A Few Descriptive and Optimization Issues on the Material Flow at a Research-Academic Institution: The Role of Simulation

Lately, significant work in the area of Intelligent Manufacturing has become public and mainly applied within the frame of industrial purposes. Special efforts have been made in the implementation of new technologies, management and control systems, among many others which have all evolved the field. Aware of all this and due to the scope of new projects and the need of turning the existing flexible ideas into more autonomous and intelligent ones, i.e.: Intelligent Manufacturing, the present paper emerges with the main aim of contributing to the design and analysis of the material flow in either systems, cells or work stations under this new "intelligent" denomination. For this, besides offering a conceptual basis in some of the key points to be taken into account and some general principles to consider in the design and analysis of the material flow, also some tips on how to define other possible alternative material flow scenarios and a classification of the states a system, cell or workstation are offered as well. All this is done with the intentions of relating it with the use of simulation tools, for which these have been briefly addressed with a special focus on the Witness simulation package. For a better comprehension, the previous elements are supported by a detailed layout, other figures and a few expressions which could help obtaining necessary data. Such data and others will be used in the future, when simulating the scenarios in the search of the best material flow configurations

Fission Yeast CSL Transcription Factors: Mapping Their Target Genes and Biological Roles

BACKGROUND: Cbf11 and Cbf12, the fission yeast CSL transcription factors, have been implicated in the regulation of cell-cycle progression, but no specific roles have been described and their target genes have been only partially mapped. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of transcriptome profiling under various conditions and genome-wide analysis of CSL-DNA interactions, we identify genes regulated directly and indirectly by CSL proteins in fission yeast. We show that the expression of stress-response genes and genes that are expressed periodically during the cell cycle is deregulated upon genetic manipulation of cbf11 and/or cbf12. Accordingly, the coordination of mitosis and cytokinesis is perturbed in cells with genetically manipulated CSL protein levels, together with other specific defects in cell-cycle progression. Cbf11 activity is nutrient-dependent and Δcbf11-associated defects are mitigated by inactivation of the protein kinase A (Pka1) and stress-activated MAP kinase (Sty1p38) pathways. Furthermore, Cbf11 directly regulates a set of lipid metabolism genes and Δcbf11 cells feature a stark decrease in the number of storage lipid droplets. CONCLUSIONS/SIGNIFICANCE: Our results provide a framework for a more detailed understanding of the role of CSL proteins in the regulation of cell-cycle progression in fission yeast

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former two implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals

Fatty acids in intramuscular fat of Ile de France lambs in two different production systems

The fatty acid (FA) composition in the intramuscular fat (IMF) of the musculus longissimus dorsi (MLD) of Ile de France purebred lambs in two different production systems in Slovakia was evaluated using gas chromatography. In the first production system, lambs and ewes were assigned to pasture without access to concentrates (P). In the second system, lambs and ewes were confined indoors with hay/silage and access to concentrates (S). An analysis of variance with the following factors was employed: production system, sex, and production system–sex interactions. The proportions of arachidonic, eicosapentaeonic, docosapentaeonic, and docosahexaenoic FAs, i.e. long-chain polyunsaturated FA (PUFA), were significantly higher in P lambs (1.83, 0.82, 0.92, 0.29&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively) than in S lambs (0.45, 0.14, 0.30, 0.09&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively). The proportions of conjugated linoleic acid (CLA), n-6 PUFA, n-3 PUFA, and essential FA (linoleic and α-linolenic) were also significantly higher in P lambs (2.10, 8.50, 4.55, and 8.80&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively) than in S lambs (0.65, 3.27, 1.50, and 3.64&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively). The proportions of palmitic acid and myristic acid as important individual saturated FAs (SFA) were significantly higher in S lambs (28.51 and 8.30&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively) than in P lambs (21.80 and 5.63&thinsp;g&thinsp;100&thinsp;g−1 FAME, respectively). The proportion of all SFAs was also significantly higher in S lambs (57.87&thinsp;g&thinsp;100&thinsp;g−1 FAME) than in P lambs (48.70&thinsp;g&thinsp;100&thinsp;g−1 FAME). From a nutrition and human health point of view (i.e. higher proportions of PUFA, CLA, and essential FAs and lower proportions of SFAs), meat from P lambs was found to be more favourable and would be more highly recommended for consumption.</p

The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis.

BACKGROUND: Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. OBJECTIVES: To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. METHODS: In this case-control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. RESULTS: Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR ) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid-derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). CONCLUSIONS: The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD

The Microevolution and Epidemiology of Staphylococcus aureus Colonization during Atopic Eczema Disease Flare.

Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the microevolution of S. aureus colonization, we deep sequenced S. aureus populations from nine children with moderate to severe AE and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE patients and control participants, with all but one of the individuals carrying colonies belonging to a single sequence type. Phylogenetic analysis showed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE cases versus controls (Fisher exact test, P = 0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.CPH was supported by Wellcome Trust (grant number 104241/z/14/z). MTGH, KAP, and KO were supported by the Scottish Infection Research Network and Chief Scientist Office through the Scottish Healthcare Associated Infection Prevention Institute consortium funding (CSO reference: SIRN10). Bioinformatics and computational biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). JP and MTGH were supported by Wellcome Trust grant 098051. AEM is supported by Biotechnology and Biological Sciences Research Council grant BB/M014088/1. SJB is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z)

Bacteremia in critical care units at Bugando Medical Centre, Mwanza, Tanzania: the role of colonization and contaminated cots and mothers’ hands in cross-transmission of multidrug resistant Gram-negative bacteria

Article of Antimicrobial Resistance and Infection Control (2020) pg, 2-14Background: Multidrug resistance (MDR) is a major clinical problem in tertiary hospitals in Tanzania and jeopardizes the life of neonates in critical care units (CCUs). To better understand methods for prevention of MDR infections, this study aimed to determine, among other factors, the role of MDR-Gram-negative bacteria (GNB) contaminating neonatal cots and hands of mothers as possible role in transmission of bacteremia at Bugando Medical Centre (BMC), Mwanza, Tanzania. Methods: This cross-sectional, hospital-based study was conducted among neonates and their mothers in a neonatal intensive care unit and a neonatology unit at BMC from December 2018 to April 2019. Blood specimens (n = 200) were sub- cultured on 5% sheep blood agar (SBA) and MacConkey agar (MCA) plates. Other specimens (200 neonatal rectal swabs, 200 maternal hand swabs and 200 neonatal cot swabs) were directly inoculated on MCA plates supplemented with 2 μg/ml cefotaxime (MCA-C) for screening of GNB resistant to third generation cephalosporins, r-3GCs. Conventional biochemical tests, Kirby-Bauer technique and resistance to cefoxitin 30 μg were used for identification of bacteria, antibiotic susceptibility testing and detection of MDR-GNB and screening of potential Amp-C beta lactamase producing GNB, respectively. Results: The prevalence of culture confirmed bacteremia was 34.5% of which 85.5% were GNB. Fifty-five (93.2%) of GNB isolated from neonatal blood specimens were r-3GCs. On the other hand; 43% of neonates were colonized with GNB r- 3GCs, 32% of cots were contaminated with GNB r-3GCs and 18.5% of hands of neonates’ mothers were contaminated with GNB r-3GCs. The prevalences of MDR-GNB isolated from blood culture and GNB r-3GCs isolated from neonatal colonization, cots and mothers’ hands were 96.6, 100, 100 and 94.6%, respectively. Significantly, cyanosis (OR[95%CI]: 3.13[1.51–6.51], p = 0.002), jaundice (OR[95%CI]: 2.10[1.07–4.14], p = 0.031), number of invasive devices (OR[95%CI]: 2.52[1.08–5.85], p = 0.031) and contaminated cot (OR[95%CI]: 2.39[1.26–4.55], p = 0.008) were associated with bacteremia due to GNB. Use of tap water only (OR[95%CI]: 2.12[0.88–5.09], p = 0.040) was protective for bacteremia due to GNB. Conclusion: High prevalence of MDR-GNB bacteremia and intestinal colonization, and MDR-GNB contaminating cots and mothers’ hands was observed. Improved cots decontamination strategies is crucial to limit the spread of MDR- GNB. Further, clinical presentations and water use should be considered in administration of empirical therapy whilst awaiting culture results