Data-Intensive Modelling and Simulation in Life Sciences and Socio-economical and Physical Sciences

First paragraph: This special issue of the journal Data Science and Engineering is a result of the work fostered by the ICT COST Action IC1406 High-Performance Modelling and Simulation for Big Data Applications (cHiPSet), an EU-funded research network across 30+ European countries and overseas partners (http://chipset-cost.eu/).Output Type: Editoria

Antigena strukturer av betydelse för ett skyddande förvärvat immunsvar mot ekvint infektiöst anemivirus (EIAV) : Antigenic structures involved in development of protective acquired immunity against equine infectious anemia

Denna litteraturstudie undersöker vilka immunogena strukturer som har betydelse för utveckling av ett skyddande förvärvat immunsvar mot ekvint infektiöst anemivirus (EIAV). Ekvin infektiös anemi (EIA) är en virussjukdom som drabbar hästdjur. Den kännetecknas av ett förlopp med periodiska viremier Symtomen som ses i samband med viremi orsakas av proinflammatoriska cytokiner från det medfödda immunsvaret. Värden blir vanligtvis asymtomatisk inom ett år efter infektion, därefter fortsätter individen att vara persistent infekterad under resten av livet. EIAV kan överföras via kanyler eller blodsugande vektorer (bromsar och stallflugor) som intar blod från hästar med viremi. Virus från blodet på insektens mundelar förs ut i cirkulationen när den biter en ny häst. Viruset infekterar och replikerar i makrofager, vilket leder till att vävnader som har rikligt med makrofager har höga virustitrar, även om halterna varierar med infektionsfas och virulens hos virusstammen. Ett cellmedierat förvärvat immunsvar förmodas vara en mycket viktig faktor för att begränsa virusreplikationen under den akuta fasen. Antagandet bygger på att virusspecifika cytotoxiska T- lymfocyter uppkommer mycket tidigt. De eliminerar infekterade celler genom lys, vilket minskar viremin och därmed även de kliniska symtomen. Det här tidiga cellmedierade svaret är riktat mot immunodominanta, variabla höljestrukturer, men specificiteten förändras under infektionens gång. Gradvis riktas specificiteten hos det cellmedierade immunsvaret till immunoressesiva, mindre mutationsbenägna epitoper på virusets hölje och till andra bevarade virala strukturer som Gag-proteinet. Det antikroppsmedierade immunsvaret riktas huvudsakligen mot höljesepitoper. Liksom det cellmedierade immunsvaret, riktas det initialt mot variabla strukturer, för att hos ett moget antikroppssvar vara både bredare och riktat mot mer bevarade strukturer. Neutraliserande antikroppar har påvisats vid olika tidpunkter; från 14 dagar PI till ett par månader efter infektion, och oftast efter att de första icke-neutraliserande antikropparna påvisats. Effekten av tidiga neutraliserande antikroppar är inte fullt förstådd, men troligen är de neutraliserande antikropparna involverade i att understödja det cellmedierade försvaret under den kroniska och subakuta fasen, samt för att upprätthålla kontroll hos asymtomatiska hästar. Adaption av det förvärvade immunsvaret skapar ett selektionstryck i virusets miljö. Hästens immunsvar förmår inte eliminera viruset helt, och mellan virusgenerationer kan stammens kontinuerliga mutationer, producera nya varianter som inte känns igen av befintligt immunsvar. Dessa så kallade escape-mutants privilegieras då av selektionstrycket, och kan replikera i högre grad än andra typer. Det första förvärvade immunsvaret driver en snabb antigendrift genom att vara riktat mot mycket få, variabla epitoper som är sannolika att mutera i högre utsträckning. Ett skyddande immunsvar verkar alltså kräva en bred specificitet mot bevarade virusstrukturer hos både det cellmedierade och antikroppsmedierade immunsvaret.The aim of this study is to account for some of the viral antigenic structures, involved in development of a protective acquired immunity in horses infected with equine infectious anaemia virus (EIAV). Equine infectious anemia (EIA) is a viral disease affecting equids, mainly E. caballus. The disease is characterized by recurrent cycles of viremia, which in turn, triggers innate immunity. Pro-inflammatory cytokines cause the symptoms seen during the acute and recurrent viremia, such as fever, lethargy, anemia, thrombocytopenia and weight-loss. Infected individuals usually recover from clinical EIA within a year post infection, thus the horse remain persistently infected throughout its life. EIAV can be transmitted through injection needles or by bloodfeeding vectors such as horse flies and stable flies. Once introduced to the circulation of a naïve recipient, the virus infects and replicate in tissue macrophages, why the tissues with a richer macrophage population is observed to have the highest virustiters. The tissue viral-burden is seemingly dependent on phase of disease and virulence of the infection strain. The cell-mediated immunity is assumed to be the first line of defense, with an important limiting effect on virus replication, as virus-specific CTLs are detected at the time when acute viremia is terminated. CTL-recognition is early directed towards immunodominant, variable epitopes at two envelope glycoproteins, gp90 and gp45. During the course of infection, the response is gradually redirected towards immunorecessive, less variable regions of gp-90 and gp-45, as well as to more conserved viral structures such as Gag-proteins. Humoral immunity is mainly targeting gp90 and gp-45, and much like the cellmediated response, it will initially recognize immunodominant, highly variable epitopes. Mature humoral immuneresponse, is typically directed towards less variable regions of the SU and TM and also becomes broader, with conformational-dependent recognition. Detection of neutralizing antibody from different studies range between at earliest 14 days PI to 3 months PI, and the contribution of these antibodies to control of early infection is unclear. However they seem important to contribute to control of long-term infection in combination with CTLs. Adaptive immunity creates an environment of selection-pressure upon the virus. During early infection, the target structure is highly specific, and recognition is narrow. Since the horse is unable to completely eliminate the virus, it is likely to select for new mutant-variants, which escape the acquired response during early infection. A mature acquired immune response is harder to escape since it is broadening with every new viral type produced, and directed to regions that allow less mutation for the virus to remain viable and virulent

Polarity Judgments: An empirical view

An electronic poster from "Polarity from Different Perspectives," New York University, 2005. The authors present an experiment that investigated to what extent six negative polarity items (slept a wink, in ages, ever, much, at all, and yet) are licensed by 9 potential licensers

Evaluation of passive transfer, apparent efficiency of absorption and health in dairy calves

Calves are born without preformed antibodies and are dependent on colostrum to acquire passive transfer of immunity from their mother. Failure of passive transfer (FPT) is a contributing factor to increased calf mortality and morbidity, and hence of economic importance to the producer. The level of passive transfer (PT) is associated with future health and productivity even in adult age. Several factors that influence the level of passive transfer in the calf are well studied, especially the importance of colostrum quality. The role of efficiency of absorption in the calf is less well understood. The aim of this study was to determine serum immunoglobulin G (S-IgG) by an enzyme-linked Immunosorbent assay (ELISA) newly established in our lab, estimate apparent efficiency of absorption (AEA) of 803 calves from two Swedish farms and investigate how they affected calf health and FPT. An ELISA protocol was established in our laboratory to determine S-IgG concentration of 700 calves at 2-7 days of age and AEA was calculated. The ELISA S-IgG values were correlated to serum total protein (STP) measured by an optic refractometer (n=224) with r=0.75 (p<0.0001) for Spearman´s rank correlation coefficient. Despite a good correlation, the ELISA was likely to overestimate S-IgG concentration and this probably affected the proportion of FPT. Proportion of FPT was clearly lower than previous study partly using the same samples (De Haan, 2018). The FPT for Lövsta was found to be 9.5% and for Röbäcksdalen 30.4%, compared to previously 16% and 44.7%, respectively. AEA range and mean of the farms were very similar, but there was a greater difference in mean S-IgG between the farms. Mean AEA of calves classified in our study to have FPT was significantly lower than the total average AEA of calves from the same farm. Surprisingly, both mean S-IgG concentration and AEA were significantly lower for healthy calves than unhealthy calves. This comparison included only calves from Lövsta, which had relatively few and mild cases of illness. Röbäcksdalen did not have sufficient data available to be included. Birth weight and amount of IgG fed first meal were not significantly correlated to AEA in this study.Placentan bland hov- och klövdjur tillåter inte passage av stora molekyler så som antikroppar. Kalvar måste därför få det passiva skyddet via råmjölken som är som rikast på antikroppar precis efter kalvning. En fullgod passiv immunitet (PT) hos kalven minskar risken för, och svårighetsgraden hos, eventuella infektioner från omgivningen och har också visat sig ha positiva effekter längre fram i livet med bättre hälsa och kortare tid till första insemination. Det finns därför ett intresse att optimera andelen kalvar med god passiv immunitet då det finns indikationer att det skulle spara lidande vid sjukdom, antimikrobiella behandlingar och ge bättre produktivitet hos djuren. Flera faktorer påverkar graden av passiv immunitet som kalven uppnår. Några av de mer väldokumenterade faktorerna är kvalitet av råmjölken som ges kalven såväl som tid och mängd av första mål råmjölk. Effekten av kalvens egen absorptionsförmåga på den passiva immuniteten är mindre klarlagd. Det främsta målet i den här studien var att anpassa en kvantitativ enzyme-linked immunosorbent assay (ELISA) för att direkt mäta koncentrationen av IgG från kalvserum och tillsammans med tillgänglig data estimera effektiviteten i upptaget per individ, kallat apparent efficiency of absorption (AEA), och relatera till graden av sjukdom och om det finns indikation på samband med graden av Failure of Passive Transfer (FPT). Serumkoncentration av immunoglobulin G (S-IgG) bestämdes i 700 prover från kalvar i åldern två till sju dygn och från två olika gårdar. Ett värde på AEA kunde därefter beräknas där data var komplett. Då flera prover analyserats med optisk refraktometer avseende serum-totalprotein (STP) som en del av en tidigare studie, kunde även korrelationen mellan de olika metoderna uppskattas. Korrelationen var r=0,75 (p<0.0001, för Spearman´s rank korrelationstest). Vid jämförelse över hur analysmetoderna klassificerade fall av FPT, var andelen FPT betydligt lägre vid mätning med ELISA jämfört med optisk refraktometer. Andelen FPT för Lövsta var 9,5 % och 30,4 % för Röbäcksdalen i denna studie jämfört med tidigare studie med delvis samma material 16,0 % and 44,7 %. Detta hör troligtvis ihop med att ELISA visade tendens att överestimera koncentrationen S-IgG. Fördelningen och medelvärde på AEA var mycket lika mellan de olika gårdarna trots att de skiljde sig i medel S-IgG. Kalvar klassificerade som FPT med vår ELISA visade sig ha signifikant lägre genomsnittlig AEA jämfört med kalvar med S-IgG över cutoff på 10g/L. Överraskande visade sig gruppen av kalvar med sjukdom ha signifikant högre AEA och S-IgG än gruppen av sjuka kalvar. Denna jämförelse inkluderade enbart kalvar från Lövsta då kalvar från Röbäcksdalen inte hade tillräckligt med data för att inkluderas. Kalvarna på Lövsta hade under perioden få och milda fall av sjukdom. Analys av korrelation mellan AEA och födelsevikt och AEA och massa IgG given vid första målet visade inget linjärt samband med statistisk signifikans

On low-frequency unsteadiness in swept shock wave–boundary layer interactions

We derive a scaling law for the characteristic frequencies of wall pressure fluctuations in swept shock wave/turbulent boundary layer interactions in the presence of cylindrical symmetry, based on analysis of a direct numerical simulations database. Direct numerical simulations in large domains show evidence of spanwise rippling of the separation line, with typical wavelength proportional to separation bubble size. Pressure disturbances around the separation line are shown to be convected at a phase speed proportional to the cross-flow velocity. This information is leveraged to derive a simple model for low-frequency unsteadiness, which extends previous two-dimensional models (Piponniau et al., J. Fluid Mech., vol. 629, 2009, pp. 87–108), and which correctly predicts growth of the typical frequency with the sweep angle. Inferences regarding the typical frequencies in more general swept shock wave/turbulent boundary layer interactions are also discussed

Aggregative oviposition varies with density in processionary moths-Implications for insect outbreak propensity

In gregarious insects, groups commonly originate from females laying eggs in masses and feeding groups are established as soon as larvae hatch. Some group-living insect species may aggregate beyond the individual parent level, such that offspring from two or more egg masses develop within a common resource. Here we show that aggregative oviposition can vary with population density at oviposition and possibly be an important factor in outbreak dynamics of phytophagous insects. We analysed density data with respect to egg mass aggregation for two species of pine processionary moths, Thaumetopoea pinivora (in Sweden 2005-2019) and T. pityocampa (in Spain 1973-1991). Both species lay their eggs in egg masses and feed in groups. During the study periods, insect population density for both species varied by at least an order of magnitude. The two species showed strikingly similar patterns of egg mass aggregation. Egg masses were overdispersed at high population density, with few trees showing a high load of egg masses. Our data suggest that aggregative oviposition can be important in explaining the previously documented higher propensity for outbreaks in insects laying eggs in clusters, compared with those laying individual eggs

JJ-factors for self-interacting dark matter in 20 dwarf spheroidal galaxies

Dwarf spheroidal galaxies are among the most promising targets for indirect dark matter (DM) searches in $\gamma$-rays. The $\gamma$-ray flux from DM annihilation in a dwarf spheroidal galaxy is proportional to the $J$-factor of the source. The $J$-factor of a dwarf spheroidal galaxy is the line-of-sight integral of the DM mass density squared times $\langle \sigma_{\rm ann} v_{\rm rel} \rangle/(\sigma_{\rm ann} v_{\rm rel})_0$, where $\sigma_{\rm ann} v_{\rm rel}$ is the DM annihilation cross-section times relative velocity $v_{\rm rel}=|{\bf v}_{\rm rel}|$, angle brackets denote average over ${\bf v}_{\rm rel}$, and $(\sigma_{\rm ann} v_{\rm rel})_0$ is the $v_{\rm rel}$-independent part of $\sigma_{\rm ann} v_{\rm rel}$. If $\sigma_{\rm ann} v_{\rm rel}$ is constant in $v_{\rm rel}$, $J$-factors only depend on the DM space distribution in the source. However, if $\sigma_{\rm ann} v_{\rm rel}$ varies with $v_{\rm rel}$, as in the presence of DM self-interactions, $J$-factors also depend on the DM velocity distribution, and on the strength and range of the DM self-interaction. Models for self-interacting DM are increasingly important in the study of the small scale clustering of DM, and are compatible with current cosmological observations. Here we derive the $J$-factor of 20 dwarf spheroidal galaxies from stellar kinematic data under the assumption of Yukawa DM self-interactions. $J$-factors are derived through a profile Likelihood approach, assuming either NFW or cored DM profiles. We also compare our results with $J$-factors derived assuming the same velocity for all DM particles in the target galaxy. We find that this common approximation overestimates the $J$-factors by up to one order of magnitude. $J$-factors for a sample of DM particle masses, self-interaction coupling constants and density profiles are provided electronically, ready to be used in other projects.Comment: 10 pages, 3 figures and 2 table

Proteolytic Processing of OPA1 Links Mitochondrial Dysfunction to Alterations in Mitochondrial Morphology

Many muscular and neurological disorders are associated with mitochondrial dysfunction and are often accompanied by changes in mitochondrial morphology. Mutations in the gene encoding OPA1, a protein required for fusion of mitochondria, are associated with hereditary autosomal dominant optic atrophy type I. Here we show that mitochondrial fragmentation correlates with processing of large isoforms of OPA1 in cybrid cells from a patient with myoclonus epilepsy and ragged-red fibers syndrome and in mouse embryonic fibroblasts harboring an error-prone mitochondrial mtDNA polymerase {gamma}. Furthermore, processed OPA1 was observed in heart tissue derived from heart-specific TFAM knock-out mice suffering from mitochondrial cardiomyopathy and in skeletal muscles from patients suffering from mitochondrial myopathies such as myopathy encephalopathy lactic acidosis and stroke-like episodes. Dissipation of the mitochondrial membrane potential leads to fast induction of proteolytic processing of OPA1 and concomitant fragmentation of mitochondria. Recovery of mitochondrial fusion depended on protein synthesis and was accompanied by resynthesis of large isoforms of OPA1. Fragmentation of mitochondria was prevented by overexpressing OPA1. Taken together, our data indicate that proteolytic processing of OPA1 has a key role in inducing fragmentation of energetically compromised mitochondria. We present the hypothesis that this pathway regulates mitochondrial morphology and serves as an early response to prevent fusion of dysfunctional mitochondria with the functional mitochondrial network

Oxidation of Fe-2.25Cr-1Mo in presence of KCl(s) at 400 \ub0C – Crack formation and its influence on oxidation kinetics

Accelerated corrosion of boiler equipment remains a challenge for efficiently utilising biomass- and waste for power production. To overcome this challenge a better understanding of the influence of corrosive species present is required. This study focuses on the influence of KCl(s) on corrosion of Fe-2.25Cr-1Mo at 400 \ub0C. This is done by well-controlled laboratory exposures and detailed microstructural investigation with ion and electron microscopy (TEM, FIB, SEM, EDX, XRD, TKD). The scale microstructures are linked to oxidation kinetics. The results indicate that KCl(s) increases the ionic diffusion through the oxide scale as well as introduces cracks and delamination resulting in a rapid periodic growth process

Predictors of fear of childbirth and depressive symptoms among pregnant women: a cross-sectional survey in Pwani region, Tanzania

Background: Many women experience fear of childbirth (FoB) and depressive symptoms (DS) during pregnancy, but little is known about FoB among Tanzanian women. The current study aimed to assess the prevalence of FoB and DS among pregnant women and determine predictors of each and both, focusing on sociodemographic and obstetric predictors. Methods: A cross-sectional study was conducted at six health facilities in two districts in Tanzania between 2018 and 2019. In total, 694 pregnant women with gestational age between 32 and 40weeks and expecting vaginal delivery were consecutively recruited and assessed for FoB and DS. We collected data through interviews using 6 and 4-points Likert Scale of the Wijma Delivery Expectancy Questionnaire Version A and Edinburgh Postnatal Depression Scale, respectively. Women who scored ≥66 and≥10 were categorised as having FoB and DS, respectively. We performed multivariable logistic regression to investigate the predictors of FoB and DS. Results: The prevalence rates of FoB and DS among pregnant women were 15.1 and 17.7%, respectively. FoB and DS were more likely in women aged above 30 years [Adjusted Odds Ratio (AOR) 6.29, 95%CI 1.43–27.84] and in single mothers (AOR 2.57, 95%CI 1.14–5.78). Women with secondary education and above (AOR 0.22, 95%CI 0.05–0.99) and those who had given birth previously (AOR 0.27, 95% CI 0.09–0.87) were less likely to have FoB in combination with DS Women who had previous obstetric complications, and those who did not receive any social support from male partners in previous childbirth were more likely to have FoB and DS. FoB was strongly associated with DS (AOR 3.42, 95%CI 2.12–5.53). DS only was more common in women who had inadequate income (AOR 2.35, 95%CI 1.38–3.99) or had previously experienced a perineal tear (AOR 2.32, 95%CI 1.31–4.08). Conclusions: Not having a formal education, having only primary education, being aged above 30 years, being single, being nulliparous, having experienced obstetric complications, and having a lack of social support from a male partner during previous pregnancy and childbirth were predictors of FoB and DS during pregnancy. FoB and DS were strongly associated with each other. It is vital to identify at-risk women early, to ofer support during pregnancy and childbirth