Behavior and Energy Loss Optimization of an Elastic Material Metastructure

Advances in additive manufacturing expand the possibilities of what can be designed and produced. One such example is producing structures that possess designed properties. Because the structure itself has the designed property, it does not require the structure\u27s base material to have it. This allows the use of materials that lack a property to gain that property through geometry. Most elastic materials such as steel do not possess any form of energy loss under loading in their elastic regime. This research asks if a structure made from an elastic material could be designed in such a way to provide energy loss. One structure of interest is curved-bistable beam switches found in MEMs machines. These switches are of interest because they have dierent loading and unloading force-displacement curves, resulting in dierent energy levels between loading and unloading. This results in the system having a hysteresic energy loss. Because individual beams have energy loss, this begs the question if a system of these beams could be designed to produce a structure with energy loss. This structure could then be used to substitute existing systems, such as a suspension system. The goal of this research is to investigate the behavior and to optimize a structure featuring these curved-bistable beams. On the system level, the deformation pattern, stresses throughout the structure, and total energy loss is calculated. To better understand how the variables of the curved beam aect energy loss, a surrogate model for Eloss is produced. This model is then used to optimize both a single beam and a structure of multiple beams. Finally, the material selection\u27s role in optimization is discussed

Energy efficiency, productivity and exporting: firm-level evidence in Latin America

This work explores the relationship between energy efficiency, productivity and exporting for a sample of firms located in thirty Latin American and Caribbean (LAC) countries. This relationship has not been studied in depth although it is important and relevant to policymaking. We apply a standard constant returns to scale Cobb-Douglas production function with labor, capital, and knowledge expanded to exports and energy efficiency. We also investigate the relationship between energy efficiency and exporting and take heterogeneity by firms and industries into account. Firm-level data come from the national representative World Bank Enterprise Survey (WBES). Our empirical analysis finds heterogeneous results by firm size and industrial sector both in the relationship between energy efficiency and productivity and between energy efficiency and exporting. These outcomes are robust to different measures of energy efficiency and controlling for heterogeneity among countries and provinces. By providing for the first time an extensive investigation of energy intensity and firm performance for such a large sample of LAC countries, this work contributes to the lively debate on LAC energy efficiency and weak productivity. By adopting a broader productivity and international trade perspective, it opens the ground to a rethinking of the priorities of energy saving policies and their environmental impacts

3d printing in alginic acid bath of in-situ crosslinked collagen composite scaffolds

Bone-tissue regeneration is a growing field, where nanostructured-bioactive materials are designed to replicate the natural properties of the target tissue, and then are processed with technolo-gies such as 3D printing, into constructs that mimic its natural architecture. Type I bovine collagen formulations, containing functional nanoparticles (enriched with therapeutic ions or biomolecules) or nanohydroxyapatite, are considered highly promising, and can be printed using support baths. These baths ensure an accurate deposition of the material, nonetheless their full removal post-printing can be difficult, in addition to undesired reactions with the crosslinking agents often used to improve the final structural integrity of the scaffolds. Such issues lead to partial collapse of the printed constructs and loss of geometrical definition. To overcome these limitations, this work presents a new alternative approach, which consists of adding a suitable concentration of crosslinking agent to the printing formulations to promote the in-situ crosslinking of the constructs prior to the removal of the support bath. To this aim, genipin, chosen as crosslinking agent, was added (0.1 wt.%) to collagen-based biomaterial inks (containing either 38 wt.% mesoporous bioactive glasses or 65 wt.% nanohydroxyapatite), to trigger the crosslinking of collagen and improve the stability of the 3D printed scaffolds in the post-processing step. Moreover, to support the material deposition, a 15 wt.% alginic acid solution was used as a bath, which proved to sustain the printed structures and was also easily removable, allowing for the stable processing of high-resolution geometries

PEG-coated large mesoporous silicas as smart platform for protein delivery and their use in a collagen-based formulation for 3d printing

Silica-based mesoporous systems have gained great interest in drug delivery applications due to their excellent biocompatibility and high loading capability. However, these materials face challenges in terms of pore-size limitations since they are characterized by nanopores ranging between 6–8 nm and thus unsuitable to host large molecular weight molecules such as proteins, enzymes and growth factors (GFs). In this work, for an application in the field of bone regeneration, large-pore mesoporous silicas (LPMSs) were developed to vehicle large biomolecules and release them under a pH stimulus. Considering bone remodeling, the proposed pH-triggered mechanism aims to mimic the release of GFs encased in the bone matrix due to bone resorption by osteoclasts (OCs) and the associated pH drop. To this aim, LPMSs were prepared by using 1,3,5-trimethyl benzene (TMB) as a swelling agent and the synthesis solution was hydrothermally treated and the influence of different process temperatures and durations on the resulting mesostructure was investigated. The synthesized particles exhibited a cage-like mesoporous structure with accessible pores of diameter up to 23 nm. LPMSs produced at 140◦C for 24 h showed the best compromise in terms of specific surface area, pores size and shape and hence, were selected for further experiments. Horseradish peroxidase (HRP) was used as model protein to evaluate the ability of the LPMSs to adsorb and release large biomolecules. After HRP-loading, LPMSs were coated with a pH-responsive polymer, poly(ethylene glycol) (PEG), allowing the release of the incorporated biomolecules in response to a pH decrease, in an attempt to mimic GFs release in bone under the acidic pH generated by the resorption activity of OCs. The reported results proved that PEG-coated carriers released HRP more quickly in an acidic environment, due to the protonation of PEG at low pH that catalyzes polymer hydrolysis reaction. Our findings indicate that LPMSs could be used as carriers to deliver large biomolecules and prove the effectiveness of PEG as pH-responsive coating. Finally, as proof of concept, a collagen-based suspension was obtained by incorporating PEG-coated LPMS carriers into a type I collagen matrix with the aim of designing a hybrid formulation for 3D-printing of bone scaffolds

Field observables near a fluctuating boundary

We review several aspects related to the confinement of a massless scalar field in a cavity with a movable conducting wall of finite mass, free to move around its equilibrium position to which it is bound by a harmonic potential, and whose mechanical degrees of freedom are described quantum mechanically. This system, for small displacements of the movable wall from its equilibrium position, can be described by an e↵ective interaction Hamiltonian between the field and the mirror, quadratic in the field operators and linear in the mirror operators. In the interacting, i.e. dressed, ground state, we first consider local field observables such as the field energy density: we evaluate changes of the field energy density in the cavity with the movable wall with respect to the case of a fixed wall, and corrections to the usual Casimir forces between the two walls. We then investigate the case of two one-dimensional cavities separated by a movable wall of finite mass, with two massless scalar fields defined in the two cavities. We show that in this case correlations between the squared fields in the two cavities exist, mediated by the movable wall, at variance with the fixed-wall case

A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction to 501 alterations was performed, selecting known driver genes and excluding very frequent/infrequent alterations and redundant ones. For each model, we used the concordance correlation coefficient (CCC) for assessing the predictive performance, and permutation importance for assessing the contribution of each alteration. In a reasonable computational time (56 min), we identified 12 compounds whose response was at least fairly sensitive (CCC > 20) to the alteration profiles. Some diversities were found in the sets of influential alterations, providing clues to discover significant drug-gene interactions. The proposed methodological framework can be helpful for mining pharmacogenomic interactions

A Key Silencing Histone Mark on Chromatin Is Lost When Colorectal Adenocarcinoma Cells Are Depleted of Methionine by Methionine γ-Lyase

Methionine is an essential amino acid used, beyond protein synthesis, for polyamine formation and DNA/RNA/protein methylation. Cancer cells require particularly high methionine supply for their homeostasis. A successful approach for decreasing methionine concentration is based on the systemic delivery of methionine γ-lyase (MGL), with in vitro and in vivo studies demonstrating its efficacy in cancer therapy. However, the mechanisms explaining how cancer cells suffer from the absence of methionine more significantly than non-malignant cells are still unclear. We analyzed the outcome of the human colorectal adenocarcinoma cancer cell line HT29 to the exposure of MGL for up to 72 h by monitoring cell viability, proteome expression, histone post-translational modifications, and presence of spurious transcription. The rationale of this study was to verify whether reduced methionine supply would affect chromatin decondensation by changing the levels of histone methylation and therefore increasing genomic instability. MGL treatment showed a time-dependent cytotoxic effect on HT29 cancer cells, with an IC50 of 30 µg/ml, while Hs27 normal cells were less affected, with an IC50 of >460 µg/ml. Although the levels of total histone methylation were not altered, a loss of the silencing histone mark H3K9me2 was observed, as well as a decrease in H4K20me3. Since H3K9me2/3 decorate repetitive DNA elements, we proved by qRT-PCR that MGL treatment leads to an increased expression of major satellite units. Our data indicate that selected histone methylation marks may play major roles in the mechanism of methionine starvation in cancer cells, proving that MGL treatment directly impacts chromatin homeostasis

HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches

Protein–protein interactions (PPI) represent attractive targets for drug design. Thus, aiming at a deeper insight into the HSV-1 envelope glycoprotein D (gD), protein–protein docking and dynamic simulations of gD-HVEM and gD-Nectin-1 complexes were performed. The most stable complexes and the pivotal key residues useful for gD to anchor human receptors were identified and used as starting points for a structure-based virtual screening on a library of both synthetic and designed 1,2,3-triazole-based compounds. Their binding properties versus gD interface with HVEM and Nectin-1 along with their structure-activity relationships (SARs) were evaluated. Four [1,2,3]triazolo[4,5-b]pyridines were identified as potential HSV-1 gD inhibitors, for their good theoretical affinity towards all conformations of HSV-1 gD. Overall, this study suggests promising basis for the design of new antiviral agents targeting gD as a valuable strategy to prevent viral attachment and penetration into the host cell