Influence of aggregate fracture on shear transfer through cracks in reinforced concrete

Design methods for shear in reinforced concrete structures typically rely upon shear transfer through cracks, which depends upon the crack opening and sliding displacements and the roughness of the crack surfaces. The effectiveness of shear transfer through aggregate interlock is commonly believed to be reduced if the coarse aggregate fractures at cracks, as is frequently the case in high-strength and lightweight aggregate concretes. This paper describes two sets of push-off tests that were carried out to investigate the effect of aggregate fracture on shear transfer through cracks. Marine dredged gravel was used in one set of specimens and limestone in the other. The cracks typically passed around the gravel aggregate but through the limestone aggregate. The experimental results are compared with the predictions of various existing analytical models including those in design codes MC90, Eurocode 2 and ACI-318. The paper also examines the contribution of aggregate interlock to the shear strength of a parallel set of reinforced concrete beams, tested by the authors, which used the same types of aggregate as the push-off specimens

Influence of beam cross-section, loading arrangement and aggregate type on shear strength

This paper describes 14 tests on simply supported and continuous reinforced concrete beams which were designed to investigate the influences of aggregate type, loading arrangement and shear reinforcement ratio on shear strength. The beams were rectangular in cross-section with a/d , 3.5 (where a is the shear span and d the effective depth). Marine dredged gravel was used in ten beams (two without shear reinforcement) and limestone in the remaining four (two without shear reinforcement). The cracks typically passed around the gravel aggregate but through the limestone aggregate. Aggregate fracture was found only to reduce the shear strength of the beams without shear reinforcement. The factors of safety for shear failure implicit in Eurocode 2, BS 8110 and CSA A.23.3-04 are examined with data from this project and elsewhere. Eurocode 2 is shown to provide the lowest factor of safety for most beams. This is particularly significant for rectangular sections where Eurocode 2 can give lower factor of safety for shear than flexural failure which is undesirable. An amendment is proposed to address this

Numerical analyses of stone column installation in Bothkennar clay

The paper presents the results of numerical simulations studying the installation effects of stone columns in a natural soft clay. Stone column installation is modelled as an undrained expansion of a cylindrical cavity, using the finite element code PLAXIS that allows for large displacements. The properties of the soft clay correspond to Bothkennar clay, a soft Carse clay from Scotland (UK). The complexity of this material is simulated via two advanced recently developed constitutive formulations able to account for the soil structure, namely S-CLAY1 and S-CLAY1S. Modified Cam Clay model is also used for comparison purposes. The paper shows the new stress field and state parameters after column installation and the subsequent consolidation process. This sets the basis for including installation effects in studying the settlement reduction caused by stone columns

Structural plasticity in I-Ag7 links autoreactivity to hybrid insulin peptides in type I diabetes

We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-Ag7-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-Ag7 complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-Ag7 binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR's complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-Ag7 structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-Ag7 molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-Ag7 molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so.Copyright © 2022 Erausquin, Serra, Parras, Santamaria and López-Sagaseta

The functional properties of a truncated form of endothelial cell protein C receptor generated by alternative splicing

BACKGROUND: A soluble form of endothelial cell protein C receptor (sEPCR) is generated by shedding of the cellular form. sEPCR binds to protein C and factor VIIa and inhibits both the activation of protein C and the activity of activated protein C and factor VIIa. High sEPCR levels may increase the risk of thrombosis. We wanted to explore the possibility of detecting soluble endothelial cell protein C receptor forms generated by alternative splicing. DESIGN AND METHODS: Reverse transcriptase polymerase chain reaction was used to look for new forms of endothelial cell protein C receptor. A yeast expression system was used to generate sufficient amounts of the distinct sEPCR forms. Surface plasmon resonance experiments, chromogenic assays, clotting assays and immunoassays were subsequently performed to characterize a new form of sEPCR that was found. RESULTS: We demonstrated, by reverse transcriptase polymerase chain reaction and sequencing, the existence of a new, soluble form of endothelial cell protein C receptor generated by alternative splicing, in which the transmembrane region is replaced by a 56-residue tail (tEPCR). Its cDNA was present in human umbilical vein endothelial cells and in most tissues as well as in lung cancer cells. tEPCR was not located in the membrane of transfected cells. We demonstrated that tEPCR binds to protein C and factor VIIa. tEPCR blocked the generation of activated protein C and inhibited the activity of both activated protein C and factor VIIa. tEPCR was detected, by immunoassays, in the supernatant of lung cancer cells and human umbilical vein endothelial cells. CONCLUSIONS: A truncated form of alternatively spliced endothelial cell protein C receptor was detected in the endothelium and cancer cells. tEPCR behaves as sEPCR generated by shedding of the cellular endothelial cell protein C receptor

Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension

Oxidative stress plays a critical role in the pathogenesis of hypertension. The NADPH oxidase constitutes a major source of superoxide anion in phagocytic cells, and its activation is associated with matrix metalloproteinase (MMP)-9 secretion by these cells. We investigated the effects of the angiotensin II type 1 receptor antagonist losartan and its metabolites (EXP3174 and EXP3179) on NADPH oxidase activity and MMP-9 secretion in human phagocytic cells. EXP3179, but not losartan and EXP3174, dose-dependently inhibited (P<0.05) phorbol myristate acetate and insulin-stimulated NADPH oxidase activity. EXP3179 also inhibited phorbol myristate acetate-induced NADPH oxidase in endothelial cells. In addition, EXP3179 inhibited (P<0.05) both phorbol myristate acetate-stimulated p47phox translocation from cytosol to membranes and protein kinase C activity. Affinity experiments and enzymatic assays confirmed that EXP3179 inhibited several protein kinase C isoforms. EXP3179 also inhibited (P<0.05) phorbol myristate acetate-stimulated MMP-9 secretion. In a study performed in 153 hypertensive patients, phagocytic NADPH oxidase activity was lower (P<0.05) in losartan-treated compared with untreated patients and in patients treated with other angiotensin II type 1 receptor antagonists or with angiotensin-converting enzyme inhibitors. Plasma levels of MMP-9 were lower (P<0.05) in losartan-treated hypertensives compared with the other group of patients. Thus, EXP3179 acts as a blocker of the NADPH oxidase in phagocytic cells by a potential mechanism that targets the protein kinase C signaling pathway. This effect can be involved in reduced MMP-9 secretion by these cells. It is proposed that the EXP3179 metabolite may confer to losartan the specific capacity to reduce oxidative stress mediated by phagocytic cells in hypertensive patients

Antibiotic removal processes from water & wastewater for the protection of the aquatic environment - a review

Currently the serious problem of contamination by antibiotics is a reality. The scientific evidence of its negative effects on the aquatic environment and human health are numerous and unquestionable. Therefore, it is essential to intensify research into effective and efficient processes for removing antibiotics from the aquatic environment. In this paper, on the one hand, a review of the concentrations detected in all types of waters of some antibiotics is developed. In concrete of Ciprofloxacin (CIP), Erythromycin (ERY), Levofloxacin (LEV), Metronidazole (MET), Norfloxacin (NOR), Ofloxacin (OFL), Sulfamethoxazole (SMX) and Trimethoprim (TIM). Of the publications consulted, it can be noted that the most detected is SMX, while those with the highest concentrations are CIP, SMX and TIM. On the other hand, some of the main methods to eliminate antibiotics from the aquatic environment are defined and classified. The methods are compared, indicating their advantages and disadvantages. Combined processes are also mentioned as a good alternative. Finally, the removal percentages achieved by each method in some representative publications are detailed. In this regard, it can be said that the methods with the best elimination percentages (range 80–100%) are biological methods (Biological Aerated Filter, Anaerobic Digestion & Biological Activated Carbon Filter) and membrane technology (Nanofiltration & Reverse Osmosis). While those with the worst results (under 80%) are chemicals (Coagulation-Flocculation) and constructed wetlands (Horizontal Subsurface Flow Constructed Wetlands)

NadA3 structures reveal undecad coiled coils and LOX1 binding regions competed by meningococcus B vaccine-elicited human antibodies

Neisseria meningitidis serogroup B (MenB) is a major cause of sepsis and invasive meningococcal disease. A multicomponent vaccine, 4CMenB, is approved for protection against MenB. Neisserial adhesin A (NadA) is one of the main vaccine antigens, acts in host cell adhesion, and may influence colonization and invasion. Six major genetic variants of NadA exist and can be classified into immunologically distinct groups I and II. Knowledge of the crystal structure of the 4CMenB vaccine component NadA3 (group I) would improve understanding of its immunogenicity, folding, and functional properties and might aid antigen design. Here, X-ray crystallography, biochemical, and cellular studies were used to deeply characterize NadA3. The NadA3 crystal structure is reported; it revealed two unexpected regions of undecad coiled-coil motifs and other conformational differences from NadA5 (group II) not predicted by previous analyses. Structure-guided engineering was performed to increase NadA3 thermostability, and a second crystal structure confirmed the improved packing. Functional NadA3 residues mediating interactions with human receptor LOX-1 were identified. Also, for two protective vaccine-elicited human monoclonal antibodies (5D11, 12H11), we mapped key NadA3 epitopes. These vaccine-elicited human MAbs competed binding of NadA3 to LOX-1, suggesting their potential to inhibit host-pathogen colonizing interactions. The data presented provide a significant advance in the understanding of the structure, immunogenicity and function of NadA, one of the main antigens of the multicomponent meningococcus B vaccine.IMPORTANCE The bacterial microbe Neisseria meningitidis serogroup B (MenB) is a major cause of devastating meningococcal disease. An approved multicomponent vaccine, 4CMenB, protects against MenB. Neisserial adhesin A (NadA) is a key vaccine antigen and acts in host cell-pathogen interactions. We investigated the 4CMenB vaccine component NadA3 in order to improve the understanding of its immunogenicity, structure, and function and to aid antigen design. We report crystal structures of NadA3, revealing unexpected structural motifs, and other conformational differences from the NadA5 orthologue studied previously. We performed structure-based antigen design to engineer increased NadA3 thermostability. Functional NadA3 residues mediating interactions with the human receptor LOX-1 and vaccine-elicited human antibodies were identified. These antibodies competed binding of NadA3 to LOX-1, suggesting their potential to inhibit host-pathogen colonizing interactions. Our data provide a significant advance in the overall understanding of the 4CMenB vaccine antigen NadA