Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors in Multiple Myeloma

In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells. In relapsed and/or refractory MM (RRMM) patients, PD-1/PD-L1 blockade was analyzed by using nivolumab, pembrolizumab, and durvalumab. Outcomes with single agents were unsatisfactory, whereas combination strategies with backbone immunomodulatory drugs (IMiDs) suggested a synergistic action in such a complex immunological landscape, even in patients previously refractory to these drugs. Nevertheless, these combinations were also associated with an increased incidence of adverse events. This review aims to analyze the available preclinical and clinical data on the role of PD-1/PD-L1 inhibitors in MM therapy, focusing on available preliminary efficacy and safety data and offering insights for future investigation

Multi-Fuel Driven Janus Micromotors

Here the first example of a chemically powered micromotor that harvests its energy from the reactions of three different fuels is presented. The new Al/Pd Janus microspheres—prepared by depositing a Pd layer on one side of Al microparticles—are propelled efficiently by the thrust of hydrogen bubbles generated from different reactions of Al in strong acidic and alkaline environments, and by an oxygen bubble thrust produced at their partial Pd coating in hydrogen peroxide media. High speeds and long lifetimes of 200 μm s^(−1) and 8 min are achieved in strong alkaline media and acidic media, respectively. The ability to autonomously adapt to the presence of a new fuel (surrounding environment), without compromising the propulsion behavior is illustrated. These data also represent the first example of a chemically powered micromotor that propels autonomously and efficiently in alkaline environments (pH > 11) without additional fuels. The ability to use multiple fuel sources to power the same micromotor offers a broader scope of operation and considerable promise for diverse applications of micromotors in different chemical environments

Multi-Fuel Driven Janus Micromotors

Here the first example of a chemically powered micromotor that harvests its energy from the reactions of three different fuels is presented. The new Al/Pd Janus microspheres—prepared by depositing a Pd layer on one side of Al microparticles—are propelled efficiently by the thrust of hydrogen bubbles generated from different reactions of Al in strong acidic and alkaline environments, and by an oxygen bubble thrust produced at their partial Pd coating in hydrogen peroxide media. High speeds and long lifetimes of 200 μm s^(−1) and 8 min are achieved in strong alkaline media and acidic media, respectively. The ability to autonomously adapt to the presence of a new fuel (surrounding environment), without compromising the propulsion behavior is illustrated. These data also represent the first example of a chemically powered micromotor that propels autonomously and efficiently in alkaline environments (pH > 11) without additional fuels. The ability to use multiple fuel sources to power the same micromotor offers a broader scope of operation and considerable promise for diverse applications of micromotors in different chemical environments

La Rete Integrata Nazionale GPS (RING) dell' INGV: una infrastruttura aperta per la ricerca scientifica

Since 2004, the Istituto Nazionale di Geofisica e Vulcanologia (INGV) is investing important energies for the creation of a continuous GPS network dislocated all over the Italian territory. Data transmission will occur in real time, integrating the experiences already existing in the different INGV institutes and developing a 3-yrs strategy for the new installations. The main targets of the network are represented by active tectonics studies, including also the seismological part as strain accumulation on faults. Within a 3-yrs funding project, it is expected, to realize for the scientific community an infrastructure which is comparable to those existing in countries where advanced crustal deformation studies are carried out. Thus, INGV have co-located the classical seismological instrumentation (broad band seismometers and accelerometers) with GPS receivers to observe and quantify the whole seismic cycle. In this short paper, we describe the CGPS network, the technological choices for the monumentation and the data transmission, the data and metadata management and, finally, the data policy and the deliverables.INGVUnpublishedreserve

The RING network: improvements to a GPS velocity field in the central Mediterranean

Since 2004, a continuous Global Positioning System (GPS) network has been operated by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) to investigate active tectonic processes in Italy and the surrounding regions, which are still largely debated. This important infrastructure is known as Rete Integrata Nazionale GPS (RING) network, and it consists of about 130 stations that are deployed all over Italy. The development and realization of a stable GPS monumentation, its integration with seismological instruments, and the choice of both satellite and internet data transmission, make this network one of the most innovative and reliable CGPS networks in the world. The technologically advanced development of the RING network has been accompanied by the development of different data processing strategies, which are mainly dependent on the use of different GPS analysis software. The different software-related solutions are here compared at different scales for this large network, and the consistency is evaluated and quantified within an RMS value of 0.3 mm/yr