Modal parameters identification and monitoring of two arches

The paper presents the results of the modal parameters identification and of the continuous monitoring of two arches built in the new area of Expo 2015 in Milan. The activities on the arches were performed during the erection stage and they were planned as a consequence of preliminary studies performed at Politecnico di Milano wind tunnel, that highlighted dynamic instability due to the wind. In particular, the first two bending modes of the structures showed a critical behaviour and for this reason a TMD (Tuned Mass Damping) system was designed in order to control these modes. At first, frequencies, damping and modal deflected shapes were evaluated in order to check the numerical FEM model, to tune the TMD system and to check its correct functioning. The two arches were then monitored for several months to observe their dynamic behaviour under different wind conditions. A good database about the strongest and the most frequent winds in the site was obtained. The accelerations registered under strong wind conditions did not reach dangerous levels for the structures, moreover these results showed a good agreement with the wind tunnel ones

Regional Differences in Cerebral Glucose Metabolism After Cardiac Arrest and Resuscitation in Rats Using [(18)F]FDG Positron Emission Tomography and Autoradiography.

BACKGROUND Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model. METHODS Ten rats underwent 8-min cardiac arrest, induced with a mixture of potassium and esmolol, and resuscitation, performed with chest compressions and epinephrine. Eight sham animals received anesthesia and experimental procedures identical to the ischemic group except cardiac arrest induction. Brain metabolism was assessed using [(18)F]FDG autoradiography and small animal-dedicated positron emission tomography. RESULTS The absolute glucose metabolism measured with [(18)F]FDG autoradiography 2 h after cardiac arrest and resuscitation was lower in the frontal, parietal, occipital, and temporal cortices of cardiac arrest animals, showing, respectively, a 36% (p = 0.006), 32% (p = 0.016), 36% (p = 0.009), and 32% (p = 0.013) decrease compared to sham group. Striatum, hippocampus, thalamus, brainstem, and cerebellum showed no significant changes. Relative regional metabolism indicated a redistribution of metabolism from cortical area to brainstem and cerebellum. CONCLUSIONS Our data suggest that cerebral regions have different susceptibility to moderate global ischemia in terms of glucose metabolism. The neocortex showed a higher sensibility to hypoxia-ischemia than other regions. Other subcortical regions, in particular brainstem and cerebellum, showed no significant change compared to non-ischemic rats

Metformin and temozolomide, a synergic option to overcome resistance in glioblastoma multiforme models

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line. In particular, combined-treatment modulated apoptosis by increasing Bax/Bcl-2 ratio, and reduced Reactive Oxygen Species (ROS) production. We also observed that MET associated with TMZ was able to reduce the expression of glioma stem cells (GSC) marker CD90 particularly in T98G cells but not that of CD133. In vivo experiments showed that combined treatment with TMZ and MET significantly slowed down growth of TMZ-resistant tumors but did not affect overall survival of TMZ-sensitive tumor bearing mice. In conclusion, our results showed that metformin is able to enhance TMZ effect in TMZ-resistant cell line suggesting its potential use in TMZ refractory GBM patients. However, the lack of effect on a GBM malignancy marker like CD133 requires further evaluation since it might influence response duration

Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease

Huntington disease (HD) is an inherited late-onset neurological disorder characterized by progressive neuronal loss and disruption of cortical and basal ganglia circuits. Cell replacement using human embryonic stem cells may offer the opportunity to repair the damaged circuits and significantly ameliorate disease conditions. Here, we showed that in-vitro-differentiated human striatal progenitors undergo maturation and integrate into host circuits upon intra-striatal transplantation in a rat model of HD. By combining graft-specific immunohistochemistry, rabies virus-mediated synaptic tracing, and ex vivo electrophysiology, we showed that grafts can extend projections to the appropriate target structures, including the globus pallidus, the subthalamic nucleus, and the substantia nigra, and receive synaptic contact from both host and graft cells with 6.6 ± 1.6 inputs cell per transplanted neuron. We have also shown that transplants elicited a significant improvement in sensory-motor tasks up to 2 months post-transplant further supporting the therapeutic potential of this approach

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood–brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10–120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body

Physical Model Tests on Spar Buoy for Offshore Floating Wind Energy Conversion

ABSTRACT: The present paper describes the experiences gained from the design methodology and operation of a 3D physical modelexperiment aimed to investigate the dynamic behaviour of a spar buoy floating offshore wind turbine. The physical model consists in a Froude-scaled NREL 5MW reference wind turbine (RWT) supported on the OC3-Hywind floating platform. Experimental tests have been performed at Danish Hydraulic Institute (DHI) offshore wave basin within the European Union-Hydralab+ Initiative, in April 2019. The floating wind turbine model has been subjected to a combination of regular and irregular wave attacks and different wind loads. Measurements of displacements, rotations, accelerations, forces response of the floating model and at the mooring lines have been carried out. First, free decay tests have been analysed to obtain the natural frequency and the modal damping ratios of each degree of freedom governing the offshore. Then, the results concerning regular waves, with orthogonal incidence to the structure, are presented. The results show that most of longitudinal dynamic response occurs at the wave frequency and most of lateral dynamic response occurs at rigid-body frequencies.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654110, HYDRALAB+

Endovascular administration of magnetized nanocarriers targeting brain delivery after stroke

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.We are grateful for the technical assistance received from the Pre-clinical imaging Platform at Vall d’Hebron Institut de Recerca, the Servei RMN at Universitat Autònoma de Barcelona, and the Unitat de Microscopia Òptica Avançada, Facultat de Medicina at the Universitat de Barcelona. This work has been supported under the Euronanomed MAGGBRIS collaborative project by grants from the Spanish Ministry of Science and Innovation (PCIN-2017-090 grant), the Instituto de Salud Carlos III (AC17/00004 with FEDER funds), the Slovak Research and Development Agency under the Contract No.APVV-19-0324 and the Italian Ministry of Health (Ricerca Corrente year 2017 funds); by the Expression of Interest (EoI) for Collaborative Projects on Regenerative Medicine 2019 P-CMR[C]); programs 2017-SGR-1427 and 2017-SGR-765 from the Generalitat de Catalunya; RETICS-INVICTUS PLUS from ISCIII (RD16/0019/0021 with FEDER funds); the ‘Severo Ochoa’ Program for Centers of Excellence in R&D (SEV-2015-0496) and the RYC-2017- 22412 and PID2019-107989RB-I00. A.G has been supported by fellowships from ISCIII (FI17/00073 and MV18/00006), A.R by a visiting-scientist fellowship from ISCIII (BA17/00052) and Y. Z has been supported by the China Scholarship Council (CSC).Peer reviewe