Ageing workforce management in manufacturing systems: state of the art and future research agenda

The workforce ageing phenomenon is recently affecting most of the Organisation for Economic Co-operation and Development (OECD) member countries, due to a general ageing of their populations and a higher average retirement age of the workforce. In this paper, the topic of ageing workforce management is addressed from a production research standpoint, with the aim of understanding how older workers can be supported and involved in a manufacturing system. First, the current state of the art related to the ageing workforce in production systems is presented. This is structured according to four main topics: (1) analysis and evaluation of ageing workers’ functional capacities, (2) consideration of ageing workers’ capacities in industrial system modelling and management, (3) analysis and exploitation of ageing workers’ expertise, (4) acknowledgement, analysis, design and integration of supporting technologies. Next, the discussion on the impact of the ageing workforce on manufacturing systems’ performances leads to the comparison of some technological advances that are related to the Industry 4.0 paradigms. Finally, a future research agenda on this topic is proposed, based on the same topics classification proposed for the literature analysis. Five different research areas are derived, suggesting future directions for appropriate research concerning the employ of older workers in production environments.     

Microfluidic motion for a direct investigation of solvent interactions with PDMS microchannels

Solid surface/liquid interactions play an important role in microfluidics and particularly in manipulation of films, drops and bubbles, a basic requirement for a number of lab-on-chip applications. The behavior of solvents in coated microchannels is difficult to be predicted considering theories; therefore, experimental methods able to estimate the properties at the interface in real time and during the operational regime are amenable. Here, we propose to use an experimental setup to evaluate the effective dynamics of solvents inside PDMS microchannels. The influence of the solvent properties as well as of the channel wall’s wettability on the fluid movements was evaluated. Modification of the channel properties was achieved by introducing Teflon coatings that allow producing stable hydrophobic microchannel walls. The results were fitted according to Washburn-type power-law and compared with theoretical calculations of the parameter β that expresses the dependence of capillary dynamics on surface tension γ, liquid viscosity η, contact angles θ and the hydraulic radius R _H. A comparison between the calculated and the experimental values reveled that parameters other than the contemplated ones influenced the measurements. The main parameter that affects the flow of solvents such as water, methanol ethanol, dimethylformamide, acetonitrile and acetone was found to be the γ/η ratio. Considering these results, the investigation tool described here is believed to be promising to predict the dynamics of common organic solvents inside integrated functional fluidic devices and to accurately control solvent flow, particularly in capillary-driven pumpless systems, a basic requirement for widening the application range of PDMS lab-on-chip devices.     

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC₅₀=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC₅₀=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.     

Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

One year of ICTP diploma courses on-line using the automated EyA recording system

The 12-month pre-Ph.D. ICTP Diploma Courses in the fields of Condensed Matter Physics, High Energy Physics, Mathematics, Earth System Physics and Basics Physics have been recorded using the automated, low cost recording system called EyA developed in-house. We discuss the technical details on how these recordings were implemented, together with some web usage statistics and students feedback. As yet, no similar endeavor has been made to put on-line a complete high-level Diploma Programme, due to the high costs involved when using alternative recording solutions. These recordings are freely available on the website www.ictp.tv.     

Densification and properties of bulk nanocrystalline functional ceramics with grain size below 50 nm

The synthesis and functional characterization of dense bulk nanometric oxides are reviewed, with particular emphasis on the modifications that a grain size in the low nanometric range (10–50 nm) introduces in their physical properties. The preparation of ceramics with low porosity and extremely small grain size is particularly challenging and mostly relies on the sintering of extremely fine nanopowder. The most popular methods for the preparation of the starting nanopowders are introduced and briefly discussed as well as the most widely employed densification techniques. The role of nanostructure in controlling phase stability, electrical and thermal transport, optical and magnetic properties of nano-oxides is discussed in details. Several examples are given where bulk materials prepared with grain size equal or below 50 nm show characteristics that are either enhanced or, in some cases, completely different from those possessed by the same materials, but with larger grain sizes.     

Myosin isoforms in skeletal muscle in patients with chronic heart decompensation: distribution and correlation with with exercise tolerance

Chronic heart failure (CHF) is accompanied by a reduced exercise capacity, and the symptoms can be at least in part explained by qualitative and quantitative changes in the skeletal muscle composition and metabolism. We have correlated the myosin heavy chain (MHC) composition of the gastrocnemius in 20 patients with different degrees of CHF to expiratory gases measured during maximal cardiopulmonary exercise testing, NYHA functional class and echocardiographic parameters. MHC composition was determined electrophoretically in skeletal muscle needle microbiopsies and the percent distribution calculated by laser densitometry. There was no correlation between ejection fraction, left ventricular end-diastolic and end-systolic diameters and MHC composition. The percentage of MHC 1 (slow aerobic isoform) was positively correlated with peak VO2 (r2 = 0.5, p = 0.0004), ventilatory threshold (VT, r2 = 0.33, p = 0.008), and O2 pulse (peak VO2/HR, r2 = 0.40, p = 0.003). There was a negative correlation between MHC 2a and 2b (fast isoforms) and peak VO2 (r2 = 0.38 and 0.37, p = 0.004, respectively), VT (r2 = 0.2, p = 0.05; r2 = 0.34, p = 0.007, respectively) and O2 pulse (r2 = 0.39, p = 0.003; r2 = 0.23, p = 0.03, respectively). NYHA functional class was also negatively correlated with the same parameters (r2 = 0.2, p = 0.01; r2 = 0.4, p = 0.001; r2 = 0.34, p = 0.006, respectively) as well as with MHC 1 (r2 = 0.62, p = 0.0001). A positive correlation was found between NYHA functional class and MHC 2a and 2b (r2 = 0.46, p = 0.001; r2 = 0.41, p = 0.002, respectively). The severity of heart failure is paralleled by a shift of the MHC pattern toward the fast MHC 2b. The correlation between the magnitude of the MHCs shift, from the slow aerobic to the fast type, with both clinical parameters (NYHA functional class) and functional measurements (peak VO2, VT, O2 pulse) of exercise capacity seem to suggest that changes in skeletal muscle composition may play a key role in exercise tolerance in patients with CHF.     

Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents

Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds.