A Multi-Hop 6LoWPAN Wireless Sensor Network for Waste Management Optimization

In the first part of this Thesis several Wireless Sensor Network technologies, including the ones based on the IEEE 802.15.4 Protocol Standard like ZigBee, 6LoWPAN and Ultra Wide Band, as well as other technologies based on other protocol standards like Z-Wave, Bluetooth and Dash7, are analyzed with respect to relevance and suitability with the Waste Management Outsmart European FP7 Project. A particular attention is given to the parameters which characterize a Large Scale WSN for Smart Cities, due to the amount of sensors involved and to the practical application requested by the project. Secondly, a prototype of sensor network is proposed: an Operative System named Contiki is chosen for its portability on different hardware platforms, its Open Source license, for the use of the 6LoW-PAN protocol and for the implementation of the new RPL routing protocol. The Operative System is described in detail, with a special focus on the uIPv6 TCP/IP stack and RPL implementation. With regard to this innovative routing proto col designed specifically for Low Power Lossy Networks, chapter 4 describes in detail how the network topology is organized as a Directed Acyclic Graph, what is an RPL Instance and how downward and upward routes are constructed and maintained. With the use of several AVR Atmel modules mounting the Contiki OS a real WSN is created and, with an Ultrasonic Sensor, the filling level of a waste basket prototype is periodically detected and transmitted through a multi-hop wireless network to a sink nodeope

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

A Multi-Hop 6LoWPAN Wireless Sensor Network for Waste Management Optimization

In the first part of this Thesis several Wireless Sensor Network technologies, including the ones based on the IEEE 802.15.4 Protocol Standard like ZigBee, 6LoWPAN and Ultra Wide Band, as well as other technologies based on other protocol standards like Z-Wave, Bluetooth and Dash7, are analyzed with respect to relevance and suitability with the Waste Management Outsmart European FP7 Project. A particular attention is given to the parameters which characterize a Large Scale WSN for Smart Cities, due to the amount of sensors involved and to the practical application requested by the project. Secondly, a prototype of sensor network is proposed: an Operative System named Contiki is chosen for its portability on different hardware platforms, its Open Source license, for the use of the 6LoW-PAN protocol and for the implementation of the new RPL routing protocol. The Operative System is described in detail, with a special focus on the uIPv6 TCP/IP stack and RPL implementation. With regard to this innovative routing proto col designed specifically for Low Power Lossy Networks, chapter 4 describes in detail how the network topology is organized as a Directed Acyclic Graph, what is an RPL Instance and how downward and upward routes are constructed and maintained. With the use of several AVR Atmel modules mounting the Contiki OS a real WSN is created and, with an Ultrasonic Sensor, the filling level of a waste basket prototype is periodically detected and transmitted through a multi-hop wireless network to a sink nod

Adapting Neutralizing Antibodies to Viral Variants by Structure-Guided Affinity Maturation Using Phage Display Technology

Neutralizing monoclonal antibodies have achieved great efficacy and safety for the treatment of numerous infectious diseases. However, their neutralization potency is often rapidly lost when the target antigen mutates. Instead of isolating new antibodies each time a pathogen variant arises, it can be attractive to adapt existing antibodies, making them active against the new variant. Potential benefits of this approach include reduced development time, cost, and regulatory burden. Here a methodology is described to rapidly evolve neutralizing antibodies of proven activity, improving their function against new pathogen variants without losing efficacy against previous ones. The reported procedure is based on structure-guided affinity maturation using combinatorial mutagenesis and phage display technology. Its use against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is demonstrated, but it is suitable for any other pathogen. As proof of concept, the method is applied to CoV-X2, a human bispecific antibody that binds with high affinity to the early SARS-CoV-2 variants but lost neutralization potency against Delta. Antibodies emerging from the affinity maturation selection exhibit significantly improved neutralization potency against Delta and no loss of efficacy against the other viral sequences tested. These results illustrate the potential application of structure-guided affinity maturation in facilitating the rapid adaptation of neutralizing antibodies to pathogen variants