H∞ loop shaping control for distributed PLL network

International audienceIn this paper, we describe a robust control law for distributed PLL network using H∞ optimization problem. The controller can be uniformly applied on all distributed nodes and guarantees good stability margins, enhanced performance and reduced jitter noise. A 2-dimensional Cartesian mesh network structure is considered without using any feedback loop phase information propagation to eliminate undesirable mode-locked states

Approche de la performance relative pour la commande de systèmes de grande dimension

International audienceDans ce papier, le problème de la synthèse de la loi de commande décentralisée pour des systèmes de grande dimension ou des systèmes de Multi-Agents composés de sous-systèmes identiques, assurant la stabilité et un niveau de performance globales, est considéré. Inspiré par l'approche entrée-sortie, le problème de synthèse est réduit à un problème de satisfaction de deux contraintes : (i) la contrainte sur la dynamique du système d'interconnexion et (ii) la contrainte sur la dynamique des sous-systèmes locaux (ou agents). Les deux problèmes ont été résolus en appliquant l'optimisation convexe sous contraintes LMI et une synthèse H ∞ standard. La méthode proposée est appliquée à la synthèse de la loi de commande pour la synchronisation du réseau de PLLs

Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis

Amniotic fluid; Neonatal mortality; ExencephalyLíquido amniótico; Mortalidad neonatal; ExencefaliaLíquid amniòtic; Mortalitat neonatal; ExencefàliaExencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.This work was supported by Prof. Jose L. Peiro internal Cincinnati Children's Hospital funding

Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord

Omega-3 fatty acids, hepatic lipid metabolism and non-alcoholic fatty liver disease

Long-chain omega-3 fatty acids belong to a family of polyunsaturated fatty acids that are known to have important beneficial effects on metabolism and inflammation. Such effects may confer a benefit in specific chronic noncommunicable diseases that are becoming very prevalent in Westernized societies [e.g., nonalcoholic fatty liver disease (NAFLD)]. Typically, with a Westernized diet, long-chain omega-6 fatty acid consumption is markedly greater than omega-3 fatty acid consumption. The potential consequences of an alteration in the ratio of omega-6 to omega-3 fatty acid consumption are increased production of proinflammatory arachidonic acid–derived eicosanoids and impaired regulation of hepatic and adipose function, predisposing to NAFLD. NAFLD represents a spectrum of liver fat–related conditions that originates with ectopic fat accumulation in liver (hepatic steatosis) and progresses, with the development of hepatic inflammation and fibrosis, to nonalcoholic steatohepatitis (NASH). If the adipose tissue is inflamed with widespread macrophage infiltration, the production of adipokines may act to exacerbate liver inflammation and NASH. Omega-3 fatty acid treatment may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function, and inflammation. Recent studies testing the effects of omega-3 fatty acids in NAFLD are showing promise and suggesting that these fatty acids may be useful in the treatment of NAFLD. To date, further research is needed in NAFLD to (a) establish the dose of long-chain omega-3 fatty acids as a treatment, (b) determine the duration of therapy, and (c) test whether there is benefit on the different component features of NAFLD (hepatic fat, inflammation, and fibrosis). </jats:p

Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression.

Background and aims: n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15–18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time.Methods: In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.Results: 92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005–0.020 mm) compared to 0.015 mm (IQR 0.007–0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized ?-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized ?-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized ?-coefficient ?0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized ?-coefficient 0.30, p &lt; 0.001) and increased DHA tissue enrichment during the 18-month study (standardized ?-coefficient ?0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18.Conclusion: Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression