SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc-/- MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc-/- MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc-/- than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc-/- MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc-/- MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

Atypical Presentation of Acute Coronary Syndrome-Not ST Elevation: A Case Report

We describe the unexpected case of a 70-year-old man, with medical history of ischemic heart disease and surgery for aneurysm of abdominal aorta, who comes to the emergency department complaining of low-back pain without other symptoms or signs of organic failure. After a few hours we see a deterioration of physical conditions with pulmonary oedema, increase of blood pressure, changing in the ECG pattern, and worsening of left ventricular function with progressive increase of biomarkers for myocardial necrosis. So this pain has revealed the premature symptom of an acute coronary syndrome (ACS). After a short time a subsequent cardiac arrest complicates the clinical situation. After resuscitation, the patient undergoes successfully to coronary angiography and performed a percutaneous transluminal coronary angioplasty (PTCA)

A survey of methods to detect and represent the human symmetry line from 3D scanned human back

Abstract This paper proposes a review of the methods to detect and represent the human symmetry line. In the last years, the development of 3D scanners has allowed to replace the traditional techniques (marking based methods) with modern methodologies that, starting from a 3D valid discrete geometric model of the back, perform the posture and vertebral column detection based on a complex processing of the acquired data. The purpose of the paper is a critical d iscussion of the state of the art in order to highlight the real potentialit ies and the limitations still present of the most important methodologies proposed for human symmetry line detection

On methods to identify the symmetry line of human back

This paper analyse and compare the methods to detect and represent the human symmetry line. In the last years, the development of 3D scanners has allowed to replace the traditional techniques (marking based methods) with modern methodologies that, starting from a 3D valid discrete geometric model of the back, perform the posture and vertebral column detection based on a complex processing of the acquired data. The purpose of the paper is a critical discussion of the state of the art in order to highlight real potentialities and limitations of the most important methodologies proposed for human symmetry line detection

Comfort driven design of innovative products: the case of the personalized mattress

The application of ergonomic principles to the design of processes, workplaces and organizations is not only a way to respond to legal requirements but also an indispensable premise for any company seeking to pursue a business logic. The evolution of Human-centred design brings designers to focus their attention not only to the ergonomic performances of products and processes but, also, to the wellbeing of the customer/worker when interacts with the product. This wellbeing is often translated as the state of perceived (dis)comfort while performing an action. So, in recent years, methods that allow for an objective evaluation of perceived comfort, in terms of postural, physiological, cognitive and environmental comfort, have received a great deal of attention from researchers. The need to have an objective method to evaluate the (dis)comfort perception is definitively due to the will of introducing the comfort evaluation in the early stage of the product development plan, and the necessity to imagine and develop new methods for a preventive evaluation (often made on the digital model of the product) of the future perception of (dis)comfort of the customer. This works deal with the experience of designing an innovative product whose product-development-plan is centred on the customer perceived comfort: a personalized mattress. The mattress is the typical product whose relevance in everyday life of people is under-evaluated. People usually spend from 1/4 to 1/3 of their life on it, but nobody spends more than some minutes for choosing the right one when buying it. Fortunately, this trend is quickly changing and the customer pays more attention and takes information about producers and product characteristics before to buy a product. This trend is more evident in the market of high-performance (that means high price) mattress. Valflex is the luxury brand of Rinaldi Group S.r.l., one of the main player in the world of luxury mattresses’ manufacturing companies. This company, together with University of Salerno, has developed methodologies both in terms of preventive comfort evaluation and in comfort-driven design. This work explains the results obtained through the profitable collaboration that allowed to develop two patents and a new reconfigurable mattress, easy to manufacture, whose layout can be tuned on the anthropometric data of the customer to improve the comfort experience during the sleep

An Application of Computer Visualisation for Solving a Mechanical Design

A computer visualisation application has been presented for fuzzy evaluation of windscreen wiper systems which must satisfy several requirements. Some requirements are modelled by fuzzy sets and a compensating arithmetic mean is utilised for computing an overall performance. A computer animation of wiper mechanism motion and rainfall is shown, which enables to experts, drivers and passengers to evaluate the degree of satisfaction and correctness of judgements. This fuzzy evaluation approach is illustrated by considering five “subjective” requirements (driver and passenger visibility, wiped surface, visibility and trouble sensations), and for three design alternatives (traditional single and double wiped systems and variable course system) the results are show

Additive manufacturing for industrial benchmarking: An application to vehicle's under-hood design

All over the world, and mainly in United States, since 1977 to 1991 the research centers of automotive companies have processed several statistical data on real accidents between vehicles and pedestrians taking care, obviously, to pedestrians' injury. In latest years, a research group of EEVC (European Enhanced Vehicle-Safety Committee) had realized some documents about "pedestrian test" procedures. In reference papers of period 1977 - 1997 and in EEVC documents, the scientists describe a proposed homologating test for child-head impact; it is represented by the impact of some standardized impactors on car bonnet, in order to evaluate the child-head injury as deceleration of its gravity center. Injury evaluation criteria is an energy criterion and is quantified by the HPC index (see below) calculated by acceleration resultant vector, measured by an accelerometer mounted in the head- impactor. Our research wants to propose a new potential-injury evaluation method based on virtual reconstruction of the surface that envelope all the deformation surfaces in internal part of the bonnet and on its rapid prototyping. This surface is so processed and rapid prototyped as a puzzle of shells with their support. This prototyped surface is super-imposed on the real under-bonnet layout of a car and allows to evaluate easily where and how much our deformed bonnet could hit the hard-parts of the engine layout. This paper shows the results of this research project

Influence of Control Parameters on Consumer FDM 3D Printing

Rapid prototyping (RP) is a set of technologies that permits building a physical model directly from its design by implementing a single automatic process using a 3D model of the object to be printed. RP systems can be based on different Additive Manufacturing (AM) technologies, such as a Fused Deposition Modeling (FDM) machine that works by extruding and melting together fused plastic filaments, drawing the boundaries and filling the model thin layer by thin layer. Low-cost FDM 3d printers do not work well automatically but require of a calibration phase because the best configuration settings in the slicing software are unknown, and the number of parameters values that needs to be manually defined is very large. The scientific literature reports many interesting articles on this topic, describing how the process can be improved by choosing the correct values of various parameters. Internet websites such RepRap.org discuss 3D printers and ppost detailed FAQ sections where users described improvements in 3D printing with simple methods but with great effort in terms of costs and time. Yet not all questions are answered. This paper would introduces: a) a new method for the analysis of the slicing software parameters that can be done with easy models; b) a second method for improving the effects of the parameters that shows a higher influence in the signal-to-noise ratio analysis