1,721,045 research outputs found
Myeloid-derived suppressor cell (MDSC) immunomodulation by c-FLIP
No full textDuring tumor progression, cancer cells secrete many different tumor-derived factors (TDFs), like cytokines, chemokines, and metabolites, which promote the development of a flexible microenvironment inducing bot the generation of new vessels and the modification of the immune responses (Balkwill, Charles et al. 2005). Probably the most pervasive and efficient strategy of “tumor escape” relies on the tumor’s ability to create a tolerant microenvironment by modification of the normal hematopoiesis. Indeed, cancers can induce the proliferation and differentiation of myeloid precursors into myeloid cells with immunosuppressive functions. These cells, named myeloid-derive suppressor cells (MDSCs), are a heterogeneous population of myeloid cells emcompassing various stages of differentiation. MDSCs prevent the activation and functionality of T lymphocytes, limiting the success of immunotherapy strategies aimed at eradicating cancer development. In this study, we demonstrated that low dose of chemotherapeutics with different molecular targets and cytotoxic action, widely used in conventional anti-cancer therapy, were able to selectively deplete monocytic-MDSCs (M-MDSCs), restoring the T cell proliferation. We also proved that these drugs exert their action through the activation of the apoptotic death pathway and with the specific modulation of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP), a well-known anti-apoptotic and drug resistance factor. In particular, recent study in mice demonstrated that the heterogeneity between the two main subsets of MDSCs, the M-MDSCs and the polymorphonuclear/granulocytic (PMN)-MDSCs, occurs from a diverse activation of the apoptotic pathways: PMN-MDSCs require the anti-apoptotic molecule MCL-1 for their development; in contrast, M-MDSC generation and survival constitutively requires the presence of c-FLIP (Haverkamp, Smith et al. 2014). Therefore, in this study we verified and demonstrated the hypothesis that c-FLIP can have also a role in driving and controlling MDSC immunosuppressive properties
POD-based representation of the alongwind equivalent static force for long-span bridges
No full textThis paper develops and discusses a method by which it is possible to evaluate the Equivalent
Static Force (ESF) of wind in the case of long-span bridges. Attention is focused on the alongwind
direction. The study herein carried out deals with the classical problems of determining the maximum
effects due to the alongwind action and the corresponding ESFs. The mean value of the maximum
alongwind displacement of the deck is firstly obtained both by the spectral analysis and the Gust
Response Factor (GRF) technique. Successively, in order to derive the other wind-induced effects acting
on the deck, the Gust Effect Factor (GEF) technique is extended to long-span bridges. By adopting the
GRF technique, it is possible to define the ESF that applied on the structure produces the maximum
alongwind displacement. Nevertheless the application of the ESF so obtained does not furnish the correct
maximum values of other wind-induced effects acting on the deck such as bending moments or shears.
Based on this observation, a new technique is proposed which allows to define an ESF able to
simultaneously reproduce the maximum alongwind effects of the bridge deck. The proposed technique is
based on the GEF and the POD techniques and represents a valid instrument of research for the
understanding of the wind excitation mechanism
Earthquake-Induced lateral-torsional pounding between three adjacent structures
No full textPounding between adjacent buildings, often characterized by different material properties, can be cause of significant or even severe structural damage. This paper presents an analytical study on the earthquake induced lateral-torsional pounding between three multi-storey adjacent buildings with substantially different dynamic properties. Both a non-linear viscoelastic model to simulate impact and a non-linear behaviour of the storey shear forces and torques are considered in the model, differently from many commercial softwares which admit just one non-linearity. In order to solve the dynamic equation of motion, a numerical algorithm is suitably programmed by using MATLAB software
Combining NDTs with digital photogrammetry survey and ambient vibration de-tection for diagnosis of pathologies in historic architectures toward conservative and compatible measures
No full textWithin the performance assessment of historic architectures, inspection, diagnostic and monitoring methods
play a crucial role toward the comprehensive knowledge of both the effects deriving from potential pathologies and the factors affecting the actual behaviour of the system, with specific attention to local vulnerabilities
and failure mechanisms. For the purpose, NDTs need to follow an integrated approach, where multidisciplinary methods, including laboratory testing, reality-based survey and detection of static and dynamic parameters, are applied. The paper is going to discuss the above-mentioned issues and present the case study of the
Town Hall of Altamura (Ba), in South Italy, where a variety of correlated experimental techniques was carried
out in order to assess causes and magnitude of a relevant cracking pattern, related to the facade rotation. Particularly, along with radar scanning, video-endoscopy and direct sampling, the investigation relied on some
innovative technologies, including digital photogrammetry for survey of unknown underground structures and
detection of ambient vibrations whose analysis allowed assessing not only the global structural safety but also
the comfort level
On the prediction of shear brittle collapse mechanisms due to the infill-frame interaction in RC buildings under pushover analysis
Get PDFA large number of research studies deal with the modeling and analysis of infilled reinforced concrete (RC) buildings under seismic actions, at the aim to understand the actual contribution given by masonry infills to the overall seismic resistance of a building. In this paper this aspect is investigated in the framework of pushover analyses, describing the theoretical and computational choices related to the involved parameters. Differently from the approaches available in literature and standards, the "double-strut model" is adopted to simulate the infill behavior, according to which an infill panel is represented by two equivalent non-parallel struts; the peculiarity is that the positions of the extremities of the two struts coincide with the points of application of the stress resultants on each side of the panel. The results show that, by adopting the double-strut model, it is possible to capture dangerous local shear failures which are usually neglected in pushover analysis and which can compromise the safety of the overall structure. By including in the analysis shear plastic hinges together with bending ones, it is evident how the additional shear forces, arising at the extremities of beams and columns, can substantially change the collapse mechanism of a structure under seismic action. The main features of the double-strut model are its low computational cost together with its accuracy, which make it particularly suitable for applications in the engineering practice. In fact it could be easily implemented in commercial calculation codes, representing a practical predictive tool able to enhance the safety level of infilled RC buildings
Commentary: Cortical Plasticity and Olfactory Function in Early Blindness
Get PDFCommentary: Cortical plasticity and olfactory function in early blindnes
Structural optimization of hollow-section steel trusses by differential evolution algorithm
No full textIntegration Algorithm for Covariance Nonstationary Dynamic Analysis of SDOF Systems using Equivalent Stochastic Linearization
No full textRandom vibration theory is the natural way to deal with some dynamic actions whose nature is deeply random, such as wind, earthquakes or sea waves. Moreover only in a few cases exact solutions are available, so that approximate solutions are usually adopted: Stochastic equivalent linearization is one of the widely used. Its application needs specific numerical techniques, whose complexity is greater in nonstationary cases than in stationary ones and that are usually approached in time domain instead of frequency domain. In this paper, an iterative integration algorithm is proposed in order to solve this problem for single-degree-of-freedom (SDOF) oscillators, using the evolutive Lyapunov equation for nonlinear mechanical linearized system by stochastic linearization technique. It updates linearized system matrix coefficients step by step, by an iterative procedure based on a predictor-corrector technique. The proposed algorithm is described and applied to an hysteretic Bouc-Wen SDOF system excited by a modulated filtered white noise nonstationary process. The accuracy and computational cost are analyzed showing the efficiency of the proposed integrating procedure
Editorial: Modulation of ferroptosis via metabolic and signaling pathways: therapeutic opportunities across malignancies and degenerative diseases
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