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Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.

Embedded memories in Automotive Systems-on-Chip usually occupy a large die area portion. Consequently, their defectivity can strongly impact production yield for any automotive device. Along with the technology ramp-up phase and for statistical process control reasons during volume production, it is a good automotive industry practice to collect diagnostic information in addition to pure testing data. Designers and technology experts must receive accurate diagnostic results from failing devices to react to misbehavior by identifying and correcting the related issues at their source and drawing correct repair strategy conclusions. A commonly used approach resorts to the generation of failure bitmaps based on collecting all failing bits coordinates to be sent one by one to the tester. More efficiently, the encountered faults can be compacted or compressed in onchip memory resources to be retrieved by the tester at the end of the memory test. This paper presents an on-chip method to compact diagnostic information during embedded memory testing. More specifically, the method is applied to diagnose embedded FLASH memories. This strategy permits the reconstruction of failure bitmaps without any loss, while compression approaches obtain an approximation. The proposed method uses a fraction of the memory requested by a coordinate-based bit mapping approach and is comparable to compression methods. At the cost of a moderate test time overhead, the proposed strategy permits dramatically increasing the number of devices that can be fully diagnosed without any bitmap reconstruction loss. Most failing devices in a real embedded FLASH production scenario were diagnosed after a single transfer from on-chip to the tester host computer.

The topmost Argille Azzurre (beds 1-2) and the basal Sabbie di Asti (beds 3-9) formations in the Villalvernia area are analysed in terms of palaeoecological and taxonomic features; the succession is 6 m thick and dates back to the middle Piacenzian within the Globorotalia bononiensis acme. The upper boundary of the clayey Bed 2 corresponds to an unconformity reflecting Pliocene tectonic activity. The study is focused on the fossil assemblages of beds 3, 4 and 9. The sandy Bed 3 yields 362 mollusc taxa; the assemblage is allochthonous and mixes infra- to circalittoral species accumulated by hyperpycnal mass-transport. The same mechanism is responsible for the origin of the overlying fossil unit (Bed 4) with numerous specimens of the Entobia-Gastrochaenolites ichnofacies. The autochthonous fossil assemblage of Bed 9 yields 308 molluscs, plus three brachiopods and ten fish taxa; most of them refer to the Posidonia meadow (HP), and their autochthony is shown by taphonomic features as skeletal integrity, mixing of successive generations or the limitation to juvenile ontogenetic stages of vagile and temporarily byssate species for which the HP performs a nursery function. Three brachiopods and 52 molluscs are here reported for the first time from the Pliocene of Piedmont. In the final chapter "Systematic Palaeontology" four brachiopods and 29 molluscs are described, among which there are eight new gastropod species: Crepidula bellardii n. sp., Conus dellabellai n. sp., Conus villalvernensis n. sp., Odetta chirlii n. sp., Ondina curta n. sp., Ondina elongata n. sp., Ondina pseudovitrea n. sp., Anisocycla subcylindrica n. sp.

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper.

Carbonatitic dykes that crop out in the central western part of Fuerteventura Basal Complex (Ajuy, Punta de la Nao), were affected by the Miocene intrusive event responsible for contact metamorphism and partial melting of part of the alkaline-carbonatitic complex. Textural characteristics, monazite enriched in LREE (La, Ce, Nd) formation processes in microfractures that affect zircon crystals, show carbonatite interactions with hydrothermal fluids and partial REE remobilization. Pyrochlore is the main mineral carrier of rare earth elements (sum REE=216694 ppm), with high LREE (LaN=185816 and CeN=165209) with respect to HREE (YbN=2589 and LuN=1814) with a rather steep pattern (La/Yb)N=72 in REE diagram. The mineral paragenesis represented by the interstratified illite/smectite, chlorite and vermiculite allows to frame the hydrothermal event in zeolite facies (T° ≈ 100-200 °C).

Background Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. Methods Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. Results Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. Conclusions Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02664-4.