Structural optimization strategies to design green products

This paper addresses the need for a structured approach to environmental assessment and improvement. We propose a computer-aided methodology, named Eco-OptiCAD, based on the integration of Structural Optimization and Life Cycle Assessment (LCA) tools. Eco-OptiCAD supports the designer during product development, highlighting when and where the core of the environmental impact lies. Furthermore, it provides effective tools to address such impacts, improving the original product, while ensuring structural and functional requirements. It foresees the synergic use of (1) virtual prototyping tools, such as 3D CAD, Finite Element Analysis (FEA) and Structural optimization, (2) function modeling methodology and (3) Life Cycle Assessment (LCA) tools. The kernel of the methodology is constituted by a set of optimization strategies and a module, named Life Cycle Mapping (LCM). In particular, we have conceived ten optimization strategies converting environmental objectives and constraints into structural and geometrical parameters. They enable the designer to generate alternative green scenarios according to the triad shape–material–production. The LCM tool has been specifically developed to easily trace the growth of environmental impacts throughout the product's life cycle and allow the user to focus his effort on the most relevant aspects. Thanks to the integration of the structural optimizer with an LCA map, the designer becomes aware of the consequences that each change in the geometry, the material or the manufacturing process will produce on the environmental impact of the product throughout its life cycle. With a complete view of the product life cycle, the designer can improve a single phase, while retaining a global perspective; thus avoiding the possibility of gaining a local green improvement at the cost of a global increase in environmental impacts.     

Reward only is not enough: Evaluating and improving the fairness policy of the P2P file sharing network eMule/eDonkey

Limiting the threat of free-riding behavior is an important design issue for peer-to-peer (P2P) file sharing networks. However, the fairness policy that rewards contributors with credit in one of the most popular P2P file sharing networks, eMule/eDonkey, hasn’t been thoroughly studied. In this paper, motivated by our experiments with the eMule/eDonkey network, we firstly theoretically analyze the content exchange process with credit in eMule/eDonkey and then verify the mathematical model by an agent-based simulation. Both the numerical and simulation-based results confirm our discovery in the experiments that eMule/eDonkey’s local credit strategy can not provide enough fairness as it doesn’t explicitly punish free-riders. To overcome this drawback, we propose a new free-riding control scheme, which can simply maintain the current credit local structure and take advantage of the credit policy. Extensive numerical evaluation and simulation indicate that this scheme significantly improves system fairness.     

Digital sculpting for historical representation: Neville tomb case study

Despite digital 3-D polygon modelling applications providing a common and powerful tool-set for archaeological, architectural and historical visualisation over recent years, the relatively recent developments in high-resolution sculpting software allow for the possibility to create digital outcomes with a degree of surface fidelity not previously obtainable from the more widely used poly-modelling software packages. Such digital sculpting applications are more commonly applied within the video games and TV/motion picture industries, the intention of this paper is to show how such tools and methodologies together with existing scanned data and some historical knowledge can remediate and re-imagine lost sculptural form. The intended research will focus on an examination and partial re-construction of the tomb of Sir John Neville, 3rd Baron Raby located at Durham Cathedral, County Durham UK.     

Abstract Interpretation as Automated Deduction

Automata theory, algorithmic deduction and abstract interpretation provide the foundation behind three approaches to implementing program verifiers. This article is a first step towards a mathematical translation between these approaches. By extending Büchi’s theorem, we show that reachability in a control flow graph can be encoded as satisfiability in an extension of the weak, monadic, second-order logic of one successor. Abstract interpreters are, in a precise sense, sound but incomplete solvers for such formulae. The three components of an abstract interpreter: the lattice, transformers and iteration algorithm, respectively represent a fragment of a first-order theory, deduction in that theory, and second-order constraint propagation. By inverting the Lindenbaum–Tarski construction, we show that lattices used in practice are subclassical first-order theories.     

Adaptive WENO Methods Based on Radial Basis Function Reconstruction

We explore the use of radial basis functions (RBF) in the weighted essentially non-oscillatory (WENO) reconstruction process used to solve hyperbolic conservation laws, resulting in a numerical method of arbitrarily high order to solve problems with discontinuous solutions. Thanks to the mesh-less property of the RBFs, the method is suitable for non-uniform grids and mesh adaptation. We focus on multiquadric radial basis functions and propose a simple strategy to choose the shape parameter to control the balance between achievable accuracy and the numerical stability. We also develop an original smoothness indicator which is independent of the RBF for the WENO reconstruction step. Moreover, we introduce type I and type II RBF-WENO methods by computing specific linear weights. The RBF-WENO method is used to solve linear and nonlinear problems for both scalar and systems of conservation laws, including Burgers equation, the Buckley–Leverett equation, and the Euler equations. Numerical results confirm the performance of the proposed method. We finally consider an effective conservative adaptive algorithm that captures moving shocks and rapidly varying solutions well. Numerical results on moving grids are presented for both Burgers equation and the more complex Euler equations.     

On sorting triangles in a delaunay tessellation

In a two-dimensional Delaunay-triangulated domain, there exists a partial ordering of the triangles (with respect to a vertex) that is consistent with the two-dimensional visibility of the triangles from that vertex. An equivalent statement is that a polygon that is star-shaped with respect to a given vertex can be extended, one triangle at a time, until it includes the entire domain. Arbitrary planar triangulations do not possess this useful property which allows incremental processing of the triangles.This work was partially supported by the National Science Foundation's US-Italy Collaborative Research Program under Grant INT-8714578 and Information, Robotics, and Intelligent Research Grant IRI-8704781.     

Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.     

Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation

Celiac disease (CD) is a complex multi-organ disease with a high prevalence of extra-intestinal involvement, including neurological and psychiatric manifestations, such as cerebellar ataxia, peripheral neuropathy, epilepsy, headache, cognitive impairment, and depression. However, the mechanisms behind the neurological involvement in CD remain controversial. Recent evidence shows these can be related to gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and in severe cases, vitamins or nutrients deficiency. Here, we have summarized new evidence related to gut microbiota and the so-called “gut-liver-brain axis” involved in CD-related neurological manifestations. Additionally, there has yet to be an agreement on whether serological or neurophysiological findings can effectively early diagnose and properly monitor CD-associated neurological involvement; notably, most of them can revert to normal with a rigorous gluten-free diet. Moving from a molecular level to a symptom-based approach, clinical, serological, and neurophysiology data might help to disentangle the many-faceted interactions between the gut and brain in CD. Eventually, the identification of multimodal biomarkers might help diagnose, monitor, and improve the quality of life of patients with “neuroCD”.     

Microglial Activation and Priming in Alzheimer’s Disease: State of the Art and Future Perspectives

Alzheimer’s Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aβ deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as “primed” microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment.     

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent.