methionines were incorporated into the protein at positions chosen based on the occurrence of methionines in TRIF homologues in different species. Crystals of the selenomethionine-labelled protein were obtained under conditions similar to the wild-type protein; these crystals diffracted X-rays to 2.5 Å resolution. The TRIF-NTD and TRIF-NTDA66M/L113M crystals have the symmetry of space groups P2 12121 and P1, and most likely contain two and four molecules in the asymmetric unit, respectively. These results provide a sound foundation for the future structure determination of this novel domain

Investigating the best methods for structural stabilization procedures for Historical earthen building conservation in Saudi Arabia: a technology-led construction analysis

[EN] Over time, the construction potentialities and traditional architecture of Saudi Arabia have declined substantially. The modern generation in Saudi Arabia has neglected the traditional structural and architectural designs for building towns, cities and homes. The materials used in the construction of traditional structures has been replaced by more westernized building materials such as concrete, cement and glass. Westernized methods of design and architecture often fail to last long due to the climatic and topographical conditions of the country, such as extreme heat and fast sand-blowing winds. Reviving traditional architectural and structural building married with westernized building technologies will yield strong structures that are capable of withstanding the harsh conditions of the country. This research seeks to identify the most applicable methods of structural procedures that can be used in historical earthen buildings in Saudi Arabia for conservation purposes. This dissertation addresses the important structural and architectural perspectives of traditional Saudi Arabian buildings. It also examines the perspectives of the Saudi population that affect the selection of building materials and architectural styles that are widely used. An examination of the old techniques employed in traditional Saudi Arabian buildings, how they can help in the formulation of a new approach for contemporary architecture and how this can be implemented in Saudi Arabia are also discussed in this dissertation. In the preparation of this dissertation, conforming processes were performed in order to fulfil the set objectives of the study. The first step was configured to examine different earthen architectural structures in Saudi Arabia. This stage involved travelling to different locations, observing the structures and also conducting interviews with older contractors. To collect more information on the topic, visits to Yemen and South Morocco were made, as these are two countries that have already married earthen architecture with modern architecture. The traditional architecture of Morocco and Yemen is similar to that of Saudi Arabia, but it has taken longer for these countries to shift to modern architecture. A laboratory examination was carried out to examine the relationship between the soil composition, stability, and strength of the structures that are built. Empirical studies were also conducted to examine the compactness, solidity, dimensional steadiness and permeability of the materials used in the constructions. These factors influence the choice of building materials for the conservation of traditional architecture and to solve the current need for cheap housing in the urban fabric. The results of this study indicate that the Adobe and Cob traditional architectural styles are two of the leading architectural styles in Saudi Arabia, with each style symbolizing the perspective of the people living in a particular locality. This dissertation also found that different architectural patterns were influenced by functionality, convenience, efficiency and availability of the construction materials needed. This explains the reason for different structural and architectural patterns in different parts of Saudi Arabia. This study concludes that mixing traditional architectural methods with modern technologies would serve to construct stronger and longer-lasting houses in Saudi Arabia. The new houses would not only serve to conserve the magnificent architecture of the country but would also help in building cheap houses, hence solving the rising demand for housing in urban areas. This study will add to the literature available on architectures in Saudi Arabia.[ES] Con el tiempo, las posibilidades de construcción con técnicas tradicionales en Arabia Saudita han disminuido considerablemente. La nueva generación de Arabia Saudita ha dejado caer en el olvido los diseños arquitectónicos y estructurales tradicionales a la hora de construir pueblos, ciudades y viviendas. Los materiales utilizados en la construcción de las estructuras tradicionales han sido sustituidos por materiales de construcción más occidentalizados, tales como el hormigón, el cemento y el vidrio. Los métodos arquitectónicos y de diseño occidentalizados no suelen perdurar mucho tiempo debido a las condiciones climáticas y topográficas del país, tales como el calor extremo y las fuertes tormentas de arena. La revitalización de la construcción de estructuras y arquitecturas tradicionales, unida a las tecnologías de construcción occidentalizadas, dará como resultado unas estructuras sólidas capaces de soportar las duras condiciones del país. Esta investigación busca identificar los métodos de construcción de estructuras más aplicables que puedan ser utilizados en edificios históricos de tierra en Arabia Saudita para fines de conservación. Esta tesis aborda la importancia de las perspectivas estructurales y arquitectónicas para los edificios tradicionales de Arabia Saudita. La tesis también analiza el punto de vista de la población saudí frente a la selección de materiales de construcción y a los estilos arquitectónicos utilizados frecuentemente. En esta investigación también se examinan las antiguas técnicas empleadas en los edificios tradicionales de Arabia Saudita, cómo éstas pueden ayudar en la formulación de un nuevo enfoque para la arquitectura contemporánea y cómo pueden introducirse en la construcción actual en Arabia Saudita. En la preparación de esta tesis se ha trabajado con una metodología que permite cumplir con los objetivos establecidos al inicio del estudio. El primer paso fue examinar las diferentes estructuras arquitectónicas de tierra de Arabia Saudita. Esta etapa consistió en viajar a diferentes lugares para observar las estructuras así como para realizar entrevistas a los antiguos constructores. Para recopilar más información sobre el tema se hicieron también visitas a Yemen y al sur de Marruecos, dado que en estos dos países ya se ha unido la arquitectura de tierra con la arquitectura contemporánea. La arquitectura tradicional de Marruecos y Yemen es similar a la de Arabia Saudita, pero en estos países la nueva arquitectura contemporánea se ha desarrollado más tarde. Se han realizado ensayos de laboratorio para determinar la relación entre la composición del suelo y la estabilidad y solidez de las estructuras construidas. También se realizaron estudios empíricos para determinar la compactación, solidez, estabilidad dimensional y la permeabilidad de los materiales utilizados en las construcciones. Estos factores influyen en la elección de materiales de construcción para la conservación de la arquitectura tradicional y para resolver la necesidad actual de construir viviendas económicas en el tejido urbano actual. Los resultados de este estudio indican que las técnicas constructivas tradicionales del adobe y el cob (pared de mano) son dos de las principales técnicas de Arabia Saudita, y cada una de ellas tiene relación con las particularidades de las poblaciones que viven en un determinado lugar. Con esta tesis también se ha determinado que los diferentes patrones arquitectónicos estaban influenciados por la funcionalidad, la comodidad, la eficiencia y la disponibilidad de los materiales de construcción necesarios. Esto explica la razón por la que existen diferentes tipologías estructurales y arquitectónicas en distintas partes de Arabia Saudita. Este estudio concluye que la unión de los métodos arquitectónicos tradicionales con las nuevas tecnologías puede servir para construir viviendas más sólidas y de larga duración en Arabi[CA] Amb el temps, les possibilitats de construcció amb tècniques tradicionals a l'Aràbia Saudita han disminuït considerablement. La nova generació d'Aràbia Saudita ha deixat caure en l'oblit els dissenys arquitectònics i estructurals tradicionals a l'hora de construir pobles, ciutats i habitatges. Els materials utilitzats en la construcció de les estructures tradicionals s'han substituït per materials de construcció més occidentalitzats, com ara formigó, ciment i vidre. Els mètodes arquitectònics y de disseny occidentalitzats no solen perdurar molt de temps degut a les condicions climàtiques i topogràfiques del país, com ara la calor extrema i les fortes tempestes d'arena. La revitalització de la construcció d'estructures i arquitectures tradicionals, unida a les tecnologies de construcció occidentalitzades, donarà com resultat unes estructures sòlides capaces de suportar les dures condicions del país. Esta investigació pretén identificar quins són els mètodes de construcció d'estructures més aplicables que es poden utilitzar en els edificis històrics de terra d'Aràbia Saudita amb fins de conservació. Esta tesi aborda la importància de les perspectives estructurals i arquitectòniques per als edificis tradicionals d'Aràbia Saudita. La tesi també analitza el punt de vista de la població saudita front a la selecció de materials de construcció y als estils arquitectònics més àmpliament utilitzats. En esta investigació també s'examinen les antigues tècniques emprades en els edificis tradicionals d'Aràbia Saudita, com estes poden ajudar en la formulació d'un nou enfocament per a l'arquitectura contemporània i com poden introduir-se en la construcció actual a Aràbia Saudita. En la preparació d'esta tesi s'ha treballat amb una metodologia que permet complir amb els objectius establerts a l'inici de l'estudi. El primer pas va ser examinar les diferents estructures arquitectòniques de terra d'Aràbia Saudita. Esta etapa va consistir en viatjar a diferents llocs per a observar les estructures així com per a realitzar entrevistes als antics constructors. Per a recopilar més informació sobre el tema es van fer també visites al Iemen i al sud del Marroc, ja que en aquests dos països ja s'ha unit l'arquitectura de terra amb l'arquitectura contemporània. L'arquitectura tradicional del Marroc i del Iemen és semblant a la d'Aràbia Saudita, però en estos països la nova arquitectura contemporània s'ha desenvolupat més tard. S'han realitzat assajos de laboratori per a determinar la relació entre la composició del sòl i l'estabilitat i solidesa de les estructures construïdes. També es van realitzar estudis empírics per a determinar la compactació, solidesa, estabilitat dimensional i la permeabilitat dels materials emprats en les construccions. Estos factors influeixen en l'elecció de materials de construcció per a la conservació de l'arquitectura tradicional i per a resoldre la necessitat actual de construir cases econòmiques en el teixit urbà actual. Els resultats d'este estudi indiquen que les tècniques constructives tradicionals de l'adob i el cob (paret de mà) són dos de les principals tècniques d'Aràbia Saudita, i cada una d'elles té relació amb les particularitats de les poblacions que viuen en una lloc determinat. Amb esta tesi també s'ha determinat que els diferents patrons arquitectònics estaven influenciats per la funcionalitat, la comoditat, l'eficiència i la disponibilitat dels materials de construcció necessaris. Açò explica la raó per la qual hi ha diferents tipologies estructurals i arquitectòniques en distintes parts d'Aràbia Saudita. Este estudi conclou que la unió dels mètodes arquitectònics tradicionals amb les noves tecnologies modernes pot servir per a construir habitatges més sòlids i de llarga duració a Aràbia Saudita.Alaidarous, AAH. (2016). Investigating the best methods for structural stabilization procedures for Historical earthen building conservation in Saudi Arabia: a technology-led construction analysis [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/68476TESI

The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins

TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 angstrom resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-beta promoter, as well as NF-kappa B-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation

Mechanism of bacterial interference with TLR4 signaling by Brucella TIR-domain-containing protein TcpB

Upon activation of Toll-like receptors (TLRs), cytoplasmic Toll/interleukin-1 receptor (TIR) domains of the receptors undergo homo- or hetero-dimerization. This in turn leads to the recruitment of adaptor proteins, activation of transcription factors, and the secretion of pro-inflammatory cytokines. Recent studies have described the TIR-domain-containing protein from Brucella melitensis, TcpB (BtpA/Btp1), to be involved in virulence and suppression of host innate immune responses. TcpB interferes with TLR4 and TLR2 signaling pathways by a mechanism that remains controversial. In this study, we show using co-immunoprecipitation analyses that TcpB interacts with MAL, MyD88, and TLR4, but interferes only with the MAL:TLR4 interaction. We present the crystal structure of the TcpB TIR domain, which reveals significant structural differences in the loop regions compared to other TIR domain structures. We demonstrate that TcpB forms a dimer in solution, and the crystal structure reveals the dimerization interface, which we validate by mutagenesis and biophysical studies. Our study advances the understanding of the molecular mechanisms of host immunosuppression by bacterial pathogens

Intimate Partner Violence Against Women in the Arab Countries: A Systematic Review of Risk Factors

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