It is shown that a global atmospheric model with horizontal resolution typical of that used in operational numerical weather prediction is able to simulate non‐gaussian probability distributions ...associated with the climatology of quasi‐persistent Euro‐Atlantic weather regimes. The spatial patterns of these simulated regimes are remarkably accurate. By contrast, the same model, integrated at a resolution more typical of current climate models, shows no statistically significant evidence of such non‐gaussian regime structures, and the spatial structure of the corresponding clusters are not accurate. Hence, whilst studies typically show incremental improvements in first and second moments of climatological distributions of the large‐scale flow with increasing model resolution, here a real step change in the higher‐order moments is found. It is argued that these results have profound implications for the ability of high resolution limited‐area models, forced by low resolution global models, to simulate reliably, regional climate change signals.
Key Points
Regimes not represented in an atmosphere model at typical climate resolution
Skillful representation of regimes at higher weather model resolution
Staphylococcus aureus can be associated with subclinical, acute, chronic, and toxic cases of bovine intramammary infections, leading to considerable financial losses for the dairy industry in ...Switzerland and worldwide. In addition, milk products are one of the most common food categories implicated in staphylococcal food poisoning in humans. Detailed information on the population structure, as well as the virulence and resistance characteristics of Staph. aureus originating from bovine mastitis milk is needed to allow for source attribution and risk assessment of Staph. aureus in a food poisoning context and to improve therapeutic approaches in cattle. Our objective was to assess the population structure, phenotypic resistance patterns, and virulence and resistance gene profiles of Staph. aureus isolates from bovine mastitis milk in Switzerland. To this end, 58 Staph. aureus strains were characterized. The DNA microarray was used to test for the presence or absence of virulence and resistance genes. In addition, minimum inhibitory concentrations of various antimicrobial agents were determined by microdilution. To assess the population structure of the isolates, we determined clonal complexes (CC) using DNA microarray hybridization profiles and performed multilocus sequence typing and spa typing. The strains were assigned to 7 clonal complexes, 10 sequence types, and 11 spa types, with CC705 (43%), CC97 (33%), and CC20 (12%) representing the most common lineages and t529 (43%) and t267 (21%) representing the most common spa types. Only 1 isolate was assigned to CC8, a clonal lineage linked to high within-herd prevalence of mastitis. A total of 14% (n = 8) of strains were classified as resistant to penicillin, and 1 strain each was classified as oxacillin and pirlimycin resistant. Although no clinical breakpoints are available for the combination of kanamycin/cefalexin, growth of all strains was inhibited by the lowest combination of kanamycin/cefalexin concentrations tested (4 µg/mL of kanamycin and 0.4 µg/mL of cefalexin). One strain assigned to CC20, ST389, and t2094 exhibited resistance to penicillin, oxacillin, and pirlimycin as well as intermediate susceptibility to erythromycin and high minimum inhibitory concentration for several antimicrobial agents, for which no breakpoints were available.
► Apple pomace was both air-dried at 40°C and vacuum-dried at 60°C. ► Phytochemical contents were studied as a function of water activity (9months, 30°C). ► Stability rankings were defined for apple ...phytochemicals. ► Phloridzin was demonstrated as not being the preferential target for degradation reactions. ► Apple pomace could be exploited for the development of foods with antidiabetic potential.
Apple pomace (mixed Red Delicious and Golden Delicious varieties) obtained from the industrial production of puree was both vacuum-dried at 40°C and air-dried at 60°C, ground and stored at water activity (aw) in the range 0.11–0.75, for 9months, at 30°C. The aims were to investigate the effect of drying and long-term storage on phytochemical contents. Air-drying at 60°C was better than vacuum-drying at 40°C in terms of anthocyanin and flavanol retention; no adverse effect of drying was observed for flavonols, dihydrochalcones and hydroxycinnamic acids. The maximum stability occurred for all apple phytochemicals at the lowest aw. At aw 0.75 degradation of all phytochemicals occurred with the following stability ranking: phloridzin>chlorogenic acid>quercetin 3-O-galactoside>epicatechin>procyanidin B2 and cyanidin 3-O-galactoside. A promising feature of pomace is its exclusive high content of phloridzin, which showed relatively high stability during long-term storage.
Recently, much attention has been devoted to better understand the internal modes of variability of the climate system. This is particularly important in mid-latitude regions like the North-Atlantic, ...which is characterized by a large natural variability and is intrinsically difficult to predict. A suitable framework for studying the modes of variability of the atmospheric circulation is to look for recurrent patterns, commonly referred to as Weather Regimes. Each regime is characterized by a specific large-scale atmospheric circulation pattern, thus influencing regional weather and extremes over Europe. The focus of the present paper is the study of the Euro-Atlantic wintertime Weather Regimes in the climate models participating to the PRIMAVERA project. We analyse here the set of coupled historical simulations (hist-1950), which have been performed both at standard and increased resolution, following the HighresMIP protocol. The models’ performance in reproducing the observed Weather Regimes is assessed in terms of different metrics, focussing on systematic biases and on the impact of resolution. We also analyse the connection of the Weather Regimes with the Jet Stream latitude and blocking frequency over the North-Atlantic sector. We find that—for most models—the regime patterns are better represented in the higher resolution version, for all regimes but the NAO-. On the other side, no clear impact of resolution is seen on the regime frequency of occurrence and persistence. Also, for most models, the regimes tend to be more tightly clustered in the increased resolution simulations, more closely resembling the observed ones. However, the horizontal resolution is not the only factor determining the model performance, and we find some evidence that biases in the SSTs and mean geopotential field might also play a role.
In theory, human diseases in which a specific cell type degenerates, such as neurodegenerative diseases, can be therapeutically addressed by replacement of the lost cells. The classical strategy for ...cell replacement is exogenous cell transplantation, but now, cell replacement can also be achieved with in situ reprogramming. Indeed, many of these disorders are age-dependent, and “rejuvenating” strategies based on cell epigenetic modifications are a possible approach to counteract disease progression. In this context, transient and/or partial reprogramming of adult somatic cells towards pluripotency can be a promising tool for neuroregeneration. Temporary and controlled in vivo overexpression of Yamanaka reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc (OSKM)) has been proven feasible in different experimental settings and could be employed to facilitate in situ tissue regeneration; this regeneration can be accomplished either by producing novel stem/precursor cells, without the challenges posed by exogenous cell transplantation, or by changing the epigenetic adult cell signature to the signature of a younger cell. The risk of this procedure resides in the possible lack of perfect control of the process, carrying a potential oncogenic or unexpected cell phenotype hazard. Recent studies have suggested that these limits can be overcome by a tightly controlled cyclic regimen of short-term OSKM expression in vivo that prevents full reprogramming to the pluripotent state and avoids both tumorigenesis and the presence of unwanted undifferentiated cells. On the other hand, this strategy can enhance tissue regeneration for therapeutic purposes in aging-related neurological diseases as well. These data could open the path to further research on the therapeutic potential of in vivo reprogramming in regenerative medicine.
Highlights • The motor protein dynein is down-regulated in resistant and vulnerable motor neurons (MNs) in ALS. • The high level of Gabra1 in oculomotor MNs in end-stage ALS patients implicates it in ...MN protection. • Parvalbumin levels are high in both resistant and vulnerable MNs in health and ALS. • Oculomotor MNs have a distinct protein signature that could explain their resistance to ALS. • SOD1G93A ALS mice could be used to predict mechanisms of MN vulnerability and protection in man.
A reversible cyclic process is analyzed in which the center of mass of an ideal gas is raised in a gravitational field during both an expansion phase and a subsequent contraction phase, with the gas ...returning to its initial height in a final step. When the properties of the gas are taken as uniform, the thermodynamic efficiency of this cycle is able to exceed that of a corresponding Carnot cycle, which is a violation of the second law of thermodynamics. The source of this discrepancy was previously claimed, when analyzing a similar heating and cooling of a sphere, to be the assumed independence of the internal energy on the gravitational field. However, this violation is only apparent since all of the effects of the gravitational field were not incorporated fully into the thermodynamic analysis of the cycle. When all the influences of the gravitational field are considered, no possible violation of the second law can occur. The evaluation of the entropy changes of the gas throughout the cycle also highlights other key inconsistencies that arise when the full effects of the gravitational field are neglected. As the analysis of the cycle provided here shows, the assumption of the independence of the internal energy, as well as other thermodynamic properties, on the gravitational field strength can still be invoked.
In amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), spinal and lower brainstem motor neurons degenerate, but some motor neuron subtypes are spared, including oculomotor neurons ...(OMNs). The mechanisms responsible for this selective degeneration are largely unknown, but the molecular signatures of resistant and vulnerable motor neurons are distinct and offer clues to neuronal resilience and susceptibility. Here, we demonstrate that healthy OMNs preferentially express
Synaptotagmin 13 (SYT13)
compared to spinal motor neurons. In end-stage ALS patients,
SYT13
is enriched in both OMNs and the remaining relatively resilient spinal motor neurons compared to controls. Overexpression of SYT13 in ALS and SMA patient motor neurons in vitro improves their survival and increases axon lengths. Gene therapy with
Syt13
prolongs the lifespan of ALS mice by 14% and SMA mice by 50% by preserving motor neurons and delaying muscle denervation. SYT13 decreases endoplasmic reticulum stress and apoptosis of motor neurons, both in vitro and in vivo. Thus, SYT13 is a resilience factor that can protect motor neurons and a candidate therapeutic target across motor neuron diseases.
The numerical simulation of atmospheric blocking, in particular over the Euro‐Atlantic region, still represents a main concern for the climate modeling community. We discuss the Northern Hemisphere ...winter atmospheric blocking representation in a set of 30 year atmosphere‐only simulations using the EC‐Earth Earth System Model with several ensemble members at five different horizontal resolutions (from 125 to 16 km). Results show that the negative bias in blocking frequency over Europe becomes negligible at resolutions of about 40 and 25 km. A combined effect by the more resolved orography and by a change in tropical precipitation is identified as the source of an upper tropospheric planetary wave. At the same time, a weakening of the meridional temperature gradient reduces the upper level baroclinicity and the zonal mean winds. Following these changes, in the high‐resolution configurations the Atlantic eddy‐driven jet stream is weakened favoring the breaking of synoptic Rossby waves over the Atlantic ridge and thus increasing the simulated European blocking frequency. However, at high‐resolution the Atlantic jet stream is too weak and the blocking duration is still underestimated. This suggests that the optimal blocking frequencies are achieved through compensation of errors between eddies found at upper levels (too strong) and eddies at lower levels (too weak). This also implies that eddies are not necessarily better represented at higher resolutions.
Key Points
25‐km resolution EC‐Earth GCM is able to simulate winter atmospheric blocking frequency over Europe with a negligible bias
Improvements are caused by the more refined orography and by the weakening of the storm track
Blocking duration and jet speed are underestimated suggesting that positive results are due to bias compensation
The sedimentation half-times t s of initially monodisperse dispersions of 750, 505, and 350 nm silica microspheres were measured in water, in ethanol, and in aqueous NaBr solutions of concentration c ...NaBr ranging from 50 to 1000 mM, where the particles may have formed clusters. In water and in ethanol, t s was about 8, 18, and 33 h for the 750, 505, and 350 nm particles, respectively. These values were the same as the ones predicted by Stokes’ law, suggesting that the particles were monodisperse and remained so during sedimentation; t s values remained the same with increasing particle weight fraction up to 0.03, indicating no hydrodynamic interactions. Three regions of NaBr concentrations with different settling behavior were found for each size. In region I or at lower c NaBr, the t s values were the same as at no salt conditions, implying that there was no significant agglomeration before particles settled. In region II, t s decreased with increasing c NaBr, suggesting that the agglomeration and sedimentation half-times of medium-size clusters were comparable. In region III, the t s values were quite similar for all particles, and independent of the NaBr concentration, indicating that at short times the particles formed large clusters which settled rapidly. The zeta potentials of the particles in water or in NaBr solutions were measured and used to predict the corresponding Fuchs–Smoluchowski stability ratios, which were sensitive to the chosen Hamaker constant values and the NaBr concentrations. Two models, based on the Smoluchowski steady-state and the more general unsteady-state agglomeration rates, were developed for obtaining the agglomeration times t an for forming clusters of size 2 N m , where N m = 1, 2, 3, ..., and the net predicted sedimentation half-time t s * for these clusters. The clusters were described by a fractal model with a fractal dimension d f. Diffusion-limited clusters (d f = 1.8) were compared to the coalescence-limit clusters (d f = 3). The models provide some useful and accurate upper bounds of t an and t s *. Moreover, the effective sizes, density differences, and volume fractions of the clusters were obtained as a function of time. The predicted trend of t s * was consistent with the experimental data. The predictions supported the inferences that the particles were unagglomerated in region I, formed medium size clusters in region II, and rapidly formed large clusters in region III.