Physical modelling of backward erosion piping in foundation beneath levee

Centrifuge model tests are performed to observe piping progression in foundation beneath levee and to examine influence of repeated seepage and thickness of foundation ground on piping progression. Once the pipe is formed beneath the levee, hydraulic gradient upstream of the pipe tip becomes larger while that along the pipe becomes rather small. Shift of this large hydraulic gradient position to the upstream with rise of the flood water level leads to the large subsidence of the slope in the protected side and marked increase in flow rate. Repeated seepage and thickness of the permeable foundation layer have influence on stability of levee against piping. Repeated seepage makes the piping progression faster and levee vulnerable to the piping formation. With the thinner permeable foundation layer beneath the levee, the levee is at higher risk to cause brittle failure while the required hydraulic gradient to cause piping is larger

Cardiac CT and MRI guide surgery in impending left ventricular rupture after acute myocardial infarction

We report the case of a 67 year-old patient who presented with worsening chest pain and shortness of breath, four days post acute myocardial infarction. Contrast enhanced computed tomography of the chest ruled out a pulmonary embolus but revealed an unexpected small subepicardial aneurysm (SEA) in the lateral left ventricular wall which was confirmed on cardiac magnetic resonance imaging. Intraoperative palpation of the left lateral wall was guided by the cardiac MRI and CT findings and confirmed the presence of focally thinned and weakened myocardium, covered by epicardial fat. An aneurysmorrhaphy was subsequently performed in addition to coronary bypass surgery and a mitral valve repair. The patient was discharged home on post operative day eight in good condition and is feeling well 2 years after surgery

Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Levels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products.</p> <p>Methods</p> <p>We have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to N^ε-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively.</p> <p>Results</p> <p>Levels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of N^ε-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera.</p> <p>Conclusions</p> <p>We report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by inflammation. We propose a working hypothesis that presumes the existence of a link between advanced glycation end-product formation and induction of autoimmunity.</p

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability

HIV-1 Envelope Subregion Length Variation during Disease Progression

The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic

The emerging role of magnetic resonance imaging and multidetector computed tomography in the diagnosis of dilated cardiomyopathy

Magnetic resonance imaging and multidetector computed tomography are new imaging methods that have much to offer clinicians caring for patients with dilated cardiomyopathy. In this article we briefly describe the clinical, pathophysiological and histological aspects of dilated cardiomyopathy. Then we discuss in detail the use of both imaging methods for measurement of chamber size, global and regional function, for myocardial tissue characterisation, including myocardial viability assessment, and determination of arrhythmogenic substrate, and their emerging role in cardiac resynchronisation therapy

Signatures of mutational processes in human cancer.

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

Human and murine APOBEC3s restrict replication of koala retrovirus by different mechanisms

Background: Koala retrovirus (KoRV) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. As for many other gammaretroviruses, the KoRV genome can potentially encode an alternate form of Gag protein, glyco-gag. Results: In this study, a convenient assay for assessing KoRV infectivity in vitro was employed: the use of DERSE cells (initially developed to search for infectious xenotropic murine leukemia-like viruses). Using infection of DERSE and other human cell lines (HEK293T), no evidence for expression of glyco-gag by KoRV was found, either in expression of glyco-gag protein or changes in infectivity when the putative glyco-gag reading frame was mutated. Since glyco-gag mediates resistance of Moloney murine leukemia virus to the restriction factor APOBEC3, the sensitivity of KoRV (wt or putatively mutant for glyco-gag) to restriction by murine (mA3) or human APOBEC3s was investigated. Both mA3 and hA3G potently inhibited KoRV infectivity. Interestingly, hA3G restriction was accompanied by extensive G → A hypermutation during reverse transcription while mA3 restriction was not. Glyco-gag status did not affect the results. Conclusions: These results indicate that the mechanisms of APOBEC3 restriction of KoRV by hA3G and mA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction