Interpreting intraplate tectonics for seismic hazard : a UK historical perspective

It is notoriously difficult to construct seismic source models for probabilistic seismic hazard assessment in intraplate areas on the basis of geological information, and many practitioners have given up the task in favour of purely seismicity-based models. This risks losing potentially valuable information in regions where the earthquake catalogue is short compared to the seismic cycle. It is interesting to survey how attitudes to this issue have evolved over the past 30 years. This paper takes the UK as an example, and traces the evolution of seismic source models through generations of hazard studies. It is found that in the UK, while the earliest studies did not consider regional tectonics in any way, there has been a gradual evolution towards more tectonically based models. Experience in other countries, of course, may differ

Electric field tunable superconductor-semiconductor coupling in Majorana nanowires

We study the effect of external electric fields on superconductor-semiconductor coupling by measuring the electron transport in InSb semiconductor nanowires coupled to an epitaxially grown Al superconductor. We find that the gate voltage induced electric fields can greatly modify the coupling strength, which has consequences for the proximity induced superconducting gap, effective g-factor, and spin-orbit coupling, which all play a key role in understanding Majorana physics. We further show that level repulsion due to spin-orbit coupling in a finite size system can lead to seemingly stable zero bias conductance peaks, which mimic the behavior of Majorana zero modes. Our results improve the understanding of realistic Majorana nanowire systems.Comment: 10 pages, 5 figures, supplemental information as ancillary fil

Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study

Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study.BackgroundAltered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease.MethodsThis study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N = 307) and patients (N = 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001.ResultsMany patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P = 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg2/dL2, P = 0.0001), PTH (1.01 per 100 pg/dL, P = 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P = 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P = 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P = 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration.ConclusionThis study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area

Quantized Majorana conductance

Majorana zero-modes hold great promise for topological quantum computing. Tunnelling spectroscopy in electrical transport is the primary tool to identify the presence of Majorana zero-modes, for instance as a zero-bias peak (ZBP) in differential-conductance. The Majorana ZBP-height is predicted to be quantized at the universal conductance value of 2e2/h at zero temperature. Interestingly, this quantization is a direct consequence of the famous Majorana symmetry, 'particle equals antiparticle'. The Majorana symmetry protects the quantization against disorder, interactions, and variations in the tunnel coupling. Previous experiments, however, have shown ZBPs much smaller than 2e2/h, with a recent observation of a peak-height close to 2e2/h. Here, we report a quantized conductance plateau at 2e2/h in the zero-bias conductance measured in InSb semiconductor nanowires covered with an Al superconducting shell. Our ZBP-height remains constant despite changing parameters such as the magnetic field and tunnel coupling, i.e. a quantized conductance plateau. We distinguish this quantized Majorana peak from possible non-Majorana origins, by investigating its robustness on electric and magnetic fields as well as its temperature dependence. The observation of a quantized conductance plateau strongly supports the existence of non-Abelian Majorana zero-modes in the system, consequently paving the way for future braiding experiments.Comment: 5 figure

A consensus research agenda for optimising nasal drug delivery

Nasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g. vaccines, biologics and drugs with action in the brain or sinuses, to local and systemic therapeutic targets. Innovations and new tools/knowledge are required to design products to deliver these therapeutic agents to the right target at the right time in the right patients. We report the outcomes of an expert meeting convened to consider gaps in knowledge and unmet research needs in terms of (i) formulation and devices, (ii) meaningful product characterization and modeling, (iii) opportunities to modify absorption and clearance. Important research questions were identified in the areas of device and formulation innovation, critical quality attributes for different nasal products, development of nasal casts for drug deposition studies, improved experimental models, the use of simulations and nasal delivery in special populations. We offer these questions as a stimulus to research and suggest that they might be addressed most effectively by collaborative research endeavors

Recent evolution of an ice‐cored moraine at the Gentianes Pass, Valais Alps, Switzerland

International audienceLateral moraines located in permafrost environments often preserve large amounts of both glacier and periglacial ice. To understand how ice‐cored moraines located in high alpine environments evolve in a context of both glacier retreat and permafrost degradation, we performed 11 terrestrial laser‐scanning measurement campaigns between 2007 and 2014 on a highly anthropogenic overprinted moraine prone to instability. Resulting comparison of the subsequent 3D models allowed to qualitatively and quantitatively analyze the morphological evolution of the moraine. The comparisons indicate a very high geomorphic activity of the moraine including large areas affected by downslope movements of blocks and 10 landslides with a volume between 24 ± 1 and 1,138 ± 47 m3. Data also indicated a very strong ice melt with a loss of ice thickness locally reaching 17.7 m at the foot of the moraine. These results, compared with resistivity and thermal measurements of the ground, suggest the combined role of ice loss at the foot of the moraine and the permafrost activity/warming in triggering these processes

Proton Pump Inhibitors Exert Anti-Allergic Effects by Reducing TCTP Secretion

BACKGROUND:Extracellular translationally controlled tumor protein (TCTP) is known to play a role in human allergic responses. TCTP has been identified outside of macrophages, in activated mononuclear cells, and in biological fluids from allergic patients. Even TCTP devoid of signal sequences, is secreted to extracellular environment by an yet undefined mechanism. This study is aimed at understanding the mechanism of TCTP release and its regulation. A secondary goal is to see if inhibitors of TCTP release can serve as potential anti-allergic asthmatic drugs. METHODOLOGY/PRINCIPAL FINDINGS:Using Western blotting assay in HEK293 and U937 cells, we found that TCTP secretion is reduced by omeprazole and pantoprazole, both of which are proton pump inhibitors. We then transfected HEK293 cells with proton pump expression vectors to search for the effects of exogeneously overexpressed H(+)/K(+)-ATPase on the TCTP secretion. Based on these in vitro data we checked the in vivo effects of pantoprazole in a murine model of ovalbumin-induced allergy. Omeprazole and pantoprazole reduced TCTP secretion from HEK293 and U937 cells in a concentration-dependent fashion and the secretion of TCTP from HEK293 cells increased when they over-expressed H(+)/K(+)-ATPase. In a murine model of ovalbumin-induced allergy, pretreatment with pantoprazole reduced infiltration of inflammatory cells, increased goblet cells, and increased TCTP secretion induced by OVA challenge. CONCLUSION:Since Omeprazole and pantoprazole decrease the secretion of TCTP which is associated with the development of allergic reaction, they may have the potential to serve as anti-allergic (asthmatic) drugs

MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting pancreatic cancer stem cells