Using the Process Digital Twin as a tool for companies to evaluate the Return on Investment of manufacturing automation

The fourth industrial revolution is gaining momentum, but still lacks full realization. Several studies suggest that many companies around the world have begun the digital transformation undertaking, but most are still far from full adoption and yet fail to see the full economic potential, being stuck in what has been called "pilot purgatory”. Digitalization is largely recognized as an accelerator and enabler for full automation in manufacturing, but companies are still struggling to assess the return on investment and the impact on operational performance indicators. Therefore, companies, especially SMEs characterized by dynamic, high-value, high-mix, and low-volume contexts, are reluctant to invest further. By incorporating simulation, data analytics and behavioral models, digital twins may also be used to support automation solutions ramp-up, demonstrate their impact evaluation, usage scenarios, eliminating the need for physical prototypes, reducing development time, and improving quality. Few forward-thinking companies are pursuing the digital transformation path, while the majority are clipping the wings of a transformation that is essential for a sustainable manufacturing. This paper describes a theoretical approach to exploit the digital twin technology to gather insights towards a realistic economical assessment of full automation solutions, to back and encourage investments to realize the potential of the digital manufacturing transformation. The approach is being tested under the European Union’s Horizon 2020 research and innovation program under grant agreement No. 958363, which provides an opportunity to assess how the various components of the method are constructed, how complex they are, and what level of effort is required, using a practical example

Combined Management of Groundwater Resources and Water Supply Systems at Basin Scale Under Climate Change

Water stress conditions associated with population growth, climate change, and groundwater contamination, represent a significant challenge for all stakeholders in the water sector. Increasing the resilience of Water Supply Systems (WSSs) becomes of fundamental importance: along with an adequate level of service, sustainability targets must be ensured. A long-term management strategy is strictly connected to a holistic approach, based on analyses at different scales. To this end, both groundwater modeling tools and water management models, with different spatial and temporal scales, are routinely and independently employed. Here, we propose a coupled approach combining: i) groundwater models (MODFLOW) to investigate different stress scenarios, involving climate change and anthropic activities; ii) water management models (Aquator), to assess the water resources availability and the best long-term management strategy for large-scale WSS. The management models are implemented starting from input and output flows derived by groundwater models: this leads to establish a comprehensive framework usually not defined in management models and including a quantitative characterization of the aquifer. The proposed methodology, general and applicable to any study area, is here implemented to the WSS of Reggio Emilia Province, and its main groundwater resource, the Enza aquifer, considering three different stress scenarios for groundwater models (BAU, ST1, and ST2), and for management strategies (BAU, BAURV2, ST2). Among the key results, we observe that coupling the two model types: i) allows evaluating water resources availability in connection with management rules; ii) leads to examining more realistic operation choices; iii) permits planning of infrastructures at basin scale

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors

Several clinical observations have confirmed that a donor immune-mediated anti-malignancy effect, called graft-versus-leukemia or graft-versus-tumor, occurs following allogeneic hematopoietic stem cell transplantation. While the potential antitumor effect mediated by donor lymphocytes has been established in many hematological malignancies, its efficacy in inducing clinically meaningful responses in solid tumors has been largely unexplored despite evidence of its potential benefit in experimental animal models. Only in recent years has the investigational application of non-myeloablative stem cell transplantation in patients with refractory non-hematological cancers proved that a graft-versus-tumor effect can be generated in patients with metastatic renal cell cancer and possibly with other solid tumors. In the present article we review the biological basis, development and early clinical results of this novel immunotherapeutic approach for solid tumors

Diffusion of biosimilar hemopoietic growth factors use in oncology practice: an Italian experience

Background: Biosimilars of hemopoietic growth factors present an important saving opportunity in oncology. However, while pharmacologists are aware of their potential benefits, biosimilars are still under-used in Italy. Improved information and guided clinical experience may help to increase the clinical acceptance of these drugs. To this aim, a collaborative educational project was set between an Hospital Oncology Unit and the Local Health Care Authority in Pavia, Italy. Methods: The project lasted 12 months. The strategy included an education-information seminar at startup, a reporting meeting at +6$+6$ months, electronic prescription monitoring and implementation of pharmacovigilance. The target was set to reach 90% of all naïve patients treated with biosimilars. Results: At the end of the study (2013), a dramatic relative increase in the prescription of biosimilar drugs was noted, with virtually 100% of new patients receiving biosimilar drugs during the last 4 months, with a positive impact on average per capita drug expenses. Active pharmacovigilance did not report any serious adverse drug reactions. An anonymous questionnaire showed that oncologists judged the experience quite positively, acquired a positive attitude toward these drugs and considered biosimilars a relevant saving opportunity, while adherence to prescription guidelines was maintained. Analysis of the year following the end of the project, 2014, showed a persistent prescription change. Conclusions: Results from this local experience suggests that specifically designed pragmatic interventions focused on information-education and monitoring may help in promoting the use and acceptance of biosimilar drugs in the real clinical setting