Relatedness, Coherence, and Coherence Dynamics Empirical Evidence from Italian Manufacturing

This paper investigates the determinants of coherence and coherence change using a sample of Italian leading firms in the period 1993-1996. Following a methodology developed by Teece et al (1994), the observed diversification patterns of our sample firms provide the information required to construct an index of relatedness between pair of sectors, which is in turn used to obtain a measure of firm’s coherence. The econometric analysis highlights that relatedness is higher when sectors share similar technological and marketing characteristics, and when they are positioned at different stages of the productive chain. Analogously, coherence is higher for firms active in industries characterised by similar R&D intensities and exploiting vertical integration links. Firms which enter the group of top 5 leaders are more coherent than the average. From a dynamic perspective, we find that coherence increases for firms with main activities in sectors which are expected to be more affected from EU integration. Finally, the results show that a deepening of vertical integration strategies is good for coherence change, while an increase of diversification brings a reduction in coherence.relatedness, coherence, diversification

A Burkholderia cenocepacia MurJ (MviN) homolog is essential for cell wall peptidoglycan synthesis and bacterial viability

The cell wall peptidoglycan (PG) of Burkholderia cenocepacia, an opportunistic pathogen, has not yet been characterized. However, the B. cenocepacia genome contains homologs of genes encoding PG biosynthetic functions in other bacteria. PG biosynthesis involves the formation of the undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide, known as lipid II, which is built on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh; this translocation step is critical to PG synthesis. We have investigated candidate flippase homologs of the MurJ family in B. cenocepacia. Our results show that BCAL2764, herein referred to as murJBc, is indispensable for viability. Viable B. cenocepacia could only be obtained through a conditional mutagenesis strategy by placing murJBc under the control of a rhamnose-inducible promoter. Under rhamnose depletion, the conditional strain stopped growing and individual cells displayed morphological abnormalities consistent with a defect in PG synthesis. Bacterial cells unable to express MurJBc underwent cell lysis, while partial MurJBc depletion sensitized the mutant to the action of β-lactam antibiotics. Depletion of MurJBc caused accumulation of PG precursors consistent with the notion that this protein plays a role in lipid II flipping to the periplasmic compartment. Reciprocal complementation experiments of conditional murJ mutants in B. cenocepacia and Escherichia coli with plasmids expressing MurJ from each strain indicated that MurJBc and MurJEc are functional homologs. Together, our results are consistent with the notion that MurJBc is a PG lipid II flippase in B. cenocepacia

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in <em>Burkholderia cenocepacia</em>

Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic resistant bacterium Burkholderia cenocepacia protects less resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sub-lethal concentrations of PmB and other bactericidal antibiotics induce reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS such as superoxide ion and hydrogen peroxide was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sub-lethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation, and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study exposes BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance, and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections

An automatic deep learning approach for coronary artery calcium segmentation

Coronary artery calcium (CAC) is a significant marker of atherosclerosis and cardiovascular events. In this work we present a system for the automatic quantification of calcium score in ECG-triggered non-contrast enhanced cardiac computed tomography (CT) images. The proposed system uses a supervised deep learning algorithm, i.e. convolutional neural network (CNN) for the segmentation and classification of candidate lesions as coronary or not, previously extracted in the region of the heart using a cardiac atlas. We trained our network with 45 CT volumes; 18 volumes were used to validate the model and 56 to test it. Individual lesions were detected with a sensitivity of 91.24%, a specificity of 95.37% and a positive predicted value (PPV) of 90.5%; comparing calcium score obtained by the system and calcium score manually evaluated by an expert operator, a Pearson coefficient of 0.983 was obtained. A high agreement (Cohen's k = 0.879) between manual and automatic risk prediction was also observed. These results demonstrated that convolutional neural networks can be effectively applied for the automatic segmentation and classification of coronary calcifications

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

“Heteroresistance” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical relevance may be considerable, since more resistant subpopulations may be selected during antimicrobial therapy. However, the use of nonstandard methods to define heteroresistance, which are costly and involve considerable labor and resources, precludes evaluating the clinical magnitude and severity of this phenomenon. We review the available literature on antibiotic heteroresistance and propose recommendations for definitions and determination criteria for heteroresistant bacteria. This will help in assessing the global clinical impact of heteroresistance and developing uniform guidelines for improved therapeutic outcomes