Assessment of uncertainty in river flow projections for the Mekong River using multiple GCMs and hydrological models

Hydrological model-related uncertainty is often ignored within climate change hydrological impact assessments. A MIKE SHE model is developed for the Mekong using the same data as an earlier semi-distributed, conceptual model (SLURP). The model is calibrated and validated using discharge at 12 gauging stations. Two sets of climate change scenarios are investigated. The first is based on a 2 °C increase in global mean temperature (the hypothesised threshold of ‘dangerous’ climate change), as simulated by seven GCMs. There are considerable differences in scenario discharge between GCMs, ranging from catchment-wide increases in mean discharge (up to 12.7%; CCCMA CGCM31, NCAR CCSM30), decreases (up to 21.6% in the upper catchments; CSIRO Mk30, IPSL CM4), and spatially varying responses (UKMO HadCM3 and HadGEM1, MPI ECHAM5). Inter-GCM differences are largely driven by differences in precipitation. The second scenario set (HadCM3, increases in global mean temperature of 1–6 °C) shows consistently greater discharge (maximum: 28.7%) in the upper catchment as global temperature increases, primarily due to increasing precipitation. Further downstream, discharge is strongly influenced by increasing PET, which outweighs impacts of elevated upstream precipitation and causes consistent discharge reductions for higher temperatures (maximum: −5.3% for the main Mekong). MIKE SHE results for all scenarios are compared with those from the SLURP catchment model and the Mac-PDM.09 global hydrological model. Although hydrological model-related uncertainty is evident, its magnitude is smaller than that associated with choice of GCM. In most cases, the three hydrological models simulate the same direction of change in mean discharge. Mac-PDM.09 simulates the largest discharge increases when they occur, which is responsible for some differences in direction of change at downstream gauging stations for some scenarios, especially HadCM3. Inter-hydrological model differences are likely attributed to alternative model structures, process representations and PET methods (Linacre for MIKE SHE and SLURP, Penman–Monteith for Mac-PDM.09)

The Schottky-Klein prime function: a theoretical and computational tool for applications

This article surveys the important role, in a variety of applied mathematical contexts, played by the so-called Schottky–Klein (S–K) prime function. While it is a classical special function, introduced by 19th century investigators, its theoretical significance for applications has only been realized in the last decade or so, especially with respect to solving problems defined in multiply connected, or ‘holey’, domains. It is shown here that, in terms of it, many well-known results pertaining only to the simply connected case (no holes) can be generalized, in a natural way, to the multiply connected case, thereby contextualizing those well-known results within a more general framework of much broader applicability. Given the wide-ranging usefulness of the S–K prime function it is important to be able to compute it efficiently. Here we introduce both a new theoretical formulation for its computation, as well as two distinct numerical methods to implement the construction. The combination of these theoretical and computational developments renders the S–K prime function a powerful new tool in applied mathematics

Dengue transmission risk in a changing climate: Bangladesh is likely to experience a longer dengue fever season in the future

Our changing climate is already affecting the transmission of dengue fever, the fastest growing vector-borne viral disease in the world. This issue presents a significant public health concern for some nations, such as Bangladesh, which already experience regular seasonal outbreaks of dengue fever under present day conditions. To provide guidance for proactive public health planning to potentially mitigate the severity of future outbreaks, we explored the impact of climate change on dengue infections by calculating the change in vectorial capacity (VC) of Aedes aegypti mosquitoes at a seasonal level for all regions in Bangladesh under two scenarios for future atmospheric greenhouse gas concentrations. For each of the four climate models used, and for both scenarios, our analysis revealed that the annual VC remains at a level that would enable potential dengue epidemic transmission in all regions in Bangladesh. We found a slight decline in VC in half of the regions examined during the last two decades of the 21st century for the lower-concentration scenario, with a pronounced decline in VC in all geographic regions beginning in 2060 for the higher-concentration scenario. The likely reason is that in many regions, warming will lead to sub-optimal mosquito breeding temperatures. However, seasonal differences in VC will dissipate as the climate warms, to the point that there is almost no observable seasonality for the higher-concentration scenario during the last two decades of this century. This finding suggests the dengue transmission season could eventually extend to all-year-round transmission, with outbreaks occurring at any time. Consequently, disease surveillance and control activities would need to be geographically and temporally adapted to mitigate dengue epidemic risk in response to climate change

JAK2V617F mediates resistance to DNA damage-induced apoptosis by modulating FOXO3A localization and Bcl-xL deamidation.

The JAK2V617F mutation is found in most patients with a myeloproliferative neoplasm (MPN). This gain-of-function mutation dysregulates cytokine signaling and is associated with increased accumulation of DNA damage, a process likely to drive disease evolution. JAK2V617F inhibits NHE-1 upregulation in response to DNA damage and consequently represses Bcl-xL deamidation and apoptosis, thus giving rise to inappropriate cell survival. However, the mechanism whereby NHE-1 expression is inhibited by JAK2V617F is unknown. In this study, we demonstrate that the accumulation of reactive oxygen species (ROS) in cells expressing JAK2V617F compromises the NHE-1/Bcl-xL deamidation pathway by repressing NHE-1 upregulation in response to DNA damage. In JAK2V617F-positive cells, increased ROS levels results from aberrant PI3K signaling, which decreases nuclear localization of FOXO3A and decreases catalase expression. Furthermore, when compared with autologous control erythroblasts, clonally derived JAK2V617F-positive erythroblasts from MPN patients displayed increased ROS levels and reduced nuclear FOXO3A. However, in hematopoietic stem cells (HSCs), FOXO3A is largely localized within the nuclei despite the presence of JAK2V617F mutation, suggesting that JAK2-FOXO signaling has a different effect on progenitors compared with stem cells. Inactivation of FOXO proteins and elevation of intracellular ROS are characteristics common to many cancers, and hence these findings are likely to be of relevance beyond the MPN field.Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the Kay Kendall Leukaemia Fund, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre, and the Leukemia & Lymphoma Society of America. DGK was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (Ottawa, ON), and a Lady Tata Memorial Trust International Award for Research in Leukaemia (London, UK). HJP was supported by a postdoctoral fellowship from the Human Frontier Science Program.This is the accepted manuscript. The final version is available at http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2015285a.html

Muscle size explains low passive skeletal muscle force in heart failure patients.

BACKGROUND: Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. METHODS: Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. RESULTS: We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. DISCUSSION: These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening

Carbonyl sulfide and carbon disulfide: Large-scale distributions over the western Pacific and emissions from Asia during TRACE-P

An extensive set of carbonyl sulfide (OCS) and carbon disulfide (CS 2) observations were made as part of the NASA Transport and Chemical Evolution over the Pacific (TRACE-P) project, which took place in the early spring 2001. TRACE-P sampling focused on the western Pacific region but in total included the geographic region 110°E to 290°E longitude, 5°N to 50°N latitude, and 0-12 km altitude. Substantial OCS and CS2 enhancements were observed for a great many air masses of Chinese and Japanese origin during TRACE-P. Over the western Pacific, mean mixing ratios of long-lived OCS and shorter-lived CS2 showed a gradual decrease by about 10% and a factor of 5-10, respectively, from the surface to 8-10 km altitude, presumably because land-based sources dominated their distribution during February through April 2001. The highest mean OCS and CS 2 levels (580 and 20 pptv, respectively, based on 2.5° × 2.5° latitude bins) were observed below 2 km near the coast of Asia, at latitudes between 25°N and 35°N, where urban Asian outflow was strongest. Ratios of OCS versus CO for continental SE Asia were much lower compared to Chinese and Japanese signatures and were strongly associated with biomass burning/biofuel emissions. We present a new inventory of anthropogenic Asian emissions (including biomass burning) for OCS and CS2 and compare it to emission estimates based on regional relationships of OCS and CS 2 to CO and CO2. The OCS and CS2 results for the two methods compare well for continental SE Asia and Japan plus Korea and also for Chinese CS2 emissions. However, it appears that the inventory underestimates Chinese emissions of OCS by about 30-100%. This difference may be related to the fact that we did not include natural sources such as wetland emissions in our inventory, although the contributions from such sources are believed to be at a seasonal low during the study period. Uncertainties in OCS emissions from Chinese coal burning, which are poorly characterized, likely contribute to the discrepancy. Copyright 2004 by the American Geophysical Union

Solid state NMR of isotope labelled murine fur: a powerful tool to study atomic level keratin structure and treatment effects

We have prepared mouse fur extensively $^{13}$C,$^{15}$N-labelled in all amino acid types enabling application of 2D solid state NMR techniques which establish covalent and spatial proximities within, and in favorable cases between, residues. $^{13}$C double quantum-single quantum correlation and proton driven spin diffusion techniques are particularly useful for resolving certain amino acid types. Unlike 1D experiments on isotopically normal material, the 2D methods allow the chemical shifts of entire spin systems of numerous residue types to be determined, particularly those with one or more distinctively shifted atoms such as Gly, Ser, Thr, Tyr, Phe, Val, Leu, Ile and Pro. Also the partial resolution of the amide signals into two signal envelopes comprising of $\alpha$-helical, and $\beta$-sheet/random coil components, enables resolution of otherwise overlapped $\alpha$-carbon signals into two distinct cross peak families corresponding to these respective secondary structural regions. The increase in resolution conferred by extensive labelling offers new opportunities to study the chemical fate and structural environments of specific atom and amino acid types under the influence of commercial processes, and therapeutic or cosmetic treatments.Medical Research Council (Grant ID: RG75828), Engineering and Physical Sciences Research Council (Ph.D. studentships), National Institute of Health Researc

Giving voters what they want? Party orientation perceptions and preferences in the British electorate

Some of the most important propositions in the political marketing literature hinge on assumptions about the electorate. In particular, voters are presumed to react in different ways to different orientations or postures. Yet there are theoretical reasons for questioning some of these assumptions, and certainly they have seldom been empirically tested. Here, we focus on one prominent example of political marketing research: Lees-Marshment’s orientations’ model. We investigate how the public reacts to product and market orientation, whether they see a trade-off between the two (a point in dispute among political marketing scholars), and whether partisans differ from non-partisan voters by being more inclined to value product over market orientation. Evidence from two mass sample surveys of the British public (both conducted online by YouGov) demonstrates important heterogeneity within the electorate, casts doubt on the core assumptions underlying some political marketing arguments and raises broader questions about what voters are looking for in a party