Synchronizing physical and digital factory: benefits and technical challenges

Abstract The Digital Twin is a representation of characteristics and behavior of a factory according to various levels of detail and the scope it addresses. Its full range of capabilities can be exploited when it is synchronized with the real world. Indeed, in this case, it can be used to mirror the real operating conditions for simulating the real-time behavior, and thus forecasting factory performances. However, we are still far from its large-scale diffusion. The purpose of this work is to analyze both the major challenges that still have to be faced and some potential solutions for each of the identified challenges

High-speed tunable photonic crystal fiber-based femtosecond soliton source without dispersion pre-compensation

We present a high-speed wavelength tunable photonic crystal fiber-based source capable of generating tunable femtosecond solitons in the infrared region. Through measurements and numerical simulation, we show that both the pulsewidth and the spectral width of the output pulses remain nearly constant over the entire tuning range from 860 to 1160 nm. This remarkable behavior is observed even when pump pulses are heavily chirped (7400 fs^2), which allows to avoid bulky compensation optics, or the use of another fiber, for dispersion compensation usually required by the tuning device.Comment: 8 pages, 11 figure

Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes

The synthesis of adequate amounts of ribosomes is an essential task for the cell. It is therefore not surprising that regulatory circuits exist to organize the synthesis of ribosomal components. It has been shown that defect in ribosome biogenesis (ribosomal stress) induces apoptosis or cell cycle arrest through activation of the tumor suppressor p53. This mechanism is thought to be implicated in the pathophysiology of a group of genetic diseases such as Diamond Blackfan Anemia which are called ribosomopathies. We have identified an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation. This leads to a translational reprogramming in the cell that involves the structurally defined group of messengers called terminal oligopyrimidine (TOP) mRNAs which encode ribosomal proteins and translation factors. In fact, while general protein synthesis is decreased by the impairment of elongation, TOP mRNAs are recruited on polysomes causing a relative increase in the synthesis of TOP mRNA-encoded proteins compared to other proteins. Therefore, in response to ribosomal stress, there is a change in the translation pattern of the cell which may help restore a sufficient level of ribosomes

FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors

FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors Background HER2-positive tumors are associated with a poor prognosis and a shortened disease-free and overall survival as well as with other unfavorable prognostic tumor characteristics (high histological grade, high proliferative index, negative or low estrogen receptor expression, etc.). HER2-positive tumors are also responsive to treatment with trastuzumab in reducing the risk of recurrence and improving survival. The aim of this study is to assess the incidence of HER2 gene amplification in selected tumors with adverse prognostic features which scored 1+ by immunohistochemistry (IHC). Methods 75 women with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) scoring 1+ by IHC were included. Forty-eight invasive breast carcinoma samples were selected according to unfavorable prognostic tumor characteristics and tested by FISH. HER2 amplification was evaluated using Vysis HER2/Cep17 probe (Path Vysion HER2 DNA Probe Kit®, Abbott Molecular, IL); ratio–based amplification was considered present when the HER2/Cep17 ratio was 2 or more and copy number-based amplification was considered present when the mean HER2 copy number was more than 6, in agreement with the ASCO/CAP/SIAPEC guidelines. Results In 2013, 331 patients with invasive breast tumors were tested by IHC; 75 cases (23%) were scored 1+ of which 62 cases (19%) of IDC and 13 cases (4%) of ILC. Forty-eight invasive breast carcinoma samples (64%) were selected according to one or more unfavorable prognostic tumor characteristics; 22 out of 48 tumors (46%) showed high histological grade (G3); 27 cases (56%) had high proliferative index (Ki-67≥30%); 32 tumor samples (67%) were node-positive; and 29 cases (60%) showed vascular invasion. FISH was performed on 31 of the 1+ patients with adverse tumor characteristics and 7 IDC out of 48 (14.6%) showed HER2 amplification. Conclusions Our preliminary retrospective data suggest that 7 patients out of 48 (14.6%) scoring 1+ by IHC show HER2 amplification, in agreement with the most recently published literature data. In order to not deny the benefit deriving from trastuzumab administration, in breast cancer patients showing IHC 1+, it is advisable to test HER2 gene amplification by FISH. Bibliografia Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N, Mastropasqua MG, Bottiglieri L, Goldhirsch A, Viale G, Colleoni M. HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol. 2012 May;23(5):1371-2. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84

BIG DATA: THE CURRENT WAVE FRONT OF THE TSUNAMI

In recent years, a real tsunami has flooded many human activities. Genomics, Astronomy, Particle Physics and Social Sciences are just a few examples of fields which have been intensively invaded by a massive amount of data coming from simulation, experiments or exploration. This huge pile of data requires a new way to deal with, a real paradigmatic shift respect to the past as for theories, technologies or approaches in data management. This work outlines the current wave front of Big Data, starting from a possible characterization of this new paradigm to its most compelling applications and tools, with an exploratory research of Big Data challenges in manufacturing engineering

The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy Among Patients with Urothelial Carcinoma: A Meta-Analysis

Background. Immune checkpoint inhibitors (ICIs) have recently represented a breakthrough in urothelial carcinoma (UC). Proton pump inhibitors (PPIs) are routinely used for extended time periods in UC patients, with these agents having potentially and frequently undervalued effects on ICIs efficacy. Methods. We performed a meta-analysis aimed at investigating the impact of concomitant PPI administration on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic UC. Results. Two studies encompassing a total of 1015 patients were included. The pooled Hazard Ratios (HRs) for OS and PFS were 1.55 (95% CI, 1.31–1.84) and 1.43 (95% CI, 1.23–1.66), respectively, suggesting that the administration of PPIs was negatively associated with PFS and with OS in UC patients treated with ICIs. Conclusions. The current meta-analysis represents the first study to provide a systematic evaluation of the impact of concomitant PPI use in UC patients treated with ICIs. Further studies are warranted on this topic to clarify the relationship between gut microbiome, antiacid exposure, and cancer immunotherapy. In the current era of medical oncology, progress in this setting will require the collaboration of basic science and clinical research to optimize systemic treatment and to improve the outcomes of UC patients receiving ICIs

Acute Myocarditis After Black Widow Spider Bite: A Case Report

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Non-plasmonic nanoantennas for surface enhanced spectroscopies with ultra-low heat conversion

Nanoplasmonics has recently revolutionized our ability to control light on the nanoscale. Using metallic nanostructures with tailored shapes, it is possible to efficiently focus light into nanoscale field 'hot spots'. High field enhancement factors have been achieved in such optical nanoantennas, enabling transformative science in the areas of single molecule interactions, highly enhanced nonlinearities and nanoscale waveguiding. Unfortunately, these large enhancements come at the price of high optical losses due to absorption in the metal, severely limiting real-world applications. Via the realization of a novel nanophotonic platform based on dielectric nanostructures to form efficient nanoantennas with ultra-low light-into-heat conversion, here we demonstrate an approach that overcomes these limitations. We show that dimer-like silicon-based single nanoantennas produce both high surface enhanced fluorescence and surface enhanced Raman scattering, while at the same time generating a negligible temperature increase in their hot spots and surrounding environments