Sistema de Análise, Seleção e Priorização de projetos de melhoria em uma Empresa do Setor Automotivo.

A alta competitividade do setor automotivo demanda uma contínua busca por redução de custos em toda a cadeia de fornecimento. A sobrevivência e crescimento dessas empresas dependem diretamente da excelência operacional na gestão de projetos de melhoria alinhados com os objetivos estratégicos, objetivos estes, que podem ser definidos no mapa estratégico e desdobrados do Balanced Scorecard. Ao verificar a eficácia, após a conclusão desses projetos, através do cálculo de retorno financeiro real em comparação com o cálculo de retorno financeiro estimado no projeto, observou-se que as metodologias de análise de viabilidade de investimentos em concordância com a estratégia da organização são pouco empregadas e, quando realizadas mostram que 74,5% dos projetos vêm apresentado resultados não desejados. O objetivo principal deste estudo é aprimorar, em uma empresa do setor automotivo, o retorno financeiro proveniente dos seus projetos de melhoria. Para atingir esse objetivo foi adaptada uma sistemática de procedimentos de análise, seleção e priorização de projetos de melhoria, além de aperfeiçoar e padronizar o sistema de gerenciamento do cálculo financeiro. A metodologia adotada nesse trabalho é a pesquisa-ação que proporcionou o desenvolvimento conjunto das melhores práticas a fim de criar uma sistemática de procedimentos que permitiram identificar projetos com maior potencial de retorno financeiro. Os resultados obtidos, após a aplicação das melhorias, mostraram que foi possível otimizar o emprego de recursos em projetos de melhoria com maior retorno financeiro, aumentando em 8% o retorno financeiro sobre o valor agregado na organização, além de evidenciar uma melhora significativa na favorabilidade dos usuários com relação à eficiência e eficácia do sistema de gerenciamento de cálculo financeiro

Efficient Transient Expression for Functional Analysis in Fruit Using the Tsukuba System Vector

Evaluating the function of genes expressed in fruit tissues of fruit tree species using a genetic transformation approach is a long process because the trees are generally recalcitrant to genetic transformation and cannot bear fruit during their long juvenile phases. Transient gene expression in fruit enables the functional analysis of genes associated with fruit traits, which may accelerate the study of fruit physiology. Here, by using the recently developed “Tsukuba system”, we successfully established an efficient transient expression system in harvested fruit tissues. The “Tsukuba system” utilizes a combination of the geminiviral replication system and a double terminator, which ensures sufficient levels of transgene expression. We used blueberry fruit as a model to characterize the applicability of this system for transient expression in fruit tissue. The pTKB3-EGFP vector was introduced by agroinfiltration into the fruit tissues of several blueberry cultivars. We found that transient GFP fluorescence in fruit peaked 4–6 days after agroinfiltration. Agrobacterium suspensions were easily injected into soft, mature fruit, and GFP was strongly expressed; however, hard, immature fruit were not penetrable by Agrobacterium suspensions, and GFP was rarely detected. We then tested the applicability of the developed system to other fruit tree species: six families, 17 species, and 26 cultivars. GFP fluorescence was detected in all species, except for Japanese apricot. In blueberry, bilberry, sweet cherry, apricot, and satsuma mandarin, GFP was highly expressed and observed in a large proportion of the flesh. In kiwifruit, hardy kiwifruits, persimmon, peach, apple, European pear, and grape, GFP fluorescence was limited to certain parts of the fruits. Finally, transient VcMYBA1 overexpression in blueberry was tested as a model for gene functional analysis in fruit. Transient VcMYBA1 overexpression induced red pigmentation in the flesh, suggesting that VcMYBA1 expression caused anthocyanin accumulation. This study provides a technical basis for the rapid evaluation of genes expressed in fruit, which will be useful for gene function evaluation studies in fruit crops with long juvenile phases

Contribution of human organic anion transporter 3-mediated transport of a major linezolid metabolite, PNU-142586, in linezolid-induced thrombocytopenia

Wang D., Ikemura K., Hasegawa T., et al. Contribution of human organic anion transporter 3-mediated transport of a major linezolid metabolite, PNU-142586, in linezolid-induced thrombocytopenia. Biomedicine and Pharmacotherapy 175, 116801 (2024); https://doi.org/10.1016/j.biopha.2024.116801.Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for linezolid-induced thrombocytopenia using two real-world clinical databases and explored its underlying mechanism through in vitro and in vivo experiments. In a retrospective analysis of 150 linezolid-treated patients, multivariate analysis identified coadministration of lansoprazole, a proton pump inhibitor, as a significant independent risk factor for thrombocytopenia (odds ratio: 2.33, p = 0.034). Additionally, analysis of the Food and Drug Administration Adverse Event Reporting System database revealed a reporting odds ratio of thrombocytopenia for lansoprazole of 1.64 (95% CI: 1.25–2.16). In vitro studies showed that the uptake of PNU-142586, a major linezolid metabolite, was significantly higher in human organic anion transporter 3-expressing HEK293 (HEK-hOAT3) cells compared to HEK-pBK cells. The apparent IC50 value of lansoprazole against hOAT3-mediated transport of PNU-142586 was 0.59 ± 0.38 µM. In a pharmacokinetic study using rats, coadministration of linezolid with lansoprazole intravenously resulted in approximately a 1.7-fold increase in the area under the plasma concentration-time curve of PNU-142586, but not linezolid and PNU-142300. Moreover, PNU-142586, but not linezolid, exhibited concentration-dependent cytotoxicity in a human megakaryocytic cell line. These findings suggest that linezolid-induced thrombocytopenia should be due to delayed elimination of PNU-142586. Furthermore, delayed elimination of PNU-142586 due to renal failure and hOAT3-mediated transport inhibition by lansoprazole should exacerbate linezolid-induced thrombocytopenia

Dissolution Properties of CO2 in the High Pressure Environment Equivalent to 3500m Deep Sea

AbstractThe purpose of the present study is to investigate the influence of CO2 hydrate formation and dissociation on the dissolution properties of liquid CO2. In order to clarify the influence of CO2 hydrate formation and dissociation, pressure and temperature are measured under both conditions of hydrate region and non-hydrate region. Hysteresis is obtained in the formation and dissociation of CO2 hydrate as a function of temperature. It is confirmed that there is hysteresis in the case of hydrate region, however, virtually no hysteresis in the case of non-hydrate region. As the result, it is confirmed that hysteresis is caused by CO2 hydrate and all hysteresis loop obtained in this study are all different, though experiment conditions is almost same. In other words, it is suggested that the amount of CO2 hydrate is constant chang

Functional relationships between cyclodextrin glucanotransferase from an alkalophilic Bacillus and α-amylases Site-directed mutagenesis of the conserved two Asp and one Glu residues

AbstractComparison of the amino acid sequences of cyclodextrin glucanotransferases (CGTases) with those of α-amylases revealed that two Asp and one Glu residues, which are considered to be the catalytic residues in α-amylases, were also conserved in CGTases. To analyze the function of the three conserved amino acid residues in CGTases, site-directed mutagenesis was carried out. The three mutant CGTases, in which Asp229, Glu257 and Asp328 were individually replaced by Asn or Gln, completely lost both their starch-degrading and β-cyclodextrin-forming activities, whereas another mutant CGTase, in which Glu264 replaced by Gln, retained these activities. The three inactive enzymes retained the ability to be bound to starch. These results suggest that Asp229, Glu257 and Asp328 play an important role in the enzymatic reaction catalyzed by CGTase and that a similar catalytic mechanism is present in both CGTases and α-amylases

eSPRESSO: topological clustering of single-cell transcriptomics data to reveal informative genes for spatio–temporal architectures of cells

[Background] Bioinformatics capability to analyze spatio–temporal dynamics of gene expression is essential in understanding animal development. Animal cells are spatially organized as functional tissues where cellular gene expression data contain information that governs morphogenesis during the developmental process. Although several computational tissue reconstruction methods using transcriptomics data have been proposed, those methods have been ineffective in arranging cells in their correct positions in tissues or organs unless spatial information is explicitly provided. [Results] This study demonstrates stochastic self-organizing map clustering with Markov chain Monte Carlo calculations for optimizing informative genes effectively reconstruct any spatio–temporal topology of cells from their transcriptome profiles with only a coarse topological guideline. The method, eSPRESSO (enhanced SPatial REconstruction by Stochastic Self-Organizing Map), provides a powerful in silico spatio–temporal tissue reconstruction capability, as confirmed by using human embryonic heart and mouse embryo, brain, embryonic heart, and liver lobule with generally high reproducibility (average max. accuracy = 92.0%), while revealing topologically informative genes, or spatial discriminator genes. Furthermore, eSPRESSO was used for temporal analysis of human pancreatic organoids to infer rational developmental trajectories with several candidate ‘temporal’ discriminator genes responsible for various cell type differentiations. [Conclusions] eSPRESSO provides a novel strategy for analyzing mechanisms underlying the spatio–temporal formation of cellular organizations

Three cases of Acanthamoeba keratitis diagnosed and treated in the early stage

Acanthamoeba keratitis (AK) is a severe infectious corneal ulcer that usually occurs in contact lens wearers. Although the number of AK cases in Japan has been increasing, many of these cases are diagnosed in the early stage and are treated adequately. This is probably because of the increased availability of various diagnostic techniques and the ever-increasing knowledge about AK among ophthalmologists. In this article, we described 3 cases of AK that were diagnosed and treated in the early stages of the disease, and we discuss why 1 of the cases had a less favorable prognosis than the other 2 cases, which had excellent prognoses, from an etiological point of view

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140