Experimental study of DED-arc additively manufactured steel double-lap shear bolted connections

An experimental study into the structural behaviour of Directed Energy Deposition-arc or wire arc additively manufactured (DED-arc AM and WAAM, respectively) steel double-lap shear bolted connections is presented. The mechanical properties of the material, which had a nominal yield stress of 420 MPa, were first determined by means of tensile coupon tests. Sixty connection specimens of two different nominal thicknesses and two print layer orientations were then tested to failure. The geometry of the test specimens was determined by 3D laser scanning, while the deformation and strain fields were measured during testing using digital image correlation. The observed failure modes included shear-out, net section tension, bearing and end-splitting, while a new hybrid mode of shear-out and net section tension was identified for the first time. The test results were compared against the predictions of current design specifications, namely AISI S100 and AS/NZS 4600 for cold-formed steel and AISC 360 and Eurocode 3 for structural steel, to evaluate their applicability to WAAM elements. Overall, the structural behaviour of the tested specimens followed the anticipated trends, and the predicted resistances determined from the current design specifications were generally reasonable. There were, however, a number of exceptions to this, highlighting the need for new design provisions, together with appropriate safety factors, that are specific to this form of manufacture

Subcoronary versus supracoronary aortic stenosis. an experimental evaluation

<p>Abstract</p> <p>Background</p> <p>Valvular aortic stenosis is the most common cause of left ventricular hypertrophy due to gradually increasing pressure work. As the stenosis develop the left ventricular hypertrophy may lead to congestive heart failure, increased risk of perioperative complications and also increased risk of sudden death. A functional porcine model imitating the pathophysiological nature of valvular aortic stenosis is very much sought after in order to study the geometrical and pathophysiological changes of the left ventricle, timing of surgery and also pharmacological therapy in this patient group.</p> <p>Earlier we developed a porcine model for aortic stenosis based on supracoronary aortic banding, this model may not completely imitate the pathophysiological changes that occurs when valvular aortic stenosis is present including the coronary blood flow. It would therefore be desirable to optimize this model according to the localization of the stenosis.</p> <p>Methods</p> <p>In 20 kg pigs subcoronary (n = 8), supracoronary aortic banding (n = 8) or sham operation (n = 4) was preformed via a left lateral thoracotomy. The primary endpoint was left ventricular wall thickness; secondary endpoints were heart/body weight ratio and the systolic/diastolic blood flow ratio in the left anterior descending coronary. Statistical evaluation by oneway anova and unpaired t-test.</p> <p>Results</p> <p>Sub- and supracoronary banding induce an equal degree of left ventricular hypertrophy compared with the control group. The coronary blood flow ratio was slightly but not significantly higher in the supracoronary group (ratio = 0.45) compared with the two other groups (subcoronary ratio = 0.36, control ratio = 0.34).</p> <p>Conclusions</p> <p>A human pathophysiologically compatible porcine model for valvular aortic stenosis was developed by performing subcoronary aortic banding. Sub- and supracoronary aortic banding induce an equal degree of left ventricular hypertrophy. This model may be valid for experimental investigations of aortic valve stenosis but studies of left ventricular hypertrophy can be studied equally well by graduated constriction of the ascending aorta.</p

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Water Policies and Conflict Resolution of Public Participation Decision-Making Processes Using Prioritized Ordered Weighted Averaging (OWA) Operators

[EN] There is a growing interest in environmental policies about how to implement public participation engagement in the context of water resources management. This paper presents a robust methodology, based on ordered weighted averaging (OWA) operators, to conflict resolution decision-making problems under uncertain environments due to both information and stakeholders' preferences. The methodology allows integrating heterogeneous interests of the general public and stakeholders on account of their different degree of acceptance or preference and level of influence or power regarding the measures and policies to be adopted, and also of their level of involvement (i.e., information supply, consultation and active involvement). These considerations lead to different environmental and socio-economic outcomes, and levels of stakeholders' satisfaction. The methodology establishes a prioritization relationship over the stakeholders. The individual stakeholders' preferences are aggregated through their associated weights, which depend on the satisfaction of the higher priority decision maker. The methodology ranks the optimal management strategies to maximize the stakeholders' satisfaction. It has been successfully applied to a real case study, providing greater fairness, transparency, social equity and consensus among actors. Furthermore, it provides support to environmental policies, such as the EU Water Framework Directive (WFD), improving integrated water management while covering a wide range of objectives, management alternatives and stakeholders.Llopis Albert, C.; Merigó-Lindahl, JM.; Liao, H.; Xu, Y.; Grima-Olmedo, J.; Grima-Olmedo, C. (2018). Water Policies and Conflict Resolution of Public Participation Decision-Making Processes Using Prioritized Ordered Weighted Averaging (OWA) Operators. 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High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Onset and evolution of discontinuously segmented chip flow in ultra-high-speed cutting Ti-6Al-4V

Increasing the cutting speed to an ultra-high level usually gives rise to a chip flow transition from continuously serrated to discontinuously segmented, which is one of the most fundamental and challenging problems in metal cutting. In this work, we experimentally performed the ultra-high-speed cutting on Ti-6Al-4V with a maximum cutting speed of 210 m/s, focusing on the physical phenomena accompanying the discontinuously segmented chip flow. It reveals that the discontinuously segmented chip flow can be attributed to the shear fracture induced by the fully matured shear banding, and there exists a ductile-brittle transition of the shear fracture as the cutting speed increases to an ultra-high level. In addition, the critical condition for the onset of segmented chip flow is presented using the momentum diffusion-based shear band evolution model, which gives good prediction for the chip segmentation

Pt-decorated nanoporous gold for glucose electrooxidation in neutral and alkaline solutions

Exploiting electrocatalysts with high activity for glucose oxidation is of central importance for practical applications such as glucose fuel cell. Pt-decorated nanoporous gold (NPG-Pt), created by depositing a thin layer of Pt on NPG surface, was proposed as an active electrode for glucose electrooxidation in neutral and alkaline solutions. The structure and surface properties of NPG-Pt were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and cyclic voltammetry (CV). The electrocatalytic activity toward glucose oxidation in neutral and alkaline solutions was evaluated, which was found to depend strongly on the surface structure of NPG-Pt. A direct glucose fuel cell (DGFC) was performed based on the novel membrane electrode materials. With a low precious metal load of less than 0.3 mg cm-2 Au and 60 μg cm-2 Pt in anode and commercial Pt/C in cathode, the performance of DGFC in alkaline is much better than that in neutral condition

Breast Tumor Cells with PI3K Mutation or HER2 Amplification Are Selectively Addicted to Akt Signaling

Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway. A variety of molecular techniques and tissue culture and in vivo xenograft models revealed that tumors with mutational activation of Akt signaling were selectively dependent on the pathway. In sensitive cells, pathway inhibition resulted in D-cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway activation were unaffected. Most importantly, the drug effectively inhibited Akt kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well-tolerated, causing only transient hyperglycemia without gross toxicity to the host despite the pleiotropic normal functions of Akt.These data demonstrate that breast cancers with PI3K mutation or HER2 amplification are selectively dependent on Akt signaling, and that effective inhibition of Akt in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of Akt may represent a therapeutic strategy for breast and other cancers that are addicted to the pathway including tumors with resistant to Herceptin

Surgical resectability of pancreatic adenocarcinoma: CTA

Imaging studies play an important role in the diagnosis and management of patients with pancreatic adenocarcinoma. Computed tomography (CT) is the most widely available and best validated modality for imaging these patients. Meticulous technique following a well-designed pancreas protocol is essential for maximizing the diagnostic efficacy of CT. After the diagnosis of pancreatic adenocarcinoma is made, the key to management is staging to determine resectability. In practice, staging often entails predicting the presence or absence of vascular invasion by tumor, for which several radiologic grading systems exist. With advances in surgical techniques, the definition of resectability is in evolution, and it is crucial that radiologists have an understanding of the implications of findings that are relevant to the determination of resectability