Measuring Occupants' Behaviour for Buildings' Dynamic Cosimulation

Measuring and identifying human behaviours are key aspects to support the simulation processes that have a significant role in buildings' (and cities') design and management. In fact, layout assessments and control strategies are deeply influenced by the prediction of building performance. However, the missing inclusion of the human component within the building-related processes leads to large discrepancies between actual and simulated outcomes. This paper presents a methodology for measuring specific human behaviours in buildings and developing human-in-the-loop design applied to retrofit and renovation interventions. The framework concerns the detailed building monitoring and the development of stochastic and data-driven behavioural models and their coupling within energy simulation software using a cosimulation approach. The methodology has been applied to a real case study to illustrate its applicability. A one-year monitoring has been carried out through a dedicated sensor network for the data recording and to identify the triggers of users' actions. Then, two stochastic behavioural models (i.e., one for predicting light switching and one for window opening) have been developed (using the measured data) and coupled within the IESVE simulation software. A simplified energy model of the case study has been created to test the behavioural approach. The outcomes highlight that the behavioural approach provides more accurate results than a standard one when compared to real profiles. The adoption of behavioural profiles leads to a reduction of the discrepancy with respect to real profiles up to 58% and 26% when simulating light switching and ventilation, respectively, in comparison to standard profiles. Using data-driven techniques to include the human component in the simulation processes would lead to better predictions both in terms of energy use and occupants' comfort sensations. These aspects can be also included in building control processes (e.g., building management systems) to enhance the environmental and system management

Application of Small Epigenetic Modulators in Pediatric Medulloblastoma

Medulloblastoma is one of the most frequent among pediatric brain tumors, and it has been classified in various subgroups. Some of them already benefit from quite good therapeutic options, whereas others urgently need novel therapeutic approaches. Epigenetic modulators have long been studied in various types of cancer. Within this review, we summarize the main preclinical studies regarding epigenetic targets (such as HDAC, SIRT, BET, EZH2, G9a, LSD1, and DNMT) inhibitors in medulloblastoma. Furthermore, we shed light on the increasing number of applications of drug combinations as well as hybrid compounds involving epigenetic mechanisms. Nevertheless, in the studies published so far, mainly un-specific or old modulators have been used, and the PKs (brain permeability) have not been well-evaluated. Thus, these findings should be considered as a starting point for further improvement and not as a final result

Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells

Schwann cells are key players in neuro-regeneration: They sense "alarm" signals released by degenerating nerve terminals and differentiate toward a proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of Schwann cells' activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2O2 rewire the expression of several RNAs at both transcriptional and translational levels. Among the genes positively regulated at both levels, we identified an enriched cluster involved in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins being the most represented family. We show that both Annexin A2 (Anxa2) transcript and protein accumulate at the tips of long pseudopods that Schwann cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this signal and to nerve injury by locally translating Anxa2 in pseudopods, and undergo an extensive cytoskeleton remodeling. Our results show that, similarly to neurons, Schwann cells take advantage of local protein synthesis to change shape and move toward damaged axonal terminals to facilitate axonal regeneration

Identification of a novel quinoline-based DNA demethylating compound highly potent in cancer cells

Background DNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported in cancer initiation and progression. To date, two DNMT inhibitors (DNMTi), 5-azacytidine (5-AZA) and 5-aza-2′-deoxycytidine (DAC), are approved for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Nevertheless, they are chemically instable and quite toxic for healthy cells; thus, the discovery of novel DNMTi is urgent. Results Here, we report the identification of a new quinoline-based molecule, MC3353, as a non-nucleoside inhibitor and downregulator of DNMT. This compound was able, in promoter demethylating assays, to induce enhanced green fluorescence protein (EGFP) gene expression in HCT116 cells and transcription in a cytomegalovirus (CMV) promoter-driven luciferase reporter system in KG-1 cells. Moreover, MC3353 displayed a strong antiproliferative activity when tested on HCT116 colon cancer cells after 48 h of treatment at 0.5 μM. At higher doses, this compound provided a cytotoxic effect in double DNMT knockout HCT116 cells. MC3353 was also screened on a different panel of cancer cells (KG-1 and U-937 acute myeloid leukemia, RAJI Burkitts lymphoma, PC-3 prostate cancer, and MDA-MB-231 breast cancer), where it arrested cell proliferation and reduced viability after 48 h of treatment with IC50 values ranging from 0.3 to 0.9 μM. Compared to healthy cell models, MC3353 induced apoptosis (e.g., U-937 and KG-1 cells) or necrosis (e.g., RAJI cells) at lower concentrations. Importantly, together with the main DNMT3A enzyme inhibition, MC3353 was also able to downregulate the DNMT3A protein level in selected HCT116 and PC-3 cell lines. Additionally, this compound provided impairment of the epithelial-to-mesenchymal transition (EMT) by inducing E-cadherin while reducing matrix metalloproteinase (MMP2) mRNA and protein levels in PC-3 and HCT116 cells. Last, tested on a panel of primary osteosarcoma cell lines, MC3353 markedly inhibited cell growth with low single-digit micromolar IC50 ranging from 1.1 to 2.4 μM. Interestingly, in Saos-2 osteosarcoma cells, MC3353 induced both expression of genes and mineralized the matrix as evidence of osteosarcoma to osteoblast differentiation. Conclusions The present work describes MC3353 as a novel DNMTi displaying a stronger in cell demethylating ability than both 5-AZA and DAC, providing re-activation of the silenced ubiquitin C-terminal hydrolase L1 (UCHL1) gene. MC3353 displayed dose- and time-dependent antiproliferative activity in several cancer cell types, inducing cell death and affecting EMT through E-cadherin and MMP2 modulation. In addition, this compound proved efficacy even in primary osteosarcoma cell models, through the modulation of genes involved in osteoblast differentiation.This work was supported by COST Action CM1406 (PBA, LA, AM, SV); by Ricerca Finalizzata 2013 PE-2013-02355271 (AM); by PRIN 2016 (prot. 20152TE5PK) (AM, LA); by AIRC grants n. 19162 (AM), 17217 (LA), and 18843 (MT); by NIH funds n. R01GM114306 (AM) and BLUEPRINT n. 282510 (AM, LA); by Programma VALERE: Vanvitelli per la Ricerca (LA) and the Italian-Flag Project-EPIGEN (LA); and by Pasteur Institute-Cenci Bolognetti Foundation (MT). MS was supported by a Waxweiler grant for cancer prevention research from the Action Lions Vaincre le Cancer. CF is a recipient of a Télévie Luxembourg fellowship. The work at LBMCC was supported by the Recherche Cancer et Sang foundation, by the Recherches Scientifiques Luxembourg association, by the Een Häerz fir kriibskrank Kanner association, by the Action LIONS Vaincre le Cancer association, and by Télévie Luxembourg. MD was supported by the Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Korea; the Tumor Microenvironment GCRC (2011-0030001) from the National Research Foundation funded by the Ministry of Science and ICT of Korea; the Creative-Pioneering Researchers Program through Seoul National University (SNU) [Funding number: 370C-20160062]; and Brain Korea (BK) 21 Plus program, Korea

Ventilation in Traditional Coverings an Analysis of The Hygrometric and Thermal Behavior

The use of ventilation technologies for roofs has become widespread in several countries in order to reduce the energy loads on air-conditioning systems. In a number of Southern European countries ventilation systems are characterised - from a technological point of view - by the fact that they are made of tiles lifted by means of wooden elements or insulating sandwiches. This brings about the presence of a ventilation chamber whose thickness varies from 2 to 6/7 cm. Nevertheless such values contrast with the data derived from the analytical models based on the classic ventilation theory and make it necessary to have higher ventilation chambers. This article is based on the results from the tests carried out on 5 types of ventilated coverings on an experimental building for a whole year. It shows that the discrepancy can be ascribed to the high air permeability characteristic of the covering mantle. The tests make it possible to prove the reduced applicability of the classic ventilation theory [Hens,1999] and provide data on the hygrometric and thermal behaviour of ventilated coverings for a whole year. In particular, the most significant results are as follows: - during the winter ventilation determines considerable increases (25%) in the thermal flows transmitted towards the outside. The results are much worse than for comparable non-ventilated coverings; - during the summer ventilation determines a remarkable decrease in incoming thermal flows towards the environment. The decrease is not directly related to the ventilation section, but seems to be influenced by the permeability in the mantle; - again during the summer the simple increase in the insulating layer in the non-ventilated covering results in an improvement comparable to that of ventilated coverings; - from the hygrometric point of view ventilation acts as a humidity dissipator only for short periods during the day and only for some periods of the year

Properties and durability of ancient bricks

The physical-mechanical properties, the compositio and the old manifacture technologies of ancient bricks, in addition to durability are aveluate