The effect of flange restraint on web crippling strength of cold-formed steel Z- and I-sections

PREFACE When considering the web crippling strength of a cold-formed steel member, the current edition of the AISI Specification for the Design of Cold-Formed Steel Structural Members does not distinguish between the behavior of a member having its flanges attached to a support member, and a member not attached to its support. To enhance the industry and design professional\u27s understanding of web crippling, a study was initiated at the University of Missouri-Rolla to explore the influence of flange attachment. This research consisted of web crippling tests on identical specimens. The specimens were tested where either cross sections were attached to a support beam or were not attached to the support beam. This enabled direct comparison and evaluation of flange attachment. The results were compared with AISI design criteria and other prediction equations, and suggested design recommendations were developed. This report is based on the thesis presented to the Faculty of the Graduate School of the University of Missouri-Rolla in partial fulfillment of the requirements for the degree of Masters of Science in Civil Engineering. This investigation was sponsored by the American Iron and Steel Institute and the Metal Building Manufacturers Association. The technical guidance provided by the AISI Subcommittee on Flexural Members and the AISI Staff is gratefully acknowledged. Members of the AISI Subcommittee are: J. N. Nunnery (chairman), R. E. Albrecht, R. E. Brown, C. R. Clauer, D. S. Ellifritt, S. J. Errera, J. M. Fisher, T. V. Galambos, M. Golovin, G. J. Hancock, A. J. Harold, R. B. Heagler, D. L. Johnson, W. J. Kile, R. A. LaBoube, M. R. Loeske, R. Madsen, T. M. Murray, T. B. Pekoz, R. M. Schuster, P. A. Seaburg, T. Sputo, T. W. Trestain, and W. W. Yu. The AISI Staff include R. B. Haws and K. L. Slaughter. Thanks are also extended to W. L. Shoemaker of the Metal Building Manufacturers Association for his assistance

PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR.

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma

Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice

Cytochrome P450 epoxygenase metabolites of arachidonic acid (EETs) have multiple cardiovascular effects, including reduction of blood pressure, protection against myocardial ischemia-reperfusion injury, and attenuation of endothelial inflammation and apoptosis. The present study was aimed to determine potential neuroprotective roles for EETs in cerebral ischemia

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein

Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood–brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS

On the Origin of the Radio/X-Ray Luminosity Correlation in Black Hole Candidates

In previous work we found that the spectral state switch and other spectral properties of both neutron star (NS) and galactic black hole candidates (GBHC), in low mass x-ray binary systems could be explained by a magnetic propeller effect that requires an intrinsically magnetic central compact object. In later work we showed that intrinsically magnetic GBHC could be easily accommodated by general relativity in terms of magnetospheric eternally collapsing objects (MECO), with lifetimes greater than a Hubble time, and examined some of their spectral properties. In this work we show how a standard thin accretion disk and corona can interact with the central magnetic field in atoll class NS, and GBHC and active galactic nuclei (AGN) modeled as MECO, to produce jets that emit radio through infrared luminosity $L_R$ that is correlated with mass and x-ray luminosity as $L_R \propto M^{0.75 - 0.92}L_x^{2/3}$ up to a mass scale invariant cutoff at the low/high spectral state switch. Comparing the MECO-GBHC/AGN model to observations, we find that the correlation exponent, the mass scale invariant cutoff, and the radio luminosity ratios of AGN, GBHC and atoll class NS are correctly predicted, which strongly implies that GBHC and AGN have observable intrinsic magnetic moments and hence do not have event horizons.Comment: 6 pages, 1 figure. Accepted by MNRA

Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy

© 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (January 2019) in accordance with the publisher’s archiving policyBackground Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. Methods Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. Results Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). Conclusions The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up

The Stem Cell Marker CD133 Associates with Enhanced Colony Formation and Cell Motility in Colorectal Cancer

CD133 is a membrane molecule that has been, controversially, reported as a CSC marker in colorectal cancer (CRC). In this study, we sought to clarify the expression and role of CD133 in CRC. Initially the size of the CD133−expressing (CD133+) population in eight well-described CRC cell lines was measured by flow cytometry and was found to range from 0% to >95%. The cell line HT29 has a CD133+ population of >95% and was chosen for functional evaluation of CD133 after gene knockdown by RNA interference. A time course assay showed that CD133 inhibition had no significant effect on cell proliferation or apoptosis. However, CD133 knockdown did result in greater susceptibility to staurosporine-induced apoptosis (p = 0.01) and reduction in cell motility (p<0.04). Since gene knockdown may cause “off-target” effects, the cell line SW480 (which has a CD133+ population of 40%) was sorted into pure CD133+ and CD133− populations to allow functional comparison of isogenic populations separated only by CD133 expression. In concordance with the knockdown experiments, a time course assay showed no significant proliferative differences between the CD133+/CD133− populations. Also greater resistance to staurosporine-induced apoptosis (p = 0.008), greater cell motility (p = 0.03) and greater colony forming efficiency was seen in the CD133+ population than the CD133− population in both 2D and 3D culture (p<0.0001 and p<0.003 respectively). Finally, the plasticity of CD133 expression in tumour cells was tested. Quantitative PCR analysis showed there was transcriptional repression in the CD133− population of SW480. Prolonged culture of a pure CD133− population resulted in re-emergence of CD133+ cells. We conclude that CD133 expression in CRCs is associated with some features attributable to stemness and that there is plasticity of CD133 expression. Further studies are necessary to delineate the mechanistic basis of these features