38 research outputs found

    Contribution of strain-hardening cementitious composites (SHCC) to shear resistance in hybrid reinforced concrete beams

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    Strain Hardening Cementitious Composite (SHCC) is an innovative type of fibre-reinforced cement-based composite that has superior tensile properties. Because of this, it holds the potential to enhance the shear capacity of reinforced concrete (RC) beams, if applied properly. This paper presents the general and distinctive properties of SHCC as well as a literature review of topics related to the contribution of SHCC layers to the shear resistance of RC beams with and without shear reinforcement. Based on the analysed results, it is concluded that the main characteristics of SHCC are its microcracking behaviour, high ductility, and increased tensile strength (between 2 and 8 MPa) at large deformations. When used in structural elements, SHCC develops multiple parallel cracks compared to concentrated cracks in conventionally reinforced concrete. The biggest disadvantage of SHCC is its significant drying shrinkage. Although showing high variability, using SHCC as laminates with a thickness of 10 mm improves the shear capacity of hybrid RC beams, but debonding of interfaces in a hybrid system occurs in some cases

    Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease

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    Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD

    Characterization of human Sec16B: indications of specialized, non-redundant functions

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    The endoplasmic reticulum (ER) represents the entry point into the secretory pathway and from here newly synthesized proteins and lipids are delivered to the Golgi. The selective cargo export from the ER is mediated by COPII-assembly at specific sites of the ER, the so-called transitional ER (tER). The peripheral membrane protein Sec16, first identified in yeast, localizes to transitional ER and plays a key role in organization of these sites. Sec16 defines the tER and is thought to act as a scaffold for the COPII coat assembly. In humans two isoforms of Sec16 are present, the larger Sec16A and the smaller Sec16B. Nevertheless, the functional differences between the two isoforms are ill-defined. Here we describe characterization of the localization and dynamics of Sec16B relative to Sec16A, provide evidence that Sec16B is likely a minor or perhaps specialized form of Sec16, and that it is not functionally redundant with Sec16A

    Sec12 Binds to Sec16 at Transitional ER Sites

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    COPII vesicles bud from an ER domain known as the transitional ER (tER). Assembly of the COPII coat is initiated by the transmembrane guanine nucleotide exchange factor Sec12. In the budding yeast Pichia pastoris, Sec12 is concentrated at tER sites. Previously, we found that the tER localization of P. pastoris Sec12 requires a saturable binding partner. We now show that this binding partner is Sec16, a peripheral membrane protein that functions in ER export and tER organization. One line of evidence is that overexpression of Sec12 delocalizes Sec12 to the general ER, but simultaneous overexpression of Sec16 retains overexpressed Sec12 at tER sites. Additionally, when P. pastoris Sec12 is expressed in S. cerevisiae, the exogenous Sec12 localizes to the general ER, but when P. pastoris Sec16 is expressed in the same cells, the exogenous Sec12 is recruited to tER sites. In both of these experimental systems, the ability of Sec16 to recruit Sec12 to tER sites is abolished by deleting a C-terminal fragment of Sec16. Biochemical experiments confirm that this C-terminal fragment of Sec16 binds to the cytosolic domain of Sec12. Similarly, we demonstrate that human Sec12 is concentrated at tER sites, likely due to association with a C-terminal fragment of Sec16A. These results suggest that a Sec12–Sec16 interaction has a conserved role in ER export

    Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

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    The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen. The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ?glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential?. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected

    Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor

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    Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3–fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors. Platelet activation in platelet-rich plasma was evaluated by P-selectin expression using flow cytometry. Contribution of platelets to whole blood clotting was assessed by rotation thromboelastometry (ROTEM). Selective signaling of Gαq or Gαi but not Gα12/13 promoted P-selectin expression. Further enhancement of P-selectin expression was achieved by ADP-induced combined signaling of Gαq and Gαi, and to more extent by U46619 at high concentration (1.5 μM) induced combined signaling of Gαq and Gα12/13 while maximal P-selectin expression was achieved by thrombin receptor-activating peptide (TRAP)-induced combined signaling of Gαq, Gαi, and Gα12/13. In ROTEM, selective activation of Gαq, Gαi, or Gα12/13 failed to affect blood clotting. Combined signaling of Gαq and Gαi or Gαq and Gα12/13 or all three G proteins shortened the clotting time and stimulated clot strength. Pretreatment of platelets with acetylsalicylic acid did not change the effect of ADP but inhibited the effect of TRAP. Signaling of Gαq and Gα12/13 triggered by U46619 also stimulated clot formation. Combined signaling of either Gαq and Gαi or Gαq and Gα12/13 is sufficient to stimulate maximal platelet activation and enhanced clot formation in platelets treated with inhibitor of integrin αIIbβ3. It could be suggested that outside-in signaling is not necessarily required to fulfill these platelet functions

    Analysis of natural-production conditions for timber harvesting in European North of Russia

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    Natural-production conditions determine operational efficiency of logging machines. This influence needs to be taken into account at different levels of forest management. It is necessary to allocate areas with similar natural-production conditions for effective forest management. It allows simplifying the decision making process for selecting logging technology and machines. The purpose of this study was to establish areas with similar natural and production conditions in the European North of Russia (ENR). In addition, for small enterprises, we recommend logging technologies and logging machines that can be used in established areas. We determined the indicators of the natural-production conditions of ENR regions and compared them. Cluster analysis was used to compare the indicators. We found that ENR can be divided into three main zones A, B, C and two subzones B1 and B2 with similar natural-production conditions. In the zones A, B and the subzones B1 and B2, small logging enterprises should use a harvester and a forwarder. In the zone C, the enterprises can use a logging system including a harvester and a forwarder or a logging system including a feller buncher, a skidder and a processor. The logging system should be based on the light class of logging machines for the zone A, the medium class or the heavy class for the zones B, C and the subzones B1, B2, the heavy class of machines for the zone C

    Effects of extensive mobilization and tension anastomosis in anorectal reconstruction (experimental study)

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    © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Purpose: Anorectoplasty and pull-through procedure can be performed with extensive mobilization or tension anastomosis, which can compromise bowel blood perfusion. We aimed to analyze the hypoxia biomarker values and histopathological findings in both conditions to correlate the occurrence of anal stenosis and defecation disorders in experimental models. Methods: We created anorectal reconstruction models with impaired vascularization of the anorectum (group I) and tension anastomosis (group II) in rats. A third group of animals underwent sham operation (group III) and another as controls (group IV). Hypoxia biomarker values were assessed in all groups. The histopathological changes on the postoperative days 3 and 35, anal stenosis and defecation disorders on day 35 were compared. Results: Hypoxia biomarker values confirmed postoperative ischemia in groups I–III compared to control. Group I and II rats had a similarly pronounced ischemia with histopathologic changes in the anorectum on the postoperative day 3 and accompanied by severe fibrosis on day 35. Compared to the sham operation, both groups showed defecation disorders with significant anal stenoses. Conclusion: Extensive rectal mobilization to about the same extent as tension anastomosis has a major impact on postoperative rectal ischemia, resulting in severe fibrotic changes in the anorectum and defecation disorders in the long term
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