The rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i

Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB

Telling Toggles: Netsuke in Context

This brochure accompanies an exhibition of the same name at the Bowdoin College Museum of Art from April 11 through June 9, 2002 --P. [2] of coverhttps://digitalcommons.bowdoin.edu/art-museum-exhibition-catalogs/1020/thumbnail.jp

Modelling and experimental characterization of secondary suspension elements for rail vehicle ride comfort simulation

Secondary suspensions play an essential role in the dynamic behaviour of rail vehicles. In particular, they are adopted to reduce the vibrations transmitted to the carbody, thus improving ride comfort. In this paper, an experimental characterization of the viscous damper and coil spring elements composing a vertical secondary suspension is presented. The elements are separately tested with the aim of analysing their dynamic behaviour. Then, modified prototypes are manufactured to reduce the transmitted force. The results of the experimental campaign are later adopted to tune the parameters of the mathematical model of the whole secondary suspension, including the dynamics of both the coil spring and the damper elements. This model allows discussing the effectiveness of the proposed modifications, proving the design of both the components to be fundamental for the improvement of ride comfort

Beyond Thirst: The Dimensions of Drink

This brochure accompanies an exhibition of the same name at the Bowdoin College Museum of Art from April 17 through June 15, 2003 --Page 2 of coverhttps://digitalcommons.bowdoin.edu/art-museum-exhibition-catalogs/1064/thumbnail.jp

Giant Prolactinoma Embedded by Pseudoaneurysm of the Cavernous Carotid Artery Treated with a Tailored Therapeutic Scheme

The coexistence of intracranial aneurysm (IA) is generally thought to be highest in patients with pituitary adenomas (PAs). Different mechanisms may play a role in aneurysm formation, but whether the PA contributes to aneurysm formation is still unclear. In the literature, there are numerous reported cases of this association; however, the analyses of the characteristics of PAs, aneurysms, and treatment management are rare and limited to a restricted number of case reports. We report a rare case of an embedded aneurysm in a macroprolactinoma treated with therapeutic management tailored to the clinical, neurological, and radiological characteristics of the patient. To select the best treatment, we reviewed the literature and reported the only cases in which the radiological characteristics of aneurysms, PAs, therapeutic management, and patient outcome are described. We aimed to understand what are the variables that determine the best therapeutic management with the best possible outcome. The presence of a large pseudoaneurysm of the internal carotid artery completely embedded in a giant macroprolactinoma is rare and needs a tailored treatment strategy. The importance of the preoperative knowledge of asymptomatic IA coexisting with PA can avoid accidental rupture of the aneurysm during surgical resection and may lead to planning the best treatment. A high degree of suspicion for an associated aneurysm is needed, and if magnetic resonance imaging shows some atypical features, digital subtraction angiography must be performed prior to contemplating any intervention to avoid iatrogenic aneurysmal rupture. Our multimodal approach with the first-line therapy of low-dose cabergoline to obtain prolactin normalization with minimum risks of aneurysms rupture and subsequent endovascular treatment with flow diverter has not been described elsewhere to our knowledge. In the cases, we suggest adopting a tailored low-dose cabergoline therapy scheme to avoid rupture during cytoreduction and initiate a close neuroradiological follow-up program

Genetic modification of a carcinoma with IL-4 gene increase the influx of dendridic cells relative to other cytokines

Tumor cells genetically modified with certain cytokine genes gain immunogenic properties that allow the development of systemic anti-tumor immunity. Whether different cytokines may influence infiltration of transduced tumors by dendritic cells (DC) has not been investigated. Therefore, we analyzed the C26 murine colon carcinoma genetically modified to release interleukin (IL)-2, IL-4, IL-12, granulocyte colony-stimulating-factor (CSF) or granulocyte-macrophage (GM)-CSF for immunostaining with the monoclonal antibody NDLC145 recognizing the DEC205 determinant which, on tumor sections, is virtually restricted to DC. Infiltrating leukocytes were also characterized for expression of co-stimulatory molecules like CD54, CD86 and major histocompatibility complex class II. The intratumoral DC content was dependent on the type of transduced cytokines with C26/IL-4 being the most abundant in DEC205+ cells. The effect of IL-4 in recruiting DC did not depend on the type of tumor since it was confirmed in the TSA mammary carcinoma. In comparison with C26/GM-CSF, C26/IL-4 had more B7.2+ cells but less Ia+ cells. Furthermore, the hypertrophic skin overlaying tumors producing GM-CSF showed numerous Langerhans cells stained by NDLC145 and the draining lymph nodes showed abundance and paucity of DC in C26/GM-CSF and C26/IL-4, respectively. When injected into the ear pinna, C26/GM-CSF stimulated, whereas C26/IL-4 inhibited DC-mediated priming of delayed-type hypersensitivity reaction by 2,4-dinitro-1-fluorobenzene. These findings prove that transduced cytokines differently influence DC recruitment at the tumor site and DC function in nearby tissues. Along with the other leukocytes and their secondary produced cytokines, DC create an environment in which T cells can be differently modulated. Such a phenomenon may have implications on genetic modification of tumor cells to be used as cancer vaccin

CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN

The design, construction and test of a charged particle detector made of scintillation counters read by Silicon Photomultipliers (SiPM) is described. The detector, which operates in vacuum and is used as a veto counter in the NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating charged particles

Combined acoustic testing of home appliances: a case study

To improve the comfort of the domestic environment, the acoustic performances of home appliances need to be optimised. During the product development stages, manufacturers typically carry out acoustic measurements to validate design strategies and to perform troubleshooting. Moreover, several experimental techniques can be used depending on the target of the analyses. In this paper, the sound field radiated by an operating washing machine is investigated. A combined acoustic testing is carried out by means of a sound intensity probe and a microphone array. The details on the tests execution and the data processing are presented. The experimental results are discussed, providing a synthesis of the two sets of measurements

Measurement and Processing of Road Irregularity for Surface Generation and Tyre Dynamics Simulation in NVH Context

Nowadays, finite element tyre models are often used to perform vehicle NVH (noise, vibration, harshness) simulations. To account for the specific operating conditions, a road surface must be properly included in the model. This paper deals with a methodology to experimentally evaluate and process road irregularity measurements, so as to generate a road surface input. These surfaces are used to simulate the tyre/road interaction at the footprint, which is modelled as a contact surface in finite element tyre models. For this reason, a linear profile of the road surface is not suitable for these simulations and the whole surface must be considered. Starting from the measurements taken through a test equipment specifically designed to carry laser sensors and scan road profiles, the Power Spectral Density (PSD) of a specific track is estimated and then interpolated considering piecewise functions. Finally, a model to generate a road surface starting from the measured PSD is developed, discussed and validated

Enhanced high-temperature mechanical behavior of an in situ TiAl matrix composite reinforced with alumina

A Ti-45Al-3Cr-2.5Nb alloy reinforced with in situ formed alumina has been produced by means of centrifugal casting by adding zirconium oxide in the crucible. The dispersion-strengthened alloy has been characterized to verify its microstructure and particle distribution. Mechanical tests carried out over the temperature range 850-950 degrees C highlighted that in situ formed alumina allows to increase the alloy yield stress by 21% at 850 degrees C and by 35% at 900 degrees C. Moreover, the in situ formed oxide particles produced an increase of the Young's modulus of about 10% at 850 degrees C and of about 8% at 900 degrees C. Considering that the tested alloy has a density that is about a half of nickel superalloys, obtaining high specific mechanical properties over the temperature range 850-950 degrees C can boost its application in the production of turbine blades