A DSS for integrated distribution of empty and full containers

A DSS integrating empty and full containers transshipment operations is presented, addressing the typically unbalanced export/import containers trading problem. The problem is modeled as a network, where nodes represent customers, leasing companies, harbors and warehouses, while arcs represent transportation routes. The underlying mathematical model operates in stages, first prioritizing and adjusting full containers demands considering available empty containers supplies, and then statically optimizing costs. Transportation routes are registered and dynamically controlled, cyclically, for a given time horizon. The DSS is flexible, allowing several parameters to be configured. Experimental examples using randomly generated parameters were conducted to evaluate the effectiveness of the system.     

Resilient overlay network for real-time interactive multimedia sessions in corporate networks

Real-time interactive multimedia communications are becoming increasingly useful for education, business, e-commerce and e-government, providing an enriched user experience in teleconferencing, e-meetings, distance training and product demonstrations. Large corporations are usually located at several sites, so real-time multipoint sessions within corporations are especially difficult. IP multicast is available or feasible within each site of an organization. Thus, corporate networks can be considered as various multicast-capable networks interconnected through a wide area network without multicast connectivity. This paper proposes a resilient self-managed overlay network to support real-time multipoint interactive sessions within corporate networks. The proposed overlay takes advantage of the configuration of corporate networks to self-organize and provide an efficient media delivery service, making use of multicast communications wherever available. Various self-healing techniques are implemented allowing for the continuity of ongoing sessions in spite of network disruptions and entity failures. Extensive simulations and tests have been carried out to assess the performance and resilience of the overlay facing several types of disruptions.     

IsoGeometric analysis using T-splines on two-patch geometries

We develop optimal approximation estimates for T-splines in the case of geometries obtained by gluing two standard tensor product patches. We derive results both for the T-spline space in the parametric domain and the mapped T-NURBS in the physical one. A set of numerical tests in complete accordance with the theoretical developments is also presented.     

Coordination components for collaborative virtual environments

This paper deals with the behavior of virtual environments from the collaboration point-of-view, in which actors (human or virtual beings) interact and collaborate by means of interdependent tasks. In this sense, actors may realize tasks that are dependent on tasks performed by other actors, while the interdependencies between tasks (through resource management and temporal relations) delineate the overall behavior of a virtual environment. Our main goal is to propose an approach for the coordination of those behaviors. Initially a generic study of possible interdependencies between collaborative tasks is presented, followed by the formal modeling (using Petri Nets) of coordination mechanisms for those dependencies. In order to implement such mechanisms, an architecture of reusable and pluggable coordination components is also introduced. These components are used in an implementation of a multi-user videogame. The presented approach is a concrete step to create virtual societies of actors that collaborate to reach common goals without the risk of getting involved in conflicting or repetitive tasks.     

Second-Order Stiffness Matrix and Loading Vector of a Beam-Column with Semirigid Connections on an Elastic Foundation

The second-order stiffness matrix and corresponding loading vector of a prismatic beam–column subjected to a constant axial load and supported on a uniformly distributed elastic foundation (Winkler type) along its span with its ends connected to elastic supports are derived in a classical manner. The stiffness coefficients are expressed in terms of the ballast coefficient of the elastic foundation, applied axial load, support conditions, bending, and shear deformations. These individual parameters may be dropped when the appropriate effect is not considered; therefore, the proposed model captures all the different models of beams and beam–columns including those based on the theories of Bernoulli–Euler, Timoshenko, Rayleigh, and bending and shear.The expressions developed for the load vector are also general for any type or combinations of transverse loads including concentrated and partially nonuniform distributed loads. In addition, the transfer equations necessary to determine the transverse deflections, rotations, shear, and bending moments along the member are also developed and presented.     

Differential Expression of Proteins in an Atypical Presentation of Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease defined as a defect in the lymphocyte apoptotic pathway. Currently, the diagnosis of ALPS is based on clinical aspects, defective lymphocyte apoptosis and mutations in Fas, FasL and Casp 10 genes. Despite this, ALPS has been misdiagnosed. The aim of this work was to go one step further in the knowledge of the disease, through a molecular and proteomic analysis of peripheral blood mononuclear cells (PBMCs) from two children, a 13-year-old girl and a 6-year-old boy, called patient 1 and patient 2, respectively, with clinical data supporting the diagnosis of ALPS. Fas, FasL and Casp10 genes from both patients were sequenced, and a sample of the total proteins from patient 1 was analyzed by label-free proteomics. Pathway analysis of deregulated proteins from PBMCs was performed on the STRING and PANTHER bioinformatics databases. A mutation resulting in an in-frame premature stop codon and protein truncation was detected in the Fas gene from patient 2. From patient 1, the proteomic analysis showed differences in the level of expression of proteins involved in, among other processes, cell cycle, regulation of cell cycle arrest and immune response. Noticeably, the most down-regulated protein is an important regulator of the cell cycle process. This could be an explanation of the disease in patient 1.     

Development and Characterization of a Factor V-Deficient CRISPR Cell Model for the Correction of Mutations

Factor V deficiency, an ultra-rare congenital coagulopathy, is characterized by bleeding episodes that may be more or less intense as a function of the levels of coagulation factor activity present in plasma. Fresh-frozen plasma, often used to treat patients with factor V deficiency, is a scarcely effective palliative therapy with no specificity to the disease. CRISPR/Cas9-mediated gene editing, following precise deletion by non-homologous end-joining, has proven to be highly effective for modeling on a HepG2 cell line a mutation similar to the one detected in the factor V-deficient patient analyzed in this study, thus simulating the pathological phenotype. Additional CRISPR/Cas9-driven non-homologous end-joining precision deletion steps allowed correction of 41% of the factor V gene mutated cells, giving rise to a newly developed functional protein. Taking into account the plasma concentrations corresponding to the different levels of severity of factor V deficiency, it may be argued that the correction achieved in this study could, in ideal conditions, be sufficient to turn a severe phenotype into a mild or asymptomatic one.     

Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents

Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel^®.     

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.