Well-posed lateral boundary conditions for spectral semi-implicit semi-Lagrangian schemes : tests in a one-dimensional model

The aim of this paper is to investigate the feasibility of well-posed lateral boundary conditions in a Fourier spectral semi-implicit semi-Lagrangian one-dimensional model. Two aspects are analyzed: (i) the complication of designing well-posed boundary conditions for a spectral semi-implicit scheme and (ii) the implications of such a lateral boundary treatment for the semi-Lagrangian trajectory computations at the lateral boundaries. Straightforwardly imposing boundary conditions in the gridpoint-explicit part of the semi-implicit time-marching scheme leads to numerical instabilities for time steps that are relevant in today's numerical weather prediction applications. It is shown that an iterative scheme is capable of curing these instabilities. This new iterative boundary treatment has been tested in the framework of the one-dimensional shallow-water equations leading to a significant improvement in terms of stability. As far as the semi-Lagrangian part of the time scheme is concerned, the use of a trajectory truncation scheme has been found to be stable in experimental tests, even for large values of the advective Courant number. It is also demonstrated that a well-posed buffer zone can be successfully applied in this spectral context. A promising (but not easily implemented) alternative to these three above-referenced schemes has been tested and is also presented here

Poboljšanje sheme vertikalne difuzije u ARPÈGE/ALADIN modelu

In atmospheric numerical weather prediction (NWP) models, the use of long time-steps as allowed by efficient numerical/dynamical schemes can lead to spurious oscillations due to the parameterized physical part. Typical examples of this are the oscillations associated with simplified parameterization schemes for vertical diffusion or shallow-convection, such as usually used for NWP. The oscillations generated by K-type vertical-diffusion schemes are well documented, and being called fibrillations; they are characterized by high temporal and vertical frequencies. Since they are linked to high vertical resolution, these spurious oscillations are generally found in the low-levels of model’s domain. In ARPÈGE, the MÉTÉO-FRANCE NWP global model, and in ALADIN, its limited-area model (LAM) version developed in cooperation with Eastern European countries, and also used for operational NWP purpose, some oscillations still remained in the evolution of the forecast fields, despite the fact that a first anti-fibrillation scheme (AFS) had been included. This study was made to examine the possible sources of these oscillations, through the 1-D (vertical) version of these models. First, the parameterization of shallow-convection (which is in fact part of the vertical diffusion scheme) was found to be an important source of oscillations, and some solutions for eliminating this problem are proposed. Second, the original AFS is shown not to completely prevent the generation of fibrillations, and a more efficient formulation is derived. All AFSs basically consist in a temporal first-order decentering of the diffusion equation, keeping an explicit form for the exchange coefficient itself. The AFS correction thus always improves the stability at the expense of the accuracy in some way. In the new AFS proposed here, the number of grid-points which need a correction is lessen from almost 90% to some 5%, resulting in a more accurate scheme. Unlike AFSs proposed in the literature, the correction has now to be applied not only for grid points of atmospheric stable conditions (i.e. Richardson number, Ri > 0) but also for atmospheric slightly unstable conditions (Ri < 0).Učinkovite numeričko-dinamičke sheme u atmosferskim numeričkim prognostičkim modelima dozvoljavaju uporabu duljeg vremenskog koraka prilikom numeričke integracije, ali često dolazi do neželjenih oscilacija uzrokovanih parametrizacijom fizikalnog dijela. Tipičan primjer je pojava oscilacija povezanih s pojednostavljenim parametrizacijskim shemama za vertikalnu difuziju ili plitku konvekciju, koje se uobičajeno koriste u numeričkoj prognozi vremena. Oscilacije koje se generiraju shemama vertikalne difuzije K-tipa do sada su detaljno razmatrane, i nazvane su fibrilacijama. Visoke prostorne i vremenske frekvencije karakteristike su fibrilacija. Zbog njihove povezanosti s velikom vertikalnom rezolucijom, ove lažne oscilacije se općenito uočavaju na nižim nivoima domene modela. U prognostičkim poljima ARPÈGE-a (numeričkom prognostičkom globalom modelu u MÉTÉO-FRANCE) i ALADIN-a (njegovoj verziji modela za ograničeno područje razvijenom u suradnji sa zemljama istočne Europe) neke oscilacije su se i dalje zadržale unatoč činjenici da je uključena prva anti-fibrilacijska shema (AFS). Ovaj rad prikazuje provedena ispitivanja mogućih izvora fibrilacija pomoću 1-D (vertikalne) verzije ovih modela. Ispitivanja su dala sljedeće rezultate: 1. znatan izvor oscilacija je pronađen u parametrizaciji plitke konvekcije (što je u stvari dio sheme vertikalne difuzije) te su predložena neka riješenja za njihovo uklanjanje, 2. pokazalo se da početna AFS ne može u potpunosti spriječiti generiranje fibrilacija te je izvedena uspješnija formulacija. Jednadžbe vertikalne difuzije prikazane u numeričkom vremenskom raspisu prvog reda, zadržavajući eksplicitnu formu samog koeficijenta izmjene, u osnovi sadrže AFS. Stoga, korekcija AFS-om uvijek poboljšava stabilnost na račun točnosti. S novom anti-fibrilacijskom shemom, broj točaka mreže u kojima je potrebno izvršiti korekciju smanjen je s gotovo 90% na približno 5%, čime je shema dobila na točnosti. Za razliku od predloženih AFS iz literature, korekcija se mora primjenjivati ne samo na točke mreže sa stabilnim atmosferskim uvijetima (Richardsonov broj, Ri > 0) već i na one točke u kojima je atmosfera blago nestabilna (Ri < 0)

Poboljšanje sheme vertikalne difuzije u ARPÈGE/ALADIN modelu

In atmospheric numerical weather prediction (NWP) models, the use of long time-steps as allowed by efficient numerical/dynamical schemes can lead to spurious oscillations due to the parameterized physical part. Typical examples of this are the oscillations associated with simplified parameterization schemes for vertical diffusion or shallow-convection, such as usually used for NWP. The oscillations generated by K-type vertical-diffusion schemes are well documented, and being called fibrillations; they are characterized by high temporal and vertical frequencies. Since they are linked to high vertical resolution, these spurious oscillations are generally found in the low-levels of model’s domain. In ARPÈGE, the MÉTÉO-FRANCE NWP global model, and in ALADIN, its limited-area model (LAM) version developed in cooperation with Eastern European countries, and also used for operational NWP purpose, some oscillations still remained in the evolution of the forecast fields, despite the fact that a first anti-fibrillation scheme (AFS) had been included. This study was made to examine the possible sources of these oscillations, through the 1-D (vertical) version of these models. First, the parameterization of shallow-convection (which is in fact part of the vertical diffusion scheme) was found to be an important source of oscillations, and some solutions for eliminating this problem are proposed. Second, the original AFS is shown not to completely prevent the generation of fibrillations, and a more efficient formulation is derived. All AFSs basically consist in a temporal first-order decentering of the diffusion equation, keeping an explicit form for the exchange coefficient itself. The AFS correction thus always improves the stability at the expense of the accuracy in some way. In the new AFS proposed here, the number of grid-points which need a correction is lessen from almost 90% to some 5%, resulting in a more accurate scheme. Unlike AFSs proposed in the literature, the correction has now to be applied not only for grid points of atmospheric stable conditions (i.e. Richardson number, Ri > 0) but also for atmospheric slightly unstable conditions (Ri < 0).Učinkovite numeričko-dinamičke sheme u atmosferskim numeričkim prognostičkim modelima dozvoljavaju uporabu duljeg vremenskog koraka prilikom numeričke integracije, ali često dolazi do neželjenih oscilacija uzrokovanih parametrizacijom fizikalnog dijela. Tipičan primjer je pojava oscilacija povezanih s pojednostavljenim parametrizacijskim shemama za vertikalnu difuziju ili plitku konvekciju, koje se uobičajeno koriste u numeričkoj prognozi vremena. Oscilacije koje se generiraju shemama vertikalne difuzije K-tipa do sada su detaljno razmatrane, i nazvane su fibrilacijama. Visoke prostorne i vremenske frekvencije karakteristike su fibrilacija. Zbog njihove povezanosti s velikom vertikalnom rezolucijom, ove lažne oscilacije se općenito uočavaju na nižim nivoima domene modela. U prognostičkim poljima ARPÈGE-a (numeričkom prognostičkom globalom modelu u MÉTÉO-FRANCE) i ALADIN-a (njegovoj verziji modela za ograničeno područje razvijenom u suradnji sa zemljama istočne Europe) neke oscilacije su se i dalje zadržale unatoč činjenici da je uključena prva anti-fibrilacijska shema (AFS). Ovaj rad prikazuje provedena ispitivanja mogućih izvora fibrilacija pomoću 1-D (vertikalne) verzije ovih modela. Ispitivanja su dala sljedeće rezultate: 1. znatan izvor oscilacija je pronađen u parametrizaciji plitke konvekcije (što je u stvari dio sheme vertikalne difuzije) te su predložena neka riješenja za njihovo uklanjanje, 2. pokazalo se da početna AFS ne može u potpunosti spriječiti generiranje fibrilacija te je izvedena uspješnija formulacija. Jednadžbe vertikalne difuzije prikazane u numeričkom vremenskom raspisu prvog reda, zadržavajući eksplicitnu formu samog koeficijenta izmjene, u osnovi sadrže AFS. Stoga, korekcija AFS-om uvijek poboljšava stabilnost na račun točnosti. S novom anti-fibrilacijskom shemom, broj točaka mreže u kojima je potrebno izvršiti korekciju smanjen je s gotovo 90% na približno 5%, čime je shema dobila na točnosti. Za razliku od predloženih AFS iz literature, korekcija se mora primjenjivati ne samo na točke mreže sa stabilnim atmosferskim uvijetima (Richardsonov broj, Ri > 0) već i na one točke u kojima je atmosfera blago nestabilna (Ri < 0)

Degraded Carrageenan Causing Colitis in Rats Induces TNF Secretion and ICAM-1 Upregulation in Monocytes through NF-κB Activation

Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM) and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-α expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-κB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype

Front Psychiatry

Background: Excessive daytime sleepiness (EDS) is central in Attention deficit hyperactivity disorder (ADHD) but its causes remain unclear. The aim of this study was to explore objective EDS and homeostatic sleep pressure buildup, evaluated by power theta-alpha frequency (PTAF), in drug-free sleepy adults with ADHD and controls. Methods: Participants were placed during a 36-h period of extended wakefulness under constant routine protocol to strictly control sleep time, sleep duration, and circadian zeitgebers. Results: Eight drug-free sleepy patients with ADHD and 7 matched controls were included. The ADHD group had significantly shorter sleep latency on the Maintenance of Wakefulness Test (MWT) throughout extended wakefulness than the control group. There was no significant difference between the groups in PTAF evolution during extended wakefulness and in kinetic sleep pressure buildup, evaluated by the time constant of saturating exponential function. Limitations: The sample was small, so the findings cannot be generalized. Moreover, psychiatric comorbidities and circadian regulation should be taken into account in future studies. Conclusion: In very controlled conditions, mean sleep latency on the MWT during the whole extended wakefulness was significantly shorter in sleepy patients with ADHD than in control subjects. However, the difficulty to remain awake during soporific circumstances observed in these patients with ADHD cannot be explained by changes in the kinetic of sleep pressure buildup. Clinical Trials Registration: www.clinicaltrials.gov/, Identifier: NCT02217371

Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.</p> <p>Methods</p> <p>This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.</p> <p>Results</p> <p>We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.</p> <p>Conclusions</p> <p>Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas.</p

Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β

Background There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression. Methodology/Principal Findings Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1β is associated with a selective reduction in Mitofusin 2 (Mfn2) expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1β increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1β-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1β increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor α (ERRα). Conclusions/Significance Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1β in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2

Resuming Training in High-Level Athletes After Mild COVID-19 Infection: A Multicenter Prospective Study (ASCCOVID-19)

BACKGROUND: There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID). OBJECTIVES: The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes. METHODS: 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR). RESULTS: 285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+)(prevalent)); 206 (28.3%) during follow-up (COVID(+)(incident))]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(-); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01). CONCLUSION: The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).L'Institut de Rythmologie et modélisation Cardiaqu