Production Process Modelling Architecture to Support Improved Cyber-Physical Production Systems

With the proliferation of intelligent networks in industrial environments, manufacturing SME’s have been in a continuous search for integrating and retrofitting existing assets with modern technologies that could provide low-cost solutions for optimizations in their production processes. Their willingness to support a technological evolution is firmly based on the perception that, in the future, better tools will guarantee process control, surveillance and maintenance. For this to happen, the digitalization of valuable and extractable information must be held in a cost-effective manner, through contemporary approaches such as IoT, creating the required fluidity between hardware and software, for implementing Cyber-Physical modules in the manufacturing process. The goal of this work is to develop an architecture that will support companies to digitize their machines and processes through an MDA approach, by modeling their production processes and physical resources, and transforming into an implementation model, using contemporary CPS and IoT concepts, to be continuously improved using forecasting/predictive algorithms and analytics.authorsversionpublishe

Multidrug-Resistant Enterobacter cloacae Complex Emerging as a Global, Diversifying Threat

The Enterobacter cloacae complex (ECC) includes common nosocomial pathogens capable of producing a wide variety of infections. Broad-spectrum antibiotic resistance, including the recent emergence of resistance to last-resort carbapenems, has led to increased interest in this group of organisms and carbapenem-resistant E. cloacae complex (CREC) in particular. Molecular typing methods based on heat-shock protein sequence, pulsed-field gel electrophoresis, comparative genomic hybridization, and, most recently, multilocus sequence typing have led to the identification of over 1069 ECC sequence types in 18 phylogenetic clusters across the globe. Whole-genome sequencing and comparative genomics, moreover, have facilitated global analyses of clonal composition of ECC and specifically of CREC. Epidemiological and genomic studies have revealed diverse multidrug-resistant ECC clones including several potential epidemic lineages. Together with intrinsic β-lactam resistance, members of the ECC exhibit a unique ability to acquire genes encoding resistance to multiple classes of antibiotics, including a variety of carbapenemase genes. In this review, we address recent advances in the molecular epidemiology of multidrug-resistant E. cloacae complex, focusing on the global expansion of CREC

Problems of modern programming used in the technology of transport processes

It is well known that information technologies are the most rapidly developing areas of modern life. New technology, designs, names and abbreviations appear almost every day.While creating the products application programming, depending on the industry in which a project is, at the forefront come priority challenges that require extraordinary solutions. This could be accuracy of the solution in the physics-mathematical calculations, the speed of calculations in the programs that implement the reaction or improved interface in products aimed for users, as well as solutions for tasks that implement specific requirements for group work.Mankind has shown interest in the search of the optimal route of application programming and mathematical solution of transportation tasks, allowing to calculate the best route at the lowest cost

The Boundary Multiplet of N=4 SU(2)xU(1) Gauged Supergravity on Asymptotically-AdS_5

We consider N=4 SU(2)xU(1) gauged supergravity on asymptotically-AdS_5 backgrounds. By a near-boundary analysis we determine the boundary-dominant components of the bulk fields from their partially gauge-fixed field equations. Subdominant components are projected out in the boundary limit and we find a reduced set of boundary fields, constituting the N=2 Weyl multiplet. The residual bulk symmetries are found to act on the boundary fields as four-dimensional diffeomorphisms, N=2 supersymmetry and (super-)Weyl transformations. This shows that the on-shell N=4 supergravity multiplet yields the N=2 Weyl multiplet on the boundary with the appropriate local N=2 superconformal transformations. Building on these results we use the AdS/CFT conjecture to calculate the Weyl anomaly of the dual four-dimensional superconformal field theories in a generic bosonic N=2 conformal supergravity background.Comment: 23 pages; to appear in JHE

The Schro¨\ddot{o}dinger-Poisson equations as the large-N limit of the Newtonian N-body system: applications to the large scale dark matter dynamics

In this paper it is argued how the dynamics of the classical Newtonian N-body system can be described in terms of the Schr$\ddot{o}$dinger-Poisson equations in the large $N$ limit. This result is based on the stochastic quantization introduced by Nelson, and on the Calogero conjecture. According to the Calogero conjecture, the emerging effective Planck constant is computed in terms of the parameters of the N-body system as $\hbar \sim M^{5/3} G^{1/2} (N/)^{1/6}$, where is $G$ the gravitational constant, $N$ and $M$ are the number and the mass of the bodies, and $$ is their average density. The relevance of this result in the context of large scale structure formation is discussed. In particular, this finding gives a further argument in support of the validity of the Schr$\ddot{o}$dinger method as numerical double of the N-body simulations of dark matter dynamics at large cosmological scales.Comment: Accepted for publication in the Euro. Phys. J.

Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence

Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance

Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.

BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR. RESULTS: Pfmdr1-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two pfmdr1 gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (P < 0.0001). Among the main pfmdr1 haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (P = 0.04). At the pfatp6 locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the pfatp6 E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The pfk13 variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the pfk13 locus occurring at low frequency were observed. CONCLUSIONS: Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries

Experimental Evolution of Resistance to Artemisinin Combination Therapy Results in Amplification of the mdr1 Gene in a Rodent Malaria Parasite

Background: Lacking suitable alternatives, the control of malaria increasingly depends upon Artemisinin Combination Treatments (ACT): resistance to these drugs would therefore be disastrous. For ACTs, the biology of resistance to the individual components has been investigated, but experimentally induced resistance to component drugs in combination has not been generated. Methodology/Principal Findings: We have used the rodent malaria parasite Plasmodium chabaudi to select in vivo resistance to the artesunate (ATN) + mefloquine (MF) version of ACT, through prolonged exposure of parasites to both drugs over many generations. The selection procedure was carried out over twenty-seven consecutive sub-inoculations under increasing ATN + MF doses, after which a genetically stable resistant parasite, AS-ATNMF1, was cloned. AS-ATNMF1 showed increased resistance to ATN + MF treatment and to artesunate or mefloquine administered separately. Investigation of candidate genes revealed an mdr1 duplication in the resistant parasites and increased levels of mdr1 transcripts and protein. There were no point mutations in the atpase6 or ubp1genes. Conclusion: Resistance to ACTs may evolve even when the two drugs within the combination are taken simultaneously and amplification of the mdr1 gene may contribute to this phenotype. However, we propose that other gene(s), as ye

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities