A General Theoretical Framework for Learning Smallest Interpretable Models

We develop a general algorithmic framework that allows us to obtain fixed-parameter tractability for computing smallest symbolic models that represent given data. Our framework applies to all ML model types that admit a certain extension property. By showing this extension property for decision trees, decision sets, decision lists, and binary decision diagrams, we obtain that minimizing these fundamental model types is fixed-parameter tractable. Our framework even applies to ensembles, which combine individual models by majority decision

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy

HCC development is associated to peripheral insulin resistance in a mouse model of NASH

NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl 4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+ CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. © 2014 De Minicis et al

Human cholangiocarcinoma development is associated with dysregulation of opioidergic modulation of cholangiocyte growth

BACKGROUND/AIMS: Incidence of cholangiocarcinoma is increasing worldwide, yet remaining highly aggressive and with poor prognosis. The mechanisms that drive cholangiocyte transition towards malignant phenotype are obscure. Cholangiocyte benign proliferation is subjected to a self-limiting mechanism based on the autocrine release of endogenous opioid peptides. Despite the presence of both, ligands interact with delta opioid receptor (OR), but not with microOR, with the consequent inhibition of cell growth. We aimed to verify whether cholangiocarcinoma growth is associated with failure of opioidergic regulation of growth control. METHODS: We evaluated the effects of OR selective agonists on cholangiocarcinoma cell proliferation, migration and apoptosis. Intracellular signals were also characterised. RESULTS: Activation of microOR, but not deltaOR, increases cholangiocarcinoma cell growth. Such an effect is mediated by ERK1/2, PI3K and Ca(2+)-CamKIIalpha cascades, but not by cAMP/PKA and PKCalpha. microOR activation also enhances cholangiocarcinoma cell migration and reduces death by apoptosis. The anti-apoptotic effect of microOR was PI3K dependent. CONCLUSIONS: Our data indicate that cholangiocarcinoma growth is associated with altered opioidergic regulation of cholangiocyte biology, thus opening new scenarios for future surveillance or early diagnostic strategies for cholangiocarcinoma

Thermodynamic Verification of the Theory of Volume Filling of Micropores for Adsorption on Activated Carbons

The thermodynamic verification of the potential theory of adsorption for the adsorption of methanol, ethanol, carbon dichloride and carbon tetrachloride on polyfurfuryl microporous carbons is presented. Using the results of adsorption isotherm measurements at different temperatures, the condition for temperature independence of a so-called ‘characteristic’ curve was checked. It is shown that this assumption is not fulfilled for four out of eight of the cases investigated. For the systems that obey this postulate, the typical minimalization procedure for the numerical calculation of the potential theory parameters (using DR, DA and DI models), usually used by other authors, was applied. Finally the adsorption enthalpy values predicted by the potential theory of adsorption equations were calculated and compared with those measured calorimetrically

Calorimetric Investigations of Molecular Interactions in the Adsorbate/Microporous Activated Carbon System. Towards the Mechanism of Adsorption in Micropores

This paper summarises the results of four years' investigation of the thermodynamics of adsorption in activated carbon micropores. Five adsorbates, i.e. methane, methanol, ethanol, carbon dichloride and carbon tetrachloride were adsorbed at three temperatures (308, 328 and 348 K) on two polymeric microporous carbons. Adsorption isotherms, as well as differential heats of adsorption, were measured using adsorption calorimetry. From the experimental results, the entropy as well as the average heat capacity of the adsorbed molecules were calculated. The data obtained lead to the mechanism of adsorption in carbon micropores as well as to the influence of the oxidation of the carbon surface on this mechanism. By comparing the isosteric and differential heats of adsorption, it is shown that the isosteric enthalpy cannot be applied for a correct description of the adsorption energetics. Finally, some empirical relationships describing low-coverage adsorption are proposed and discussed

A Comparison of Isosteric and Differential Heats of Gas Adsorption on Microporous Active Carbons

A comparison of both isosteric and differential heats of single gas adsorption on microporous active carbons has been undertaken. The experimental data obtained indicate strong differences between the analysed quantities for the studied adsorbents. It is deduced from thermodynamical considerations that a molecular sieve effect is responsible for these differences

Effect of the Carbon Surface Layer Chemistry on Benzene Adsorption from the Vapor Phase and from Dilute Aqueous Solutions

Wepresent a complex study of benzene adsorption on chemically modified commercial activated carbons. The porosity of studied carbons is almost the same, whereas the chemical composition and the acid-base properties of surface layers differ drastically from amphoteric (initial de-ashed carbon D43/1, Carbo-Tech, Essen, Germany) and acidic (carbon modified with concentrated HNO3 and fuming H2SO4) to strongly basic (carbon modified with gaseousNH3). Benzene adsorption isotherms measured from aqueous solution at three temperatures (298, 313, and 323 K) and at the neutral pH level are reported. They are supported by studies of water and benzene adsorption from the gaseous phase (volumetric and calorimetric data) and the data of benzene temperature-programmed desorption (TPD). Moreover, the data of the enthalpy of immersion in water and benzene are also presented. Obtained data of benzene adsorption from the gaseous phase are approximated by applying the method of Nguyen and Do (ND) and the Dubinin-Astakhov (DA) equation. The data of adsorption from solution are described by the hybrid DA-Freundlich (DA-F) model. We show that there are similarities in the mechanisms of benzene adsorption from the gaseous phase and from aqueous solutions and that the pore-blocking effect is the main stage of the adsorption mechanism. This effect strongly depends on the polarity of the carbon surface. The larger the ratio of the enthalpy of carbon immersion in water to the enthalpy of immersion in benzene, the larger the reduction in adsorption from solution, compared to that in the gaseous phase, that is observed