Eulerian CFD modeling of nozzle geometry effects on ECN Sprays A and D: assessment and analysis

This is the author's version of a work that was accepted for publication in International Journal of Engine Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published as https://doi.org/10.1177/1468087419882500.[EN] Diesel spray modeling is a multi-scale problem with complex interactions between different flow regions, that is, internal nozzle flow, near-nozzle region and developed spray, including evaporation and combustion. There are several modeling approaches that have proven particularly useful for some spray regions although they have struggled at other areas, while Eulerian modeling has shown promise in dealing with all characteristics at a reasonable computational effort for engineering calculations. In this work, the sigma -Y single-fluid diffuse-interface model, based on scale separation assumptions at high Reynolds and Weber numbers, is used to simulate the engine combustion network Sprays A and D within a Reynolds-averaged Navier-Stokes turbulence modeling approach. The study is divided into two parts. First of all, the larger diameter Spray D is modeled from the nozzle flow till evaporative spray conditions, obtaining successful prediction of numerous spray metrics, paying special attention to the near-nozzle region where spray dispersion and interfacial surface area can be validated against measurements conducted at the Advanced Photon Source at Argonne National Laboratory, including both the ultra-small-angle X-ray scattering and the X-ray radiography. Afterwards, an analysis of the modeling predictions is made in comparison with previous results obtained for Spray A, considering the nozzle geometry effects in the modeling behavior.The authors thank the freely shared X-ray radiography and ultra-small-angle X-ray scattering measurements performed at Argonne National Laboratory by the following authors: Daniel J. Duke, Jan Ilavsky, Katarzyna E. Matusik., Brandon A. Sforzo., Alan L. Kastengren and Christopher F. Powell. They also thankfully acknowledge the computer resources at Picasso and the technical support provided by Universidad de Malaga (UMA; RES-FI-2018-1-0039).Pandal, A.; García-Oliver, JM.; Pastor Enguídanos, JM. (2020). Eulerian CFD modeling of nozzle geometry effects on ECN Sprays A and D: assessment and analysis. International Journal of Engine Research. 21(1):73-88. https://doi.org/10.1177/1468087419882500S7388211PAYRI, R., GARCIA, J., SALVADOR, F., & GIMENO, J. (2005). 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Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Factors Associated with Participation in a Multidomain Web-Based Dementia Prevention Trial: Evidence from Maintain Your Brain (MYB)

Background: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. Objective: To describe characteristics associated with participation in MYB. Methods: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55-77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. Results: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70-5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11-0.32). A family history of Alzheimer's disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. Conclusion: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation

Autoantibodies to αS1-Casein Are Induced by Breast-Feeding

BACKGROUND: The generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human αS1-casein (CSN1S1) was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood. METHODS: 62 sera of healthy adult individuals who were (n = 37) or were not (n = 25) breast-fed against human CSN1S1 were investigated by a new SD (surface display)-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV) antibodies by a commercial ELISA. RESULTS: IgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SD-ELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum), but exhibited significant serum reaction against human CSN1S1 nonetheless. CONCLUSION: We postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood

A comparison of clinical outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India

The problem considered: This multi-centric study analyzed data of COVID-19 patients and compared differences in symptomatology, management, and outcomes between vaccinated and vaccine-naive patients. Methods: All COVID-19 positive individuals treated as an in-or out-patient from the 1stMarch to 15th May 2021 in four selected study sites were considered for the study. Treatment details, symptoms, and clinical course were obtained from hospital records. Chi-square was used to test the association of socio-demographic and treatment variables with the vaccination status and binary logistic regression were used to obtain the odds ratio with a 95% confidence interval. Results: The analysis was of 1446 patients after exclusion of 156 with missing data of which males were 57.3% and females 42.7%. 346 were vaccinated; 189 received one dose and 157 both doses. Hospitalization was more in vaccinated (38.2% vs 27.4%); ICU admissions were less in vaccinated (3.5% vs 7.1%). More vaccinated were symptomatic (OR = 1.5); half less likely to be on non-invasive ventilation (OR = 0.5) while vaccine naive patients had 4.21 times the risk of death. Conclusion: Severe infection, duration of hospital stays, need for ventilation and death were significantly less among vaccinated when compared with vaccine naive patients

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors