Formulations for an inventory routing problem

In this paper, we present and compare formulations for the inventory routing problem (IRP) where the demand of customers has to be served, over a discrete time horizon, by capacitated vehicles starting and ending their routes at a depot. The objective of the IRP is the minimization of the sum of inventory and transportation costs. The formulations include known and new mathematical programming formulations. Valid inequalities are also presented. The formulations are tested on a large set of benchmark instances. One of the most significant conclusions is that the formulations that use vehicle‐indexed variables are superior to the more compact, aggregate formulations.     

Comparative Antimicrobial Activity of Silver Nanoparticles Obtained by Wet Chemical Reduction and Solvothermal Methods

The synthesis of nanoparticles from noble metals has received high attention from researchers due to their unique properties and their wide range of applications. Silver nanoparticles (AgNPs), in particular, show a remarkable inhibitory effect against microorganisms and viruses. Various methods have been developed to obtain AgNPs, however the stability of such nanostructures over time is still challenging. Researchers attempt to obtain particular shapes and sizes in order to tailor AgNPs properties for specific areas, such as biochemistry, biology, agriculture, electronics, medicine, and industry. The aim of this study was to design AgNPs with improved antimicrobial characteristics and stability. Two different wet chemical routes were considered: synthesis being performed (i) reduction method at room temperatures and (ii) solvothermal method at high temperature. Here, we show that the antimicrobial properties of the obtained AgNPs, are influenced by their synthesis route, which impact on the size and shape of the structures. This work analyses and compares the antimicrobial properties of the obtained AgNPs, based on their structure, sizes and morphologies which are influenced, in turn, not only by the type or quantities of precursors used but also by the temperature of the reaction. Generally, AgNPs obtained by solvothermal, at raised temperature, registered better antimicrobial activity as compared to NPs obtained by reduction method at room temperature.     

Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

Alterations in mitochondrial function are an important control variable in the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), while also noted by increased de novo lipogenesis (DNL) and hepatic insulin resistance. We hypothesized that the organization and function of a mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. We addressed this question using a transgenic mouse model with increased hepatic insulin resistance and DNL due to constitutively active human SREBP-1c. The abundance of ETC complex subunits and components of key metabolic pathways are regulated in the liver of these animals. Further omics approaches combined with functional assays in isolated liver mitochondria and primary hepatocytes revealed that the SREBP-1c-forced fatty liver induced a substrate limitation for oxidative phosphorylation, inducing enhanced complex II activity. The observed increased expression of mitochondrial genes may have indicated a counteraction. In conclusion, a shift of available substrates directed toward activated DNL results in increased electron flows, mainly through complex II, to compensate for the increased energy demand of the cell. The reorganization of key compounds in energy metabolism observed in the SREBP-1c animal model might explain the initial increase in mitochondrial function observed in the early stages of human MAFLD.     

Zur Rolle von EDA-Komplexen bei kationischen Polymerisationen. VI[1]. Wechselwirkung von Halogenidionen mit organischen aπ-Elektronenacceptoren

The Role of Donor-Acceptor Complexes in Cationic Polymerisations. The Interaction of Halide Ions with Organic aπ-Acceptors The anions of salts of the type Kat⁺X⁻ (Kat⁺  Li⁺, Na⁺, Et₄N⁺; X⁻  Cl⁻, Br⁻, I⁻) form donor-acceptor complexes with organic a π-acceptors. The long-wave charge-transfer absorption show a bathochrome shift with higher periodic numbers of X⁻ and increasing electron affinity of the acceptors Acc. Strong acceptors form radical ions very rapidly with X  I and slowly with X  Br. Cl. The interactions in the system Kat⁺X⁻ → Acc are influenced by solvents in a very complex way. As acceptors they interact preferably with the halide ion X⁻ and, hence, reduce its donicity for the competing acceptor Acc. As donors they change the dissociation of the ion pair Kat⁺X⁻ by solvation of the cation Kat⁺ and influence in that indirect way also the donicity of X⁻ for the acceptor Acc.     

Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies

(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (¹H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using ¹H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the ‘fear neurocircuitry’ in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.     

Algorithmic probabilistic game semantics

We present a detailed account of a translation from probabilistic call-by-value programs with procedures to Rabin’s probabilistic automata. The translation is fully abstract in that programs exhibit the same computational behaviour if and only if the corresponding automata are language-equivalent. Since probabilistic language equivalence is decidable, we can apply the translation to analyse the behaviour of probabilistic programs and protocols. We illustrate our approach on a number of case studies.     

Analyzing probabilistic pushdown automata

The paper gives a summary of the existing results about algorithmic analysis of probabilistic pushdown automata and their subclasses.