Multiple haptic targets for motion-impaired computer users

Although a number of studies have reported that force feedback gravity wells can improve performance in "point-and-click" tasks, there have been few studies addressing issues surrounding the use of gravity wells for multiple on-screen targets. This paper investigates the performance of users, both with and without motion-impairments, in a "point-and-click" task when an undesired haptic distractor is present. The importance of distractor location is studied explicitly. Results showed that gravity wells can still improve times and error rates, even on occasions when the cursor is pulled into a distractor. The greatest improvement is seen for the most impaired users. In addition to traditional measures such as time and errors, performance is studied in terms of measures of cursor movement along a path. Two cursor measures, angular distribution and temporal components, are proposed and their ability to explain performance differences is explored.

Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs

While selenium (Se) is an essential micronutrient for humans, epidemiological studies have raised concern that supranutritional Se intake may increase the risk to develop Type 2 diabetes mellitus (T2DM). We aimed to determine the impact of Se at a dose and source frequently ingested by humans on markers of insulin sensitivity and signalling. Male pigs were fed either a Se-adequate (0.17 mg Se/kg) or a Se-supranutritional (0.50 mg Se/kg; high-Se) diet. After 16 weeks of intervention, fasting plasma insulin and cholesterol levels were non-significantly increased in the high-Se pigs, whereas fasting glucose concentrations did not differ between the two groups. In skeletal muscle of high-Se pigs, glutathione peroxidase activity was increased, gene expression of forkhead box O1 transcription factor and peroxisomal proliferator-activated receptor- coactivator 1 were increased and gene expression of the glycolytic enzyme pyruvate kinase was decreased. In visceral adipose tissue of high-Se pigs, mRNA levels of sterol regulatory element-binding transcription factor 1 were increased, and the phosphorylation of Akt, AMP-activated kinase and mitogen-activated protein kinases was affected. In conclusion, dietary Se oversupply may affect expression and activity of proteins involved in energy metabolism in major insulin target tissues, though this is probably not sufficient to induce diabetes.

What influence will future solar activity changes over the 21st century have on projected global near-surface temperature changes?

During the 20th century, solar activity increased in magnitude to a so-called grand maximum. It is probable that this high level of solar activity is at or near its end. It is of great interest whether any future reduction in solar activity could have a significant impact on climate that could partially offset the projected anthropogenic warming. Observations and reconstructions of solar activity over the last 9000 years are used as a constraint on possible future variations to produce probability distributions of total solar irradiance over the next 100 years. Using this information, with a simple climate model, we present results of the potential implications for future projections of climate on decadal to multidecadal timescales. Using one of the most recent reconstructions of historic total solar irradiance, the likely reduction in the warming by 2100 is found to be between 0.06 and 0.1 K, a very small fraction of the projected anthropogenic warming. However, if past total solar irradiance variations are larger and climate models substantially underestimate the response to solar variations, then there is a potential for a reduction in solar activity to mitigate a small proportion of the future warming, a scenario we cannot totally rule out. While the Sun is not expected to provide substantial delays in the time to reach critical temperature thresholds, any small delays it might provide are likely to be greater for lower anthropogenic emissions scenarios than for higher-emissions scenarios.

Modelling predicts that heat stress, not drought, will increase vulnerability of wheat in Europe

New crop cultivars will be required for a changing climate characterised by increased summer drought and heat stress in Europe. However, the uncertainty in climate predictions poses a challenge to crop scientists and breeders who have limited time and resources and must select the most appropriate traits for improvement. Modelling is a powerful tool to quantify future threats to crops and hence identify targets for improvement. We have used a wheat simulation model combined with local-scale climate scenarios to predict impacts of heat stress and drought on winter wheat in Europe. Despite the lower summer precipitation projected for 2050s across Europe, relative yield losses from drought is predicted to be smaller in the future, because wheat will mature earlier avoiding severe drought. By contrast, the risk of heat stress around flowering will increase, potentially resulting in substantial yield losses for heat sensitive cultivars commonly grown in northern Europe.

Proteinase-activated receptors, targets for kallikrein signaling

Serine proteinases like thrombin can signal to cells by the cleavage/activation of proteinase-activated receptors (PARs). Although thrombin is a recognized physiological activator of PAR(1) and PAR(4), the endogenous enzymes responsible for activating PAR(2) in settings other than the gastrointestinal system, where trypsin can activate PAR(2), are unknown. We tested the hypothesis that the human tissue kallikrein (hK) family of proteinases regulates PAR signaling by using the following: 1) a high pressure liquid chromatography (HPLC)-mass spectral analysis of the cleavage products yielded upon incubation of hK5, -6, and -14 with synthetic PAR N-terminal peptide sequences representing the cleavage/activation motifs of PAR(1), PAR(2), and PAR(4); 2) PAR-dependent calcium signaling responses in cells expressing PAR(1), PAR(2), and PAR(4) and in human platelets; 3) a vascular ring vasorelaxation assay; and 4) a PAR(4)-dependent rat and human platelet aggregation assay. We found that hK5, -6, and -14 all yielded PAR peptide cleavage sequences consistent with either receptor activation or inactivation/disarming. Furthermore, hK14 was able to activate PAR(1), PAR(2), and PAR(4) and to disarm/inhibit PAR(1). Although hK5 and -6 were also able to activate PAR(2), they failed to cause PAR(4)-dependent aggregation of rat and human platelets, although hK14 did. Furthermore, the relative potencies and maximum effects of hK14 and -6 to activate PAR(2)-mediated calcium signaling differed. Our data indicate that in physiological settings, hKs may represent important endogenous regulators of the PARs and that different hKs can have differential actions on PAR(1), PAR(2), and PAR(4).

How large are projected 21st century storm track changes?

Projected changes in the extra-tropical wintertime storm tracks are investigated using the multi-model ensembles from both the third and fifth phases of the World Climate Research Programme's Coupled Model Intercomparison Project (CMIP3 and CMIP5). The aim is to characterize the magnitude of the storm track responses relative to their present-day year-to-year variability. For the experiments considered, the ‘middle-of-the-road’ scenarios in each CMIP, there are regions of the Northern Hemisphere where the responses of up to 40% of the models exceed half of the inter-annual variability, and for the Southern Hemisphere there are regions where up to 60% of the model responses exceed half of the inter-annual variability.

On the role of the ocean in projected atmospheric stability changes in the Atlantic polar low region

The occurrence of destructive mesoscale ‘polar low’ cyclones in the subpolar North Atlantic is projected to decline under anthropogenic change, due to an increase in atmospheric static stability. This letter reports on the role of changes in ocean circulation in shaping the atmospheric stability. In particular, the Atlantic Meridional Overturning Circulation (AMOC) is projected to weaken in response to anthropogenic forcing, leading to a local minimum in warming in this region. The reduced warming is restricted to the lower troposphere, hence contributing to the increase in static stability. Linear correlation analysis of the CMIP3 climate model ensemble suggests that around half of the model uncertainty in the projected stability response arises from the varied response of the AMOC between models.

Molecular targets underlying SUMO-mediated neuroprotection in brain ischemia

SUMOylation (small ubiquitin-like modifier conjugation) is an important post-translational modification which is becoming increasingly implicated in the altered protein dynamics associated with brain ischemia. The function of SUMOylation in cells undergoing ischemic stress and the identity of small ubiquitin-like modifier (SUMO) targets remain in most cases unknown. However, the emerging consensus is that SUMOylation of certain proteins might be part of an endogenous neuroprotective response. This review brings together the current understanding of the underlying mechanisms and downstream effects of SUMOylation in brain ischemia, including processes such as autophagy, mitophagy and oxidative stress. We focus on recent advances and controversies regarding key central nervous system proteins, including those associated with the nucleus, cytoplasm and plasma membrane, such as glucose transporters (GLUT1, GLUT4), excitatory amino acid transporter 2 glutamate transporters, K+ channels (K2P1, Kv1.5, Kv2.1), GluK2 kainate receptors, mGluR8 glutamate receptors and CB1 cannabinoid receptors, which are reported to be SUMO-modified. A discussion of the roles of these molecular targets for SUMOylation could play following an ischemic event, particularly with respect to their potential neuroprotective impact in brain ischemia, is proposed.

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

The drivers of projected North Atlantic sea level change

Sea level change predicted by the CMIP5 atmosphere–ocean general circulation models (AOGCMs) is not spatially homogeneous. In particular, the sea level change in the North Atlantic is usually characterised by a meridional dipole pattern with higher sea level rise north of 40°N and lower to the south. The spread among models is also high in that region. Here we evaluate the role of surface buoyancy fluxes by carrying out simulations with the FAMOUS low-resolution AOGCM forced by surface freshwater and heat flux changes from CO2-forced climate change experiments with CMIP5 AOGCMs, and by a standard idealised surface freshwater flux applied in the North Atlantic. Both kinds of buoyancy flux change lead to the formation of the sea level dipole pattern, although the effect of the heat flux has a greater magnitude, and is the main cause of the spread of results among the CMIP5 models. By using passive tracers in FAMOUS to distinguish between additional and redistributed buoyancy, we show that the enhanced sea level rise north of 40°N is mainly due to the direct steric effect (the reduction of sea water density) caused by adding heat or freshwater locally. The surface buoyancy forcing also causes a weakening of the Atlantic meridional overturning circulation, and the consequent reduction of the northward ocean heat transport imposes a negative tendency on sea level rise, producing the reduced rise south of 40°N. However, unlike previous authors, we find that this indirect effect of buoyancy forcing is generally less important than the direct one, except in a narrow band along the east coast of the US, where it plays a major role and leads to sea level rise, as found by previous authors.

The projected hand illusion: component structure in a community sample, and association with demographics, cognition and psychotic-like experiences

The projected hand illusion (PHI) is a variant of the rubber hand illusion (RHI), and both are commonly used to study mechanisms of self-perception. A questionnaire was developed by Longo et al. (2008) to measure qualitative changes in the RHI. Such psychometric analyses have not yet been conducted on the questionnaire for the PHI. The present study is an attempt to validate minor modifications of the questionnaire of Longo et al. to assess the PHI in a community sample (n = 48) and to determine the association with selected demographic (age, sex, years of education), cognitive (Digit Span), and clinical (psychotic-like experiences) variables. Principal components analysis on the questionnaire data extracted four components: Embodiment of “Other” Hand, Disembodiment of Own Hand, Deafference, and Agency—in both synchronous and asynchronous PHI conditions. Questions assessing “Embodiment” and “Agency” loaded onto orthogonal components. Greater illusion ratings were positively associated with being female, being younger, and having higher scores on psychotic-like experiences. There was no association with cognitive performance. Overall, this study confirmed that self-perception as measured with PHI is a multicomponent construct, similar in many respects to the RHI. The main difference lies in the separation of Embodiment and Agency into separate constructs, and this likely reflects the fact that the “live” image of the PHI presents a more realistic picture of the hand and of the stroking movements of the experimenter compared with the RHI.

Projected changes in wind energy potentials over Iberia

Wind energy potential in Iberia is assessed for recent–past (1961–2000) and future (2041–2070) climates. For recent–past, a COSMO-CLM simulation driven by ERA-40 is used. COSMO-CLM simulations driven by ECHAM5 following the A1B scenario are used for future projections. A 2 MW rated power wind turbine is selected. Mean potentials, inter-annual variability and irregularity are discussed on annual/seasonal scales and on a grid resolution of 20 km. For detailed regional assessments eight target sites are considered. For recent–past conditions, the highest daily mean potentials are found in winter over northern and eastern Iberia, particularly on high-elevation or coastal regions. In northwestern Iberia, daily potentials frequently reach maximum wind energy output (50 MWh day−1), particularly in winter. Southern Andalucía reveals high potentials throughout the year, whereas the Ebro valley and central-western coast show high potentials in summer. The irregularity in annual potentials is moderate (<15% of mean output), but exacerbated in winter (40%). Climate change projections show significant decreases over most of Iberia (<2 MWh day−1). The strong enhancement of autumn potentials in Southern Andalucía is noteworthy (>2 MWh day−1). The northward displacement of North Atlantic westerly winds (autumn–spring) and the strengthening of easterly flows (summer) are key drivers of future projections.

Extratropical cyclones and the projected decline of winter Mediterranean precipitation in the CMIP5 models

The Mediterranean region has been identified as a climate change "hot-spot" due to a projected reduction in precipitation and fresh water availability which has potentially large socio-economic impacts. To increase confidence in these projections, it is important to physically understand how this precipitation reduction occurs. This study quantifies the impact on winter Mediterranean precipitation due to changes in extratropical cyclones in 17 CMIP5 climate models. In each model, the extratropical cyclones are objectively tracked and a simple approach is applied to identify the precipitation associated to each cyclone. This allows us to decompose the Mediterranean precipitation reduction into a contribution due to changes in the number of cyclones and a contribution due to changes in the amount of precipitation generated by each cyclone. The results show that the projected Mediterranean precipitation reduction in winter is strongly related to a decrease in the number of Mediterranean cyclones. However, the contribution from changes in the amount of precipitation generated by each cyclone are also locally important: in the East Mediterranean they amplify the precipitation trend due to the reduction in the number of cyclones, while in the North Mediterranean they compensate for it. Some of the processes that determine the opposing cyclone precipitation intensity responses in the North and East Mediterranean regions are investigated by exploring the CMIP5 inter-model spread.

Separating the influence of projected changes in air temperature and wind on patterns of sea level change and ocean heat content

We present ocean model sensitivity experiments aimed at separating the influence of the projected changes in the “thermal” (near-surface air temperature) and “wind” (near-surface winds) forcing on the patterns of sea level and ocean heat content. In the North Atlantic, the distribution of sea level change is more due to the “thermal” forcing, whereas it is more due to the “wind” forcing in the North Pacific; in the Southern Ocean, the “thermal” and “wind” forcing have a comparable influence. In the ocean adjacent to Antarctica the “thermal” forcing leads to an inflow of warmer waters on the continental shelves, which is somewhat attenuated by the “wind” forcing. The structure of the vertically integrated heat uptake is set by different processes at low and high latitudes: at low latitudes it is dominated by the heat transport convergence, whereas at high latitudes it represents a small residual of changes in the surface flux and advection of heat. The structure of the horizontally integrated heat content tendency is set by the increase of downward heat flux by the mean circulation and comparable decrease of upward heat flux by the subgrid-scale processes; the upward eddy heat flux decreases and increases by almost the same magnitude in response to, respectively, the “thermal” and “wind” forcing. Regionally, the surface heat loss and deep convection weaken in the Labrador Sea, but intensify in the Greenland Sea in the region of sea ice retreat. The enhanced heat flux anomaly in the subpolar Atlantic is mainly caused by the “thermal” forcing.