The diffusion of international standards on managerial practices

This article presents a comprehensive framework which identifies the relevant factors that can influence the standard adoption process, along with insights for performing a qualitative perspective analysis on the possible market diffusion of a specific standard under development or under review. This article also shows an example of framework application to the ISO 22400 standard, evidencing organizational and managerial implications on the standard adoption process

Tau Modulates VGluT1 Expression

Abstract Tau displacement from microtubules is the first step in the onset of tauopathies and is followed by toxic protein aggregation. However, other non-canonical functions of Tau might have a role in these pathologies. Here, we demonstrate that a small amount of Tau localizes in the nuclear compartment and accumulates in both the soluble and chromatin-bound fractions. We show that favoring Tau nuclear translocation and accumulation, by Tau overexpression or detachment from MTs, increases the expression of VGluT1, a disease-relevant gene directly involved in glutamatergic synaptic transmission. Remarkably, the P301L mutation, related to frontotemporal dementia FTDP-17, impairs this mechanism leading to a loss of function. Altogether, our results provide the demonstration of a direct physiological role of Tau on gene expression. Alterations of this mechanism may be at the basis of the onset of neurodegeneration

Identification of an ERK inhibitor as a therapeutic drug against tau aggregation in a new cell-based assay

Formation of Tau aggregates is a common pathological feature of tauopathies and their accumulation directly correlates with cytotoxicity and neuronal degeneration. Great efforts have been made to understand Tau aggregation and to find therapeutics halting or reversing the process, however, progress has been slowed due to the lack of a suitable method for monitoring Tau aggregation. We developed a cell-based assay allowing to detect and quantify Tau aggregation in living cells. The system is based on the FRET biosensor CST able to monitor the molecular dynamic of Tau aggregation in different cellular conditions. We probed candidate compounds that could block Tau hyperphosphorylation. In particular, to foster the drug discovery process, we tested kinase inhibitors approved for the treatment of other diseases. We identified the ERK inhibitor PD-901 as a promising therapeutic molecule since it reduces and prevents Tau aggregation. This evidence establishes the CST cell-based aggregation assay as a reliable tool for drug discovery and suggests that PD-901 might be a promising compound to be tested for further preclinical studies on AD

The molecular mechanisms of nuclear Tau influence on gene expression

Tau is a microtubule (MT) binding protein involved in a large number of dementias known as tauopathies. Canonically, the cytoplasmic role of Tau has been blamed for pathogenesis: hyperphosphorylated Tau detaches from MTs and forms toxic aggregates that engulf the cell cytoplasm and spread to neighbouring cells. However, Tau has roles in various subcellular compartments that might contribute to the onset of dementia and explain early symptoms. In my thesis, I investigated the role of Tau in the nucleus: nuclear Tau is able to modulate the expression of target genes involved in the glutamate pathway, in particular the vesicular glutamate transporter VGluT1, in accordance with the excitotoxicity phenotype. A large number of additional pathways are deregulated, including both neuron-specific features like axon guidance and synaptic potentiation, and systemic outcomes on immunity and glucose metabolism. This widespread deregulation correlates with the relocalization of epigenetic remodellers, suggesting that it might involve the disruption of a silencing complex, to establish an open chromatin state. The resulting transcriptional profile in our cell model of Tau-overexpressing differentiated SH-SY5Y cells is highly consistent with early disease phases in the brain and blood of AD patients. Thus, nuclear Tau might make a significant contribution to the onset of tauopathies

Proposal for a classification of ISO22400 KPIs for manufacturing operations management

The ISO22400 standard defines key performance indicators for manufacturing operation management. Its visionary goal is to be applicable to all industry types, regardless the production methodology and the process configuration. Pursuing this objective, a challenging trade-off between generality and specificity in the definitions must be found. In the cited standard, the former approach has been preferred: thus, several indicators seem too vaguely defined and result to be difficulty usable in real contexts. Our aim is to refine the ISO22400 standard definitions and in this paper, by means of a designed classification method combined with the explicit and implicit existing information, the indicators are analysed according to their specific initial application context. Afterward, context extensions are proposed to overcome the recognised shortcomings and to better support performance measurement. In this step on the road to the improvement of the ISO standard, we managed to refer each indicator to work orders, production orders, work units, to the entire process, and to possible combination of these. This information is crucial to proceed towards a better interpretation of the standard and, thus, its diffusion in the real world

Key performance indicators for manufacturing operations management - Gap analysis between process industrial needs and ISO 22400 standard

ISO 22400 has defined a set of Key Performance Indicators (KPIs) to evaluate the performance of manufacturing operation. Despite it's conceived to be industry-neutral, the defined KPIs seem not to be perfectly suitable for process industry. Based on a survey performed in a process industrial company, this paper highlights the specific process industry's needs for evaluating the operational performance. Taking cue from this survey and by analyzing the characteristics and the needs of performance evaluation in process industry, the relevance of defined KPIs and comparison analysis between defined KPIs and needs-based KPIs are discussed, and some modifications are proposed

Key performance indicators for manufacturing operations management in the process industry

The international standard ISO 22400 has defined a set of Key Performance Indicators (KPIs) to evaluate the performance of manufacturing operation. However, the defined KPIs seem to be inspired from the discrete production context, and hence do not automatically fit the process industry context. The process industry is defined as the industry in which the raw material undergoes conversion during a continuous process in order to become finished products. To make the defined KPIs more suitable for evaluating the operational performance in process industry, this paper analyzes the different characteristics of process industry and discrete industry, and proposes a new framework for organizing KPIs in process industry. Some modifications are discussed to make the proposed ISO 22400 KPIs fit to the process industry. Such a study can provide useful ideas for manufacturing engineers and decision-makers to define and measure suitable KPIs for performance evaluation in process industry

KPIs for Manufacturing Operations Management : driving the ISO22400 standard towards practical applicability

A set of key performance indicators (KPIs) for manufacturing operation management is introduced in the ISO 22400 standard. However, KPIs are only defined at a high abstraction level and this hampers the standard's practical adoption. In this paper, a framework is introduced in order to solve this weakness. Starting from the analysis of the relevant measurements used in the KPIs’ formulas, a classification model is introduced defining three possible application scopes - work orders, work units and production orders - to analyze each basic element of the standard. As a result, the KPIs defined in the ISO 22400 standard are more precisely specified and, as a consequence, also suitable to be straightforwardly implemented in performance measurement systems

Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies