Optimizing with Minimum Satisfiability

International audienceMinSAT is the problem of finding a truth assignment that minimizes the number of satisfied clauses in a CNF formula. When we distinguish between hard and soft clauses, and soft clauses have an associated weight, then the problem, called Weighted Partial MinSAT, consists in finding a truth assignment that satisfies all the hard clauses and minimizes the sum of weights of satisfied soft clauses. In this paper we describe a branch-and-bound solver for Weighted Partial MinSAT equipped with original upper bounds that exploit both clique partitioning algorithms and MaxSAT technology. Then, we report on an empirical investigation that shows that solving combinatorial optimization problems by reducing them to MinSAT is a competitive generic problem solving approach when solving MaxClique and combinatorial auction instances. Finally, we investigate an interesting correlation between the minimum number and the maximum number of satisfied clauses on random CNF formulae

Engineered inhalable nanocatalytic therapeutics for Parkinson's disease by inducing mitochondrial autophagy

Reactive oxygen species (ROS) - induced oxidative stress damage of dopaminergic neurons is the principal etiology of Parkinson's disease (PD). While most nanoenzymes can catalyze the breakdown of ROS present in the brain, they cannot eradicate the source of ROS production attributed to damaged mitochondria. Herein, we introduce a Co-doped Prussian blue (PB/Co) nanozyme that demonstrates multi-enzyme-like coordinated activity for scavenging present ROS and triggers mitophagy to remove damaged mitochondria. To further augment the brain entry efficiency of PB/Co nanozyme, we encapsulated it in 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 2,3-bis (palmitoyloxy)propyl-2-(trimethylammonio)ethylphosphate (DPPC) cationic liposomes and developed a non-invasive inhalable nanospray ((PB/Co)@DD) that permeates the brain via the olfactory bulb. In the PD mice model, (PB/Co)@DD nanospray induced mitophagy in the striatum to eliminate the ROS production source, preventing excessive ROS-induced sustained damage to dopaminergic neurons and averting the buildup of α-synuclein deposits, thereby ultimately restoring motor function in PD mice. Our research lays the foundation for catalytic therapy to eliminate abnormal mitochondria via the induction of mitophagy in PD mice models and highlights the potential of inhalable nanoenzymes as a non-invasive therapeutic strategy for the treatment of neuroinflammatory diseases

Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells

Abstract Background Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Thus, the aim of this study was to investigate the protective effect and mechanism of sodium butyrate (SB) on RV-induced apoptosis of IPEC-J2 cells. Results The RV infection led to significant cell apoptosis, increased the expression levels of ER stress (ERS) markers, phosphorylated protein kinase-like ER kinase (PERK), eukaryotic initiation factor 2 alpha (eIF2α), caspase9, and caspase3. Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis. The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78 (GRP78), PERK, and eIF2α. In addition, SB treatment restrained the ERS-mediated apoptotic pathway, as indicated by downregulation of C/EBP homologous protein (CHOP) mRNA level, as well as decreased cleaved caspase9 and caspase3 protein levels. Furthermore, siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis. Conclusions These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2α signaling pathway via GPR109a, which provide new ideas for the prevention and control of RV

A Prospective 10-year Observational Study of Reduction of Radiotherapy Clinical Target Volume and Dose in Early-stage Nasopharyngeal Carcinoma

10.1016/j.ijrobp.2020.03.029International Journal of Radiation Oncology - Biology - Physics1074672 - 68