Validation of earthquake ground-motion models in southern California, USA, using precariously balanced rocks

Accurate estimates of earthquake ground shaking rely on uncertain ground-motion models derived from limited instrumental recordings of historical earthquakes. A critical issue is that there is currently no method to empirically validate the resultant ground-motion estimates of these models at the timescale of rare, large earthquakes; this lack of validation causes great uncertainty in ground-motion estimates. Here, we address this issue and validate ground-motion estimates for southern California utilizing the unexceeded ground motions recorded by 20 precariously balanced rocks. We used cosmogenic 10Be exposure dating to model the age of the precariously balanced rocks, which ranged from ca. 1 ka to ca. 50 ka, and calculated their probability of toppling at different ground-motion levels. With this rock data, we then validated the earthquake ground motions estimated by the Uniform California Earthquake Rupture Forecast, Version 3 (UCERF3) seismic-source characterization and the Next Generation Attenuation (NGA)-West2 ground-motion models. We found that no ground-motion model estimated levels of earthquake ground shaking consistent with the observed continued existence of all 20 precariously balanced rocks. The ground-motion model I14 estimated ground-motion levels that were inconsistent with the most rocks; therefore, I14 was invalidated and removed. At a 2475 year mean return period, the removal of this invalid ground-motion model resulted in a 2−7% reduction in the mean and a 10−36% reduction in the 5th−95th fractile uncertainty of the ground-motion estimates. Our findings demonstrate the value of empirical data from precariously balanced rocks as a validation tool for removing invalid ground-motion models and, in turn, reducing the uncertainty in earthquake ground-motion estimates

Magnetorelaxometry Assisting Biomedical Applications of Magnetic Nanoparticles

Due to their biocompatibility and small size, iron oxide magnetic nanoparticles (MNP) can be guided to virtually every biological environment. MNP are susceptible to external magnetic fields and can thus be used for transport of drugs and genes, for heat generation in magnetic hyperthermia or for contrast enhancement in magnetic resonance imaging of biological tissue. At the same time, their magnetic properties allow one to develop sensitive and specific measurement methods to non-invasively detect MNP, to quantify MNP distribution in tissue and to determine their binding state. In this article, we review the application of magnetorelaxometry (MRX) for MNP detection. The underlying physical properties of MNP responsible for the generation of the MRX signal with its characteristic parameters of relaxation amplitude and relaxation time are described. Existing single and multi-channel MRX devices are reviewed. Finally, we thoroughly describe some applications of MRX to cellular MNP quantification, MNP organ distribution and MNP-based binding assays. Providing specific MNP signals, a detection limit down to a few nanogram MNP, in-vivo capability in conscious animals and measurement times of a few seconds, MRX is a valuable tool to improve the application of MNP for diagnostic and therapeutic purposes

Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus—A Mechanism of Action for Anti-Influenza Agents

Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds

Disparities in healthy food zoning, farmers’ market availability, and fruit and vegetable consumption among North Carolina residents

Background Context and purpose of the study. To examine (1) associations between county-level zoning to support farmers’ market placement and county-level farmers’ market availability, rural/urban designation, percent African American residents, and percent of residents living below poverty and (2) individual-level associations between zoning to support farmers’ markets; fruit and vegetable consumption and body mass index (BMI) among a random sample of residents of six North Carolina (NC) counties. Methods Zoning ordinances were scored to indicate supportiveness for healthy food outlets. Number of farmers’ markets (per capita) was obtained from the NC-Community Transformation Grant Project Fruit and Vegetable Outlet Inventory (2013). County-level census data on rural/urban status, percent African American, and percent poverty were obtained. For data on farmers’ market shopping, fruit and vegetable consumption, and BMI, trained interviewers conducted a random digit dial telephone survey of residents of six NC counties (3 urban and 3 rural). Pearson correlation coefficients and multilevel linear regression models were used to examine county-level and individual-level associations between zoning supportiveness, farmers’ market availability, and fruit and vegetable consumption and BMI. Results At the county-level, healthier food zoning was greater in more urban areas and areas with less poverty. At the individual-level, self-reported fruit and vegetable consumption was associated with healthier food zoning. Conclusions Disparities in zoning to promote healthy eating should be further examined, and future studies should assess whether amending zoning ordinances will lead to greater availability of healthy foods and changes in dietary behavior and health outcomes.ECU Open Access Publishing Support Fun

Zebrafish: A See-Through Host and a Fluorescent Toolbox to Probe Host–Pathogen Interaction

In many ways, the zebrafish represents a hybrid between mouse and invertebrate infection models. Powerful forwardgenetic tools that have made invertebrates justifiably famous are not only relatively accessible in the zebrafish, but have been exploited to yield new insights into human infectious diseases, including leprosy and tuberculosis [1]. Transgenic technologies have enabled detailed, non-invasive in vivo visualization of macrophages and neutrophils in pitched battle with bacteria and fungi [2,3]. Reverse genetics with morpholinos, vivo-morpholinos, and zinc-finger nucleases (but unfortunately not homologous recombination, which for the moment remains out of reach in this organism) enable examination of the roles of specific genes during infection. Flexible genetic systems such as Gal4-UAS and Cre-Lox permit tissue-specific transformation and ablation ([3]; Figure 1)

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2–8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy

FLPe functions in zebrafish embryos

To assay the efficiency of the FLP/FRT site-specific recombination system in Danio rerio, a construct consisting of a muscle-specific promoter driving EGFP flanked by FRT sites was developed. FLPe capped RNA was microinjected into transgenic single cell stage zebrafish embryos obtained by crossing hemizygous transgenic males with wild-type females. By 48 h post fertilization (hpf), the proportion of embryos displaying green fluorescence following FLPe RNA microinjection was significantly lower (7.7%; P < 0.001) than would be expected from a cross in the absence of the recombinase (50%). Embryos that retained fluorescence displayed marked mosaicism. Inheritance of the excised transgene in non-fluorescent, transgenic embryos was verified by PCR analysis and FLPe-mediated recombination was confirmed by DNA sequencing. Sperm derived from confirmed transgenic males in these experiments was used to fertilize wild-type eggs to determine whether germline excision of the transgene had occurred. Clutches sired by FLPe-microinjected males contained 0–4% fluorescent embryos. Transgenic males that were phenotypically wild-type produced no fluorescent progeny, demonstrating complete excision of the transgene from their germline. FLPe microinjected males that retained some fluorescent muscle expression produced a small proportion of fluorescent offspring, suggesting that in mosaic males not all germline cells had undergone FLPe-mediated transgene excision. Our results show that FLPe, which is derived from Saccharomyces cerevisiae, is an efficient recombinase in zebrafish maintained at 28.5°C