Strength of welded thin-walled square hollow section T-joint connections by FE simulations and experiments

Hollow section members are widely used in industrial applications for the design of many machine and structural components. These components are often fabricated at lower cost by welding rather than by casting or forging. For instance, in agricultural machinery, the hollow tubes are typically connected together through welding to form T-joints. Such T-joint connections are also employed in other engineering applications such as construction machinery, offshore structures, bridges, and vehicle frames. In this dissertation, the behaviour of tubular T-joint connections, in particular square hollow section (SHS)-to-SHS T-joints, subjected to static and cyclic loads is studied both experimentally and numerically. The techniques used for the fabrication of the T-joint connections can affect their strengths to different degrees. With modern advances in manufacturing technologies, there are many alternatives for the fabrication of the T-joint connections. For instance, in recent years, the use of the laser beam has become increasingly common in industrial applications. From a manufacturing point of view, the T-joint connections can be fabricated by using traditional mechanical cutting or laser cutting techniques. Currently, for the fabrication of the T-joint connections, the straight edge of one tube is cut using mechanical tools (e.g., flame cutting) and then welded to the body of the other tube. A major contribution of this research work is investigating the feasibility of using laser cutting to produce welded square hollow-section T-joints with similar or higher fatigue strengths than their conventional mechanical cut counterparts. For this purpose, a total of 21 full-scale T-joint samples, typical of those found in the agricultural machinery, are included for the study. Finite Element (FE) models of the T-joints manufactured with the different cutting techniques are also developed and the FE results are verified with the experiments. The results of the numerical and experimental study on the full-scale T-joint samples show that the fatigue strength of the samples that are manufactured with laser cutting is higher than those fabricated with conventional mechanical cutting. From a structural analysis view point, despite of the wide use of tubular T-joint connections as efficient load carrying members, a practical but yet simple and accurate approach for their design and analysis is not available. For this purpose, engineers must often prepare relatively complicated and time consuming FE models made up of shell or solid elements. This is because unlike solid-section members, when hollow section members are subjected to general loadings, they may experience severe deformations of their cross-sections that results in stress concentrations in the connection’s vicinity. One of the objectives/contributions of this research work is the better understanding of the behaviour of SHS-to-SHS T-joint connections under in-plane bending (IPB) and out-of-plane bending (OPB) loading conditions. Through a detailed Finite Element Analysis (FEA) using shell and solid elements, the stiffness and stress distribution at the connection of the tubular T-joints are obtained for different loading conditions. It is observed that at a short distance away from the connection of the T-joints, the structure behaves similar to beams when subjected to loadings. The beam like stresses cease to be valid only in the vicinity of the connection. Therefore, several parameters are defined to recognize the joint’s stress concentrations and the bending stiffness reduction. These parameters permit the accurate modelling of the tubes and the T-connection by simple beam elements with certain modifications. The models consisting of beam elements are significantly easier to prepare and analyze. Through several numerical examples, it is shown that the modified beam models provide accurately all important information of the structural analysis (i.e. the stresses, displacements, reaction forces, and the natural frequencies) at substantially reduced computational effort in comparison with the complicated Finite Element (FE) models built of shell or solid elements. Another contribution of this research work is the FE modelling of the weld geometry and its effect on the stresses at the vicinity of the connection. The results of the FE modelling are verified through a detailed experimental study. For the experimental study, two test fixtures with hydraulic actuators capable of applying both static and cyclic loadings are designed and used. Strain gauges are installed at several locations on full-scale T-joint samples to validate the developed FE models. It is shown that the membrane stresses which occur at the mid-surface of the tubes remain similar regardless of the weld geometry. The weld geometry only affects the bending stresses. It is also shown that this effect on bending stresses is highly localized and disappears at a distance of about half of the weld thickness away from the weld-toe. To reduce the stress concentrations at the T-joint, plate reinforcements are used in a number of different arrangements and dimensions to increase the load carrying capacity of the connection

Gastrointestinal absorption of heparins

Heparin, a highly sulfated and acidic glycosaminoglycan, has been clinically used in parenteral formulations to prevent and/or treat thromboembolic disorders for more than 90 years. Actions of heparin are not limited to anticoagulation and antithrombosis. Rather heparin has several other important actions which include fat clearing, antitumor and anti-inflammatory effects. However, use of heparin for such applications has been limited by its route of administration. Historically, it has been believed that heparin is not absorbed following oral administration and therefore is only available for clinical use by parenteral administration. This belief has been challenged several times by our laboratory and other researchers showing heparin binding to endothelium following oral administration as well as prevention of thrombosis and lowering blood pressure, etc. However, the site of oral heparin absorption and the mechanism responsible for absorption have not been investigated. This in vitro study was designed to address these important questions. We mounted pieces of rat gastrointestinal mucosa in a vertical diffusion Ussing chamber with both sides of the mucosal membrane exposed to Kreb’s bicarbonate buffer solution containing mannitol on the mucosal side (lumen) and glucose on the serosal side. Electrical properties across the membrane including potential difference (PD), resistance (R), and short circuit current (Isc) were recorded following heparin addition to the mucosal buffer under different mucosal buffer pH conditions. Mucosal and serosal buffer and tissue were collected and extracted for heparin and heparin recovery was performed by gel electrophoresis and anticoagulation tests. The first chapter (chapter 4) was designed to investigate if stomach mucosal tissue is a site for unfractionated heparin (UFH) absorption when mounted in the Ussing chamber. We found that stomach mucosa is able to transport UFH in an intact form when both mucosal and serosal buffers are at neutral pH of 7.4. When the mucosal buffer pH is made more acidic, at pH 4, transport is facilitated. The second study (chapter 5) was designed to investigate if stomach mucosal tissue is also capable of transporting low molecular weight heparins (LMWHs). We showed that LMWHS were transported across stomach mucosa. However, the rate of transport was faster at mucosal buffer pH of 7.4 compared to pH 4. The third study (chapter 6) investigated the effect of molecular weight on rate of heparin transport across stomach mucosal tissue since pH dependency of this transport was evident from both previous studies. This study suggested that decreasing the molecular weight increases the rate of heparin transport across stomach tissue under neutral pH but not acidic pH conditions. The fourth study (chapter 7) investigated how UFH is transported across the ileal mucosa and if Peyer’s patches contribute to this transport. It was shown that UFH is transported across ileal mucosa containing Peyer’s patches at a rate faster than ileal mucosa without Peyer’s patches. Making the mucosal buffer pH acidic facilitated UFH transport in the absence of Peyer’s patches but not when ileal mucosa contained Peyer’s patches. The final study (chapter 8) investigated the mechanism of UFH transport across stomach mucosa mounted in the Ussing chamber using pharmacological inhibitors sodium fluoride, colchicine, and amiloride. Results showed that UFH is transported across the stomach mucosa at physiological acidic pH by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. From this, we conclude that oral heparins are absorbed across the gastrointestinal tract. The acidic environment of the stomach is a better absorption site for UFH. On the other hand, the more basic environment of the intestine is a better site for absorption of LMWHs. UFH is mainly absorbed across the stomach mucosa by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. Considering the very much larger surface area of the intestine than the stomach and that intestine, especially the ileum, contains many Peyer’s patches where UFH transport is not pH-dependent, larger amounts of UFH may be transported across the intestinal tissue compared to the stomach

Experimental study of a two-DOF five bar closed-loop mechanism

This research is to carry out an experimental study to examine and verify the effectiveness of the control algorithms and strategies developed at the Advanced Engineering Design Laboratory (AEDL). For this purpose, two objectives are set to be achieved in this research. The first objective is to develop a generic experiment environment (test bed) such that different control approaches and algorithms can be implemented on it. The second objective is to conduct an experimental study on the examined control algorithms, as applied to the above test bed. To achieve the first objective, two main test beds, namely, the real-time controllable (RTC) mechanism and the hybrid machine, have been developed based on a two degree of freedom (DOF) closed-loop five-bar linkage. The 2-DOF closed-loop mechanism is employed in this study as it is the simplest of multi-DOF closed-loop mechanisms, and control approaches and conclusions based on a 2-DOF mechanism are generic and can be applied to a closed-loop mechanism with a higher number of degrees of freedom. The RTC mechanism test bed is driven by two servomotors and the hybrid machine is driven by one servomotor and a traditional CV motor. To achieve the second objective, an experimental study on different control algorithms has been conducted. The Proportional Derivative (PD) based control laws, i.e., traditional iii PD control, Nonlinear-PD (NPD) control, Evolutionary PD (EPD) control, non-linear PD learning control (NPD-LC) and Adaptive Evolutionary Switching-PD (AES-PD) are applied to the RTC mechanism; and as applied to the Hybrid Actuation System (HAS), the traditional PD control and the SMC control techniques are examined and compared. In the case of the RTC mechanism, the experiments on the five PD-based control algorithms, i.e., PD control, NPD control, EPD, NPD-LC, and AES-PD, show that the NPD controller has better performance than the PD controller in terms of the reduction in position tracking errors. It is also illustrated by the experiments that iteration learning control (ILC) techniques can be used to improve the trajectory tracking performance. However, AES-PD showed to have a faster convergence rate than the other ILC control laws. Experimental results also show that feedback ILC is more effective than the feedforward ILC and has a faster convergence rate. In addition, the results of the comparative study of the traditional PD and the Computed Torque Control (CTC) technique at both low and high speeds show that at lower speeds, both of these controllers provide similar results. However, with an increase in speed, the position tracking errors using the CTC control approach become larger than that of the traditional PD control. In the case of the hybrid machine, PD control and SMC control are applied to the mechanism. The results show that for the control of the hybrid machine and the range of speed used in this experimental study, PD control can result in satisfactory performance. However, SMC proved to be more effective than PD control

Vasodilator action of ghrelin

Ghrelin is a 28-amino acid peptide predominantly produced in the stomach and secreted into the circulation. Ghrelin is found in plasma and tissues in two major forms of n-octanoyl-modified at its N-terminal third serine residue and des-acyl ghrelin. The n-octanoyl group of ghrelin is essential for its growth hormone (GH)-releasing activity and appetite regulation mediated through growth hormone secretagogue receptor (GHS-R). We demonstrated that both ghrelin and des-acyl ghrelin evoke vasodilatation at remarkably low concentrations compared to acetylcholine (ACh) in phenylephrine (PE)-constricted perfused rat mesenteric vascular bed (MVB). This was abolished in endothelium-denuded preparations and in endothelium-intact preparations exposed to either a calcium-activated potassium channel (KCa) blocker or a depolarizing stimulus. While KATP channel blockade, nitric oxide synthase and cyclooxygenase inhibition had no effect, the responses were abolished in the presence of combinations of apamin and charybdotoxin, apamin and TRAM-34, and ouabain and Ba2+. The GHS-R antagonist, [D-Lys3]-GHRP-6, per se evoked vasodilatation. Inclusion of L-756867, a peptide antagonist of classical GHS-R, failed to evoke any vasodilator response or to affect vasodilatation evoked by ghrelin. Both non-peptide agonists of GHS-R, L-166446 and L-163255, demonstrated concentration-dependent decreases in perfusion pressure. All short peptides encompassing the first 20, 16, 10, 6, 4, and 3 residues of des-acyl ghrelin were able to evoke vasodilator responses to the same extent as des-acyl ghrelin. However, vasodilatation to single amino acids, L-serine and glycine, were significantly attenuated. Streptozotocin (STZ)-induced diabetes increased plasma ghrelin concentration. Diabetes for 4-weeks did not cause any significant reduction in ghrelin-evoked vasodilatation, whereas 8-weeks diabetes significantly reduced ghrelin-evoked vasodilatation. In contrast to ghrelin, there was a duration-dependent fall in vasodilator response to ACh from 4- to 8-weeks diabetes. These data suggest that the vasodilatation evoked by ghrelin is mediated by endothelium-dependent hyperpolarization (EDHF) by mechanism(s) that are independent of classical GHS-R activation. In addition, EDHF-dependent ghrelin-evoked vasodilator responses may not be affected, at least in the early stages of STZ diabetes, whereas the responses to ACh, predominantly mediated through nitric oxide, are progressively diminished right from the early stages of endothelial dysfunction in STZ diabetic rats

Dicer-Independent Primal RNAs Trigger RNAi and Heterochromatin Formation

SummaryAssembly of fission yeast pericentromeric heterochromatin and generation of small interfering RNAs (siRNAs) from noncoding centromeric transcripts are mutually dependent processes. How this interdependent positive feedback loop is first triggered is a fundamental unanswered question. Here, we show that two distinct Argonaute (Ago1)-dependent pathways mediate small RNA generation. RNA-dependent RNA polymerase complex (RDRC) and Dicer act on specific noncoding RNAs to generate siRNAs by a mechanism that requires the slicer activity of Ago1 but is independent of pre-existing heterochromatin. In the absence of RDRC or Dicer, a distinct class of small RNAs, called primal small RNAs (priRNAs), associates with Ago1. priRNAs are degradation products of abundant transcripts, which bind to Ago1 and target antisense transcripts that result from bidirectional transcription of DNA repeats. Our results suggest that a transcriptome surveillance mechanism based on random association of RNA degradation products with Argonaute triggers siRNA amplification and heterochromatin assembly within DNA repeats

Insights into ALS pathomechanisms:from flies to humans

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease causing the death of motor neurons with consequent muscle atrophy and paralysis. Several neurodegenerative diseases have been modeled in Drosophila and genetic studies on this model organism led to the elucidation of crucial aspects of disease mechanisms. ALS, however, has lagged somewhat behind possibly because of the lack of a suitable genetic model. We were the first to develop a fly model for ALS and over the last few years, we have implemented and used this model for a large scale, unbiased modifier screen. We also report an extensive bioinformatic analysis of the genetic modifiers and we show that most of them are associated in a network of interacting genes controlling known as well as novel cellular processes involved in ALS pathogenesis. A similar analysis for the human homologues of the Drosophila modifiers and the validation of a subset of them in human tissues confirm and expand the significance of the data for the human disease. Finally, we analyze a possible application of the model in the process of therapeutic discovery in ALS and we discuss the importance of novel “non-obvious” models for the disease

Assembly of the SIR Complex and Its Regulation by O-Acetyl-ADP-Ribose, a Product of NAD-Dependent Histone Deacetylation

SummaryAssembly of silent chromatin domains in budding yeast involves the deacetylation of histone tails by Sir2 and the association of the Sir3 and Sir4 proteins with hypoacetylated histone tails. Sir2 couples deacetylation to NAD hydrolysis and the synthesis of a metabolite, O-acetyl-ADP-ribose (AAR), but the functional significance of NAD hydrolysis or AAR, if any, is unknown. Here we examine the association of the Sir2, Sir3, and Sir4 proteins with each other and histone tails. Our analysis reveals that deacetylation of histone H4-lysine 16 (K16), which is critical for silencing in vivo, is also critical for the binding of Sir3 and Sir4 to histone H4 peptides in vitro. Moreover, AAR itself promotes the association of multiple copies of Sir3 with Sir2/Sir4 and induces a dramatic structural rearrangement in the SIR complex. These results suggest that Sir2 activity modulates the assembly of the SIR complex through both histone deacetylation and AAR synthesis

Regulation of Spo12 Phosphorylation and Its Essential Role in the FEAR Network

Background: In budding yeast, the protein phosphatase Cdc14 coordinates late mitotic events and triggers exit from mitosis. During early anaphase, Cdc14 is activated by the FEAR network, but how signaling through the FEAR network occurs is poorly understood. Results: We find that the FEAR network component Spo12 is phosphorylated on S118. This phosphorylation is essential for Spo12 function and is restricted to early anaphase, when the FEAR network is active. The anaphase-specific phosphorylation of Spo12 requires mitotic CDKs and depends on the FEAR network components Separase and Slk19. Furthermore, we find that CDC14 is required to maintain Spo12 in the dephosphorylated state prior to anaphase. Conclusions: Our results show that anaphase-specific phosphorylation of Spo12 is essential for FEAR network function and raise the interesting possibility that Cdc14 itself helps to prevent the FEAR network from being prematurely activated.National Institutes of Health (U.S.) (grant GM 056800)Howard Hughes Medical Institute (Investigator

The isolation and characterisation of temperature-dependent Ricin A chain molecules in Saccharomyces cerevisiae.

Ricin is a heterodimeric plant protein that is potently toxic to mammalian cells. Toxicity results from the catalytic depurination of eukaryotic ribosomes by ricin A chain (RTA) that follows toxin endocytosis to, and translocation across, the endoplasmic reticulum (ER) membrane. To ultimately identify proteins required for these later steps in the entry process, it will be useful to express the catalytic subunit within the ER of yeast cells in a manner that initially permits cell growth. A subsequent switch in conditions to provoke innate toxin action would permit only those strains containing defects in genes normally essential for toxin retro-translocation, refolding or degradation to survive. As a route to such a screen, several RTA mutants with reduced catalytic activity have previously been isolated. Here we report the use of Saccharomyces cerevisiae to isolate temperaturedependent mutants of endoplasmic reticulum-targeted RTA. Two such toxin mutants with opposing phenotypes were isolated. One mutant RTA (RTAF108L/L151P) allowed the yeast cells that express it to grow at 37°C while the same cells did not grow at 23ºC. Both mutations were required for temperature-dependent growth. The second toxin mutant (RTAE177D) allowed cells to grow at 23°C but not at 37°C. Interestingly, RTAE177D has been previously reported to have reduced catalytic activity, but this is the first demonstration of a temperature-sensitive phenotype. To provide a more detailed characterisation of these mutants we have investigated their N-glycosylation, stability, catalytic activity and, where appropriate, a three dimensional structure. The potential utility of these mutants is discussed

Evaluation of COVID-19 Information-Seeking Behavior

The rapid spread of COVID-19 and its transformation into a pandemic has caused anxiety and worry, especially in patients with underlying diseases such as Cancer. The present study aimed to investigate the information-seeking behaviors to prevent COVID-19 disease in cancer patients in Kerman in 2020. The present study is an applied study of objectives and a descriptive-correlational study in its design and methodology. The research population included cancer patients admitted to Shahid Bahonar, Afzalipoor Hospitals, and Javadalameh Clinic in Kerman. Out of 3000 patients, the sample size was randomly estimated to be 250 persons. This study's findings indicated that most patients needed Information about a healthy diet to boost their immune system against COVID-19 disease. Moreover, the patients were more likely to search for COVID-19 Information through simple search (common words that came to their mind). They frequently used COVID-19-related TV programs as a source of Information to raise awareness of the disease. The patients reported that reading or hearing shocking Information about COVID-19 made it difficult to access sources and Information related to the disease. Besides, the retrieved Information helped them to identify COVID-19 symptoms. Most of the patients also stated that they washed their hands regularly with soap and water to prevent COVID-19 disease