scholarly journals A diagnostic interface for the ICOsahedral Non-hydrostatic (ICON) modelling framework based on the Modular Earth Submodel System (MESSy v2.50)

2016 ◽  
Vol 9 (10) ◽  
pp. 3639-3654
Author(s):  
Bastian Kern ◽  
Patrick Jöckel

Abstract. Numerical climate and weather models have advanced to finer scales, accompanied by large amounts of output data. The model systems hit the input and output (I/O) bottleneck of modern high-performance computing (HPC) systems. We aim to apply diagnostic methods online during the model simulation instead of applying them as a post-processing step to written output data, to reduce the amount of I/O. To include diagnostic tools into the model system, we implemented a standardised, easy-to-use interface based on the Modular Earth Submodel System (MESSy) into the ICOsahedral Non-hydrostatic (ICON) modelling framework. The integration of the diagnostic interface into the model system is briefly described. Furthermore, we present a prototype implementation of an advanced online diagnostic tool for the aggregation of model data onto a user-defined regular coarse grid. This diagnostic tool will be used to reduce the amount of model output in future simulations. Performance tests of the interface and of two different diagnostic tools show, that the interface itself introduces no overhead in form of additional runtime to the model system. The diagnostic tools, however, have significant impact on the model system's runtime. This overhead strongly depends on the characteristics and implementation of the diagnostic tool. A diagnostic tool with high inter-process communication introduces large overhead, whereas the additional runtime of a diagnostic tool without inter-process communication is low. We briefly describe our efforts to reduce the additional runtime from the diagnostic tools, and present a brief analysis of memory consumption. Future work will focus on optimisation of the memory footprint and the I/O operations of the diagnostic interface.

2016 ◽  
Author(s):  
Bastian Kern ◽  
Patrick Jöckel

Abstract. Numerical climate and weather models have advanced to finer scales, accompanied by large amount of output data. The model systems hit the input and output (I/O) bottleneck of modern High Performance Computing (HPC) systems. We aim to apply diagnostic methods on-line during the model simulation instead of applying them as a post-processing step to written output data, to reduce the amount of I/O. To include diagnostic tools into the model system, we implemented a standardised, easy-to-use interface based on the Modular Earth Submodel System (MESSy) into the ICOsahedral Non-hydrostatic (ICON) modelling framework. The integration of the diagnostic interface into the model system is briefly described. Furthermore, we present a prototype implementation of an advanced on-line diagnostic tool for the aggregation of model data onto a user-defined regular coarse grid. This diagnostic tool will be used to reduce the amount of model output in future simulations. Performance tests of the interface and of two different diagnostic tools show, that the interface itself introduces no overhead in form of additional runtime to the model system. The diagnostic tools, however, have significant impact on the model system's runtime. This overhead strongly depends on the characteristics and implementation of the diagnostic tool. The diagnostic tool with high inter-process communication introduces large overhead, whereas the additional runtime of the diagnostic tool without inter-process communication is low. We briefly describe our efforts to reduce the additional runtime from the diagnostic tools, and present a brief analysis of memory consumption. Future work will focus on optimisation of the memory footprint and the I/O operations of the diagnostic interface.


Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4175
Author(s):  
John Archer ◽  
Rebecca Barksby ◽  
Tom Pennance ◽  
Penelope Rostron ◽  
Faki Bakar ◽  
...  

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 × 101 copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH2O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7–96.9) and 100% (±69.1–100), respectively. Positive and negative predictive values were 100% (±97.5–100) and 50% (±27.2–72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Maxwell W. Waema ◽  
Gerald Misinzo ◽  
John M. Kagira ◽  
Eric L. Agola ◽  
Helena A. Ngowi

Porcine cysticercosis is a neglected and underestimated disease caused by metacestode stage of the tapeworm, Taenia solium (T. solium). Pigs are the intermediate hosts of T. solium while human are the only known definitive host. The disease has an economic consequence because the affected farmers lose 50−100 percent of the value of pigs if they are infected. Lack of affordable, easy to use, sensitive, and specific molecular diagnostic tools for detection of infections at the farm level hinders the control of porcine cysticercosis in endemic areas. A number of DNA based diagnostic assays for the detection of T. solium infections in pigs have been developed and evaluated but none is applicable at low-resource areas where this disease is an endemic. This review focuses mainly on DNA based diagnostic methods, their sensitivity, specificity, and utilization at low-resource areas. We summarized data from 65 studies on the current DNA-detection based diagnostic techniques for T. solium cysticercosis in porcine, published in English between the years 2000–2018, identified through PubMed search engine. Of the different polymerase chain reaction (PCR) assays developed for identification of T. solium, the most sensitive (97−100%) and specific (100%) one is nested PCR. One study utilized loop-mediated isothermal amplification (LAMP) as a diagnostic tool for the detection of T. solium infections though its field use was never determined. Recombinase polymerase amplification (RPA) has been evaluated as a diagnostic tool for a variety of diseases, but has never been exploited for the diagnosis of cysticercosis/taeniasis. In conclusion, several molecular methods have been developed and evaluated in lab settings. However, there is need to validate these methods as a diagnostic tool to diagnose porcine cysticercosis in low-resource areas.


Author(s):  
Andrea Springer ◽  
Antje Glass ◽  
Julia Probst ◽  
Christina Strube

AbstractAround the world, human health and animal health are closely linked in terms of the One Health concept by ticks acting as vectors for zoonotic pathogens. Animals do not only maintain tick cycles but can either be clinically affected by the same tick-borne pathogens as humans and/or play a role as reservoirs or sentinel pathogen hosts. However, the relevance of different tick-borne diseases (TBDs) may vary in human vs. veterinary medicine, which is consequently reflected by the availability of human vs. veterinary diagnostic tests. Yet, as TBDs gain importance in both fields and rare zoonotic pathogens, such as Babesia spp., are increasingly identified as causes of human disease, a One Health approach regarding development of new diagnostic tools may lead to synergistic benefits. This review gives an overview on zoonotic protozoan, bacterial and viral tick-borne pathogens worldwide, discusses commonly used diagnostic techniques for TBDs, and compares commercial availability of diagnostic tests for humans vs. domestic animals, using Germany as an example, with the aim of highlighting existing gaps and opportunities for collaboration in a One Health framework.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gustavo Henrique Pereira Boog ◽  
João Vitor Ziroldo Lopes ◽  
João Vitor Mahler ◽  
Marina Solti ◽  
Lucas Tokio Kawahara ◽  
...  

Abstract Purpose Increasing incidences of syphilis highlight the preoccupation with the occurrence of neurosyphilis. This study aimed to understand the current diagnostic tools and their performance to detect neurosyphilis, including new technologies and the variety of existing methods. Methods We searched databases to select articles that reported neurosyphilis diagnostic methods and assessed their accuracy, presenting sensitivity and specificity values. Information was synthesized in tables. The risk of bias was examined using the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations. Results Fourteen studies were included. The main finding was a remarkable diversity of tests, which had varied purposes, techniques, and evaluation methodologies. There was no uniform criterion or gold standard to define neurosyphilis. The current basis for its diagnosis is clinical suspicion and cerebrospinal fluid analysis. There are new promising tests such as PCR tests and chemokine measurement assays. Conclusions The diagnosis of neurosyphilis is still a challenge, despite the variety of existing and developing tests. We believe that the multiplicity of reference standards adopted as criteria for diagnosis reveals the imprecision of the current definitions of neurosyphilis. An important next step for the scientific community is to create a universally accepted diagnostic definition for this disease.


Author(s):  
S. Jelbart ◽  
K. U. Kristiansen ◽  
P. Szmolyan ◽  
M. Wechselberger

AbstractSingular exponential nonlinearities of the form $$e^{h(x)\epsilon ^{-1}}$$ e h ( x ) ϵ - 1 with $$\epsilon >0$$ ϵ > 0 small occur in many different applications. These terms have essential singularities for $$\epsilon =0$$ ϵ = 0 leading to very different behaviour depending on the sign of h. In this paper, we consider two prototypical singularly perturbed oscillators with such exponential nonlinearities. We apply a suitable normalization for both systems such that the $$\epsilon \rightarrow 0$$ ϵ → 0 limit is a piecewise smooth system. The convergence to this nonsmooth system is exponential due to the nonlinearities we study. By working on the two model systems we use a blow-up approach to demonstrate that this exponential convergence can be harmless in some cases while in other scenarios it can lead to further degeneracies. For our second model system, we deal with such degeneracies due to exponentially small terms by extending the space dimension, following the approach in Kristiansen (Nonlinearity 30(5): 2138–2184, 2017), and prove—for both systems—existence of (unique) limit cycles by perturbing away from singular cycles having desirable hyperbolicity properties.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1162
Author(s):  
Seohyun Kim ◽  
Sangmin Ji ◽  
Hye Ran Koh

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has recently gained growing attention as a diagnostic tool due to its capability of specific gene targeting. It consists of Cas enzymes and a guide RNA (gRNA) that can cleave the target DNA or RNA based on the sequence of the gRNA, making it an attractive genetic engineering technique. In addition to the target-specific binding and cleavage, the trans-cleavage activity was reported for some Cas proteins, including Cas12a and Cas13a, which is to cleave the surrounding single-stranded DNA or RNA upon the target binding of Cas-gRNA complex. All these activities of the CRISPR-Cas system are based on its target-specific binding, making it applied to develop diagnostic methods by detecting the disease-related gene as well as microRNAs and the genetic variations such as single nucleotide polymorphism and DNA methylation. Moreover, it can be applied to detect the non-nucleic acids target such as proteins. In this review, we cover the various CRISPR-based diagnostic methods by focusing on the activity of the CRISPR-Cas system and the form of the target. The CRISPR-based diagnostic methods without target amplification are also introduced briefly.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Owen D. Jarman ◽  
Olivier Biner ◽  
John J. Wright ◽  
Judy Hirst

AbstractMitochondrial complex I (NADH:ubiquinone oxidoreductase) is a crucial metabolic enzyme that couples the free energy released from NADH oxidation and ubiquinone reduction to the translocation of four protons across the inner mitochondrial membrane, creating the proton motive force for ATP synthesis. The mechanism by which the energy is captured, and the mechanism and pathways of proton pumping, remain elusive despite recent advances in structural knowledge. Progress has been limited by a lack of model systems able to combine functional and structural analyses with targeted mutagenic interrogation throughout the entire complex. Here, we develop and present the α-proteobacterium Paracoccus denitrificans as a suitable bacterial model system for mitochondrial complex I. First, we develop a robust purification protocol to isolate highly active complex I by introducing a His6-tag on the Nqo5 subunit. Then, we optimize the reconstitution of the enzyme into liposomes, demonstrating its proton pumping activity. Finally, we develop a strain of P. denitrificans that is amenable to complex I mutagenesis and create a catalytically inactive variant of the enzyme. Our model provides new opportunities to disentangle the mechanism of complex I by combining mutagenesis in every subunit with established interrogative biophysical measurements on both the soluble and membrane bound enzymes.


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