Nonlinear conjugate gradient method for vector optimization on Riemannian manifolds with retraction and vector transport

In this paper, we propose nonlinear conjugate gradient methods for vector optimization on Riemannian manifolds. The concepts of Wolfe and Zoutendjik conditions are extended for Riemannian manifolds. Specifically, we establish the existence of intervals of step sizes that satisfy the Wolfe conditions. The convergence analysis covers the vector extensions of the Fletcher--Reeves, conjugate descent, and Dai--Yuan parameters. Under some assumptions, we prove that the sequence obtained by the algorithm can converge to a Pareto stationary point. Moreover, we also discuss several other choices of the parameter. Numerical experiments illustrating the practical behavior of the methods are presented

Extended Formulation of Stress Concentration Factors for CFST T-Joints

In previous research, the authors numerically investigated 212 finite-element (FE) models of concrete-filled steel tubular (CFST) T-joints under axial force in the brace to derive formulae for stress concentration factors (SCFs). The formulations involve four nondimensional parameters: diameter ratio β, diameter-to-thickness ratio of chord 2γ, thickness ratio τ, and relative chord length α. In the current study, the earlier formulation was extended to include four additional loading conditions: in-plane bending (IPB) in the brace, out-of-plane bending (OPB) in the brace, axial compression in the chord, and IPB in the chord. The validity of the new SCF formulae was demonstrated by comparing the SCFs obtained using the formulae with the results of numerical analysis

Citrobacter rodentium NleB Protein Inhibits Tumor Necrosis Factor (TNF) Receptor-associated Factor 3 (TRAF3) Ubiquitination to Reduce Host Type I Interferon Production

Citation: Gao, X. F., Pham, T. H., Feuerbacher, L. A., Chen, K. M., Hays, M. P., Singh, G., . . . Hardwidge, P. R. (2016). Citrobacter rodentium NleB Protein Inhibits Tumor Necrosis Factor (TNF) Receptor-associated Factor 3 (TRAF3) Ubiquitination to Reduce Host Type I Interferon Production. Journal of Biological Chemistry, 291(35), 18232-18238. doi:10.1074/jbc.M116.738278Interferon signaling plays important roles in both intestinal homeostasis and in the host response to pathogen infection. The extent to which bacterial pathogens inhibit this host pathway is an understudied area of investigation. We characterized Citrobacter rodentium strains bearing deletions in individual type III secretion system effector genes to determine whether this pathogen inhibits the host type I IFN response and which effector is responsible. The NleB effector limited host IFN- production by inhibiting Lys(63)-linked ubiquitination of TNF receptor-associated factor 3 (TRAF3). Inhibition was dependent on the glycosyltransferase activity of NleB. GAPDH, a target of NleB during infection, bound to TRAF3 and was required for maximal TRAF3 ubiquitination. NleB glycosyltransferase activity inhibited GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination. Collectively, our data reveal important interplay between GAPDH and TRAF3 and suggest a mechanism by which the NleB effector inhibits type I IFN signaling

Histone ubiquitination-related gene CUL4B promotes lung adenocarcinoma progression and cisplatin resistance

Background: The role of the histone ubiquitination-related gene in the cisplatin resistance of lung adenocarcinoma (LUAD) remains an intricate subject.Methods: We accessed transcriptome data of both wild type and cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50.Results: Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile, in vitro experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8+ T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy.Conclusion: These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target

Regulated Intramembrane Proteolysis in Anabaena Variabilis

In order to response to environmental changes, cells must transduce signals across their membranes to elicit transcriptional responses. One mechanism by which information is transduced across the membrane involves regulated intramembrane proteolysis (RIP) of a membrane-tethered transcription factor (MTF) by a site-2 proteases (S2P), releasing an active form of transcription factor. RIP is conserved from bacteria to humans and governs many important signaling pathways. There has been no genome-wide study of RIP in any organism so far. A systematic exploration of RIP in Anabaena variabilis is reported here. Five S2Ps (Ava_1070, Ava_1730, Ava_1797, Ava_3438 and Ava_4785) were identified in A. variabilis. Their proteolytic activities were confirmed in a reconstituted Escherichia coli system using Bacillus subtilis Pro-σK(1-126)-S20G as an artificial substrate. Substitution of glutamate to glutamic acid in the conserved HEXXH motif of these five proteases completely abolished their proteolytic activities. Among them, ava_4785 is found to be required for cold acclimation. Ava_4785 knockout mutant failed to survive through cold acclimation treatment compared with wild-type. Due to unavailability of a replicating vector in A. variabilis, the complementary experiment was carried out in its closely related strain Anabaena 7120 since the knockout of all1844, the homologue to ava_4785, had the same phenotype as the ava_4785 knockout mutant. The complementation result ensured that all1844 causes the mutant’s phenotype. The promoter activity of ava_4785 and all1844 were monitored by a transcriptionally fused gfp. GFP fluorescence results showed that expression of ava_4785 and all1844 are upregulated by a cold signal. A new approach was developed to simultaneously inactivate genes in cyanobacteria and monitor their promoter activities. This approach was successfully applied in studies of Fox- genes ava_2679 and ava_0744 from A. variabilis. Fourteen putative MTFs were identified among 150 annotated transcriptional regulators in the A. variabilis genome by transmembrane prediction programs. Among them, Ava_4934, a homologue to B. subtilis RsiW whose cognate S2P is YluC, was found to be cleaved by Ava_1730. Protein-protein interaction was detected between Ava_4933 (sigma factor E) and Ava_4934 (anti-sigma factor) in western blot analysis using a native protein gel

Evaluation of Criteria for Out-of-Plane Stability of Steel Arch Bridges in Major Design Codes by FE Analysis

The provisions for out-of-plane stability of steel arch bridges in three major design codes are presented in this paper. By employing an existing steel arch bridge as a model, the influence of bridge type, arch rib to lateral bracing stiffness ratio, rise-to-span ratio, arch rib spacing, and range of lateral bracing arrangements on the out-of-plane critical axial force of the arch rib is studied using FE analysis. The accuracy of the critical axial force provisions is then evaluated against the FE analysis. The results show that the influence of the rise-to-span ratio on critical axial force is generally small. The critical axial force decreases with increasing arch rib spacing when the stiffness ratio is relatively large. A smaller ratio of arch rib length provided with lateral bracing (γ-value) significantly reduces the critical axial force and normalized critical axial force decreases with increasing stiffness ratio. The critical axial force of half-through type arch bridges is lowest when the stiffness ratio is relatively small. A deck-type bridge has a larger critical axial force than a through-type bridge when the stiffness ratio is relatively large, while the results are the opposite when the ratio is small. The different assumptions made in the provisions result in the various parameters having different impacts on the out-of-plane critical axial force in each code, thus affecting code accuracy. Considering the influence of the rise-to-span ratio, ratio of lateral bracing, and arch rib spacing with different stiffness ratios, factors to improve the accuracy of the critical axial force obtained by the three codes are proposed for a practical design process

Evaluation of Criteria for Out-of-Plane Stability of Steel Arch Bridges in Major Design Codes by FE Analysis

The provisions for out-of-plane stability of steel arch bridges in three major design codes are presented in this paper. By employing an existing steel arch bridge as a model, the influence of bridge type, arch rib to lateral bracing stiffness ratio, rise-to-span ratio, arch rib spacing, and range of lateral bracing arrangements on the out-of-plane critical axial force of the arch rib is studied using FE analysis. The accuracy of the critical axial force provisions is then evaluated against the FE analysis. The results show that the influence of the rise-to-span ratio on critical axial force is generally small. The critical axial force decreases with increasing arch rib spacing when the stiffness ratio is relatively large. A smaller ratio of arch rib length provided with lateral bracing (γ-value) significantly reduces the critical axial force and normalized critical axial force decreases with increasing stiffness ratio. The critical axial force of half-through type arch bridges is lowest when the stiffness ratio is relatively small. A deck-type bridge has a larger critical axial force than a through-type bridge when the stiffness ratio is relatively large, while the results are the opposite when the ratio is small. The different assumptions made in the provisions result in the various parameters having different impacts on the out-of-plane critical axial force in each code, thus affecting code accuracy. Considering the influence of the rise-to-span ratio, ratio of lateral bracing, and arch rib spacing with different stiffness ratios, factors to improve the accuracy of the critical axial force obtained by the three codes are proposed for a practical design process

Research on the Fatigue Performance of Composite Girders with CSW and ST Truss

To study the fatigue performance of a composite girder with corrugated steel web (CSW) and steel tube (ST) truss, based on an engineering object, a test and finite element (FE) analysis were carried out. The fatigue failure mode and the sensitivities of the hot spot stress to the geometric parameters of the composite girder above were studied. The position with the maximum hot spot stress and the fatigue crack position were discussed and determined. Furthermore, a fatigue life evaluation method was discussed. It was found that linear extrapolation was applicable to finding the hot spot stress. The fatigue performance evolution comprised three stages, including initiation, expansion, and failure of the fatigue crack. The fatigue crack initiation stage accounted for about 95.6% of its fatigue life, and the fatigue crack was opening type I. The maximum hot spot stress emerged at the endpoint of the inclined web of CSW (point S). The main reason for the behavior was that the inclined web had a small out-of-plane flexural stiffness but had to bear an out-of-plane bending moment. Moreover, for the same section of the CSW, the hot spot stress on the molding side was less than that on the non-molding side. The hot spot stress exhibited negative correlations with the chord diameter, chord thickness, and bend radius, meanwhile, it had the highest sensitivity to the chord diameter. The existing S-N curves were not suitable to evaluate the fatigue life of the composite girder with CSW and ST truss. Since the intersecting weld between the CSW and the chord was located in longitudinal welded joints, the hot spot stress method suggested adopting the basic fatigue strength of 100 MPa, corresponding to 2,000,000 load cycles. Meanwhile, an empirical calculation model of the S-N curve for the composite girder with CSW and ST truss was created

Test of Broken Suspender Specimen and Equivalent Static Calculation Method for Half-Through and Through Concrete-Filled Steel Tubular Arch Bridges

In response to the frequent collapse of main girders caused by the breakage of suspenders on half-through and through arch bridges, a test specimen has been designed and fabricated with a through concrete-filled steel tube (CFST) arch bridge as the engineering background. A new electromagnetic disconnect trigger is employed to realize the rapid suspender breakage in the test specimen. Dynamic response tests of the residual structure of the arch bridge after suspender failures employing the test specimen have been carried out. A finite element model accounting for the suspender breakage dynamic process has been constructed by implementing ANSYS/LS-DYNA, and the results of the test and finite element analysis are compared. In order to simplify the dynamic response calculation process of the residual structure after hanger failures, the dynamic coefficient is introduced, and an equivalent static calculation method (ESCM) considering the dynamic effect of the suspender fracture is presented. Eleven kinds of CFST standard arch bridges with different spans are constructed, the static and dynamic effects of the standard arch bridge with various dynamic coefficients are compared, and then their corresponding dynamic coefficients for various suspender fractures are determined. The obtained results reveal that the proposed electromagnetic suspender breakage trigger can realize the hanger fracturing within 0.1 s, which accurately simulates the fracture process of an actual bridge suspender, and the influence on the value of the dynamic coefficient can be ignored when the duration for suspender fracture is less than or equal to 0.15 s. The influence of suspender fracture on the displacement and stress of the longitudinal beam is more notable than those of the arch rib. In particular, the long suspender breakage has the highest influence on the displacement and stress of the longitudinal beam and arch rib. The fracture of the second short suspender has a remarkable impact on the suspender force of the adjacent hanger. When the ESCM is utilized to assess the mechanical behavior of the half-through and through CFST arch bridge, the dynamic coefficients of the longitudinal beam (suspender) were evaluated to be, conservatively, 1.8 (1.8) and 1.8 (1.7), respectively

Research on the Fatigue Performance of Composite Girders with CSW and ST Truss

To study the fatigue performance of a composite girder with corrugated steel web (CSW) and steel tube (ST) truss, based on an engineering object, a test and finite element (FE) analysis were carried out. The fatigue failure mode and the sensitivities of the hot spot stress to the geometric parameters of the composite girder above were studied. The position with the maximum hot spot stress and the fatigue crack position were discussed and determined. Furthermore, a fatigue life evaluation method was discussed. It was found that linear extrapolation was applicable to finding the hot spot stress. The fatigue performance evolution comprised three stages, including initiation, expansion, and failure of the fatigue crack. The fatigue crack initiation stage accounted for about 95.6% of its fatigue life, and the fatigue crack was opening type I. The maximum hot spot stress emerged at the endpoint of the inclined web of CSW (point S). The main reason for the behavior was that the inclined web had a small out-of-plane flexural stiffness but had to bear an out-of-plane bending moment. Moreover, for the same section of the CSW, the hot spot stress on the molding side was less than that on the non-molding side. The hot spot stress exhibited negative correlations with the chord diameter, chord thickness, and bend radius, meanwhile, it had the highest sensitivity to the chord diameter. The existing S-N curves were not suitable to evaluate the fatigue life of the composite girder with CSW and ST truss. Since the intersecting weld between the CSW and the chord was located in longitudinal welded joints, the hot spot stress method suggested adopting the basic fatigue strength of 100 MPa, corresponding to 2,000,000 load cycles. Meanwhile, an empirical calculation model of the S-N curve for the composite girder with CSW and ST truss was created