We present the extension to the thermosphere of a Martian general circulation model, the first able to self‐consistently study the whole Martian atmosphere from the surface to the exosphere. We ...describe the parameterizations developed to include physical processes important for thermospheric altitudes. The results of a simulation covering 1 full Martian year are presented, focusing on the seasonal, diurnal, and day‐to‐day variability of the temperatures in the exobase region. The seasonal variation of the zonal mean temperatures in the upper atmosphere is of about 100 K, mostly due to the variation of the solar forcing. The temperature of the mesopause ranges between 115 and 130 K, with little seasonal and day‐night variations. Its pressure level undergoes significant seasonal and day‐night variations. Comparisons with SPICAM observations show that the modeled mesopause is too low and too warm. A similar study for the homopause shows that it is located higher in the atmosphere during solstices, owing to reinforced mixing by a stronger circulation. Important day‐night temperature differences are found in the thermosphere, ranging from about 60 K at aphelion to 110 K at perihelion. This diurnal cycle is slightly perturbed by the day‐to‐day variations of temperature, dominated by waves with periods of 2 to 6 sols and amplitude of 30 K. The model reproduces the observed solar cycle variation in temperatures when using a UV heating efficiency of 16%, slightly lower than the theoretical value. The seasonal variation of temperatures is overestimated by the model, in comparison with the available measurements.
Rationale
Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced ...sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied.
Objectives
To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life.
Methods
We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed.
Results
Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (
B
= 0.417;
p
= 2.1e − 6,
R
2
= 0.156) and nocturnal CIS (
B
= 0.411;
p
= 7.7e − 6,
R
2
= 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life.
Conclusions
The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended.
Trial registration
Clinical Trials (
https://clinicaltrials.gov
) under reference NCT04197037.
The Fas-associated death domain (FADD) adaptor protein FADD/Mort-1 is recruited by several members of the tumor necrosis factor receptor (TNFR) superfamily during cell death activated via death ...receptors. Since most studies have focused on the interaction of FADD with plasma membrane proteins, FADD's subcellular location is thought to be confined to the cytoplasm. In this report, we show for the first time that FADD is present in both the cytoplasm and the nucleus of cells, and that its nuclear localization relies on strong nuclear localization and nuclear export signals (NLS and NES, respectively) that reside in the death-effector domain (DED) of the protein. Specifically, we found that a conserved basic KRK35 sequence of the human protein is necessary for FADD's nuclear localization, since disruption of this motif leads to the confinement of FADD in the cytoplasm. Furthermore, we show that the leucine-rich motif LTELKFLCL28 in the DED is necessary for FADD's nuclear export. Functionally, mutation of the NES of FADD and its seclusion in the nucleus reduces the cell death-inducing efficacy of FADD reconstituted in FADD-deficient T cells.
Multilayer (14 layers, 115-122 nm thick each) BiFeO
3
/CoFe
2
O
4
/substrate (BFO/CFO) and CoFe
2
O
4
/BiFeO
3
/substrate (CFO/BFO) nanocomposites were obtained by the method of sol-gel synthesis. It ...is shown that all samples of the obtained nanocomposites have multiferroic properties at room temperature. At the same time, there is a clearly demonstrated effect of the layering order on the values of remnant polarization and magnetization of these samples. This influence originates from the much smaller size of the crystallites in the BiFeO
3
layers for the samples deposited in order (BFO/CFO) at various annealing temperatures (700, 725, and 750 °C).
A ground‐to‐exosphere Martian general circulation model is applied to study the thermal and dynamical structure of the upper Martian atmosphere during solstitial conditions. Special attention is paid ...to the reproduction of the thermospheric polar warming observed by Mars Odyssey during southern hemisphere (SH) summer solstice. The intensity and latitudinal distribution of this polar warming are successfully reproduced by the model. The heating balance and the dynamical structure of the upper atmosphere are studied. It is shown that a strong interhemispheric transport produces a convergence and descent of air over the winter pole, producing an adiabatic heating and a polar warming. This structure confirms previous results made by other models. The most novel aspect of this study is a sensitivity study showing the importance of the tides excited in situ in the upper atmosphere. These tides are critical to the simulated thermal and dynamical structure and remain key components of the interhemispheric transport mechanism responsible for the thermospheric polar warming. The day‐night temperature differences created by these in situ tides produce a day‐night transport that reinforces the summer‐to‐winter circulation and the descent of air over the pole, becoming an essential factor for this thermospheric polar warming. The effect of upward propagating nonmigrating tides is also studied.
Activation of protein kinase C (PKC) triggers cellular signals that inhibit Fas/CD95-induced cell death in Jurkat T-cells by poorly defined mechanisms. Previously, we have shown that one effect of ...PKC on Fas/CD95-dependent cell death occurs through inhibition of cell shrinkage and K(+) efflux (Gómez-Angelats, M., Bortner, C. D., and Cidlowski, J. A. (2000) J. Biol. Chem. 275, 19609-19619). Here we report that PKC alters Fas/CD95 signaling from the plasma membrane to the activation of caspases by exerting a profound action on survival/cell death decisions. Specific activation of PKC with 12-O-tetradecanoylphorbol-13-acetate or bryostatin-1 induced translocation of PKC from the cytosol to the membrane and effectively inhibited cell shrinkage and cell death triggered by anti-Fas antibody in Jurkat cells. In contrast, inhibition of classical PKC isotypes with Gö6976 exacerbated the effect of Fas activation on both apoptotic volume decrease and cell death. PKC activation/inhibition did not affect anti-Fas antibody binding to the cell surface, intracellular levels of FADD (Fas-associated protein with death domain), or c-FLIP (cellular FLICE-like inhibitory protein) expression. However, processing/activation of both caspase-8 and caspase-3 and BID cleavage were markedly blocked upon PKC activation and, conversely, were augmented during PKC inhibition, suggesting a role for PKC upstream of caspase-8 processing and activation. Analysis of death-inducing signaling complex (DISC) formation was carried out to examine the influence of PKC on recruitment of both FADD and procaspase-8 to the Fas receptor. PKC activation blocked FADD recruitment and caspase-8 activation and thus DISC formation in both type I and II cells. In contrast, inhibition of classical PKCs promoted the opposite effect on the Fas pathway by rapidly increasing FADD recruitment, caspase-8 activation, and DISC formation. Together, these data show that PKC finely modulates Fas/CD95 signaling by altering the efficiency of DISC formation.
A fast method to incorporate the UV heating and the photochemistry of the neutral upper atmosphere of Mars into general circulation models (GCMs) is presented. On the basis of more detailed ...one‐dimensional (1‐D) models, the scheme we propose makes use of a division of the UV spectrum in 36 subintervals of 20 nm average width. Photoabsorption coefficients are computed allowing for overlapping and are tabulated as a function of suitable column abundances. The photochemistry proposed includes 12 compounds and uses the approximation of photochemical equilibrium for the three fastest species, OH, O(1D), and HO2. The behavior of the fast scheme is shown against detailed 1‐D calculations. The resulting acceleration is about a factor 200 in the UV heating, while in the photochemistry it is about a factor 100 at 120 km and much larger below. The proposed scheme has already been implemented into the GCM developed at the Laboratoire de Météorologie Dynamique‐CNRS in Paris (LMD), which therefore becomes the first single Martian GCM to cover the whole range of altitudes from the planet surface to the upper thermosphere. We present typical results of the Martian thermosphere obtained with the present scheme and the LMD‐GCM, in order to illustrate its behavior and stability. In particular, we show the sensitivity of the Martian upper atmosphere's thermal structure to the local photochemistry. Comparisons with previous models are also presented, as first steps in an ongoing validation study, necessarily extensive for this kind of GCM, which will include more detailed comparisons with recent and future data from space missions.
The electrocardiogram (ECG) is widely considered a standard part of the syncope workup, and it is recommended to be obtained in all children with syncope. Nevertheless, a newly recognized cardiac ...cause is rare and largely incidental findings are commonly seen, leading to unneeded worry, additional testing, and added health care costs.
The aim of this study was to analyze the performance of ECG in the evaluation of childhood syncope in the emergency department (ED).
This was a descriptive, retrospective, multicenter pilot study of patients younger than 14 years diagnosed with syncope in which an ECG was obtained in the ED in 2015 and 2016.
During the study period, 440 patients were diagnosed with syncope, of which an ECG was performed in 197 (44.7%). Of these, 64 (32.5%) were related to any concerning features associated with the event, including 33 occurring during or after physical exertion. No major alteration of the ECG was noted, and the ECG revealed multiple minor findings in 38 (19.2%; 95% confidence interval, 14.4-25.4). Twenty-five (12.7%) children were referred to a pediatric cardiologist. No patient was noted to have a previously undiagnosed cardiac cause of syncope.
A newly recognized cardiac cause is extremely rare among children evaluated for syncope in the ED, and ECG is not systematically obtained in this population. Larger studies are needed to clarify if it is possible to identify a group of children that can be safely managed without a systematic ECG. Best practices need to be better implemented for an adequate management of pediatric syncope in the ED.
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