Labour productivity in mixed-model manual assembly 4.0

Manual assembly lines productivity is threatened by the increased complexity brought by mass customisation demand trends. Industry 4.0 offers potential solutions to address this situation, but the methodology to implement it is still a subject of study. As a preliminary step, this article aims to identify the dominant factors affecting the Key Performance Indicators of mixed-model assembly lines. To do so, parametric and discrete-events simulation models were developed, and Design of Experiments techniques were used. The results show that the key drivers for assembly line performance are number of work stations and batch size, and that increasing the work content ratio of the products assembled does not interact negatively with other factors. The results presented here pave the way for developing Industry 4.0 projects that address specifically the most relevant factors that affect assembly lines performance

Operator-centred Lean 4.0 framework for flexible assembly lines

This article provides a starting point for developing a methodology to successfully implement Industry 4.0 technology for assembly operations. It presents a novel multi-layer human-centred conceptual model in line with Lean philosophy which identifies the assembly operator functions and relates them to other production departments, identifying how they would be affected by incorporating new digital technologies. The model shows that assembly operators would only be directly supported by hardware digital technologies, while the production support departments would mainly employ Industry 4.0 software technologies. The work presented here paves the way for developing a methodology for implementing Lean Assembly 4.0

Lean manual assembly 4.0: A systematic review

In a demand context of mass customization, shifting towards the mass personalization of products, assembly operations face the trade-off between highly productive automated systems and flexible manual operators. Novel digital technologies—conceptualized as Industry 4.0—suggest the possibility of simultaneously achieving superior productivity and flexibility. This article aims to address how Industry 4.0 technologies could improve the productivity, flexibility and quality of assembly operations. A systematic literature review was carried out, including 234 peer-reviewed articles from 2010–2020. As a result, the analysis was structured addressing four sets of research questions regarding (1) assembly for mass customization; (2) Industry 4.0 and performance evaluation; (3) Lean production as a starting point for smart factories, and (4) the implications of Industry 4.0 for people in assembly operations. It was found that mass customization brings great complexity that needs to be addressed at different levels from a holistic point of view; that Industry 4.0 offers powerful tools to achieve superior productivity and flexibility in assembly; that Lean is a great starting point for implementing such changes; and that people need to be considered central to Assembly 4.0. Developing methodologies for implementing Industry 4.0 to achieve specific business goals remains an open research topic

Models to evaluate the performance of high-mix low-volume manual or semi-automatic assembly lines

To address mass customisation demand trends, assembly line flexibility and productivity are critical. Industry 4.0 technologies could support assembly operations to this end. However, clear implementation methodologies are still lacking. This article presents two models for evaluating the most relevant Key Performance Indicators (KPIs) of manual or semi-automatic assembly lines, allowing to maximise the return of investment of any digital technology addition. MATLAB® was used to implement a parametric model, and FlexSim® was employed to build a discrete event simulation model. The models were validated using data of two industrial study cases from a global white goods manufacturer

Nitric oxide inactivates rat hepatic methionine adenosyltransferase In vivo by S-nitrosylation

We investigated the mechanism of nitric oxide (NO) action on hepatic methionine adenosyltransferase (MAT) activity using S-nitrosoglutathione (GSNO) as NO donor. Hepatic MAT plays an essential role in the metabolism of methionine, converting this amino acid into S-adenosylmethionine. Hepatic MAT exists in two oligomeric states: as a tetramer (MAT I) and as a dimer (MAT III) of the same subunit. This subunit contains 10 cysteine residues. In MAT I, S-nitrosylation of 1 thiol residue per subunit was associated with a marked inactivation of the enzyme (about 70%) that was reversed by glutathione (GSH). In MAT III, S-nitrosylation of 3 thiol residues per subunit led to a similar inactivation of the enzyme, which was also reversed by GSH. Incubation of isolated rat hepatocytes with S-nitrosoglutathione monoethyl ester (EGSNO), a NO donor permeable through the cellular membrane, induced a dose-dependent inactivation of MAT that was reversed by removing the NO donor from the cell suspension. MAT, purified from isolated rat hepatocytes, contained S-nitrosothiol groups and the addition of increasing concentrations of EGSNO to the hepatocyte suspension led to a progressive S-nitrosylation of the enzyme. Removal of the NO donor from the incubation media resulted in loss of most NO groups associated to the enzyme. Finally, induction in rats of the production of NO, by the administration of bacterial lipopolysaccharide (LPS), induced a fivefold increase in the S-nitrosylation of hepatic MAT, which led to a marked inactivation of the enzyme. Thus, the activity of liver MAT appears to be regulated in vivo by S-nitrosylation

Acidified milk for feeding dairy calves in tropical raising systems

The objective of this study was to evaluate the effect of milk acidification in tropical climate conditions on dairy calves’ growth, health and selected blood metabolites. Thirty-two Holstein calves were blocked according to sex, birth date and weight, and distributed to the following treatments: 1. refrigerated milk kept at 5 °C (RM) or 2. acidified milk (with added lactic acid to a pH of 4.2) kept at ambient temperature (ACM). After birth, calves were fed colostrum and from the second day received 6 l/day of RM or ACM heated to 38 °C until weaning at day 56. Calves were individually housed with free access to water and starter diet. Feed intake and health problems were monitored daily; calves were weighed and measured weekly. Blood samples were collected weekly to evaluate the levels of metabolites. Feed intake, body weight and daily gain did not differ between treatments, but heart girth and wither height was higher for animals fed RM. The faecal score was lower for RM group, however in calves fed ACM it also did not suggest a diarrheal process (1.98). In addition, the first case of diarrhoea in calves fed ACM was later than in calves fed RM (15.4 vs 8.6 days, respectively; P < 0.01). So, the acidification of milk is an adequate method of preserving milk in tropical ambient temperatures. It resulted in health benefits to calves, delaying the first case of diarrhoea.Fil: Coelho, M. G.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Silva, F. L. M.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Silva, M. D.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Silva, A. P.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Cezar, A. M.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Slanzon, G. S.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Miqueo, Evangelina. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toledo, A. F.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Bittar, C. M. M.. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasi

Cartilage intermediate layer protein 1 (CILP1): a novel mediator of cardiac extracellular matrix remodelling

Heart failure is accompanied by extracellular matrix (ECM) remodelling, often leading to cardiac fibrosis. In the present study we explored the significance of cartilage intermediate layer protein 1 (CILP1) as a novel mediator of cardiac ECM remodelling. Whole genome transcriptional analysis of human cardiac tissue samples revealed a strong association of CILP1 with many structural (e.g. COL1A2 r2¿=¿0.83) and non-structural (e.g. TGFB3 r2¿=¿0.75) ECM proteins. Gene enrichment analysis further underscored the involvement of CILP1 in human cardiac ECM remodelling and TGFß signalling. Myocardial CILP1 protein levels were significantly elevated in human infarct tissue and in aortic valve stenosis patients. CILP1 mRNA levels markedly increased in mouse heart after myocardial infarction, transverse aortic constriction, and angiotensin II treatment. Cardiac fibroblasts were found to be the primary source of cardiac CILP1 expression. Recombinant CILP1 inhibited TGFß-induced ¿SMA gene and protein expression in cardiac fibroblasts. In addition, CILP1 overexpression in HEK293 cells strongly (5-fold p¿<¿0.05) inhibited TGFß signalling activity. In conclusion, our study identifies CILP1 as a new cardiac matricellular protein interfering with pro-fibrotic TGFß signalling, and as a novel sensitive marker for cardiac fibrosis

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP

T1 measurements identify extracellular volume expansion in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy

Background—Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV). Methods and Results—Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH−, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH− mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH−, controls, respectively; P≤0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58; P60% of overt patients with HCM but absent from G+/LVH− subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM. Conclusions—Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis