A structural modeling approach for the understanding of initiation and elongation of ALS-linked superoxide dismutase fibrils

Familial amyotrophic lateral sclerosis caused by mutations in copper-zinc superoxide dismutase (SOD1) is characterized by the presence of SOD1-rich inclusions in spinal cords. It has been shown that a reduced intra-subunit disulfide bridge apo-SOD1 can rapidly initiate fibrillation forming an inter-subunits disulfide under mild, physiologically accessible conditions. Once initiated, elongation can proceed via recruitment of either apo or partially metallated disulfide-intact SOD1 and the presence of copper, but not zinc, ions inhibit fibrillation. We propose a structural model, refined through molecular dynamics simulations, that, taking into account these experimental findings, provides a molecular explanation for the initiation and the elongation of SOD1 fibrils in physiological conditions. The model indicates the occurrence of a new dimeric unit, prone to interact one with the other due to the presence of a wide hydrophobic surface and specific electrostatic interactions. The model has dimensions consistent with the SOD1 fibril size observed through electron microscopy and provides a structural basis for the understanding of SOD1 fibrillation

Dynamic control strategies for distributed microgeneration and waste heat recovery power plants

In this paper the modeling activity on a waste heat recovery microgeneration ORC plant is presented together with the results of the application of two different load diagrams and three different control strategies. The overall energy production and the average efficiency were compared and a proper control strategy was evaluated to optimize the energy recovery process as well as the dynamic response of the plant

An energy saving solution applied to the final use of electrical and lighting systems of school buildings managed by Perugia Province

In this paper, a study and design of energy conservation actions and the obtention of Energy Efficiency Titles, according to the Italian Ministerial Decree 20th July 2004, applied to lighting and electrical systems in a school district managed by Perugia Province (Italy), is presented. Specifically, the analysis regarded the replacement of neon lamps with high efficiency ones, and the power factor correction of the electrical system with a lower value. The work was carried out through an energy audit of some school buildings. From the results of this energy audit, project solutions were developed and a technical and economical feasibility study was made. This study was then extended to the whole school building fleet managed by Perugia Province. The results of this work were validated by a commercial feasibility assessment through an ESCo

Numerical modelling of the response of an unsaturated silty soil under wetting and gravitational loading processes

This paper presents the results of a numerical study aiming at simulating the response of an unsaturated fine-grained soil under wetting and gravitational loading processes. This study is based on the results of some centrifuge tests carried out to assess the influence of partial saturation on the laterally loaded pile response. The hydro-mechanical behaviour of the silty soil is described using a constitutive model adapted to unsaturated conditions. The model predictions are compared with the measurements provided by LVDTs and laser transducers in the first phases of the experimental study. Besides validating the model, the numerical study aimed at investigating the influence of the after-compaction conditions on both the displacement field and the evolution of the more significant state variables during imbibition and gravitational loading processes. Finally, an additional analysis is conducted to determine the effects of the pile installation on the soil response

Sustainable food waste management in supermarkets

ood waste represents a significant burden to waste management systems, exacerbating food insecurity and contributing to global pollution, climate change, and biodiversity loss. Supermarkets bear partial responsibility for food waste, yet their sustainability efforts could also contribute to a solution. The present work aims at evaluating a sustainable approach to food waste management within supermarkets. To this end, we conducted a multi-criteria analysis, incorporating the perspectives of academic experts and 505 Italian consumers. Experts deemed residual value apps the most sustainable solution for food waste management in supermarkets, while also emphasising the influence of price and brand image. The consumer analysis corroborated these results. Specifically, consumers expressed a willingness to pay 36 % less for a bag of goods set to expire within 2–3 days, which increased to 60 % for goods set to expire within 24 h. The findings point to opportunities for mutual benefit between consumers and suppliers when food waste is effectively managed in store, thereby highlighting the need for further, product-focused research

Multivariate assessments of activity-related skeletal changes: Interpreting Bell Beaker specialized male archery and social organization in Central Europe

Objectives The Bell Beaker period witnessed the rise of individual inhumations with “wealthy” burial contexts containing archery-related grave goods, leading archaeologists to label the individuals in these tombs as “archers.” This study looks to (1) compare the skeletons from male “archer” burials with those from male “non-archer” burials—those not having archery-related grave goods—in order to assess a possible link between burial context and physical activity, and (2) apply a biomechanics profile to evaluate whether the individuals associated with these “archer” burials practiced specialized archer activity. Materials and Methods The corpus (males only) included 46 “archers” and 40 “non-archers” from Bell Beaker individual inhumations. Osteological data included measurements, scores of entheseal changes, and a diagnosis of certain pathologies. Data analyses involved visual observations, hypothesis tests, dimension reduction, and MANOVA, with approaches aimed at exploring the treatment of data missingness. Results Measurement data revealed no differences between the two groups. Evaluations of entheseal changes found that “non-archers” had consistently more instances of bone surface modifications than “archers.” Individual assessments of specialized archer occupation identified 11 possible specialized archers. Discussion These findings indicate a possible labor differentiation represented through the presence of a probably prestigious “archer” burial context. This suggests a link between grave good presence and labor, but not between a Bell Beaker archery occupation and an “archer” burial context. Data analyses support the application of biomechanics to osteological analyses in order to assess specialized activity on the skeleton

Multi-objective optimization of CCHP system with hybrid chiller under new electric load following operation strategy

The performance of combined cooling, heating and power (CCHP) system is greatly affected by its operating strategy and design. In this paper, a new electric load following (NELF) strategy was developed. It is based on the alternation between absorption cooling and electric cooling according to the building energy requirements, for hybrid chiller based CCHP systems. A comparison of the new proposed strategy with the modified electric load following (MELF) and electric load following (ELF) strategies is performed. A multi-objective optimization approach based on genetic algorithm is carried out to predict the optimal capacity of CCHP systems. Performance criteria like primary energy consumption, annual total cost and carbon dioxide emission were considered as objective functions. The performances of these CCHP systems and operation strategies were examined and compared with the separated production (SP) system for a Mosque complex located in Algiers, Algeria. Results show that hybrid chiller CCHP based NELF strategy is the best choice, which can reduce the primary energy consumption by 34.45 GWh/year, annual total cost by 0.313 million €/year and carbon dioxide emission by 8.37 kton/year. Compared to the other configurations and strategies, the hybrid CCHP based NELF achieves better energetic, economic and environmental performance under the optimized conditions

From Object to Icon: The Unpredictable Path to Everlastingness

This thesis explores how a squeaky-clean object transformed into a girl-next-door icon and became a role model for generations to come. And in an industry built on illusions and dreams, reality wore many masks. Still in its beginning stages and looking to sell tickets, the motion picture industry needed to reconstruct its current downscale public image by presenting a much-improved polished and upscale public image to audiences, all while silencing contradictory images and information. Appealing to a middle-class sensibility to boost this new public image gave the motion picture industry the acceptance it was seeking. By marketing to middle-class audiences, producers promoted only the cultivated images and middlebrow narratives they wanted people to see. Fan magazines contributed to these illusions by enhancing stories to satisfy the growing curiosities that audiences developed about players. And soon, the motion picture industry revolved around manufacturing and selling illusions to middle-class audiences, while simultaneously concealing contradictory private images. And in addition to selling illusions, the motion picture industry discovered that selling the American Dream to American audiences generated substantial profits. This thesis focuses on three special female stars: Lois Weber, Doris Day, and Karen Carpenter, and their images, both public and private, and their lives, both public and private. And it examines what these stars shared in common, their assets and their liabilities, while following their career paths before and after they were stars and by taking a brief look at their biographies, which include their objectification in their separate industries controlled by men. Additionally, my thesis researches the rise of celebrity culture and the importance of star studies since its inception not only in academia but in society as well. Weber, Day, and Carpenter, three prominent stars with wholesome, girl-next-door appeal and middle-class beginnings and values, did not need glitter or glitz to shine. Each star sparkled in her own unique way. And in studying the intricacies of these women’s lives and careers, it became clear why these stars and their exceptional gifts did not go unnoticed. Thus, when a contradictory private image escaped their purview, camouflaged charisma came to the rescue. (Inevitably, there was always a rescue.) Yet some misconceptions linger, and the true illusion persists to some extent that Weber, Day, and Carpenter were stars of everyday ordinariness, when in reality, they were stars of the utmost extraordinariness. Keywords: Stars, Celebrities, Celebrity Culture, Doris Day, Karen Carpenter, Lois Weber, Fame, Girl Next Door, Wholesome, Star Studie

Life cycle assessment of synthetic natural gas production from different CO2 sources: A cradle⇂to-gate study

Fuel production from hydrogen and carbon dioxide is considered an attractive solution as long‐term storage of electric energy and as temporary storage of carbon dioxide. A large variety of CO2 sources are suitable for Carbon Capture Utilization (CCU), and the process energy intensity depends on the separation technology and, ultimately, on the CO2 concentration in the flue gas. Since the carbon capture process emits more CO2 than the expected demand for CO2 utilization, the most sustainable CO2 sources must be selected. This work aimed at modeling a Power‐to‐Gas (PtG) plant and assessing the most suitable carbon sources from a Life Cycle Assessment (LCA) perspective. The PtG plant was supplied by electricity from a 2030 scenario for Italian electricity generation. The plant impacts were assessed using data from the ecoinvent database version 3.5, for different CO2 sources (e.g., air, cement, iron, and steel plants). A detailed discussion on how to handle multi‐functionality was also carried out. The results showed that capturing CO2 from hydrogen production plants and integrated pulp and paper mills led to the lowest impacts concerning all investigated indicators. The choice of how to handle multi‐functional activities had a crucial impact on the assessment

TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo

Toll-like receptors (TLRs) are a family of highly conserved transmembrane proteins expressed in epithelial and immune cells that recognize pathogen associated molecular patterns. Besides their role in immune response against infections, numerous studies have shown an important role of different TLRs in cancer, indicating these receptors as potential targets for cancer therapy. We previously demonstrated that the activation of TLR3 by the synthetic double-stranded RNA analogue poly I:C induces apoptosis of androgen-sensitive prostate cancer (PCa) LNCaP cells and, much less efficiently, of the more aggressive PC3 cell line. Therefore, in this study we selected LNCaP cells to investigate the mechanism of TLR3-mediated apoptosis and the in vivo efficacy of poly I:C-based therapy. We show that interferon regulatory factor-3 (IRF-3) signalling plays an essential role in TLR3-mediated apoptosis in LNCaP cells through the activation of the intrinsic and extrinsic apoptotic pathways. Interestingly, hardly any apoptosis was induced by poly I:C in normal prostate epithelial cells RWPE-1. We also demonstrate for the first time the direct anticancer effect of poly I:C as a single therapeutic agent in a well-established human androgen-sensitive PCa xenograft model, by showing that tumour growth is highly impaired in poly I:C-treated immunodeficient mice. Immunohistochemical analysis of PCa xenografts highlights the antitumour role of poly I:C in vivo both on cancer cells and, indirectly, on endothelial cells. Notably, we show the presence of TLR3 and IRF-3 in both human normal and PCa clinical samples, potentially envisaging poly I:C-based therapy for PCa