Modelling a silent epidemic:A review of the in vitro models of latent tuberculosis

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance

Renewable energy scenario and environmental aspects of soil emission measurements

European Commission has set clear targets for 2020 regarding energy and environment policy; these targets include 20% cut in greenhouse gas emissions against the 1990 levels. It is believed that adopted strategy has encouraged the renewable energy applications during the last two decades. Moreover, measurement deviations of carbon dioxide flux occurring in respiration chambers has been seen of a great importance to explain the biochemical parameters affecting the climate change issue. This is attributed on many occasions to chamber design constraints and the way they are coupled with the studied site location. This is illustrated by external disturbances whereby when they happen while gas measurements are taken measurement deviations become more evident. This paper surveys the different soil physical, biological and geotechnical parameters and links them to meteorological ones. Consequently it explores their direct and indirect effects to the produced soil efflux. Furthermore this paper proposes several soil temperature models according to the studied case constraints to see what affects soil efflux production. Moreover a clear understanding of what affects the measurement process was achieved through surveying all the internal and external pressure parameters and how they influence the chamber in relation to time. The conclusion is that respiration chamber designers need to preserve chamber internal temperature and pressure to be equal to the outer atmosphere for the case of stabile external conditions. For the case of unstable external conditions design counter measures are incorporated. Furthermore the appropriate gas sensor needs to be selected professionally with emphasis on the importance of installation location inside the chamber. Likewise soil bacterial type and soil temperature also has an influence on efflux production

Prediction of the gas emission from porous media with the concern of energy and environment

Measuring soil carbon dioxide efflux is a challenging task even when it is performed using respiration chambers. While gas samples are taken, measurement deviations become more evident according to the used chamber design especially when external disturbances occur. This paper studies the carbon dioxide concentration profiles within the top soil layers, and investigates the controlling factors affecting the process. The considered factors are diffusion, temperature and viscosity. The efflux equation is discussed and then it is linked with the soils geotechnical parameters, while a relationship between the Reynolds number within the soil and efflux is found. Emphasis on the importance of the external geometrical design considerations is shown through studying external boundary layer effects due to the chamber outer shell shape and how it interacts with blowing winds. Chamber stability on site of deployment is also of a significant importance considering external blowing winds. Internal geometrical considerations are linked with the flow turbulence within the dynamic chambers. It is highly recommended that respiration chamber designers need to work in parallel with a multidisciplinary team in order to make a chamber design that ensures the least disturbance to occur at the location of study

A numerical and experimental study of a new design of closed dynamic respiration chamber

Carbon dioxide soil efflux modelling in closed dynamic respiration chambers is a challenging task. This is attributed on many occasions to the very small concentrations of carbon dioxide being transported between soil and the atmosphere. This paper describes a portable device which was made exclusively to accurately measure carbon dioxide efflux from soil locations. The blowing fan creates a forced convective flow to occur in the chamber making the K-Epsilon turbulence model a necessity to model the occurring flow in the respiration chamber gas domain. Furthermore the Darcy model is applied on the porous domain to model the flow pattern within the soil. The measurement process was achieved through measuring carbon dioxide concentration, temperature and relative humidity inside the chamber in relation to time. Simulation and experimental data is obtained using ANSYS and MATLAB. A significant agreement between the experimental and numerical results was achieved

Time-Varying Dark Energy Constraints From the Latest SN Ia, BAO and SGL

Based on the latest SNe Ia data provided by Hicken et al. (2009) with using MLCS17 light curve fitter, together with the Baryon Acoustic Oscillation(BAO) and strong gravitational lenses(SGL), we investigate the constraints on the dark energy equation-of-state parameter $w$ in the flat universe, especially for the time-varying case $w(z)=w_0+w_zz/(1+z)$. The constraints from SNe data alone are found to be: (a) $(\Omega_M, w)=(0.358, -1.09)$ as the best-fit results; (b) $(w_0, w_z)=(-0.73^{+0.23}_{-0.97}, 0.84^{+1.66}_{-10.34})$ for the two parameters in the time-varying case after marginalizing the parameter $\Omega_M$; (c) the likelihood of parameter $w_z$ has a high non-Gaussian distribution; (d) an extra restriction on $\Omega_M$ is necessary to improve the constraint of the SNe Ia data on the parameters ($w_0$, $w_z$). A joint analysis of SNe Ia data and BAO is made to break the degeneracy between $w$ and $\Omega_M$, and leads to the interesting maximum likelihoods $w_0 = -0.94$ and $w_z = 0$. When marginalizing the parameter $\Omega_M$, the fitting results are found to be $(w_0, w_z)=(-0.95^{+0.45}_{-0.18}, 0.41^{+0.79}_{-0.96})$. After adding the splitting angle statistic of SGL data, a consistent constraint is obtained $(\Omega_M, w)=(0.298, -0.907)$ and the constraints on time-varying dark energy are further improved to be $(w_0, w_z) = (-0.92^{+0.14}_{-0.10}, 0.35^{+0.47}_{-0.54})$, which indicates that the phantom type models are disfavored.Comment: 24 pages, 9 figures, to be published in JCA

Common and low frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

5-HT₄ Receptor Agonist Effects on Functional Connectivity in the Human Brain:Implications for Procognitive Action

Background: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown.Methods: We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design.Results: Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions.Conclusions: Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations

Stress-Strain Response Modelling of Glass Fibre Reinforced Epoxy Composite Pipes under Multiaxial Loadings

This paper presents the modelling of the stress strain response of glass fiber reinforced epoxy (GRE) composite pipes subjected to multiaxial loadings at room temperature (RT). This particular modeling work was developed to predict the non-linear stress strain response caused by the fatigue cyclic and static loading in the multiaxial ultimate elastic wall stress (UEWS) tests by considering the effects of matrix cracking within the laminates. The UEWS test, whilst not yet standardized, appears to offer an attractive alternative to existing procedures of qualifying GRE pipes. The ply properties initially expressed as a function of crack density were computed as a function of increasing stress and strain using shear lag approximation. The results show that the model developed from the classical laminate theory which takes into account whether the effects of transverse matrix micro-cracks on stiffness and strains is capable of predicting the resulted elastic properties. The predictions are found to be in good agreement with the data from multiaxial UEWS tests on ±55° filament wound glass-reinforced epoxy pipes

Antiturcica Iterata – another Look at Croatian anti-Turkish Writings during the Renaissance

Otpor »Turcima«, održavanje granice prema Osmanskome Carstvu, jedna je od dominantnih tema u ranonovovjekovnoj Hrvatskoj. Sukladno tome, »turska tema« prisutna je i u književnosti. Problematizirana je u velikom vremenskom rasponu, na različitim jezicima, u različitim žanrovima, s različitim intencijama. Važnu podskupinu tekstova ove tematike – izravne i neizravne pozive na otpor osmanskim napadima i osvajanjima u razdoblju 1436-1600 – ovdje smo pokušali popisati što potpunije i što konzistentnije. Uvodno dajemo pregled istraživanja i interpretacija hrvatskoga protuturskog korpusa od 1945. do 2014. Potom upozoravamo na probleme vezane uz konstituiranje korpusa i iznosimo načela po kojima smo korpus uspostavili. Zatim opisujemo korpus prema očuvanosti popisanih tekstova, prema pisanom mediju u kojem su prenošeni (rukopisi ili tiskovine), prema jeziku (latinski, hrvatski, talijanski), načinu izražavanja (proza, poezija), književnim vrstama, kronologiji (upozoravamo i na diskontinuitete, na godine kad se javlja manje protuturskih tekstova), te prema prostorima koji su u tekstovima posebno isticani. Razmatramo i autore, prema broju tekstova, prema porijeklu i društvenom statusu. Naposljetku skiciramo sinoptičku interpretaciju korpusa, posebnu pozornost poklanjajući tekstovima koji se pojavljuju istodobno ili su vremenski bliski. Bibliografska skica hrvatskog protuturskog korpusa prilog je radu, a dostupna je i kao baza podataka na internetu.In the 15th and 16th centuries, Croatian writing about the Ottoman threat was both a reaction to the continuous crisis of several states, their societies, and culture, and an attempt to overcome this crisis by developing new ideas and new ways of consolidating the society. It has been claimed that this desperate attempt laid the foundations of modern Croatia. To be able to identify continuities and discontinuities of the so-called Croatian anti-Turkish writings, we have compiled a list of as many such works as possible. In Croatian literary history, the anti-Turkish writings seem to have first been presented as a group by Mihovil Kombol in 1945. In 1974, Marin Franičević tried to consider together texts from this group written in different languages (Latin and Croatian). In 1983, Vedran Gligo selected and published a canonical collection of sixteen (Latin) »anti-Turkish speeches« from the Renaissance. At the same time, Tomislav Raukar interpreted the anti-Turkish theme as a stimulus to Early Modern Croatia. In 2004, Davor Dukić proposed an imagological interpretation of the anti-Turkish corpus. All researchers, however, worked with a restricted number of texts, and there was not even an estimate of the actual size of the corpus. To construe a corpus with some pretence to comprehensiveness, we had to establish whether (and to what degree) a text addresses the anti-Turkish theme, whether it could be considered a »Croatian« text, whether it could be considered a literary and a public as opposed to a documentary or a private text). Such considerations led us to exclude some famous texts (such as Judita by Marko Marulić),while including e. g. an Oratio contra Turcam which Ivan Pergošić reprinted from the book by Johannes Avenarius. The fuzzy boundaries between confidentiality and publicity have been demonstrated by the fate of reports by the papal nuntio Antonius Fabregues, whose official dispatches about the Battle of Krbava field have appeared also in print as propagandistic broadsheets. In our corpus, a Croatian anti-Turkish work is a text urging Christian action against the Turks in defence of Dalmatia, Croatia, Hungary, and Christian Europe as a whole, written by an author significantly connected with Croatia, and calling to arms either by direct appeals or by a more indirect strategy of reporting, celebrating and lamenting events in the Christian-Turkish struggle. The corpus currently comprises basic bibliographic data on 141 texts written between 1436 and 1600. It exists as a list (see the Appendix to the article) and as a database published by the TeMrežaH project (temrezah.ffzg.unizg.hr/antiturcica-biblio.html). We have included data on a few texts that are not preserved, and on texts by unknown authors. Ninety-four texts first appeared as manuscripts, 44 in print (two exist in roughly contemporaneous handwritten and printed versions). Two texts (poems in Croatian from 1565 and 1596) were first printed almost a hundred years after the events they describe (in 1655). One hundred and four texts are in Latin, 26 in Croatian, nine in Italian; 75 texts are in prose, 66 in verse. An especially active period of production falls in 1493-1548 (when three fifths of all texts in the corpus were written). There are three longer periods of silence, when just a few anti-Turkish texts appear: the years 1504-1509, 1546-1560, 1575-1591. Christian Europe is the central topic in 46 texts, the Kingdom of Hungary in 31, Croatia itself in 20, Dalmatia (and Dubrovnik) in 20, the Levant in 15, the Venetian Republic in 11; this distribution follows the geopolitical situation of Croatian regions during the Renaissance, but Croatia and Dalmatia are treated in about the same number of texts, while the Kingdom of Hungary was thematised significantly more often than Venice. The texts were written by 61 authors (seven are anonymous), 40 of which wrote just one text; fourteen are known as authors only because of their anti-Turkish works. The five authors with most anti-Turkish texts are Fran Trankvil Andreis, Damjan Beneša, Marko Marulić, Ludovik Paskalić, Ivan Vitez od Sredne. Beneša and Paskalić were absent from the Croatian »canon« of anti-Turkish authors. Four of the authors are not Croatian by birth (Tideo Acciarini, Antonio Fabregues, Francesco Marcello, Bernard Zane), but they were all connected to Dalmatia by office, as teachers, diplomats or Church officials. Most of the authors can be regarded as humanists (17) or priests (24, or 34 including priests serving as diplomats); there were 15 diplomats, five of them lay persons. The authors whose anti-Turkish writings appear during the longest chronological span are Fran Trankvil Andreis from Trogir (53 years), Mavro Vetranović from Dubrovnik (writing in Croatian over 45 years), and Frano Božićević Natalis from Split (35 years). A chronological analysis also reveals two main generations of anti-Turkish writers. The first one was active during 1500-1535, and the second during 1520-1570. Among the authors those from Dalmatia and Dubrovnik prevail; they belong mostly to the civic patriciate, to the lesser nobility, or even to the general citizenry. A synoptic analysis of dates, genres, authors and contexts suggests a discontinuity in the corpus of Croatian anti-Turkish writings: some time after 1530-1540 public speeches and appeals disappear, to be replaced by administrative reports to the authorities of the Habsburg empire, by sensational testimonies about travels or battles, and by highly individual »grassroots« entreaties, often, seemingly, without significant political support, often without the benefit of print or of larger print runs. The discontinuity may be connected with the agony of the Kingdom of Hungary and Croatia (after the Battle of Mohács), and with the gradual disappearance of the generation of Croatian humanists that had tried to play significant roles in this kingdom

Breeding systems of floral colour forms in the Drosera cistiflora species complex

The study was supported by the National Research Foundation of South Africa (Grant 46372 to SDJ).Variation in plant breeding systems has implications for pollinator‐mediated selection on floral traits and the ecology of populations. Here we evaluate pollinator contribution to seed production, self‐compatibility and pollen limitation in different floral colour forms of Drosera cistiflora sensu lato (Droseraceae). These insectivorous perennial plants are endemic to fynbos and renosterveld vegetation in the Cape Floristic Region of South Africa, and the species complex includes five floral colour forms (pink, purple, red, white and yellow), some of which are known to be pollinated by beetles. Controlled hand‐pollination experiments were conducted in 15 populations of D. cistiflora s.l. (two to four populations per floral colour form) to test whether the colour forms vary in their degree of self‐compatibility and their ability to produce seeds through autonomous self‐fertilization. Yellow‐flowered forms were highly self‐incompatible, while other floral colour forms exhibited partial self‐compatibility. Seed set resulting from autonomous selfing was very low, and pollinator dependence indices were high in all populations. Since hand cross‐pollination resulted in greater seed set than open pollination in 13 of the 15 populations, we inferred that seed production is generally pollen‐limited.Drosera cistiflora s.l. typically exhibits high levels of pollinator dependence and pollen limitation. This is unusual among Drosera species worldwide and suggests that pollinators are likely to mediate strong selection on attractive traits such as floral colour and size in D. cistiflora s.l. These results also suggest that the floral colour forms of D. cistiflora s.l. which are rare and threatened are likely to be vulnerable to local extinction if mutualisms were to collapse indefinitely.PostprintPeer reviewe