Numerical experiment based on non-linear micropolar finite element to study micro-rotations generated by the non-symmetric Maxwell stress tensor

Funding for open access publishing: Universidad de Granada/CBUA.The main aim of the present work is to investigate the role of the Maxwell stress tensor in the study of active materials. Despite the importance of this tensor in modeling mechatronic devices used in sophisticated applications, its non-symmetry still generates controversies in the literature, probably because classical continuum mechanics assumes a symmetric Cauchy stress, although the sum of Cauchy and Maxwell stresses is non-symmetric. In the framework of generalised continuum mechanics-a more advanced formalism than the classical one-, each material point has an associated microstructure so that the micro-rotations of the electric/magnetic dipoles present in real active materials may be simulated. To this end, a modified total stress formulation, including an angular momentum balance, is developed and implemented into a finite element research code using a complex-step formulation. It is concluded that generalised mechanics allows for incorporating both symmetric and non-symmetric contributions of the Maxwell tensor. Consequently, the rotations generated by the electromagnetic field may be analysed. The influence of the complete Maxwell tensor in a magnetostrictive actuator is studied by several magneto-mechanical numerical experiments of a Terfenol-D rod encircled by air, and several conclusions are highlighted.Universidad de Granada/CBU

Optimal measurement setup for damage detection in piezoelectric plates

[EN] An optimization of the excitation-measurement configuration is proposed for the characterization of damage in PZT-4 piezoelectric plates, from a numerical point of view. To perform such an optimization, a numerical method to determine the location and extent of defects in piezoelectric plates is developed by combining the solution of an identification inverse problem, using genetic algorithms and gradient-based methods to minimize a cost functional, and using an optimized finite element code and meshing algorithm. In addition, a semianalytical estimate of the probability of detection is developed and validated, which provides a flexible criterion to optimize the experimental design. The experimental setup is optimized upon several criteria: maximizing the probability of detection against noise effects, ensuring robust search algorithm convergence and increasing the sensitivity to the presence of the defect. The measurement of voltage phi is concluded to provide the highest identifiability, combined with an excitation of the specimen by a mechanical traction transverse to the polarization direction. Sufficient accuracy is predicted for the damage location and sizing under realistic noise levels. (c) 2008 Elsevier Ltd. All rights reserved.This research was supported by the Ministry of Education of Spain through Grant No. FPU AP-2006-02372.Rus, G.; Palma Guerrero, R.; Pérez-Aparicio, JL. (2009). Optimal measurement setup for damage detection in piezoelectric plates. International Journal of Engineering Science. 47(4):554-572. https://doi.org/10.1016/j.ijengsci.2008.09.006S55457247

Antibody-based immunotoxins for colorectal cancer therapy

Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

First tests of the applicability of γ\gamma-ray imaging for background discrimination in time-of-flight neutron capture measurements

In this work we explore for the first time the applicability of using $\gamma$-ray imaging in neutron capture measurements to identify and suppress spatially localized background. For this aim, a pinhole gamma camera is assembled, tested and characterized in terms of energy and spatial performance. It consists of a monolithic CeBr$_3$ scintillating crystal coupled to a position-sensitive photomultiplier and readout through an integrated circuit AMIC2GR. The pinhole collimator is a massive carven block of lead. A series of dedicated measurements with calibrated sources and with a neutron beam incident on a $^{197}$Au sample have been carried out at n_TOF, achieving an enhancement of a factor of two in the signal-to-background ratio when selecting only those events coming from the direction of the sample.Comment: Preprint submitted to Nucl. Instr. and Meth.

Expression of p53 Protein and Tumor Angiogenesis as Prognostic Factors in Nasopharyngeal Carcinoma Patients.

The objective of this study was to evaluate the possible prognostic significance of p53 protein overexpression and tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients, together with other clinicopathological variables. Forty-two NPC patients were evaluated in relation to survival. Nuclear p53 overexpression in neoplastic and endothelial cells was detected by immunohistochemistry (IHC) with the monoclonal antibody DO-7 and the polyclonal antibody against factor VIII-related antigen, respectively. Thereafter, we evaluated p53 cases in order to determine their nuclear immunoreactivity from negative (-) to positive (+, ++, +++). In addition, microvessels were counted in the most active areas of tumor neovascularization or hotspots using an image computer analyzer (MicroImage®). A Cox multiple regression survival analysis was used to determine the best prognostic indicators in NPC patients. As a result, tumor microvessel count, considered as a continuous variable, was the most important independent prognostic indicator in relation to survival (p = 0.0273), with a relative risk of death of 2,4399 [95% confidence interval = 1.1051 ; 5.3871] associated with the highest microvessel counts. Moreover, the only clinicopathological variable that demonstrated prognostic value in a Cox multiple regression survival analysis was histological type (p = 0.05). In addition, we did not observe any statistical association between intratumoral microvessel density (IMD), clinicopathological variables and p53 protein expression. Key words: p53 protein - Angiogenesis - Morphometry - Prognosis - Nasopharyngeal carcinom

In vivo potential of recombinant granulysin against human melanoma

9-kDa granulysin is a protein expressed into the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It has been shown to exert cytolysis on microbes and tumors. We showed previously that 9-kDa granulysin exerted cell death by apoptosis in vitro on hematological tumor cell lines and also on cells from B-cell chronic lymphocytic leukemia (B-CLL) patients. In addition, we have shown the anti-tumor efficiency of granulysin as a single agent in two in vivo models of human tumor development in athymic mice, the MDA-MB-231 mammary adenocarcinoma and the NCI-H929 multiple myeloma, without signs of overt secondary effects by itself. In this work, we have tested recombinant 9-kDa granulysin in an in vivo and especially aggressive model of melanoma development, xenografted UACC62 cells in athymic mice. Recombinant granulysin was administered once UACC62-derived tumors were detectable and it substantially retarded the in vivo development of this aggressive tumor. We could also detect apoptosis induction and increased NK cell infiltration inside granulysin-treated tumor tissues. These observations are especially interesting given the possibility of treating melanoma by intra-tumor injection

Conjugation of the 9-kDa isoform of Granulysin with liposomes potentiates its cytotoxicity

Nine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of recombinant granulysin was demonstrated, both in vitro and in vivo. In the present work, we developed lipid nanoparticles whose surfaces can bind recombinant granulysin through the formation of a complex of coordination between the histidine tail of the protein and Ni2+ provided by a chelating lipid in the liposome composition and termed them LUV-GRNLY, for granulysin-bound large unilamellar vesicles. The objective of this formulation is to increase the granulysin concentration at the site of contact with the target cell and to increase the cytotoxicity of the administered dose. The results obtained in this work indicate that recombinant granulysin binds to the surface of the liposome with high efficiency and that its cytotoxicity is significantly increased when it is in association with liposomes. In addition, it has been demonstrated that the main mechanism of death induced by both granulysin and LUV-GRNLY is apoptosis. Jurkat-shBak cells are resistant to GRNLY and also to LUV-GRNLY, showing that LUV-GRNLY uses the mitochondrial apoptotic pathway to induce cell death. On the other hand, we show that LUV-GRNLY induces the expression of the pro-apoptotic members of the Bcl-2 family Bim and especially PUMA, although it also induced the expression of anti-apoptotic Bcl-xL. In conclusion, we demonstrate that binding of GRNLY to the surfaces of liposomes clearly augments its cytotoxic potential, with cell death executed mainly by the mitochondrial apoptotic pathway

The MetNet vehicle: a lander to deploy environmental stations for local and global investigations of Mars

Investigations of global and related local phenomena on Mars such as atmospheric circulation patterns, boundary layer phenomena, water, dust and climatological cycles and investigations of the planetary interior would benefit from simultaneous, distributed in situ measurements. Practically, such an observation network would require low-mass landers, with a high packing density, so a large number of landers could be delivered to Mars with the minimum number of launchers. The Mars Network Lander (MetNet Lander; MNL), a small semi-hard lander/penetrator design with a payload mass fraction of approximately 17 %, has been developed, tested and prototyped. The MNL features an innovative Entry, Descent and Landing System (EDLS) that is based on inflatable structures. The EDLS is capable of decelerating the lander from interplanetary transfer trajectories down to a surface impact speed of 50-70 ms(-1) with a deceleration of < 500 g for < 20 ms. The total mass of the prototype design is approximate to 24 kg, with approximate to 4 kg of mass available for the payload. The EDLS is designed to orient the penetrator for a vertical impact. As the payload bay will be embedded in the surface materials, the bay's temperature excursions will be much less than if it were fully exposed on the Martian surface, allowing a reduction in the amount of thermal insulation and savings on mass. The MNL is well suited for delivering meteorological and atmospheric instruments to the Martian surface. The payload concept also enables the use of other environmental instruments. The small size and low mass of a MNL makes it ideally suited for piggy-backing on larger spacecraft. MNLs are designed primarily for use as surface networks but could also be used as pathfinders for high-value landed missions

A Performance/Cost Model for a CUDA Drug Discovery Application on Physical and Public Cloud Infrastructures

Virtual Screening (VS) methods can considerably aid drug discovery research, predicting how ligands interact with drug targets. BINDSURF is an efficient and fast blind VS methodology for the determination of protein binding sites, depending on the ligand, using the massively parallel architecture of graphics processing units(GPUs) for fast unbiased prescreening of large ligand databases. In this contribution, we provide a performance/cost model for the execution of this application on both local system and public cloud infrastructures. With our model, it is possible to determine which is the best infrastructure to use in terms of execution time and costs for any given problem to be solved by BINDSURF. Conclusions obtained from our study can be extrapolated to other GPU‐based VS methodologiesIngeniería, Industria y Construcció