Probabilistic Verification at Runtime for Self-Adaptive Systems

An effective design of effective and efficient self-adaptive systems may rely on several existing approaches. Software models and model checking techniques at run time represent one of them since they support automatic reasoning about such changes, detect harmful configurations, and potentially enable appropriate (self-)reactions. However, traditional model checking techniques and tools may not be applied as they are at run time, since they hardly meet the constraints imposed by on-the-fly analysis, in terms of execution time and memory occupation. For this reason, efficient run-time model checking represents a crucial research challenge. This paper precisely addresses this issue and focuses on probabilistic run-time model checking in which reliability models are given in terms of Discrete Time Markov Chains which are verified at run-time against a set of requirements expressed as logical formulae. In particular, the paper discusses the use of probabilistic model checking at run-time for self-adaptive systems by surveying and comparing the existing approaches divided in two categories: state-elimination algorithms and algebra-based algorithms. The discussion is supported by a realistic example and by empirical experiments

Suzaku and SWIFT-BAT observations of a newly discovered Compton-thick AGN

Obscured AGN are fundamental to understand the history of Super Massive Black Hole growth and their influence on galaxy formation. However, the Compton-thick AGN (NH>1e24 cm^-2) population is basically unconstrained, with less than few dozen confirmed Compton-thick AGN found and studied so far. A way to select heavily obscured AGN is to compare the X-ray emission below 10 keV (which is strongly depressed) with the emission from other bands less affected by the absorption, i.e. the IR band. To this end, we have cross-correlated the 2XMM catalogue with the IRAS Point Source catalogue and, by using the X-ray to infrared flux ratio and X-ray colors, we selected a well defined sample of Compton-thick AGN candidates at z<0.1. The aim of this work is to confirm the nature and to study one of these local Compton-thick AGN candidates, the nearby (z=0.029) Seyfert 2 galaxy IRAS 04507+0358, by constraining the amount of intrinsic absorption (NH) and thus the intrinsic luminosity. To this end we obtained deep (100 ks) Suzaku observations (AO4 call) and performed a joint fit with SWIFT-BAT data. We analyzed XMM-Newton, Suzaku and SWIFT-BAT data and we present here the results of this broad-band (0.4-100 keV) spectral analysis. We found that the broad-band X-ray emission of IRAS 04507+0358 requires a large amount of absorption (larger than 1e24 cm^-2) to be well reproduced, thus confirming the Compton-thick nature of this source. In particular, the most probable scenario is that of a mildly (NH (1.3-1.5)x1e24 cm^-2, L(2-10 keV) (5-7)x1e43 erg s^-1) Compton-thick AGN.Comment: Accepted for publication in A&A; 8 pages, 7 figure

Modeling DNA-binding of Escherichia coli σ70 exhibits a characteristic energy landscape around strong promoters

We present a computational model of DNA-binding by σ70 in Escherichia coli which allows us to extract the functional characteristics of the wider promoter environment. Our model is based on a measure for the binding energy of σ70 to the DNA, which is derived from promoter strength data and used to build up a non-standard weight matrix. Opposed to conventional approaches, we apply the matrix to the environment of 3765 known promoters and consider the average matrix scores to extract the common features. In addition to the expected minimum of the average binding energy at the exact promoter site, we detect two minima shortly upstream and downstream of the promoter. These are likely to occur due to correlation between the two binding sites of σ70. Moreover, we observe a characteristic energy landscape in the 500 bp surrounding the transcription start sites, which is more pronounced in groups of strong promoters than in groups of weak promoters. Our subsequent analysis suggests that the characteristic energy landscape is more likely an influence on target search by the RNA polymerase than a result of nucleotide biases in transcription factor binding sites

Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection

Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii-infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

Recent Innovations & Daily Problems. A new prosthesis in inguinal hernia repair:preliminary results of a pilot study.

Introduction: Elective surgery for inguinal hernia is affected by very low mortality « 1 per 10000 operation); in contrast, when surgery is carried out for complicated inguinal hernia, risks of postoperative complication are higher. TAPP is a world-wide accepted surgical practice in the treatment of elective bilateral or recurrent inguinal hernia, above all in young patients. Few exploratory studies were published on laparoscopic approach in the treatment of urgent complicated inguinal hernia. Aim of this study was to analyze feasibility (operative time, conversion rate), safety (postoperative morbidity, length of hospital stay) and quality of life (acute and chronic pain, return to work) of trans-abdominal pre-peritoneal laparoscopic hernia repair in acute incarcerated inguinal hernia. Rationale of laparoscopic trans-abdominal approach is the easier hernia reduction under vision and a better exploration of the abdominal cavity. Methods: from September 2012 to September 2013, 15 consecutive patients admitted in emergency at the Division of General Surgery of University "Sapienza", Polo Pontino, for acute incarcerated inguinal hernia were submitted to TAPP using 3 trocars (1 of 10 mm and 2 of 5mm) and polyester prosthesis fixed by fibrin glue. Exclusion criteria for laparoscopic approach were age III, previous abdominal surgery, signs of strangulated hernia. All of them were evaluated for operative time, conversion rate, postoperative morbidity, organ resection or other surgery required. All patients were scored for pain by Visual Analogic Scale (VAS) during postoperative in hospital stay at 7 days, 1,6 and 12 months after surgery. Results: median follow-up was 16 months and 12 as minimum. In all cases reduction of hernia was always possible and none conversion to open surgery was recorded, median operative time was 89 minutes (55-137 as range), omental resection was carried out in one patient (6,6%), no other organ resections needed, whereas contralateral hernia was diagnosed and repaired at the same time in 4 patients (26,6%). No major complications were observed, median blood loss was 100 ml, minor morbidity was contained to 18% represented by fever and wound infection of surgical umbilical scar. Median in hospital stay was 1,5 days with 1-5 days as range. Postoperative median acute pain, measured by visual analogic scale (VAS), was 2 (range:0-4), none patient referred any pain during follow-up. Median time of return to work was 6,5 days, ranged between 3 to 15 days. Patients' compliance to treatment and to follow-up was complete as well their satisfaction. Conclusions: In centres skilled for laparoscopy in emergency, TAPP could be considered a feasible and safe technique. In well-selected patients (especially if emolled in controlled clinical trial) TAPP could represent an alternative surgical approach for complicated incarcerated inguinal hernia to conventional open surgery even in urgency. The main advantages of laparoscopic approach are the ability to perform surgical hernia reduction under vision, a better exploration and evaluation of abdominal cavity and diagnosis and treatment of eventual contralateral defect of wall, otherwise often missed. Finally, the good control of acute and chronic pain, faster return to normal activity and work, better aesthetic results contributed to total satisfaction and compliance of the patients

A Novel Signaling Network Essential for Regulating Pseudomonas aeruginosa Biofilm Development

The important human pathogen Pseudomonas aeruginosa has been linked to numerous biofilm-related chronic infections. Here, we demonstrate that biofilm formation following the transition to the surface attached lifestyle is regulated by three previously undescribed two-component systems: BfiSR (PA4196-4197) harboring an RpoD-like domain, an OmpR-like BfmSR (PA4101-4102), and MifSR (PA5511-5512) belonging to the family of NtrC-like transcriptional regulators. These two-component systems become sequentially phosphorylated during biofilm formation. Inactivation of bfiS, bfmR, and mifR arrested biofilm formation at the transition to the irreversible attachment, maturation-1 and -2 stages, respectively, as indicated by analyses of biofilm architecture, and protein and phosphoprotein patterns. Moreover, discontinuation of bfiS, bfmR, and mifR expression in established biofilms resulted in the collapse of biofilms to an earlier developmental stage, indicating a requirement for these regulatory systems for the development and maintenance of normal biofilm architecture. Interestingly, inactivation did not affect planktonic growth, motility, polysaccharide production, or initial attachment. Further, we demonstrate the interdependency of this two-component systems network with GacS (PA0928), which was found to play a dual role in biofilm formation. This work describes a novel signal transduction network regulating committed biofilm developmental steps following attachment, in which phosphorelays and two sigma factor-dependent response regulators appear to be key components of the regulatory machinery that coordinates gene expression during P. aeruginosa biofilm development in response to environmental cues

Co-Orientation of Replication and Transcription Preserves Genome Integrity

In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over ∼1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization

A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)

Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) con-centrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, L\uf8nborg et al., 2023) compiling previously pub-lished and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC &gt; DON &gt; DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concen-tration in coastal waters (average \ub1 standard deviation (SD): 182 \ub1 314 μmol C L−1; median: 103 μmol C L−1) is13-fold higher than the average coastal DON concentration (13.6 \ub1 30.4 μmol N L−1; median: 8.0 μmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 \ub1 1.11 μmol P L−1; median:0.18 μmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochem-ical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters