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The copious scientific literature produced after the detection of GW170817 electromagnetic counterpart demonstrated the importance of a prompt and accurate localization of the gravitational wave within the co-moving volume. In this letter, we present FIGARO, a ready to use and publicly available software that relies on Bayesian non-parametrics. FIGARO is designed to run in parallel with parameter estimation algorithms to provide updated three-dimensional volume localization information. Differently from any existing algorithms, the analytical nature of the FIGARO reconstruction allows a ranking of the entries of galaxy catalogues by their probability of being the host of a gravitational wave event, hence providing an additional tool for a prompt electromagnetic follow up of gravitational waves. We illustrate the features of FIGARO on binary black holes as well as on GW170817. Finally, we demonstrate the robustness of FIGARO by producing so-called pp-plots and we present a method based on information entropy to assess when, during the parameter estimation run, it is reasonable to begin releasing skymaps., 9 pages, 5 figures

Persistence of HIV-1-infected cells during antiretroviral therapy is well documented, but may be modulated by early initiation of antiretroviral therapy in infants.Here, we longitudinally analyzed the proviral landscape in 9 infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length next-generation proviral sequencing.We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional underrepresentation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harbouring intact proviruses, and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated in genic and accessible chromatin locations.Together, these results permit rare insight into the evolution of the HIV-1 reservoir in HIV-1-infected infants and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Sensitive technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution and sensitive analysis of HIV-1 reservoir cells following early ART initiation in infants.

In this article, a noninvasive remote monitoring method of error of electricity energy meter (EM) is introduced and its achievable precision is investigated. The aim of the method is to determine remotely the smart EM active power relative measurement error using the reference EM connected at the input of a low-voltage distribution grid segment. The meter error estimation is carried out despite other customers’ electrical load changes observable by the reference meter and power fluctuations in the distribution network. The method is based on the real-time analysis of natural customer power consumption profiles without any additional load injection for error-monitoring needs. A power step in the customer power consumption profile is detected by the meter under test and then the step magnitude is delivered for the comparison with the power step magnitude estimated synchronously by the reference meter. The analysis of the method error is conducted by applying simulation of the benchmark distribution grid which includes 26 EMs and utilizing the open data power consumption profiles. It is shown that after two to three days of averaging (including approximately 170 power steps) of the meter error estimates, it becomes possible to achieve an uncertainty of meter error estimation approximately 0.63%. The feasibility of the method implementation scenarios with the state-of-the-art EM data collection protocols in advanced measurement infrastructure (AMI) by means of occupancy index modeling is performed.

The monitoring and the management of smart grid require an advanced communication infrastructure. The time synchronization is among the most important services such an infrastructure should offer. Several solutions are available to disseminate the time information in a distributed system; for instance, most of the times a global positioning system (GPS) receiver is used to recover accurate time information. However, GPS receivers need a clear view of the sky. Other solutions, like the use of a network-based synchronization mechanism, require a dedicated communication infrastructure, which is not always feasible for economical reason. Thus, the use of the power grid itself to disseminate a time signal is extremely interesting. The aim of this article is to investigate the possibility to distribute a time signal over a medium voltage (MV) grid using a chirp-based modulation. The timing data are coded using IRIG-B time code. Such an approach does not require the installation of a dedicated infrastructure, and it is noninvasive, because the signal is transmitted on a different band with the respect to power line communication (PLC). The effectiveness of the approach has been experimentally evaluated on a test MV line available in a laboratory. Although the tested chirp-based symbol has a limited frequency bandwidth (80 kHz), the jitter in the identification of the start of frame is on the order of 7.5 $\mu \text{s}$ , fulfilling the requirements of the most smart grid applications.

The LoRaWAN technology, an example of low power wide area network, is considered a possible IoT-derived solution for realizing private cellular (single-hop) communications in the industrial domain. However, despite LoRaWAN promises long range and dense environments with many obstacles (as the industrial ones), it may suffer from coverage issue. Additionally, the inverse relationship between data rates and range may be unacceptable for many industrial applications. In this article, an innovative LoRaWAN range extender (based on an enhanced LoRaWAN node) is described, and its integration in the infrastructure of industrial Internet of Things (IIoT)-enabled industrial wireless networks is presented. A frame relay strategy is suggested, thus avoiding to tradeoff the highest data rates against an increased sensitivity. The feasibility of the solution is formally verified and the features of the realized proof-of-concept prototype, based on commercially available hardware, are discussed. The experimental results, obtained with a purposely designed test bench, show the effectiveness of the proposed approach. In particular, the range extender is transparent for legacy LoRaWAN networks as confirmed by correct relaying of uplink and downlink for different types of LoRaWAN message.

OBJECTIVE To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life. DESIGN Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV. METHODS Western blot analysis and ELISA defined 14 HIV-seropositive and six seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR. RESULTS Gp140-specific T cells and B cells persist at similar levels in both groups. A higher production of IL-21 in gp140-specific T cells was found in seropositives vs. seronegatives (P = 0.003). Gene expression in switched IgM-IgD- gp140-specific memory B cells after stimulation with HIV peptides in vitro demonstrated a differential expression of genes involved in signal transduction and activation after BCR/TLR triggering and B-cell activation. Genes relating to antibody production (PRDM1) and T-B cognate stimulation (CXCR4, IL21R) were differentially induced after in-vitro stimulation in seronegatives vs. seropositives suggesting a truncated process of B-cell maturation. CONCLUSION HIV-specific memory B and T cells persist in early treated regardless their serological status. Seronegatives and seropositives are distinguished by gp140-specific T-cell function and by distinct transcriptional signatures of gp140-specific B cells after in-vitro stimulation, presumably because of a different antigen exposure. Such qualitative insights may inform future immunotherapeutic interventions.

Background: Despite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of 'namely' atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells (T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation. Methods: We studied 40 PHIV who started treatment by the 2nd year of life and maintained virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-disciplinary approach including immunological B and T cell phenotype, plasma proteomics analysis, and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity. Results: Phenotypic signs of B cell hyperactivation were elevated in subjects starting ART later (%DN T-bet+CD11c+ p=0.03; %AM T-bet+CD11c+ p=0.02) and were associated with detectable cell-associated HIV-1 RNA (%AM T-bet+CD11c+ p=0.0003) and transient elevation of the plasma viral load (spike). Furthermore, B-cell hyperactivation appeared to be present in individuals with higher frequency of exhausted T-cells, in particular: %CD4 TIGIT+ were associated with %DN (p=0.008), %DN T-bet+CD11c+ (p=0.0002) and %AM T-bet+CD11c+ (p=0.002) and %CD4 PD-1 were associated with %DN (p=0.048), %DN T-bet+CD11c+ (p=0.039) and %AM T-bet+CD11c+ (p=0.006). The proteomic analysis revealed that subjects with expansion of these atypical B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Furthermore, we observed that higher levels of ABCs were associated a reduced capacity to maintain vaccine-induced antibody immunity against measles (%B-cells CD19+CD10- T-bet+, p=0.035). Conclusion: We identified that the levels of hyperactivated B cell subsets were strongly affected by time of ART start and associated with clinical, viral, cellular and plasma soluble markers. Furthermore, the expansion of ABCs also had a direct impact on the capacity to develop antibodies response following routine vaccination. PENTA-ID Foundation - ViiV Healthcare UK United States Department of Health & Human Services National Institutes of Health (NIH) - USA (R01AI127347-05) CFAR (P30AI073961) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of General Medical Sciences (NIGMS) 8.786 JCR (2021) Q1, 33/161 Inmunology 2.321 SJR (2021) Q1, 31/241 Inmunology No data IDR 2021 UEM

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 experiencing viral Spike (transient elevation of HIV-1 VL, 50-999 copies/ml). We employed a multiomics approach including deep immunological B and T cell phenotype in PBMC, with aging B cells defined by the expression of T-bet and CD11c; plasma proteomics analysis by mass spectrometry and serum level of anti-measles antibodies as correlates of humoral response. We found that individuals with expansion of aging B cell, defined by the expression of T-bet+CD11c+, were those starting treatment later, presenting detectable levels of cell-associated HIV-1 RNA, history of Spikes, and a higher frequency of exhausted T-cells, including those expressing PD-1, LAG3, TIGIT. Accordingly, the proteomic analysis revealed that subjects with expansion of aging B cells and exhausted T cells had enrichment of proteins involved in immune inflammation and complement activation pathways, such as CLU and APCS which are also involved in tumor progression. Signs of precocious aging were associated with a reduced capacity to maintain virological memory against measles vaccination. To our knowledge, this is the first study focusing on precocious B-cell aging and dysfunctionality in PHIV with long-term virological suppression. Our experimental strategy enabled identification of clinical, viral, cellular and plasma soluble markers associated with B-cells aging. Our results pave the way to further define risk of disease progression or lymphoproliferative disorders in PHIV.Author summaryDespite a successful antiretroviral therapy (ART), adolescence living with perinatally acquired HIV (PHIV) experience B-cells dysfunction, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. It is thus paramount to define novel and precise correlates of precious aging B cell for the definition of novel therapeutic strategies. Here, we studied 40 PHIV who started treatment by 2nd year of life and maintain virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-omics approach including immunological B and T cell phenotype, plasma proteomics analysis and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity. We found that levels of aging B cells were positively associated with age at ART start, cell associated HIV-1 RNA (caHIV-1 RNA) and the presence of Spikes. Individuals with increased proportions of aging B cells had concomitant expansion of exhausted T cells and were unable to maintain vaccine-induced immunity over time. B-cell aging, and T-cell exhaustion were also associated with proteins involved in immune inflammation. The factors found here to be associated with aging B-cell could inform further therapeutic studies.

The growing presence of Renewable Energy Sources (RESs) is heavily affecting the control and management of distribution grids. Battery Energy Storage Systems (BESSs) are increasingly adopted to mitigate the adverse impacts caused by the uncertainty of RES generators. Most of the existing works in the literature aims at using BESSs to maximize the self-consumption of energy provided by RES generators or focuses on the mitigation of voltage and/or frequency drift effects. More recently, some research works also studied the effects that BESSs have on the active power flows at the Point of Common Coupling (PCC) of prosumers. All these studies are based on the definition of proper energy Key Performance Indicators (KPIs) based on heterogeneous information collected from several measurement devices deployed in the field. This also means that the results of such studies could be significantly affected by the quality of data, particularly concerning the time resolution of the measurements. To better highlight this concern, this paper proposes an analysis of the impact of the time resolution of measurements on the evaluation of the absolute power ramp reduction at the PCC of prosumers in presence of BESS installations. The analysis was performed on real data collected from the eLUX lab of the University of Brescia, Italy, by varying the time resolution from 5 s to 15 min. The results of the analysis demonstrated that the time resolution has a great impact on the evaluation of the considered KPI, by leading to completely different performance assessments.

During the last years, the industrial automation field was radically revolutionized by Industry 4.0 paradigm. The possibility to interconnect industrial machinery to the cyber world through Cyber Physical System (CPS) enables innovative services, but open new challenges on communication and data management sides. In fact, it is important to identify not only which CPS generated an information, but also where it is located on the production plant, since the configuration of the automation could dynamically change in function of the product being produced. In our research work, a low-cost (and low power) approach for the estimation of the relative position of CPS in industrial plant has been investigated. The proposed solution exploits the Direction Finding service introduced by Bluetooth 5.0. The Angle of Arrival (AoA) method in connection-less mode is used to estimate the angle between a tag and the receiving anchors. In this way, the computational power (and, the relative power consumption) of the tag is limited. The preliminary characterization of this solution shows as the maximum error angle is about 5° at a distance of 4 m between anchor and tag. This result is promising, although the application of the BLE Direction Finding service requires a careful design of the array of antennas and of its radiation pattern to allow a proper localization in the three-dimensional space.

HIV eradication is hindered by the existence of latent HIV reservoirs in CD4+ T cells. Therapeutic strategies targeting latent cells are required to achieve a functional cure, however the study of latently infected cells from HIV infected persons is extremely challenging due to the lack of biomarkers that uniquely characterize them. In this study, the dual reporter virus HIVGKO was used to investigate latency establishment and maintenance in lymphoid-derived CD4+ T cells. Single cell technologies to evaluate protein expression, host gene expression, and HIV transcript expression were integrated to identify and analyze latently infected cells. FDA-approved, JAK1/2 inhibitors were tested in this system as a potential therapeutic strategy to target the latent reservoir. Latent and productively infected tonsillar CD4+ T cells displayed similar activation profiles as measured by expression of CD69, CD25, and HLADR, however latent cells showed higher CXCR5 expression 3 days post-infection. Single cell analysis revealed a small set of genes, including HIST1-related genes and the inflammatory cytokine, IL32, that were upregulated in latent compared to uninfected and productively infected cells suggesting a role for these molecular pathways in persistent HIV infection. In vitro treatment of HIV-infected CD4+ T cells with physiological concentrations of JAK1/2 inhibitors, ruxolitinib and baricitinib, used in clinical settings to target inflammation, reduced latent and productive infection events when added 24 hr after infection and blocked HIV reactivation from latent cells. Our methods using an established model of HIV latency and lymphoid-derived cells shed light on the biology of latency in a crucial anatomical site for HIV persistence and provides key insights about repurposing baricitinib or ruxolitinib to target the HIV reservoir.

The monitoring of pollutants in industrial plants is a major concern, in order to satisfy the requirements dictated by the related norms. Recently, the problem of odor monitoring gained importance since, despite the generally low dangerous nature of the emission, people usually correlate bad smell to unhealthy air condition. In this paper, we focus on the wastewater treatment application scenario and propose a versatile air pollution control solution. In particular, a distributed eN ose, based on low-cost, but highly configurable sensing probes, is suggested. The Internet of Things (IoT) paradigm has been followed, thanks to the adoption of a communication infrastructure based on the widely adopted LoRaWAN technology. Such an approach, on one hand, would allow to easily cope with the administration and local population; on the other hand, it paves the way to use analytics to predict emission events in advance. The need for managing multiple transducers per each probe has been solved using an innovative acquisition strategy, exploiting both the volt-amperometric and resistance-to-time (integral) approaches, implemented by low-cost microcontroller and ancillary electronics. A proof-of-concept prototype has been realized and preliminary experiments have been carried out. Experimental results have demonstrated the solidity of the proposed approach, with relative error below 1 % and relative standard deviation below 0.5% over the whole considered resistive range of more than two decades.

Ambient assisted-living (AAL) systems, including wearables and home automation, could improve the quality of life of fragile people. As analyzed in this paper, the typical architecture of AAL systems is based on wireless sensors networks and proprietary gateways and it can be complex, expensive, and hardly includes interoperable multivendor devices. Emerging Android-based gateways can help in reducing costs, but flexibility and interoperability issues will still remain. On the basis of this fact, the development of an AAL system by a framework-oriented approach is presented. Thanks to the use of the SAndroidE framework, the proposed approach leads to the reduction of the programming effort as well as improves interoperability among different vendors ensuring high customization levels. Results obtained in a typical use case indicate that the programming effort in integrating multivendor devices is reduced by a factor of ten. The presented approach paves the way to the implementation of new open multivendor AAL systems, also encouraging redundant architectures and improving robustness of these emerging solutions.

Immune checkpoint molecules (ICMs) regulate T cell responses. In chronic viral infections and cancer, where antigens can persistently stimulate the immune system, ICMs can serve as a barrier to effective immune responses. The role of ICMs in the setting of systemic low-grade inflammation as in aging and antiretroviral therapy (ART)-suppressed HIV infection is not known. In this study, we made use of stored samples from the FLORAH cohort of HIV-infected ART-suppressed adults (age range 19–77 years.) and age-matched HIV-uninfected controls. We measured the expression levels of ICMs: PD-1, LAG-3, TIGIT, TIM-3, and 2B4 on resting CD4 and CD8 T cells and maturation subsets. To determine how expression of these molecules can affect T cell function, we stimulated peripheral blood mononuclear cell with HIV Gag or p09/H1N1 antigen and performed intracellular cytokine staining by multiparameter flow cytometry. ICMs were expressed at higher levels in CD8 compared with CD4. PD-1 was the only molecule that remained significantly higher in HIV-infected individuals compared with controls. LAG-3 expression increased with age in CD4 and CD8 T cells. 2B4 expression on CD8 T cells was negatively associated with IL-2 production but showed no effect on CD4 T cell function. TIM-3 expression was negatively associated with IL-21 production in CD4 and CD8 T cells and also negatively correlated with flu vaccine responses in HIV-negative individuals. Taken altogether, this study demonstrates the marked variation in ICM expression in T cells among adults and sheds light on the biology of these molecules and their effects on antigen-specific T cell functions. Overall, our results point to TIM-3 as a potential biomarker for immune function in HIV(+) individuals on ART.

The Low Power Wide Area Networks (LPWANs) have been proposed as viable wireless connection method for the implementation of the Internet of Things (IoT), thanks to their wide coverage, low complexity and low power consumption. In this scenario, LoRaWAN emerged as a de-facto leading technology, because of its openness and the current availability of many devices (like sensors and gateways). Several implementations of the LoRaWAN specifications have appeared in the market, each one showing support for different hardware, different software architectures, and different operating systems. Thus, the need of test procedures for comparing them is evident. In this paper, a test methodology for the experimental assessment of architectural delays of LoRaWAN implementations is presented. The new approach is composed of: a mapping phase, needed for highlighting the LoRaWAN blocks inside the implementation under test; followed by a measurement phase, in which the relevant timestamps are taken along the information path from LoRaWAN node to LoRaWAN customer application. The use and the effectiveness of the proposed methodology are shown by means of use cases that involve different LoRaWAN implementations and several hardware platforms. The experiments described in the paper are not intended to evaluate particular implementations but they are aimed to assess the suitability of the proposed methodology. The results demonstrate that the proposed approach can be used to compare the performance of entire LoRaWAN systems, helping the owner of the infrastructure and the user in making choices and optimizations.

Background and objectives: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined. Methods: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies. Results: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001). Conclusions: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC.

Low Power Wide Area Networks (LPWANs) are wireless technologies well accepted in the Internet of Things (IoT) scenarios because they operate in both public and private infrastructure using unlicensed frequency bands. Differently from other wireless standards, the LPWAN target applications are low-rate, sporadic-transmission, low-energy systems. Surely, fast response time and high reliable communication are out of the original LPWAN scope. In this work, a first investigation about the use LoRaWAN (one the most diffused LPWAN protocols) for notification of emergency messages across industrial plants is reported. The opportunity of using recently proposed low-cost repeaters, and the creation of a clever replication pattern of radio messages are the keys of the proposed approach. The results of the preliminary analytical feasibility assessment are presented, confirming the possibility to increase success ratio of notification and respective confirmation in case of emergencies.

Differential capacitive sensors, especially if implemented as MEMS (Micro Electro Mechanical Systems) are a widely employed sensor solution, especially after the widespread adoption of the IoT (Internet of things) paradigm. These sensors target very different applications, including accelerometers, gyroscopes, barometers, just to mention a few, because they can take advantage from lower power consumption, better temperature coefficient and manufacturability. The readout circuit plays a central and fundamental role in ensuring optimal overall performance. In this paper, a frontend for interfacing differential capacitive sensors with microcontroller-based systems is discussed and performance is evaluated. In particular, the use of voltage mode is considered and, consequently, the stray capacitance can deeply affect the readouts. The proposed interface evaluates the mismatch between the current flowing in the two sensor equivalent capacitors and estimates the parasitic value. Additionally, the information about the current unbalance is used to improve the measurand estimation. In particular, the proposed approach is able to decrease of one order of magnitude the measurand estimation error, when large stray capacitance affects the sensor.

One of the most widespread applications of IoT technologies is smart metering. Despite remote metering in smart grids is not a novelty, the advent of Low Power Wide Area Network (LPWAN) wireless technologies allowed to extend the concept to gas and water distribution. However, these battery-supplied meters must ensure an operating lifetime longer than 10 years without any maintenance, thus leading to battery oversizing. This work focuses on LoRaWAN and proposes an innovative adaptive strategy for equalizing the message time duration in order to maximize the battery exploitation. A simulator has been purposely designed to evaluate the performance in a real-world scenario, considering a node density of hundreds of nodes per square km. The simulation results demonstrate that a better exploitation of the battery is possible, ensuring an increase by 10 times of the amount of the amount of useful user data bytes transferred by meters.

An early Alzheimer Disease (AD) diagnosis is fundamental for maximizing the effectiveness of treatment administration. Unfortunately, distinguish AD from other neurodegenerative dementias, such as Frontotemporal Dementia (FTD) is not trivial. Transcranial Magnetic Stimulation (TMS) emerged as an effective non-invasive, easy to apply and not time-consuming solution. TMS-based techniques generally require expensive ad hoc clinical equipment that suffer from poor flexibility and user friendliness in defining the specific diagnostic protocol. In this work, a low-cost BeagleBone Black single board computer (BBB-SBC) has been used to implement all the functionalities required to manage a TMS-based instrument. Timeliness of signal generation is guaranteed by dedicated programmable real-time units hosted by the BBB-SBC System on Chip. Web-based interface, complemented by IoT-like features, provide a high degree of versatility and permit the execution of many different diagnostic protocols. In particular, the experimental validation confirms timing error in the sub-microsecond range, more than enough for the considered application.

Location based services (LBS) have emerged as an active area of research aimed to filter and organize the information present on the internet. This work deals with LBS applied to industrial Internet of Things (IoT) applications, ranging from distributed measurement systems (DMS) to distributed human -machine interface (HMI). The goal is to investigate the available techniques to determine the location of assets (e.g., sensors and actuators) and then to characterize some application scenarios. In detail, the use cases have been implemented exploiting the eLUX Living Laboratory in Brescia, Italy, which resembles a smart grid, smart living and Industry 4.0 real scenario thanks to the numerous installed plants (including renewable sources, indoor sensory systems and electric vehicles). The ranging performance of beacon based and ultrawide band -based localization principles have been experimentally assessed.

Background: Immune Activation (IA) has been previously documented in both pregnant (PG) and non-PG HIV-1 infected (HIV+) women as well as in HIV- uninfected PG women; the latter as a result of the fetal allograft. To determine whether the combined effects of HIV and pregnancy result in increased IA and whether IA is associated with Microbial Translocation (MT), we performed a prospective, longitudinal, controlled study during pregnancy and the postpartum (PP) period. Methods: HIV+ PG women had biomarkers of IA and MT tested at 12-20 weeks (T1), and 24-36 weeks (T2) of pregnancy and at 6-8 weeks Postpartum (T3). HIV+, non-PG women were tested at comparable time points. HIV- PG women were tested at T1 only. HIV+ women were not started on antiretroviral therapy (ART) until T1. Biomarkers of IA assessed included: CD4DR+, CD4CD38+, CD4DR+CD38+, CD8DR+, CD8CD38+, and CD8DR+CD38+. Biomarkers of MT included LPS, sCD14, and 16SrDNA. Results: 30 HIV+PG women, 18 HIV+ non-PG and 10 HIV-PG were enrolled. In the HIV+ women, there were no differences in median age, viral load, % or absolute CD4 at entry. Significant differences between T1 and T2 and between T1 and T3 were noted in CD8DR+CD38+ in HIV+PG women after ART. CD4DR+, CD4DR+CD38+, and CD8DR+ decreased post ART in HIV+PG women but a decline in IA was less evident in HIV+ non-PG. LPS decreased post ART by T3 in both HIV+PG and HIV+ non-PG groups; 16SrDNA was elevated at all time points in both groups when compared to control values, and declined post ART in the HIV+PG group. A subgroup of HIV-PG at T1 had IA and MT as evidenced by several IA markers and increased LPS. Conclusion: The degree of IA and MT was similar among HIV+PG and HIV+ non-PG women followed longitudinally. There was no incremental increase due to the combined effects of HIV and pregnancy. Several markers of IA and MT (LPS, 16SrDNA) decreased post ART. IA and MT occurred in a subgroup of HIV-PG women during the 1st trimester. Further study must be done to confirm whether MT consistently occurs in some healthy women during PG.

Information and operational technologies merge into the so-called industrial Internet of Things, which is one of the basic pillars of the Industry 4.0 paradigm. Roughly speaking, yet-to-come services will be offered in the automation scenario by industrial devices having an internet connection for sharing data in the cloud. Currently, most efforts are in the development of protocols able to ensure horizontal interoperability among heterogeneous applications. Consequently, poor attention is devoted to time-related performance. In this paper, a new, full software, platform-independent approach is proposed for experimentally evaluating the delay in transferring information across local and intercontinental routes by applications leveraging on messaging middleware. The application is realized using the node-RED web-based framework, due to its availability on different platforms; the widely accepted message queue telemetry transport protocol has been chosen thanks to its low overhead and complexity. For sake of completeness, five different, private and public, brokers are used. The adopted industrial-grade hardware, complemented by global positioning system time reference, permits an overall synchronization and timestamping accuracy of a few milliseconds. The vast measurement campaign highlighted that, generally, quality of service (QoS) type 1 offers low end-to-end delay (average value less than 0.5 s) with reduced variability (0.1 s). However, the maximum end-to-end one-way delay ranges from 1 s for QoS 0 to less than 1.5 s for fully acknowledged QoS 2.

This paper investigates the ultimate limits of White Rabbit (WR), an high-accuracy time distribution system based on field-programmable gate array (FPGA). The knowledge of such limits is essential for new emerging applications that are evaluating WR. In this paper, we identify and study the key elements in the WR synchronization: the digital dual mixer time difference phase detector and the Gigabit Ethernet transceiver. The benchmarks and experimental analysis of these key elements allow us to determine the WR switch (WRS) performance limits and evaluate their evolution with newer FPGAs. The identified performance limits are achievable by the present-day generation of WRS. The ultimate limits of short-term synchronization performance due to FPGA implementation have been derived through analysis and then demonstrated using the existing WRS enhanced with an additional daughterboard. This combination (WRS and daughterboard) achieves a tenfold improvement in terms of phase noise, jitter, and short-term stability with respect to the current WR performance. Both phase detectors and Gigabit transceivers have a similar phase noise contribution equal to a short-term stability of modified Allan deviation 4E−13 at $\tau = 1$ s (dominated by flicker phase modulation noise).

BACKGROUND: Assays to estimate human immunodeficiency virus (HIV) reservoir size require large amounts of blood, which represents a drawback especially in pediatric settings. We investigated whether HIV-antibody repertoire could estimate the viral reservoir size. Moreover, we assessed the magnitude of HIV-antibody response as a predictor of time of antiretroviral therapy (ART) initiation. METHODS: Human immunodeficiency virus-antibody responses to 10 different viral proteins were evaluated by HIV Western blot (WB) kit and a WB score was assigned to each patient. Patients were classified in 2 subgroups based on the timing of ART initiation (early treated [ET], 0–24 weeks and late treated [LT], >24 weeks). Human immunodeficiency virus-deoxyribonucleic acid (DNA) was quantified using real-time quantitative polymerase chain reaction on total peripheral blood mononuclear cells. Logistic regression and principal component analysis were built on these data to test the ability of WB score to predict the expected value of HIV-DNA and the timing of ART initiation. RESULTS: Sixty-nine perinatally HIV-infected children were evaluated. Reduced HIV-specific antibody responses and lower size of HIV-DNA were observed in ET compared with LT patients (P < .001 and P = .02, respectively). We found that WB score correlates with HIV-DNA (P = .032) and timing of ART initiation (P < .001). Based on the logistic regression analysis, we found that WB score can predict the HIV-DNA size and the timing of ART initiation with an Akaike information criterion of −118.13 and −151.51, respectively. CONCLUSIONS: Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies.

HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012–2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders. All children had a history of prior influenza vaccinations. At T0, the frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells, which provide help to B cells for developing into Ab-secreting cells, were similar between responders and nonresponders. However, in response to in vitro stimulation with influenza A/California/7/2009 (H1N1) Ag, differential gene expression related to pTfh cell function was observed by Fluidigm high-density RT-PCR between responders and nonresponders. In responders, H1N1 stimulation at T0 also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells and IL21 gene induction in pTfh cells that were strongly associated with H1N1-specific B cell responses postvaccination. In contrast, CD4 T cells of nonresponders exhibited increased expression of IL2 and STAT5 genes, which are known to antagonize peripheral Tfh cell function. These results suggest that the quality of pTfh cells at the time of immunization is important for influenza vaccine responses and provide a rationale for targeted, ex vivo Ag-driven molecular profiling of purified immune cells to detect predictive biomarkers of the vaccine response.

The time synchronization of smart grid devices is a critical feature for the successful application of advanced grid monitoring and control techniques. Synchronization mechanisms based on the accurate estimation of the Time of Arrival (ToA) of network messages - sent over power line cables - are a promising solution to achieve synchronization tasks over distribution lines. In this paper, a chirp-based synchronization technique over the Medium Voltage (MV) grid has been proposed and characterized. Such approach has the benefit of not requiring the installation of a dedicated infrastructure, thanks to the exploitation of power distribution lines for the transmission of time synchronization data. The effectiveness of the approach has been experimentally evaluated on a simplified MV line available in a testing laboratory. Although, the tested chirp has a limited frequency bandwidth (80 kHz), the maximum variation of the ToA estimation is on the order of 3.5 µs, which fulfills the requirements of most smart grid applications.

In the last years, the industrial automation has experienced a deep transformation known as Industry4.0, and it is driven by Internet of Things (IoT) paradigm. The IoT-based automation is based on well-defined data models, which make easy the interaction among devices. Generally, the data generated by IoT sensors are elaborated to obtain value added services (such as predictive maintenance), exploiting cloud services and remote servers. An accurate timestamp of the data generated by sensors is required to maintain an adequate level of such services: an “easy” task in the case of a new deployment, but a nightmare when existing plants or machinery are retrofitted. In this case, the data are timestamped at cloud level, using the remote time. In such situations, a knowledge of the sense of time of cloud services is fundamental to guarantee the quality of data elaboration. The target of the research is an experimental characterization and a comparison of time awareness of different commercial cloud service providers (i.e. Amazon AWS, Google Cloud and Microsoft Azure). The characterization highlights as, generally, the performance provided by different platform is comparable each other. The time offset of NTP (Network Time Protocol) clients running on different Virtual Machines (VMs) has an uncertainty ranging from 0.05 ms up to 0.6 ms depending by the client configuration. Such results demonstrate that extreme care must be taken when using the time of remote VMs.

In this paper, a statistical analysis of low voltage customers' load power profiles is carried out aiming to suggest a remote non-invasive energy meter error monitoring technique. The synthesized open access 1 s resolution load power profiles are used for the analysis. A detection procedure for power steps in a sampled load power profile is defined. Power steps are classified into overlapping and non-overlapping. It is shown that the probability distribution function of the differences of power step magnitudes acquired by a meter under test and a reference sum meter is sensitive to the errors of the meter despite the presence of overlapping power steps at other meters in the grid. A noninvasive error monitoring technique is found possible by acquiring, comparing and statistically processing simultaneous power steps at the energy meter under monitoring and reference sum meter.

Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1–10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.

Breast cancer treatment has deeply changed in the last decades, since clinical and oncological cure cannot be achieved without patient's satisfaction in term of aesthetic outcomes. Several methods have been proposed to objectively assess these results. However, Italian breast centers have not yet agreed on measurable, reproducible and validated aesthetic outcome indicators to monitor their performance.The study was designed and conducted by Senonetwork, a not-for-profit association of Italian breast centers. Ten breast centers were selected based on specific eligibility criteria. This multicentre observational prospective study recruited 6515 patients with diagnosis of in situ or invasive breast cancer who underwent breast surgery in the years 2013-2016. Thirteen indicators of aesthetic results and of related quality of care were analyzed. Data collection and analysis were conducted using a common study database.On average, seven out of ten centers were able to collect data on the proposed indicators with a proportion of missing values 25%. By expert consensus based on study results, some seven indicators have been defined as "mandatory" while the remaining six have been defined as "recommended" because they require further refinement before they can be proposed for monitoring aesthetic outcomes or because there are doubts on the feasibility of data collection. The minimum standard is reached for 5 of 13 indicators. This finding and the wide range between centers reveal that there is ample room for improvement.From the present study useful measurable aesthetic parameters have emerged, leading to the definition of target objectives that breast centers can use for benchmarking and improvement of quality of care.

Nowadays, wireless technologies penetrate all aspects of our lives. “Internet of Things” (IoT) and “Location- Based Services” are the pillars of Smart City concept. The IoT smart objects surrounding us are an integral part of the Internet, thanks to their computational and communication capabilities. In such applications, location information can be exploited in all the layers of the stack, from the application level (e.g., to correctly interpret measurements from sensor nodes deployed on the field), down to the physical level (e.g., for sensing coverage). One of the most viable solutions for Smart City wireless connectivity seems to be the use of long-range, low-power and low-throughput low-power wide area networks (LPWANs). In this work, the authors devise the jointly use of LPWANs with widely-diffused and well-accepted localization techniques, as the Global Positioning Systems (GPS, outdoor) and real-time location systems (RTLS, indoor), for Smart Campus applications. In particular, a LoRaWAN node equipped with both GPS and Ultra Wide Bandbased UWB-RTLS has been developed and tested in real-world scenarios. Experimental results demonstrate the feasibility of the proposed approach; in particular, location errors are in the order of few tens of meters for GPS and in the order of few tens of centimeters for UWB.

It is widely known that physical activity helps preventing several diseases. However, unsupervised training often results in low exercise quality, ineffective training, and, in worst cases, injuries. Automatic tracking and quantification of exercises by means of wearable devices could be an effective mean for the monitoring of exercise correctness. As a consequence, such devices could help motivating people, thus improving the quantity of performed physical exercise, with positive effects on users’ health conditions. However, despite the availability of several commercial devices, the performance and effectiveness are not well documented. This work proposes a new solution for fitness workout supervision exploiting machine learning techniques, in particular Linear Discriminant Analysis for analyzing data coming from wearable Inertial Measurement Units. Efforts have been done in order to reduce the computational requirements, thus assuring compatibility in perspective of embedded implementation. The experimental tests carried out to assess the proposed approach performance showed an accuracy in exercise detection over 93% and error in exercise counting less than 6%.

The Smart City (SC) paradigm is based on the integration of Information and Communication Technology (ICT) into the urban asset, for the optimal management of the energies and resources. The Internet of Thing (IoT) technology seems the proper solution to achieve this target, thanks to its capability to abstract the object in the real world. The deployment of IoT devices at different level in urban infrastructures is causing the presence of thousands of intelligent devices, large part of them with unused computational capabilities. Such devices could be integrated in a cluster in order to share the unused resources with other devices with limited computational resources. The use of a cluster of IoT Sensors has several benefits, including, but not limited to: high availability, sharing of computational resources, reduced response time with the respect of centralized cloud computing solution. The main bottleneck of this approach is represented by the communication infrastructure, typically based on wireless connection and, thus with a limited available bandwidth. The aim of the work related to this paper is to analyze the impact the communication infrastructure has on computational performance of a cluster of IoT sensors. An experimental set-up for the characterization of the performance of a cluster of low-cost off-the-shelf devices has been described. The experimental validation highlighted as the network infrastructure is loaded only during the data transfer and the maximum network load, with a cluster of ten IoT nodes is approximately 2 Mb/s with the considered benchmark.

Anti-retroviral therapy (ART) improves life expectancy in people living with HIV (PWH), but it remains unclear how chronic HIV infection affects normal aging of the immune system. Plasma cell-free protein expression and immune phenotypes were assessed in blood from ART treated PWH (19–77yrs, n=106) and age-matched, HIV-negative controls (HC, n=103). Age-associated parameters were identified in HC and PWH independently by univariate Spearman correlation (p Plasma biomarker analysis resulted in 8-parameter inflammatory index that was higher in PWH compared to HC and correlated with age. Combining flow and plasma data generated 277 and 491 age-associated parameters (out of total 1,357) in HC and PWH, respectively. PWH exhibited different immunological profiles associated with age compared to HC. However, CD38 expression on T cells declined with age in both HC and PWH. Predictive modeling using age-associated parameters in HC generated a 14-parameter signature with 76.9% accuracy to predict chronological age in HC, however this model failed to predict age in PWH (18.6% accuracy) highlighting the effect of HIV infection on immunological aging. A 25-parameter model (IMmunological Age Prediction, IMAP-25) however showed 70% and 53% accuracy in HC and PWH and was used to show an accelerated aging rate in PWH by 5.6 yrs compared to HC. We applied a statistical approach to generate immune signatures, easily monitored in human blood samples, that could be used as an indicator of one’s ‘immunological age’ during ART-treated HIV infection.

Distributed monitoring and control systems are mandatory for the efficient management of the distribution grid, due to the growing presence of renewable energy sources. Time synchronization among devices deployed in distribution grid plays a key role, since a common time reference is essential to correlate power quality and high sampling frequency measure, and generally coordinate any distributed actions. The design and the deployment of a time synchronization system over an existing heterogeneous network is investigated in the paper. The Network Time Protocol (NTP) has been chosen due to its backward compatibility, the good security level, and the intrinsically robust hierarchy. Several NTP synchronization architectures have been proposed and then applied to a real (operating) distribution grid, both at Medium Voltage (MV) and Low Voltage (LV). The experimental validation was carried out during several weeks on the live system. The results in the MV grid highlight the trade-off existing between synchronization accuracy and availability: the synchronization accuracy over MV Broadband Power Line (BPL) links decreases from 20ms to 50ms when a more reliable architecture, from the point of view of time synchronization, is used. On the other hand, experimental results show as end-nodes connected on LV grid by means of BPL have a mean offset typically below 50ms, and a synchronization accuracy on the order of 150ms. These results are due to the limitation of the synchronization protocol deployed in the LV end-nodes and to scalability issues of power line communication networks when the number of nodes increases.

Distributed measurement and control systems often rely on time synchronization protocols over Ethernet. Recently, it has been shown that estimating and compensating for not only time offsets, but also frequency skews is of crucial importance to meet the accuracy requirements of high-end applications. In this respect, this paper presents a new technique capable of: 1) measuring the jitter of multiple reference signals received by a single node over different network paths and 2) combining them in order to synthesize a downstream signal with a more stable frequency than using a single reference. The proposed algorithm can exploit the native frequency transport of Synchronous Ethernet and relies on a module for outlier identification and removal, a Kalman filter, and a linear quadratic regulator that drives a local voltage-controlled oscillator. The algorithm performance has been evaluated through both simulations and experiments using a prototype platform based on a field-programmable gate array. Simulation and experimental results confirm that the proposed approach can strongly decrease the jitter and wander of the generated signal. For instance, the time deviation is reduced on average by about 30% when three stable input references are merged and by several orders of magnitude when one of the input signals is affected by a large frequency step.

The installation of Power Quality (PQ) meters is becoming mandatory in many countries to face the problems introduced by the increasing number of renewable energy sources with intermittent generation. Unfortunately, the current situation is unbalanced: PQ meters are installed on High Voltage (HV) transmission lines and sometimes on Medium Voltage (MV) lines, while the highest number of renewable generators is connected to Low Voltage (LV) grid. In this paper, a novel measurement system for the analysis of voltage dips is proposed. If compared with existing similar systems, the proposed distributed measuring system has the following new characteristics: it is composed of a network of PQ meters on HV, MV and also on LV lines; it uses a heterogeneous communication infrastructure to interconnect meters; it has a cost-effective network-based time synchronization instead of costly GPS solutions; it implements a distributed algorithm to determine the origin of PQ problems. This novel approach overcomes scalability issue, which currently is limiting a larger penetration of PQ systems. The proposed distributed system for monitoring of voltage dips has been deployed in a real distribution grid in Italy. The paper reports analyses on data collected during an entire year. Voltage dips have been correlated and analyzed thanks to the time synchronization of the system.

In the Industry 4.0 the communication infrastructure is derived from the Internet of Things (IoT), and it is called Industrial IoT or IIoT. Smart objects deployed on the field collect a large amount of data which is stored and processed in the Cloud to create innovative services. However, differently from most of the consumer applications, the industrial scenario is generally constrained by time-related requirements and its needs for real-time behavior (i.e., bounded and possibly short delays). Unfortunately, timeliness is generally ignored by traditional service provider, and the Cloud is treated as a black box. For instance, Cloud databases (generally seen as &ldquo, Database as a service&rdquo, &mdash, DBaaS) have unknown or hard-to-compare impact on applications. The novelty of this work is to provide an experimental measurement methodology based on an abstract view of IIoT applications, in order to define some easy-to-evaluate metrics focused on DBaaS latency (no matter the actual implementation details are). In particular, the focus is on the impact of DBaaS on the overall communication delays in a typical IIoT scalable context (i.e., from the field to the Cloud and the way back). In order to show the effectiveness of the proposed approach, a real use case is discussed (it is a predictive maintenance application with a Siemens S7 industrial controller transmitting system health status information to a Cloudant DB inside the IBM Bluemix platform). Experiments carried on in this use case provide useful insights about the DBaaS performance: evaluation of delays, effects of involved number of devices (scalability and complexity), constraints of the architecture, and clear information for comparing with other implementations and for optimizing configuration. In other words, the proposed evaluation strategy helps in finding out the peculiarities of Cloud Database service implementations.