Hadron production in deep inelastic lepton-nucleus scattering

Predictions for semi-inclusive deep inelastic lepton-nucleus scattering are presented. Both the effects of gluon radiation by the struck quark and the absorption of the produced hadron are considered. The gluon radiation covers a larger window in virtuality $Q^2$ because of the increased deconfinement of quarks inside nuclei. The absorption of hadrons formed inside the nucleus is described with a flavor dependent cross section. Calculations for rescaled fragmentation functions and nuclear absorption are compared with the EMC and HERMES data for N, Cu and Kr targets with respect to the deuteron target. Predictions for Ne and Xe targets in the HERMES kinematic regime are given.Comment: 27 pages, 12 figures. Section 2 on rescaling modified. Extended discussion of the results in Sec. 5 and 6. To be published in Nucl.Phys.

Equity in development and access to health services in the Wild Coast of South Africa: the community view through four linked cross-sectional studies between 1997 and 2007

<p>Abstract</p> <p>Background</p> <p>After election in 1994, the South African government implemented national and regional programmes, such as the Wild Coast Spatial Development Initiative (SDI), to provoke economic growth and to decrease inequities. CIET measured development in the Wild Coast region across four linked cross-sectional surveys (1997-2007). The 2007 survey was an opportunity to look at inequities since the original 1997 baseline, and how such inequities affect access to health care.</p> <p>Methods</p> <p>The 2000, 2004 and 2007 follow-up surveys revisited the communities of the 1997 baseline. Household-level multivariate analysis looked at development indicators and access to health in the context of inequities such as household crowding, access to protected sources of water, house roof construction, main food item purchased, and perception of community empowerment. Individual multivariate models accounted for age, sex, education and income earning opportunities.</p> <p>Results</p> <p>Overall access to protected sources of water increased since the baseline (from 20% in 1997 to 50% in 2007), yet households made of mud and grass, and households who bought basics as their main food item were still less likely to have protected sources of water. The most vulnerable, such as those with less education and less water and food security, were also less likely to have worked for wages leaving them with little chance of improving their standard of living (less education OR 0.59, 95%CI 0.37-0.94; less water security OR 0.67, 95%CI 0.48-0.93; less food security OR 0.43, 95%CI 0.29-0.64). People with less income were more likely to visit government services (among men OR 0.28, 95%CI 0.13-0.59; among women OR 0.33, 95%CI 0.20-0.54), reporting decision factors of cost and distance; users of private clinics sought out better service and medication. Lower food security and poorer house construction was also associated with women visiting government rather than private health services. Women with some formal education were nearly eight times more likely than women with no education to access health services for prevention rather than curative reasons (OR 7.65, 95%CI 4.10-14.25).</p> <p>Conclusion</p> <p>While there have been some improvements, the Wild Coast region still falls well below provincial and national standards in key areas such as access to clean water and employment despite years of government-led investment. Inequities remain prominent, particularly around access to health services.</p

Radial fast-neutron fluence gradients during rotating 40Ar/39Ar sample irradiation recorded with metallic fluence monitors and geological age standards

Characterizing the neutron-irradiation parameter J is one of the major uncertainties in 40Ar/39Ar dating. The associated uncertainty of the individual J-value for a sample of unknown age depends on the accuracy of the age of the geological standards, the fast-neutron fluence distribution in the reactor, and the distances between standards and samples during irradiation. While it is generally assumed that rotating irradiation evens out radial neutron fluence gradients, we observed axial and radial variations of the J-values in sample irradiations in the rotating channels of two reactors. To quantify them, we included three-dimensionally distributed metallic fast- (Ni) and thermal- (Co) neutron fluence monitors in three irradiations and geological age standards in three more. Two irradiations were carried out under Cd shielding in the FRG1 reactor in Geesthacht, Germany, and four without Cd shielding in the LVR-15 reactor in Rez, Czech Republic. The 58Ni(nf,p)58Co activation reaction and gamma-spectrometry of the 811 keV peak associated with the subsequent decay of 58Co to 58Fe allow one to calculate the fast-neutron fluence. The fast-neutron fluences at known positions in the irradiation container correlate with the J-values determined by mass spectrometric 40Ar/39Ar measurements of the geological age standards. Radial neutron fluence gradients are up to 1.8 %/cm in FRG1 and up to 2.2 %/cm in LVR-15; the corresponding axial gradients are up to 5.9 and 2.1 %/cm. We conclude that sample rotation might not always suffice to meet the needs of high precision dating and gradient monitoring can be crucial

Does personality affect premating isolation between locally-adapted populations?

Background: One aspect of premating isolation between diverging, locally-adapted population pairs is female mate choice for resident over alien male phenotypes. Mating preferences often show considerable individual variation, and whether or not certain individuals are more likely to contribute to population interbreeding remains to be studied. In the Poecilia mexicana-species complex different ecotypes have adapted to hydrogen sulfide (H2S)-toxic springs, and females from adjacent non-sulfidic habitats prefer resident over sulfide-adapted males. We asked if consistent individual differences in behavioral tendencies (animal personality) predict the strength and direction of the mate choice component of premating isolation in this system. Results: We characterized focal females for their personality and found behavioral measures of ‘novel object exploration’, ‘boldness’ and ‘activity in an unknown area’ to be highly repeatable. Furthermore, the interaction term between our measures of exploration and boldness affected focal females’ strength of preference (SOP) for the resident male phenotype in dichotomous association preference tests. High exploration tendencies were coupled with stronger SOPs for resident over alien mating partners in bold, but not shy, females. Shy and/or little explorative females had an increased likelihood of preferring the non-resident phenotype and thus, are more likely to contribute to rare population hybridization. When we offered large vs. small conspecific stimulus males instead, less explorative females showed stronger preferences for large male body size. However, this effect disappeared when the size difference between the stimulus males was small. Conclusions: Our results suggest that personality affects female mate choice in a very nuanced fashion. Hence, population differences in the distribution of personality types could be facilitating or impeding reproductive isolation between diverging populations depending on the study system and the male trait(s) upon which females base their mating decisions, respectively

New Insights into Autoinducer-2 Signaling as a Virulence Regulator in a Mouse Model of Pneumonic Plague

ABSTRACT The Enterobacteriaceae family members, including the infamous Yersinia pestis, the causative agent of plague, have a highly conserved interbacterial signaling system that is mediated by the autoinducer-2 (AI-2) quorum-sensing molecule. The AI-2 system is implicated in regulating various bacterial virulence genes in diverse environmental niches. Deletion of the gene encoding the synthetic enzyme for the AI-2 substrate, luxS, leads to either no significant change or, paradoxically, an increase in in vivo bacterial virulence. We showed that deletion of the rbsA and lsrA genes, components of ABC transport systems that interact with AI-2, synergistically disrupted AI-2 signaling patterns and resulted in a more-than-50-fold decrease in Y. pestis strain CO92 virulence in a stringent pneumonic plague mouse model. Deletion of luxS or lsrK (encoding AI-2 kinase) from the ΔrbsA ΔlsrA background strain or complementation of the ΔrbsA ΔlsrA mutant with the corresponding gene(s) reverted the virulence phenotype to that of the wild-type Y. pestis CO92. Furthermore, the administration of synthetic AI-2 in mice infected with the ΔrbsA ΔlsrA ΔluxS mutant strain attenuated this triple mutant to a virulence phenotype similar to that of the ΔrbsA ΔlsrA strain in a pneumonic plague model. Conversely, the administration of AI-2 to mice infected with the ΔrbsA ΔlsrA ΔluxS ΔlsrK mutant did not rescue animals from lethality, indicating the importance of the AI-2–LsrK axis in regulating bacterial virulence. By performing high-throughput RNA sequencing, the potential role of some AI-2-signaling-regulated genes that modulated bacterial virulence was determined. We anticipate that the characterization of AI-2 signaling in Y. pestis will lead to reexamination of AI-2 systems in other pathogens and that AI-2 signaling may represent a broad-spectrum therapeutic target to combat antibiotic-resistant bacteria, which represent a global crisis of the 21st century. IMPORTANCE Yersinia pestis is the bacterial agent that causes the highly fatal disease plague. The organism represents a significant concern because of its potential use as a bioterror agent, beyond the several thousand naturally occurring human infection cases occurring globally each year. While there has been development of effective antibiotics, the narrow therapeutic window and challenges posed by the existence of antibiotic-resistant strains represent serious concerns. We sought to identify novel virulence factors that could potentially be incorporated into an attenuated vaccine platform or be targeted by novel therapeutics. We show here that a highly conserved quorum-sensing system, autoinducer-2, significantly affected the virulence of Y. pestis in a mouse model of pneumonic plague. We also identified steps in autoinducer-2 signaling which had confounded previous studies and demonstrated the potential for intervention in the virulence mechanism(s) of autoinducer-2. Our findings may have an impact on bacterial pathogenesis research in many other organisms and could result in identifying potential broad-spectrum therapeutic targets to combat antibiotic-resistant bacteria, which represent a global crisis of the 21st century

New Host-Directed Therapeutics for the Treatment of Clostridioides difficile Infection

Clostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile. Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile. However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils

Protective immunity elicited by oral immunization of mice with Salmonella enterica serovar Typhimurium Braun lipoprotein (Lpp) and acetyltransferase (MsbB) mutants

We evaluated the extent of attenuation and immunogenicity of the ∆lppAB and ∆lppAB ∆msbB mutants of Salmonella enterica serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and triggered robust innate and adaptive immune responses. Comparable levels of IgG and its isotypes were produced in mice infected with wild-type (WT) S. Typhimurium or its aforementioned mutant strains. The ∆lppAB ∆msbB mutant-immunized animals resulted in the production of higher levels of fecal IgA and serum cytokines during later stages of vaccination (adaptive response). A significant production of interleukin-6 from T-cells was also noted in the ∆lppAB ∆msbB mutant-immunized mice when compared to that of the ∆lppAB mutant. On the other hand, IL-17A production was significantly more in the serum of ∆lppAB mutant-immunized mice (innate response) with a stronger splenic T-cell proliferative and tumor-necrosis factor-α production. Based on 2-dimensional gel analysis, alterations in the levels of several proteins were observed in both the mutant strains when compared to that in WT S. Typhimurium and could be associated with the higher immunogenicity of the mutants. Finally, both ∆lppAB and ∆lppAB ∆msbB mutants provided complete protection to immunized mice against a lethal oral challenge dose of WT S. Typhimurium. Thus, these mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens