The physics models of FLUKA: status and recent development

A description of the intermediate and high energy hadronic interaction models used in the FLUKA code is given. Benchmarking against experimental data is also reported in order to validate the model performances. Finally the most recent developments and perspectives for nucleus-nucleus interactions are described together with some comparisons with experimental data.Comment: talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 10 pages, p

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy- relevant energies down to stopping

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100– 200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments

Oral health behaviour and lifestyle factors among overweight young adults in Europe:a cross-sectional questionnaire study

Being overweight is a risk factor for many chronic diseases including oral diseases. Our aim was to study the associations between oral health behavior, lifestyle factors and being overweight among young European adults, 2011–2012. The subjects constituted a representative sample of adult population aged 18–35 years from eight European countries participating in the Escarcel study. The participants completed a self-administered questionnaire on dietary habits, oral health behavior, smoking, exercise, height, and weight. Overweight was defined as body mass index (BMI) ¥ 25 kg/m2 using theWorld Health Organization criteria. Mean BMI was 23.2 (SD 3.48) and 24.3% of the study population were overweight. Those who were overweight drank more soft drinks (p = 0.005) and energy drinks (p = 0.006) compared with those who were non-overweight. Brushing once a day (OR 1.6; 95% CI 1.3–2.0), emergency treatment as the reason for last dental visit (OR 1.6; 95% CI 1.3–1.9) and having seven or more eating or drinking occasions daily (OR 1.4; 95% CI 1.1–1.7) were statistically significantly associated with overweight. Associations were found between oral health behavior, lifestyle and overweight. A greater awareness of the detrimental lifestyle factors including inadequate oral health habits among overweight young adults is important for all healthcare providers, including oral health care professionals

SOHLH1 and SOHLH2 control Kit expression during postnatal male germ cell development

How Kit expression is regulated in the germline remains unknown. SOHLH1 and SOHLH2, two bHLH transcription factors specifically expressed in germ cells, are involved in spermatogonia and oocyte differentiation. In the male, deletion of each factor causes loss of Kit-expressing spermatogonia in the prepuberal testis. In the female, SOHLH1 and SOHLH2 ablations cause oocyte loss in the neonatal ovary. To investigate whether Kit expression is regulated by these two factors in male germ cells, we examined SOHLH1 and SOHLH2 expression during fetal and postnatal mouse development. We found a strong positive correlation between Kit and the two transcription factors only in postnatal spermatogonia. SOHLH2 was enriched in undifferentiated spermatogonia, whereas SOHLH1 expression was maximal at Kit-dependent stages. Expression of SOHLH1, but not SOHLH2, was increased in postnatal mitotic germ cells by treatment with all-trans retinoic acid. We found that E-box sequences within the Kit promoter and its first intron can be transactivated in transfection experiments overexpressing Sohlh1 or Sohlh2. Co-transfection of both factors showed a cooperative effect. EMSA experiments showed that SOHLH1 and SOHLH2 can independently and cooperatively bind an E-box-containing probe. In vivo co-immunoprecipitations indicated that the two proteins interact and overexpression of both factors increases endogenous Kit expression in embryonic stem cells. SOHLH1 was found by ChIP analysis to occupy an E-box-containing region within the Kit promoter in spermatogonia chromatin. Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression

Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2.

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has been no scientific evidence to recommend mouth rinses with an anti-SARS-CoV-2 effect to control the viral load in the oral cavity. This critical review indicates that current knowledge of these reagents would likely improve trends in salivary viral load status. This finding is a strong sign to encourage clinical research for which quality protocols are already available in the literature

The application of FLUKA to dosimetry and radiation therapy

The FLUKA Monte Carlo code has been evolving over the last several decades and is now widely used for radiation shielding calculations. In order to facilitate the use of FLUKA in dosimetry and therapy applications, supporting software has been developed to allow the direct conversion of the output files from standard CT-scans directly into a voxel geometry for transport within FLUKA. Since the CT-scan information essentially contains only the electron density information over the scanned volume, one needs the specific compositions for each voxel individually. We present here the results of a simple algorithm to assign tissues in the human body to one of four categories: soft-tissue, hard-bone, trabecular-bone and porous-lung. In addition, we explore the problem of the pathlength distributions in porous media such as trabecular bone. A mechanism will be implemented within FLUKA to allow for variable multipal fixed density materials to accommodate the pathlength distributions discovere

Fine needle diagnosis in lumbar osteomyelitis

Lumbar vertebral body and disk infection, presenting as low back pain, is a relatively uncommon disease but is seen more often in drug addicts. Radiographs show typical changes of infection of the lumbar vertebrae and adjacent disc. Under local anesthesia a fine needle is placed, saline injected, and aspirated. The entire needle-syringe unit is submitted to the bacteriology department. Pseudomonas infection is usually found. This method of diagnosis is simple, cost effective, well accepted by the patients, and can be done on outpatients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46772/1/256_2004_Article_BF00357774.pd

Inhibition of Competence Development, Horizontal Gene Transfer and Virulence in Streptococcus pneumoniae by a Modified Competence Stimulating Peptide

Competence stimulating peptide (CSP) is a 17-amino acid peptide pheromone secreted by Streptococcus pneumoniae. Upon binding of CSP to its membrane-associated receptor kinase ComD, a cascade of signaling events is initiated, leading to activation of the competence regulon by the response regulator ComE. Genes encoding proteins that are involved in DNA uptake and transformation, as well as virulence, are upregulated. Previous studies have shown that disruption of key components in the competence regulon inhibits DNA transformation and attenuates virulence. Thus, synthetic analogues that competitively inhibit CSPs may serve as attractive drugs to control pneumococcal infection and to reduce horizontal gene transfer during infection. We performed amino acid substitutions on conserved amino acid residues of CSP1 in an effort to disable DNA transformation and to attenuate the virulence of S. pneumoniae. One of the mutated peptides, CSP1-E1A, inhibited development of competence in DNA transformation by outcompeting CSP1 in time and concentration-dependent manners. CSP1-E1A reduced the expression of pneumococcal virulence factors choline binding protein D (CbpD) and autolysin A (LytA) in vitro, and significantly reduced mouse mortality after lung infection. Furthermore, CSP1-E1A attenuated the acquisition of an antibiotic resistance gene and a capsule gene in vivo. Finally, we demonstrated that the strategy of using a peptide inhibitor is applicable to other CSP subtype, including CSP2. CSP1-E1A and CSP2-E1A were able to cross inhibit the induction of competence and DNA transformation in pneumococcal strains with incompatible ComD subtypes. These results demonstrate the applicability of generating competitive analogues of CSPs as drugs to control horizontal transfer of antibiotic resistance and virulence genes, and to attenuate virulence during infection by S. pneumoniae