Protein microarray analysis of aberrant signaling pathways in Acute Myeloid Leukemia to predict the patients responsiveness to PI3K/Akt/mTOR inhibitors

Mapping of deregulated kinases and protein signalling networks within tumors can provide a means to stratify patients with shared biological characteristics to the most optimal treatment, and identify drug targets. In particular, the PI3K/AKT/mTOR signaling pathways are frequently activated in blast cells from patients with acute myelogenous leukemia (AML), a neoplastic disorder characterized by the accumulation of genetically altered myelogenous cells displaying deregulated intracellular signalling pathways and aggressive clinical behavior with poor prognosis. Using Reverse Phase Protein Microarrays (RPMA), we have analyzed the phosphorylated epitopes of signal pathway proteins of 81 peripheral blood and bone marrow specimens with newly diagnosed AML. Patients are diagnosed according to blast content, FAB classification and cytogenetic analysis. Samples are enriched for leukemic cells by performing Ficoll separation to yield a mononuclear fraction with >60% blast cells. The objective of the study was to predict the sensitivity of each patient to PI3K/Akt/mTor inhibitors, to avoid unnecessary and toxic ineffective treatment of non-responsive patients. To this goal, fresh blast cells were grown for 16 h untreated or treated with phase I or phase II mTor or Akt inhibitors either alone or in combination. Remarkably, by unsupervised hierarchical clustering a strong phosphorylation/activity of most of the sampled members of the PI3K/Akt/mTOR pathway was observed in 70% of samples from AML patients. This confirms that this pathway might indeed represent a pharmacological target in many patients. Moreover, treatment with the above inhibitors had no effect on the phosphorylation of other selected targets, demonstrating the specificity of the above results (more than one different inhibitor was used to avoid off-target effects). More importantly, by the use of the above drugs, we have been able to discriminate within the “high pAkt” population a PI3K/Akt/mTOR inhibitor-responsive group of patients and a PI3K/Akt/mTOR inhibitor non-responsive group. In addition, our data indicate that the Akt pathway is hyper-activated in M4, M5 patients, compared to M0, M2 patients, and that a strong activation of most upstream and downstream Akt effectors correlates with an over-expression of the c-kit receptor (CD117). We believe these data are important because they, have the potential to define a profile for the personalized administration of targeted drugs

The Laboratory Definition of the Thermal Resistance of Growing Media for Green Roofs: New Experimental Setups

Green roofs are one of the most extensively investigated roofing technologies. Most of the bibliographical studies show results of researches focused on the analysis of different configurations of green roofs, but only few researches deal with the calculation of the growing media thermal resistance using laboratory tests. From 2009 to 2013, ITC-CNR, the Construction Technologies Institute of the National Research Council of Italy, carried out a first laboratory experimental campaign focused on the definition of thermal performances curves of growing media for green roofs as a function of both density and percentage of internal moisture. During this campaign, the experimental results underlined some existing gaps, such as the absence of specific standards concerning the sample laboratory preparation, the absence of shared references concerning the compaction level reached by samples in real working conditions and the evaluation of the internal moisture content of growing media exposed to atmospheric agents. For this reason, the ITC-CNR has set up a second experimental campaign focused on the solution of the gaps underlined by the first phase concerning the preparation of samples for the laboratory calculation of the thermal resistance of growing media for green roofs. This paper proposes and presents methodological approaches, methods and new test devices implemented to solve these gaps, and the results obtained

Assessment of the Impact of Cool Roofs in Temperate Climates through a Comparative Experimental Campaign in Outdoor Test Cells

Over the last few decades many bibliographical studies have been conducted on cool roofs, by analyzing both the energy performance during summer and winter seasons and their contribution in mitigating the urban heat island effect. This paper describes the experimentation carried out in three outdoor test cells to comparatively assess the behavior of a cool roof solution with respect to a ventilated-roof and a warm-roof. The monitored data have confirmed that in summer cool roofs are the best solution, with respect to traditional tile roofing, sensibly reducing surface temperatures as a function of the solar direct radiation level (15–25 °C for I > 600 W/m2 and 5–15 °C for I < 300 W/m2, independently of the season). Furthermore, cool roofs involve an energy saving related to summer cooling by about 20% as to a warm-roof and 15%–20% as to a vented-roof. During winter, cool roofs improve the heating energy performance of a vented-roof by about 12%, against a slightly increased consumption (<5%) if compared to a warm-roof. These data confirm that, in temperate climates, cool roofs are appropriate solutions to sensibly improve summer energy performances with a negligible negative impact during winter, and to positively contribute to the mitigation of the heat island effect

The Energy Impact in Buildings of Vegetative Solutions for Extensive Green Roofs in Temperate Climates

Many bibliographical studies have highlighted the positive effects of green roofs as technological solutions both for new and renovated buildings. The one-year experimental monitoring campaign conducted has investigated, in detail, some aspects related to the surface temperature variation induced by the presence of different types of vegetation compared to traditional finishing systems for flat roofs and their impact from an energy and environmental point of view. The results obtained underlined how an appropriate vegetative solution selection can contribute to a significant reduction of the external surface temperatures (10 °C–20 °C for I > 500 W/m2 and 0 °C–5 °C for I < 500 W/m2, regardless of the season) compared to traditional flat roofs. During the winter season, the thermal gradients of the planted surface temperatures are close to zero compared to the floor, except under special improving conditions. This entails a significant reduction of the energy loads from summer air conditioning, and an almost conservative behavior with respect to that from winter heating consumption. The analysis of the inside growing medium temperatures returned a further interesting datum, too: the temperature gradient with respect to surface temperature (annual average 4 °C–9 °C) is a function of solar radiation and involves the insulating contribution of the soil

The Laboratory Definition of the Thermal Resistance of Growing Media for Green Roofs: New Experimental Setups

Green roofs are one of the most extensively investigated roofing technologies. Most of the bibliographical studies show results of researches focused on the analysis of different configurations of green roofs, but only few researches deal with the calculation of the growing media thermal resistance using laboratory tests. From 2009 to 2013, ITC-CNR, the Construction Technologies Institute of the National Research Council of Italy, carried out a first laboratory experimental campaign focused on the definition of thermal performances curves of growing media for green roofs as a function of both density and percentage of internal moisture. During this campaign, the experimental results underlined some existing gaps, such as the absence of specific standards concerning the sample laboratory preparation, the absence of shared references concerning the compaction level reached by samples in real working conditions and the evaluation of the internal moisture content of growing media exposed to atmospheric agents. For this reason, the ITC-CNR has set up a second experimental campaign focused on the solution of the gaps underlined by the first phase concerning the preparation of samples for the laboratory calculation of the thermal resistance of growing media for green roofs. This paper proposes and presents methodological approaches, methods and new test devices implemented to solve these gaps, and the results obtained

Measurement of Thermal Properties of Growing Media for Green Roofs: Assessment of a Laboratory Procedure and Experimental Results

While the Italian standard UNI 11235:2015 establishes minimum performance criteria, the thermal resistance of the growing medium of green roofs is not included in national regulations. Instead, thermal transmittance limits for roofs are obtained by referring to other stratigraphic layers. In the absence of specific national and international standards for laboratory calculations of the thermal performance of growing media for green roofs, a multi-year laboratory testing campaign was carried out on 8 samples which aimed to define the thermal resistance reference values of growing media as a function of density and water content. Thermal conductivity varies between 0.046–0.179 W/mK for dry samples as a function of density and between 0.046–0.47 W/mK as a function of moisture content. Defining a reference method, laboratory tests and restitution of the output in performance curves, was based on 108 tests carried out according to and deviating from the standard based on both guarded hot plate and heat flow meter methods. The significance of the results has prompted researchers and industrial partners to engage in further investment and ongoing tests in this area, targeting the definition of a standard laboratory method to be presented worldwide

Assessment of the Performance of a Ventilated Window Coupled with a Heat Recovery Unit through the Co-Heating Test

The aim of the article is to describe the results of an experimental campaign based on the assessment of a heat recovery unit coupled with a dynamic window. Two fully monitored and calibrated outdoor test cells are used, in order to evaluate the energy performance and the related thermal comfort. The former presents a traditional window with double-glazing, aluminum frame and indoor blind and a centrifugal extractor for the air circulation. The latter is equipped with a dynamic window with ventilated and blinded double-glazing provided with a heat exchanger. The connection of the dynamic window and heat recovery unit provides different actions: heat recovery; heat transfer reduction; pre-heating before the exchanger. Different operating configurations allowed the trends of the dynamic system to be assessed in different seasons in terms of energy saving, thermal comfort behavior and energy efficiency. The results showed an overall lower consumption of the innovative system, both in winter and summer, with 20% and 15% energy saving, respectively. In general, the dynamic system provided the best comfort conditions, even if it involves a worse behavior than expected, in the summer season

Correlation between Indoor Environmental Data and Biometric Parameters for the Impact Assessment of a Living Wall in a ZEB Lab

Users’ satisfaction in indoor spaces plays a key role in building design. In recent years, scientific research has focused more and more on the effects produced by the presence of greenery solutions in indoor environments. In this study, the Internet of Things (IoT) concept is used to define an effective solution to monitor indoor environmental parameters, along with the biometric data of users involved in an experimental campaign conducted in a Zero Energy Building laboratory where a living wall has been installed. The growing interest in the key theory of the IoT allows for the development of promising frameworks used to create datasets usually managed with Machine Learning (ML) approaches. Following this tendency, the dataset derived by the proposed infield research has been managed with different ML algorithms in order to identify the most suitable model and influential variables, among the environmental and biometric ones, that can be used to identify the plant configuration. The obtained results highlight how the eXtreme Gradient Boosting (XGBoost)-based model can obtain the best average accuracy score to predict the plant configuration considering both a selection of environmental parameters and biometric data as input values. Moreover, the XGBoost model has been used to identify the users with the highest accuracy considering a combination of picked biometric and environmental features. Finally, a new Green View Factor index has been introduced to characterize how greenery has an impact on the indoor space and it can be used to compare different studies where green elements have been used

1130 Supporting sustainable policies through an Urban Energy-Environmental Model and a Multi-Criteria Analysis: a case study in an Italian province

Public Authorities (PAs) need to define cross-cutting strategies for urban planning including policies for sustainable and energy-efficient buildings and innovative urban solutions. The article presents a decision support tool that combines an Urban Energy Environmental Model (UEEM) and a Multi-Criteria Analysis (MCA) to support the development of sustainable local policies. The UEEM, developed with a bottom-up approach incorporating energy and environmental items, provides a~representation of the performance of local urban areas and quantifies the impact of new interventions in expansion areas. The UEEM is based on the definition of virtual archetypes built on the characteristics of the area under consideration. 92 building archetypes and 40 urban archetypes are developed. The energy performance of each building archetype is calculated with a dynamic simulation tool. The environmental performance of urban areas (overheating risk and outdoor thermal comfort) is analysed through a Grasshopper-based parametric model. In addition, soil permeability is calculated. The UEEM results are aggregated into a single index using the MCA, providing a Municipal Rating Index (MRI). The weights of the MCA are estimated through the Analytical Hierarchy Process (AHP) based on a survey submitted to local stakeholders (municipalities, environmental associations, experts). The model is applied to the province of Monza and Brianza in northern Italy