Agri-food building performance evaluation by an integration of different measurement techniques: Case study of a bakery in south Italy

Abstract The performance of a building plays a key role in its sustainability, since a building cannot be sustainable if the needs of its users are not satisfied. In fact, the priority of a sustainable building is to meet the user requirements in an adequate manner, while limiting its environmental impact. The aim of this study is to supply a suitable Building Performance Evaluation method (BPE) to technicians, facility managers and designers, in order to improve the quality of management, design and construction by providing more sustainable agri-food buildings. In this study, in order to measure building performance with respect to user requirements, the simultaneous application of three different measurement techniques was proposed: a User survey by means of a questionnaire; an analysis of building documents and a walkthrough analysis by experts; and instrumental measurements and a direct survey of building characteristics. The proposed BPE method was based on a fuzzy weighted average at three levels. The fuzzy method proved to be particularly suitable for describing the vagueness of users when answering the questionnaire, for translating the document analysis, or considering the instrumental measurements for performance measures. The proposed method was applied to a typical agri-food building in southern Italy. This application demonstrated the correctness of the setting, its ease of application, and its ability to manage real cases. The method allowed for the evaluation of building performance by taking advantage of the positive characteristics of each measurement technique: the users' and occupants' perception, the knowledge and critical sense of expert technicians, and the accuracy and objectivity of instrumental measures. The results of the model were represented by mean fuzzy membership functions, which preserved the "vagueness" of the initial performance attributes. To obtain more synthetic values, a normalization procedure was applied to obtain a value performance judgment, expressed by a number in the range of 0 and 1 (where 0 is the worst and 1 is the best). The general performance of functional areas and the differences in performance in the same functional area were compared using this operation. The results of the case study demonstrated the reliability of the proposed method; in particular, it can determine the state of the building's functionality, drawing attention to weak points that should be monitored to prevent potential faults. The method proposed is a key element intended to help develop agri-food buildings that are effective and efficient and perform as expected and it contributes to improve the general quality of agri-food buildings

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30-40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI

Vegetated ditches for the mitigation of pesticides runoff in the po valley

In intensive agricultural systems runoff is one of the major potential diffuse pollution path- ways for pesticides and poses a risk to surface water. Ditches are common in the Po Valley and can potentially provide runoff mitigation for the protection of watercourses. The effec- tiveness depends on ditch characteristics, so there is an urgent need for site-specific field trials. The use of a fugacity model (multimedia model) can allows recognition of the mitiga- tion main processes. A field experiment was conducted in order to evaluate the mitigation capacity of a typical vegetated ditch, and results were compared with predictions by a fugacity model. To evaluate herbicide mitigation after an extreme runoff, the ditch was flooded with water containing mesotrione, S-metolachlor and terbuthylazine. Two other sub- sequent floods with uncontaminated water were applied 27 and 82 days later to evaluate herbicides release. Results show that the ditch can immediately reduce runoff concentration of herbicides by at least 50% even in extreme flooding conditions. The half-distances were about 250 m. As a general rule, a runoff of 1 mm from 5 ha is mitigated by 99% in 100 m of vegetated ditch. Herbicides retention in the vegetated ditch was reversible, and the second flood mobilized 0.03-0.2% of the previous one, with a concentration below the drinking water limit of 0.1 \u3bcg L-1. No herbicide was detected in the third flood, because the residual amount in the ditch was too low. Fugacity model results show that specific physical-chemi- cal parameters may be used and a specific soil-sediment-plant compartment included for modelling herbicides behaviour in a vegetated ditch, and confirm that accumulation is low or negligible for herbicides with a half-life of 40 days or less. Shallow vegetated ditches can thus be included in a general agri-environment scheme for the mitigation of pesticides runoff together with wetlands and linear buffer strips. These structures are present in the land- scape, and their environmental role can be exploited by proper management

Influence of Dietary Supplementation with Prebiotic, Oregano Extract, and Vitamin E on Fatty Acid Profile and Oxidative Status of Rabbit Meat

The effect of dietary supplementation with vitamin E, oregano, and prebiotic on fatty acids and oxidative profiles of rabbit meat (loin and hind leg) was evaluated. New Zealand white rabbits weaned at 30 days of age were fed with one of six diets until 80 days of age: standard diet includingω3 polyunsaturated fatty and conjugated linolenic acids sources (S) and five diets adding vitamin E (150 ppm, E), oregano water extract (2 g/kg feed diet, O), prebiotic (THEPAX® 1.5 g/kg feed diet, T), vitamin E plus prebiotic (TE), and oregano water extract plus prebiotic (TO), respectively. The lipid oxidative status (TBARS) showed lower values with respect to S, mainly when vitamin E was administered. In particular, all the experimental diets decreased TBARS values with respect to the control group in the loin, but no effect was found in the hind leg. In all feed samples, the amounts of fatty acid classes increased in the following order: polyunsaturated fatty acids > monounsaturated fatty acid > saturated fatty acid. The dietary supplementations did not affect the fatty acid composition of meat. The experimented diets compared to the control were not able to provide a selective increase of bioactive fatty acid in meat samples; however, the six nutritional strategies led to highly nutritional rabbit meat with an interesting value of theω6/ω3 ratio

MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors

MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where MYCN amplification occurs in about 25% of the cases. Intriguingly, MRE11 is highly expressed and predicts bad prognosis in MYCN-amplified neuroblastoma. Due to the lack of direct means to target MYCN, we explored the possibility to trigger intolerable levels of replication stress-dependent DNA damage, by inhibiting MRE11 in MYCN-amplified preclinical models. Indeed, either MRE11 knockdown or its pharmacological inhibitor mirin induce accumulation of replication stress and DNA damage biomarkers in MYCN-amplified cells. The consequent DDR recruits p53 and promotes a p53-dependent cell death, as indicated by p53 loss- and gain-of-function experiments. Encapsulation of mirin in nanoparticles allowed its use on MYCN-amplified neuroblastoma xenografts in vivo, which resulted in a sharp impairment of tumor growth, associated with DDR activation, p53 accumulation, and cell death. Therefore, we propose that MRE11 inhibition might be an effective strategy to treat MYCN-amplified and p53 wild-type neuroblastoma, and suggest that targeting replication stress with appropriate tools should be further exploited to tackle MYCN-driven tumors

A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors

Corrigendum: Current drive at plasma densities required for thermonuclear reactors

Nature Communications 1: Article number: 55 (2010); Published: 10 August 2010; Updated:19 September 2013. In Fig. 3 of this Article, the colours of the blue and green curves were accidentally interchanged while the manuscript was being revised. In addition, the x axis labels on Fig. 4 should have read 'Frequency (MHz)'