Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, but not the lab strain 19606, can infect alveolar macrophages and produce ACVs in vivo in a murine pneumonia model. Both strains initially interact with the macrophage endocytic pathway, as indicated by EEA1 and LAMP1 markers; however, the fate of these strains diverges at a later stage. While 19606 is eliminated in an autophagy pathway, 398 replicates in ACVs and are not degraded. We show that 398 reverts the natural acidification of the phagosome by secreting large amounts of ammonia, a by-product of amino acid catabolism. We propose that this ability to survive within macrophages may be critical for the persistence of clinical A. baumannii isolates in the lung during a respiratory infection

The Italian genome reflects the history of Europe and the Mediterranean basin

Recent scientific literature has highlighted the relevance of population genetic studies both for disease association mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of the Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single-nucleotide polymorphisms in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which have produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population's ancestry, identifying the genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., ‘barbarian invasion' of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe

Peptidoglycan editing provides immunity to Acinetobacter baumannii during bacterial warfare

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacteriu

On Measuring CPCP Violation in Neutral BB-meson Decays at the Υ(4S)\Upsilon (4S) Resonance

Within the standard model we carry out an analysis of $CP$-violating observables in neutral $B$-meson decays at the $\Upsilon (4S)$ resonance. Both time-dependent and time-integrated $CP$ asymmetries are calculated, without special approximations, to meet various possible measurements at symmetric and asymmetric $e^{+}e^{-}$ $B$ factories. We show two ways to distinguish between direct and indirect $CP$-violating effects in the $CP$-eigenstate channels such as $B^{0}_{d}/\bar{B}^{0}_{d}\rightarrow \pi^{+}\pi^{-}$ and $\pi^{0} K_{S}$. Reliable knowledge of the Cabibbo-Kobayashi-Maskawa phase and angles can in principle be extracted from measurements of some non-$CP$-eigenstate channels, e.g. $B^{0}_{d}/\bar{B}^{0}_{d}\rightarrow D^{\pm}\pi^{\mp}$ and $\stackrel{(-)}{D}$$^{(*)0}K_{S}$, even in the presence of significant final-state interactions.Comment: Latex file 13 pages, CERN-TH.7194/94 and PVAMU-HEP-94-2 (Phys. Lett. B328 (1994) 477). (A few minor typing errors have been corrected.

SOLO: Search Online, Learn Offline for Combinatorial Optimization Problems

We study combinatorial problems with real world applications such as machine scheduling, routing, and assignment. We propose a method that combines Reinforcement Learning (RL) and planning. This method can equally be applied to both the offline, as well as online, variants of the combinatorial problem, in which the problem components (e.g., jobs in scheduling problems) are not known in advance, but rather arrive during the decision-making process. Our solution is quite generic, scalable, and leverages distributional knowledge of the problem parameters. We frame the solution process as an MDP, and take a Deep Q-Learning approach wherein states are represented as graphs, thereby allowing our trained policies to deal with arbitrary changes in a principled manner. Though learned policies work well in expectation, small deviations can have substantial negative effects in combinatorial settings. We mitigate these drawbacks by employing our graph-convolutional policies as non-optimal heuristics in a compatible search algorithm, Monte Carlo Tree Search, to significantly improve overall performance. We demonstrate our method on two problems: Machine Scheduling and Capacitated Vehicle Routing. We show that our method outperforms custom-tailored mathematical solvers, state of the art learning-based algorithms, and common heuristics, both in computation time and performance

Distance Properties of Short LDPC Codes and their Impact on the BP, ML and Near-ML Decoding Performance

Parameters of LDPC codes, such as minimum distance, stopping distance, stopping redundancy, girth of the Tanner graph, and their influence on the frame error rate performance of the BP, ML and near-ML decoding over a BEC and an AWGN channel are studied. Both random and structured LDPC codes are considered. In particular, the BP decoding is applied to the code parity-check matrices with an increasing number of redundant rows, and the convergence of the performance to that of the ML decoding is analyzed. A comparison of the simulated BP, ML, and near-ML performance with the improved theoretical bounds on the error probability based on the exact weight spectrum coefficients and the exact stopping size spectrum coefficients is presented. It is observed that decoding performance very close to the ML decoding performance can be achieved with a relatively small number of redundant rows for some codes, for both the BEC and the AWGN channels

Genetic Variation Among Endosymbionts of Widely Distributed Vestimentiferan Tubeworms

Vestimentiferan tubeworms thriving in sulfidic deep-sea hydrothermal vents and cold seeps are constrained by their nutritional reliance on chemoautotrophic endosymbionts. In a recent phylogenetic study using 16S ribosomal DNA, we found that endosymbionts from vent and seep habitats form two distinct clades,vith little variation within each clade. In the present study, we used two different approaches to assess the genetic variation among biogeographically distinct vestimentiferan symbionts, DNA sequences were obtained for the noncoding, internal transcribed spacer (ITS) regions of the rRNA operons of symbionts associated with six different genera of vestimentiferan tubeworms. ITS sequences from endosymbionts of host genera collected from different habitats and widely distributed vent sites were surprisingly conserved. Because the ITS region was not sufficient for distinguishing endosymbionts from different habitats or locations, we used a DNA fingerprinting technique, repetitive extragenic-palindrome PCR (REP-PCR), to reveal differences in the distribution of repetitive sequences in the genomes of the bacterial endosymbionts. Most of the endosymbionts displayed unique REP-PCR patterns. A cladogram generated from these fingerprints reflected relationships that may be influenced by a variety of factors, including host genera, geographic location, and bottom type

Electroweak and Dark Matter Constraints on a Z' in Models with a Hidden Valley

We consider current precision electroweak data, Z' searches and dark matter constraints and analyse their implications for an extension of the SM that includes an extra U(1)' massive gauge boson and a particular hidden sector ("hidden valley") with a confining (QCD-like) gauge group. The constraints on the Z' with arbitrary Z-Z' kinetic mixing coming from direct searches and precision tests of the Standard Model are analysed and shown to lead to a lower limit of 800 GeV on its mass. Renormalisable interactions involving the Z' probe the physics of the hidden valley sector which contains a pseudoscalar dark matter candidate. We find that dark matter constraints place an upper bound on the mass of the Z' of O(10) TeV. A TeV mass scale is needed for the hidden valley states, and the Sommerfeld factor for p-wave dark matter annihilation is found significantly to suppress the allowed parameter space of the model.Comment: 35 pages, 14 figure

Alliance or acquisition? A mechanisms‐based, policy‐capturing analysis

Research summary: While alliance researchers view prior partner‐specific alliance experience as influencing firms' subsequent alliance or acquisition decisions, empirical evidence on the alliance versus acquisition decision is surprisingly mixed. We offer a reconciliation by proposing and testing an analytical framework that recognizes prior partner‐specific experiences as heterogeneous along three fundamental dimensions: partner‐specific trust, routines, and value certainty. This allows us to use a policy‐capturing methodology to rigorously operationalize and test our mechanism‐level predictions. We find that all three mechanisms can increase the likelihood of a subsequent alliance or acquisition, and in terms of the comparative choice between alliances versus acquisitions, partner‐specific trust pulls towards alliances, and value certainty pulls towards acquisitions. We conclude with a discussion of the theoretical and empirical implications of our approach and method. Managerial summary: This study focuses on an important corporate decision: When a firm has had an alliance with another firm, how would that experience affect the likelihood of a future alliance or acquisition with that same firm? We first suggest that it will depend on three factors: the level of trust that existed in that prior alliance, the extent to which specific work routines were developed, and the degree to which the firm was able to confidently assess the value of the partner firm's resources. We then find that trust is a particularly strong predictor of future alliances, while confidence regarding value more strongly predicts future acquisitions. In this way, we demonstrate more precisely how past corporate choices can affect (consciously or unconsciously) future ones