Experimental Investigation of Scour and Pressures on a Single Span Arch Bridge Under Inundation

This paper presents two experiments, carried out in a 605mm-wide flume, to investigate scour and hydrodynamic pressure on a scaled model of a single span arch bridge. The geometry of the bridge model is scaled down according to a prototype bridge, with hydraulic conditions of the experiments representing a small river. Measured scour depths showed that flow vertical contraction by the arch bridge is higher than that of flat-deck bridges. Effect of a single cylindrical debris on scour was also evaluated and found to be negligible at the considered flow depth. Temporal variation of hydrodynamic pressure with scour evolution was also measured. It was found that temporal evolution of scour can reduce hydrodynamic pressure significantly at the initial base of the abutment at downstream face of the bridge, which can erode mortar from the masonry composition of an arch bridge

Additive manufacture and the gas turbine combustor: challenges and opportunities to enable low-carbon fuel flexibility

Advances in gas turbine (GT) combustion are enabled by metal additive manufacturing (AM) using selective laser melting (SLM) and other methods. In future low-carbon energy systems, AM will be critical for GTs operating on fuels such as hydrogen, ammonia, and biofuels. This paper evaluates the impact of AM on GT combustors, focusing on design freedom for novel geometries, reduced product development timelines, multiple component integration, and high-temperature materials suitable for harsh environments. Current AM challenges and research needs for GT combustors are discussed with industry input. These challenges are shown to be priority R&D areas across the GT value chain. Recent academic advances show the positive influence of widening access to SLM platforms and AM facilitates research using materials and geometries relevant to the GT community. Micro GTs are well-suited to SLM platforms, enabling novel geometries incorporating multiple functional parts including heat exchangers and porous media using advanced metal alloys. For industrial GTs, AM reduces new combustor product development time, as rapid prototyping and testing complements numerical methods. This review provides compelling evidence for continued AM R&D for GT combustion applications to meet future decarbonization goals

Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion

Purpose: Recent studies indicated that dysregulation of noncoding KNAs (ncRNA) such as miRNAs is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC). Experimental Design: We performed in vitro functional assays on TNBC cell lines to investigate the role of mi R-34a in FOLM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a. Results: In this study, we investigated the role of p53-driven ncRNA miR-34a and found that miR-34a is associated with significantly longer patient survival in TNBC and inversely correlated with levels of proto-oncogenic eEF2K, which was associated with significantly shorter overall patient survival, We showed that miR-34a directly binds to the 3'-untranslated region of eEF2K and FOXM1 mRNAs and suppresses their expression, leading to inhibition of TNBC cell proliferation, motility, and invasion. Notably, restoring miR-34a expression recapitulated the effects of inhibition of eEF2K and FOXM1, the transcription factor for eEF2K and the direct target of p53, in TNBC cell lines, whereas overexpression of eEF2K and FOXM1 rescued the effects and signaling pathways mediated by miR-34a. Moreover, in vivo therapeutic delivery of miR-34a nanopartides by systemic intravenous administration delayed tumor growth of two different orthotopic TNBC tumor xenograft models by inhibiting eEF2K and FOXM1, intratumoral proliferation and angiogenesis, and inducing apoptosis. Conclusions: Overall, our findings provide new insights into the tumor suppressor role of miR-34a by dual-targeting of FOXM1/eEF2K signaling axis and suggest that miR-34a-based gene therapy may be a potential therapeutic strategy in TNBC. (C)2018 AACR.NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R21CA199050, P30CA016672]; noncoding RNA center; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672] Funding Source: NIH RePORTERThis work was supported in part by grants from the NIH/NCI (R21CA199050 and P30CA016672) and the funding from noncoding RNA center and used the Functional Proteomics RPPA Core Facility

Prognostic impact of BCL2, BCL6 and MYC status in de novo diffuse large B-cell lymphoma: a regional study of 43 patients

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We aimed to evaluate the status of MYC, BCL2, BCL6 in patients with DLBCL.Methods: Herein, we have investigated the prognostic relevance of MYC, BCL2 and BCL6 from 43 de novo DLBCL patients.Results: In this study, protein overexpression of BCL2 and BCL6 was encountered in 46.5% (n=20) and 27.9% (n=12) of the tumors, respectively.  Rearrangements in MYC, BCL6, and BCL2 were detected in 9.3% (n=4), 25.6% (n=11), and 4.7% (n=2) of the cases, respectively. Any statistically significant difference could not be found between Bcl-2, Bcl-6 expression, C-MYC rearrangement and the survival.Conclusions: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, so more mechanism-based therapy should be explored. A larger study is warranted to better understand the immunophenotypic and molecular features of DLBCL and their respective impact on patient survival

Experimental Study on Scour at a Sharp-Nose Bridge Pier with Debris Blockage

Previous experimental research on the effects of debris on pier scour has focused primarily on circular and rectangular piers with debris present just under flow free surface. Debris-induced scour around sharp-nose piers, which are typical of masonry bridge piers, and the effect of debris elevation on pier scour have seldom been studied before. This paper aims to fill this knowledge gap. It presents results from flume experiments investigating scour around a sharp-nose pier under shallow flow conditions with angle of attack relative to the pier being zero. Uniform sand is used as bed material. Debris is modeled as stationary and extending only upstream of the pier. Three simplified debris geometries (cylinder, half-pyramid, and plate) are studied. Results show that scour depth decreases as debris gets closer to the bed with maximum scour depth occurring when debris is located just under the flow free surface. Interestingly, scour depths produced by debris in shallow flow are observed to be comparable to those produced by deep flow in the absence of debris. This finding highlights the importance of monitoring debris accumulation at bridges in nonflood conditions. Results also show that the volume of the scour hole around a pier increases quadratically with maximum scour depth. This information is useful for postflood scour remedial works. Lastly, the collected laboratory measurements are used to compare four popular equations for scour estimation on their ability to predict debris-induced scour. The Colorado State University (CSU) equation is found to offer the most accurate predictions

MicroRNA 603 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting elongation factor 2 kinase

Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of defined molecular targets, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and is associated with high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC represents an unmet therapeutic challenge. Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent serine/threonine kinase that promotes TNBC tumorigenesis, progression, and drug resistance, representing a potential novel molecular target. However, the mechanisms regulating eEF2K expression are unknown. Here, we report that eEF2K protein expression is highly up-regulated in TNBC cells and patient tumors and it is associated with poor patient survival and clinical outcome. We found that loss/reduced expression of miR-603 leads to eEF2K overexpression in TNBC cell lines. Its expression results in inhibition of eEF2K by directly targeting the 3-UTR and the inhibition of tumor cell growth, migration and invasion in TNBC. In vivo therapeutic gene delivery of miR-603 into TNBC xenograft mouse models by systemic administration of miR-603-nanoparticles led to a significant inhibition of eEF2K expression and tumor growth, which was associated with decreased activity of the downstream targets of eEF2K, including Src, Akt, cyclin D1 and c-myc. Our findings suggest that miR-603 functions as a tumor suppressor and loss of miR-603 expression leads to increase in eEF2K expression and contributes to the growth, invasion, and progression of TNBC. Taken together, our data suggest that miR-603-based gene therapy is a potential strategy against TNBC