Homeomorphic Embedding for Online Termination of Symbolic Methods

Well-quasi orders in general, and homeomorphic embedding in particular, have gained popularity to ensure the termination of techniques for program analysis, specialisation, transformation, and verification. In this paper we survey and discuss this use of homeomorphic embedding and clarify the advantages of such an approach over one using well-founded orders. We also discuss various extensions of the homeomorphic embedding relation. We conclude with a study of homeomorphic embedding in the context of metaprogramming, presenting some new (positive and negative) results and open problems

Enhancement of Methacholine-Evoked Tracheal Contraction Induced by Bacterial Lipopolysaccharides Depends on Epithelium and Tumor Necrosis Factor

Inhaled bacterial lipopolysaccharides (LPSs) induce an acute tumour necrosis factor-alpha (TNF-α-) dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4) via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh). We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity), which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Nine weeks of supplementation with a multi-nutrient product augments gains in lean mass, strength, and muscular performance in resistance trained men

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare the effects of supplementation with Gaspari Nutrition's SOmaxP Maximum Performance™ (SOmaxP) versus a comparator product (CP) containing an equal amount of creatine (4 g), carbohydrate (39 g maltodextrin), and protein (7 g whey protein hydrolysate) on muscular strength, muscular endurance, and body composition during nine weeks of intense resistance training.</p> <p>Methods</p> <p>Using a prospective, randomized, double-blind design, 20 healthy men (mean ± SD age, height, weight, % body fat: 22.9 ± 2.6 y, 178.4 ± 5.7 cm, 80.5 ± 6.6 kg, 16.6 ± 4.0%) were matched for age, body weight, resistance training history, bench press strength, bench press endurance, and percent body fat and then randomly assigned via the ABBA procedure to ingest 1/2 scoop (dissolved in 15 oz water) of SOmaxP or CP prior to, and another 1/2 scoop (dissolved in 15 oz water) during resistance exercise. Body composition (DEXA), muscular performance (1-RM bench press and repetitions to failure [RTF: 3 sets × baseline body weight, 60-sec rest between sets]), and clinical blood chemistries were measured at baseline and after nine weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and follow a specific, progressive overload resistance training program (4-days/wk, upper body/lower body split) during the study. An intent-to-treat approach was used and data were analyzed via ANCOVA using baseline values as the covariate. Statistical significance was set <it>a priori </it>at p ≤ 0.05.</p> <p>Results</p> <p>When adjusted for initial differences, significant between group post-test means were noted in: 1-RM bench press (SOmaxP: 133.3 ± 1.3 kg [19.8% increase] vs. CP: 128.5 ± 1.3 kg [15.3% increase]; p < 0.019); lean mass (SOmaxP: 64.1 ± 0.4 kg [2.4% increase] vs. 62.8 ± 0.4 kg [0.27% increase], p < 0.049); RTF (SOmaxP: 33.3 ± 1.1 reps [44.8% increase] vs. 27.8 ± 1.1 reps [20.9% increase], p < 0.004); and fat mass (SOmaxP: 12.06 ± 0.53 kg [9.8% decrease] vs. 13.90 ± 0.53 kg [4.1% increase], p < 0.024). No statistically significant differences in vital signs (heart rate, systolic and diastolic blood pressures) or clinical blood chemistries were noted.</p> <p>Conclusions</p> <p>These data indicate that compared to CP, SOmaxP administration augments and increases gains in lean mass, bench press strength, and muscular performance during nine weeks of intense resistance training. Studies designed to confirm these results and clarify the molecular mechanisms by which SOmaxP exerts the observed salutary effects have begun. Both SOmaxP and the CP were well-tolerated, and no supplement safety issues were identified.</p

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experiment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z ≥ 3 fragments and an emulsion spectrometer for Z ≤ 3 fragments. The first data taking was performed in 2019 at the GSI facility (Darmstadt, Germany). In this study, the charge identification of fragments induced by exposing an emulsion detector, embedding a C2 H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identification is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response

Measuring the Impact of Nuclear Interaction in Particle Therapy and in Radio Protection in Space: the FOOT Experiment

In Charged Particle Therapy (PT) proton or 12C beams are used to treat deep-seated solid tumors exploiting the advantageous characteristics of charged particles energy deposition in matter. For such projectiles, the maximum of the dose is released at the end of the beam range, in the Bragg peak region, where the tumour is located. However, the nuclear interactions of the beam nuclei with the patient tissues can induce the fragmentation of projectiles and/or target nuclei and needs to be carefully taken into account when planning the treatment. In proton treatments, the target fragmentation produces low energy, short range fragments along all the beam path, that deposit a non-negligible dose especially in the first crossed tissues. On the other hand, in treatments performed using 12C, or other (4He or 16O) ions of interest, the main concern is related to the production of long range fragments that can release their dose in the healthy tissues beyond the Bragg peak. Understanding nuclear fragmentation processes is of interest also for radiation protection in human space flight applications, in view of deep space missions. In particular 4He and high-energy charged particles, mainly 12C, 16O, 28Si and 56Fe, provide the main source of absorbed dose in astronauts outside the atmosphere. The nuclear fragmentation properties of the materials used to build the spacecrafts need to be known with high accuracy in order to optimise the shielding against the space radiation. The study of the impact of these processes, which is of interest both for PT and space radioprotection applications, suffers at present from the limited experimental precision achieved on the relevant nuclear cross sections that compromise the reliability of the available computational models. The FOOT (FragmentatiOn Of Target) collaboration, composed of researchers from France, Germany, Italy and Japan, designed an experiment to study these nuclear processes and measure the corresponding fragmentation cross sections. In this work we discuss the physics motivations of FOOT, describing in detail the present detector design and the expected performances, coming from the optimization studies based on accurate FLUKA MC simulations and preliminary beam test results. The measurements planned will be also presented

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experi- ment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z &gt;= 3 fragments and an emulsion spectrometer for Z &lt;= 3 fragments. The first data taking was performed in 2019 at the GSI facility(Darmstadt, Germany). In this study, the charge identifi-cation of fragments induced by exposing an emulsion detector, embedding a C2H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identifica-tion is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response

CC9 Livestock-Associated Staphylococcus aureus Emerges in Bloodstream Infections in French Patients Unconnected With Animal Farming

We report 4 bloodstream infections associated with CC9 agr type II Staphylococcus aureus in individuals without animal exposure. We demonstrate, by microarray analysis, the presence of egc cluster, fnbA, cap operon, lukS, set2, set12, splE, splD, sak, epiD, and can, genomic features associated with a high virulence potential in human