(Pro)renin Revisited: New Insights from Studies in Mast Cells

Angiotensin synthesis at tissue sites is well-established, and interference with tissue angiotensin is now believed to underlie the beneficial effects of renin-angiotensin system blockers. At first it was thought that the renin required to synthesize angiotensin at tissue sites was also synthesized locally. Recent studies show, however, that this is not the case at important cardiovascular sites like the heart and vessel wall. Moreover, extrarenal sites that do express the renin gene release prorenin, the inactive precursor of renin, instead of renin. This chapter provides an update on the sources of (pro)renin in the body, lists the known stimulants and inhibitors of its production, and discusses the concept that prorenin rather than renin determines tissue angiotensin generation

Level-3 Calorimetric Resolution available for the Level-1 and Level-2 CDF Triggers

As the Tevatron luminosity increases sophisticated selections are required to be efficient in selecting rare events among a very huge background. To cope with this problem, CDF has pushed the offline calorimeter algorithm reconstruction resolution up to Level 2 and, when possible, even up to Level 1, increasing efficiency and, at the same time, keeping under control the rates. The CDF Run II Level 2 calorimeter trigger is implemented in hardware and is based on a simple algorithm that was used in Run I. This system has worked well for Run II at low luminosity. As the Tevatron instantaneous luminosity increases, the limitation due to this simple algorithm starts to become clear: some of the most important jet and MET (Missing ET) related triggers have large growth terms in cross section at higher luminosity. In this paper, we present an upgrade of the Level 2 Calorimeter system which makes the calorimeter trigger tower information available directly to a CPU allowing more sophisticated algorithms to be implemented in software. Both Level 2 jets and MET can be made nearly equivalent to offline quality, thus significantly improving the performance and flexibility of the jet and MET related triggers. However in order to fully take advantage of the new L2 triggering capabilities having at Level 1 the same L2 MET resolution is necessary. The new Level-1 MET resolution is calculated by dedicated hardware. This paper describes the design, the hardware and software implementation and the performance of the upgraded calorimeter trigger system both at Level 2 and Level 1.Comment: 5 pages, 5 figures,34th International Conference on High Energy Physics, Philadelphia, 200

A Probabilistic Assessment of Soil Erosion Susceptibility in a Head Catchment of the Jemma Basin, Ethiopian Highlands

Soil erosion represents one of the most important global issues with serious effects on agriculture and water quality, especially in developing countries, such as Ethiopia, where rapid population growth and climatic changes affect widely mountainous areas. The Meskay catchment is a head catchment of the Jemma Basin draining into the Blue Nile (Central Ethiopia) and is characterized by high relief energy. Thus, it is exposed to high degradation dynamics, especially in the lower parts of the catchment. In this study, we aim at the geomorphological assessment of soil erosion susceptibilities. First, a geomorphological map was generated based on remote sensing observations. In particular, we mapped three categories of landforms related to (i) sheet erosion, (ii) gully erosion, and (iii) badlands using a high-resolution digital elevation model (DEM). The map was validated by a detailed field survey. Subsequently, we used the three categories as dependent variables in a probabilistic modelling approach to derive the spatial distribution of the specific process susceptibilities. In this study we applied the maximum entropy model (MaxEnt). The independent variables were derived from a set of spatial attributes describing the lithology, terrain, and land cover based on remote sensing data and DEMs. As a result, we produced three separate susceptibility maps for sheet and gully erosion as well as badlands. The resulting susceptibility maps showed good to excellent prediction performance. Moreover, to explore the mutual overlap of the three susceptibility maps, we generated a combined map as a color composite where each color represents one component of water erosion. The latter map yields useful information for land-use managers and planning purposes

The Evidence for a Pentaquark Signal and Kinematic Reflections

Several recent experiments have reported evidence for a narrow baryon resonance with positive strangeness ($\Theta^+$) at a mass of 1.54 GeV/$c^2$. Baryons with $S=+1$ cannot be conventional $qqq$ states and the reports have thus generated much theoretical speculation about the nature of possible $S=+1$ baryons, including a 5-quark, or pentaquark, interpretation. We show that narrow enhancements in the $K^+n$ effective mass spectrum can be generated as kinematic reflections resulting from the decay of mesons, such as the $f_2(1275)$, the $a_2(1320)$ and the $\rho_3(1690)$.Comment: 4 pages, 4 figure

Oral Lubrication Matters: Effects on Satiety

As overeating, overweight and obesity remain public health concerns, it is crucial to design satiety-enhancing foods that suppress appetite and lower snack intake. Existing research identifies oro-sensory targets to promote satiation and satiety within the “satiety cascade” yet it remains unclear as to whether it is ‘chewing’ or ‘oral lubrication’ that might amplify satiation signals.Here we have combined techniques from experimental psychology, food material science and mechanical engineering to measure the role of chewing and lubrication using novel, model foods as preloads on subjective appetite and intake of a salty snack. Three mint flavoured hydrogels were engineered to vary in their texture (fracture stress) and lubrication (inverse of friction coefficient) properties, and a control group received a mint tea. Results showed that snack intake was suppressed by 32% after eating the low chewing/high lubricating preload as compared to the high chewing/low lubricating preload (p<0.05). No other significant effects were found for snack intake. Hunger ratings decreased from t1 to t3 (p<0.05), however differences between conditions were subtle and not significant. Thus, this proof-of-concept study demonstrates that manipulating oral lubrication is a promising new construct to reduce snack intake that merits future research in the oro-sensory satiety domain

Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo) Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer

Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) \u3e= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (\u3e= 10 percentage points from baseline to LVEF\u3c 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received \u3e= one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed \u3e= 95% of the planned radiation dose with dela

Braided racks, Hurwitz actions and Nichols algebras with many cubic relations

We classify Nichols algebras of irreducible Yetter-Drinfeld modules over groups such that the underlying rack is braided and the homogeneous component of degree three of the Nichols algebra satisfies a given inequality. This assumption turns out to be equivalent to a factorization assumption on the Hilbert series. Besides the known Nichols algebras we obtain a new example. Our method is based on a combinatorial invariant of the Hurwitz orbits with respect to the action of the braid group on three strands.Comment: v2: 35 pages, 6 tables, 14 figure

On relating rheology and oral tribology to sensory properties in hydrogels

The aim of this study was to understand the relationship between rheological, tribological and sensory properties (n = 11 panellists) of hydrogels differing in hydrocolloid type, concentration and degree of inhomogeneity. Fracture properties of hydrogels containing different ratios of κ-carrageenan (κC) and/or locust bean gum (LBG), sodium alginate (NaA), 300/1000 μm calcium alginate beads (CaA) at 1–4 wt% concentration were determined. Viscosity and friction coefficients (μ) of the hydrogel-boli after simulated oral processing were characterized. Tribology measurements were conducted in a polydimethylsiloxane ball/disc set-up with pre-adsorbed artificial salivary film at 37 °C. ’Scaling’ with boli viscosity showed good agreement of observed data with the Stribeck master curve, however only in the mixed regime i.e. at intermediate values of the product of velocity and lubricant viscosity (Uη). Low μ values of gel boli in the boundary regime were largely driven by the formation of a viscous layer of bolus fragments between opposing surfaces. Fracture properties of hydrogels and boli viscosity were correlated with all chewing-related texture attributes i.e. ‘firm’, ‘elastic’, ‘chewy’ and ‘cohesive’ and inversely correlated with lubrication-related attributes ‘melting’ and ‘pasty’ (p<0.05). On the other hand, μ of the bolus filtrate at orally relevant speeds (50 mm/s) was inversely correlated with lubrication-related attributes ‘pasty’ and positively with ‘slippery’ (p<0.05). The lack of correlations with ‘smooth’ could be explained due to sample inhomogeneity and the absence of ‘ball-bearing’-ability of the gel beads. A combination of initial fracture properties, boli viscosity and tribology of bolus filtrates (mixed regime) impacted the lubrication-related attribute ‘salivating’ (p<0.05)

The (pro)renin receptor. A decade of research: What have we learned?

The discovery of a (pro)renin receptor ((P)RR) in 2002 provided a long-sought explanation for tissue renin-angiotensin system (RAS) activity and a function for circulating prorenin, the inactive precursor of renin, in end-organ damage. Binding of renin and prorenin (referred to as (pro)renin) to the (P)RR increases angiotensin I formation and induces intracellular signalling, resulting in the production of profibrotic factors. However, the (pro)renin concentrations required for intracellular signalling in vitro are several orders of magnitude above (patho)physiological plasma levels. Moreover, the phenotype of prorenin-overexpressing animals could be completely attributed to angiotensin generation, possibly even without the need for a receptor. The efficacy of the only available putative (pro)renin receptor blocker handle region peptide remains doubtful, leading to inconclusive results. The fact that, in contrast to other RAS components, (P)RR knock-outs, even tissue-specific, are lethal, points to an important, (pro)renin-independent, function of the (P)RR. Indeed, recent research has highlighted ancillary functions of the (P)RR as an essential accessory protein of t

Epigenetic alterations differ in phenotypically distinct human neuroblastoma cell lines

<p>Abstract</p> <p>Background</p> <p>Epigenetic aberrations and a CpG island methylator phenotype have been shown to be associated with poor outcomes in children with neuroblastoma (NB). Seven cancer related genes (<it>THBS-1, CASP8, HIN-1, TIG-1, BLU, SPARC</it>, and <it>HIC-1</it>) that have been shown to have epigenetic changes in adult cancers and play important roles in the regulation of angiogenesis, tumor growth, and apoptosis were analyzed to investigate the role epigenetic alterations play in determining NB phenotype.</p> <p>Methods</p> <p>Two NB cell lines (tumorigenic LA1-55n and non-tumorigenic LA1-5s) that differ in their ability to form colonies in soft agar and tumors in nude mice were used. Quantitative RNA expression analyses were performed on seven genes in LA1-5s, LA1-55n and 5-Aza-dC treated LA1-55n NB cell lines. The methylation status around <it>THBS-1, HIN-1, TIG-1 </it>and <it>CASP8 </it>promoters was examined using methylation specific PCR. Chromatin immunoprecipitation assay was used to examine histone modifications along the <it>THBS-1 </it>promoter. Luciferase assay was used to determine <it>THBS-1 </it>promoter activity. Cell proliferation assay was used to examine the effect of 5-Aza-dC on NB cell growth. The soft agar assay was used to determine the tumorigenicity.</p> <p>Results</p> <p>Promoter methylation values for <it>THBS-1</it>, <it>HIN-1</it>, <it>TIG-1</it>, and <it>CASP8 </it>were higher in LA1-55n cells compared to LA1-5s cells. Consistent with the promoter methylation status, lower levels of gene expression were detected in the LA1-55n cells. Histone marks associated with repressive chromatin states (H3K9Me3, H3K27Me3, and H3K4Me3) were identified in the <it>THBS-1 </it>promoter region in the LA1-55n cells, but not the LA1-5s cells. In contrast, the three histone codes associated with an active chromatin state (acetyl H3, acetyl H4, and H3K4Me3) were present in the <it>THBS-1 </it>promoter region in LA1-5s cells, but not the LA1-55n cells, suggesting that an accessible chromatin structure is important for <it>THBS-1 </it>expression. We also show that 5-Aza-dC treatment of LA1-55n cells alters the DNA methylation status and the histone code in the <it>THBS-1 </it>promoter modifies cell morphology, and inhibits their ability to form colonies in soft agar.</p> <p>Conclusion</p> <p>Our results suggest that epigenetic aberrations contribute to NB phenotype, and that tumorigenic properties can be inhibited by reversing the epigenetic changes with 5-Aza-dC.</p