Systems analysis of host-parasite interactions.

Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies

Migrating to Cloud-Native Architectures Using Microservices: An Experience Report

Migration to the cloud has been a popular topic in industry and academia in recent years. Despite many benefits that the cloud presents, such as high availability and scalability, most of the on-premise application architectures are not ready to fully exploit the benefits of this environment, and adapting them to this environment is a non-trivial task. Microservices have appeared recently as novel architectural styles that are native to the cloud. These cloud-native architectures can facilitate migrating on-premise architectures to fully benefit from the cloud environments because non-functional attributes, like scalability, are inherent in this style. The existing approaches on cloud migration does not mostly consider cloud-native architectures as their first-class citizens. As a result, the final product may not meet its primary drivers for migration. In this paper, we intend to report our experience and lessons learned in an ongoing project on migrating a monolithic on-premise software architecture to microservices. We concluded that microservices is not a one-fit-all solution as it introduces new complexities to the system, and many factors, such as distribution complexities, should be considered before adopting this style. However, if adopted in a context that needs high flexibility in terms of scalability and availability, it can deliver its promised benefits

The long-wave potential-vorticity dynamics of coastal fronts

This paper studies the propagation of free, long waves on a potential vorticity front in the presence of a vertical coast, using a -layer, quasi-geostrophic model with piecewise-constant potential vorticity. The coastal boundary induces flow through image vorticity and a Kelvin wave, either of which can reinforce or oppose the Rossby wave dynamics at the front. The behaviour of the front depends strongly on the relative strengths of these three mechanisms, which are explicit in our model. The richest behaviour, which includes kink solitons (under-compressive shocks) and compound-wave structures, occurs in the regime where vortical effects are dominant. The evolution of the front is described by a fully nonlinear finite-amplitude equation including first-order dispersive effects, which is related to the modified Korteweg–de Vries equation. The different behaviours are classified using the canonical example of the Riemann problem, which we analyse using El’s technique of ‘dispersive shock-fitting’. Contour-dynamic simulations show that the dispersive long-wave theory captures the behaviour of the full quasi-geostrophic system to a high degree of accuracy

Hydraulic control of continental shelf waves

This paper studies the hydraulic control of continental shelf waves using an inviscid barotropic quasi-geostrophic model with piecewise-constant potential vorticity, in which the shelf is represented by a flat step of variable width. A coastal-intensified geostrophic current generates topographic Rossby waves, which can become critical at a local decrease in shelf width when the background current opposes Rossby wave propagation. That is, the shelfbreak perturbation permanently modifies the flow field over arbitrarily large distances and the flow transitions from subcritical to supercritical as it crosses the perturbation. Critically controlled flows also lead to the exchange of significant volumes of water between the shelf and the deep ocean. We derive the boundaries for which critical control occurs in terms of a Froude number and the dimensionless magnitude of the perturbation, and analyse the possible transitions between controlled and far-field flow. When first-order dispersive terms are included in the model, transitions are resolved by dispersive shock waves, which remain attached to the forcing region when the Froude number is close to the boundary for critical flow. Contour dynamic simulations show that the dispersive long-wave model captures the quantitative behaviour of the full quasi-geostrophic system for slowly varying shelves, and replicates the qualitative behaviour even when the long-wave parameter is order one

Vortex competition in coastal outflows

Experiments and field observations have shown that there are at least two modes of behavior for river plumes. In many cases, the plume turns to the right (in the Northern Hemisphere) on leaving the river mouth and follows the direction of Kelvin-wave propagation. Alternatively, a “bulge” can form in the plume and a fraction of the outflow volume becomes trapped near the mouth. This paper discusses how bulge formation can be affected by the vorticity profile at the river mouth. Due to the image effect, regions of cyclonic vorticity tend to propagate rightwards, whereas regions of anticyclonic vorticity propagate leftward upon exit from the source. If an outflow consists of regions of cyclonic vorticity to the left of regions of anticyclonic vorticity, the two image effects are in competition. We explore this phenomenon using a quasi-geostrophic model with piecewise-constant potential vorticity, which allows the vorticity profile at the source to be set as part of the problem. We present analytic solutions valid in the source region and at the head of the plume and show that all of the outflow travels rightwards if and only if the region of cyclonic vorticity is dominant. The initial-value problem for the model is integrated numerically using the method of contour dynamics, and the full parameter space is explored. We find that if the cyclonic and anticyclonic contributions cancel, as in the experiments of Avicola and Huq (2003), then steady solutions are unstable and a bulge can form downstream of the river mouth

Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial.

Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction (LEADER) trial. Three polymorphisms in the peroxisome proliferator activated receptor alpha (PPARalpha) gene were investigated (L162V, G>A in intron 2 and G>C in intron 7), two in the apolipoprotein CIII (APOC3) gene (-482C>T and -455T>C) and one in the beta-fibrinogen (FIBB) gene (-455G>A). The presence of diabetes (n=158) was associated with 15% higher triglyceride levels at baseline compared to non-diabetics (n=654) (PC substitution. In the non-diabetic patients, the PPARalpha V162 allele was significantly associated with 9% higher baseline triglyceride levels (P<0.03) and a similar, but non-significant trend was seen for the intron 7 polymorphism. Overall, triglyceride levels fell by 26% with 3 months of bezafibrate treatment, and current smokers showed a poorer response compared to ex/non-smokers (23% fall compared to 28% P=0.03), but none of the genotypes examined had a significant influence on the magnitude of response. Carriers of the -455A polymorphism of the FIBB gene had, as expected, marginally higher baseline fibrinogen levels, 3.43 versus 3.36 g/l (P=0.055), but this polymorphism did not affect response to treatment. Overall, fibrinogen levels fell by 12%, with patients with the highest baseline fibrinogen levels showing the greatest decrease in response to bezafibrate. For both the intron 2 and the L162V polymorphisms of the PPARalpha gene there was a significant interaction (both P<0.01) between genotype and baseline levels of fibrinogen on the response of fibrinogen levels to bezafibrate, such that individuals carrying the rare alleles in the lowest tertile showed essentially no overall decrease compared to a 0.18 g/l fall in homozygotes for the common allele. Thus while these genotypes are a minor determinant of baseline triglyceride and fibrinogen levels, there is little evidence from this study that the magnitude of response to bezafibrate treatment in men with peripheral vascular disease is determined by variation at these loci

A hybrid frequency response function formulation for MDOF nonlinear systems

This paper introduces a hybrid technique for formulation of frequency response functions (FRFs) for nonlinear MDOF systems, based on the Structural modification using frequency response function (SMURF) technique. The technique can produce FRFs at the desired coordinates on the structure. The term “hybrid” indicates that the underlying linear system is reduced by expressing it in FRF form, while the nonlinearities are treated in the form of describing functions based on spatial elements. The method uses several FRFs instead of the spatial model therefore it is characterized by lower computational costs. Moreover, the experimentally measured FRFs of the underlying linear structure can be applied in this technique. A system with cubic stiffness and friction damping nonlinearities is used as a numerical case study to verify the proposed technique

Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia.

BACKGROUND: Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males. METHODS: Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett's multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls. RESULTS: The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique. CONCLUSION: TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis

FRF-based model updating using SMURF technique

Finite element (FE) method is a well-known technique in structural dynamic analysis. However, FE models may be inaccurate or even incorrect due to erroneous modeling, geometrical over-simplification or uncertainties in the element and joint properties. In contrast, modal models are generally considered to be correct or at least closely matching the actual dynamic behavior of a structure. Therefore, a model updating procedure should be introduced for adjusting the analytical model in order to reconcile theoretical and experimental results. In this paper, a new FRF-based model updating method is proposed based on the Structural modification using experimental frequency response functions (SMURF) method. It is demonstrated that the proposed method updates the parameters accurately using just a few frequency response functions from the mis-modeled regions. A 12-DOF mass-spring system is considered as a test case in a simulated experiment. The convergence of the method and its capacity to improve the accuracy of the FE model are evaluated. Moreover, the paper considers the effect of the number of modes, the frequency range of interest used in the calculations as well as the coordinate incompleteness and noise on the quality of the updated model. The updated models are compared in terms of the predicted natural frequencies, mode shapes and frequency response functions