On the Design of Sidelink for Cellular V2X: A Literature Review and Outlook for Future

Connected and fully automated vehicles are expected to revolutionize our mobility in the near future on a global scale, by significantly improving road safety, traffic efficiency, and traveling experience. Enhanced vehicular applications, such as cooperative sensing and maneuvering or vehicle platooning, heavily rely on direct connectivity among vehicles, which is enabled by sidelink communications. In order to set the ground for the core contribution of this paper, we first analyze the main streams of the cellular-vehicle-to-everything (C-V2X) technology evolution within the Third Generation Partnership Project (3GPP), with focus on the sidelink air interface. Then, we provide a comprehensive survey of the related literature, which is classified and critically dissected, considering both the Long-Term Evolution-based solutions and the 5G New Radio-based latest advancements that promise substantial improvements in terms of latency and reliability. The wide literature review is used as a basis to finally identify further challenges and perspectives, which may shape the C-V2X sidelink developments in the next-generation vehicles beyond 5G

Performance Analysis of Sidelink 5G-V2X Mode 2 through an Open-Source Simulator

The Third Generation Partnership Project (3GPP) has recently published a new set of specifications to enable advanced driving applications in fifth generation (5G) vehicle-to-everything (V2X) scenarios, with particular effort dedicated to the sidelink resource allocation in the autonomous mode, named Mode 2. In this paper, we conduct a comprehensive analysis of Mode 2 performance via an open-source system-level simulator, which implements the 5G New Radio (NR) flexible numerology and physical layer aspects together with the newly specified sidelink resource allocation modes for V2X communications and different data traffic patterns. Results collected through extensive simulation campaigns, under a wide variety of vehicle density, data transmission settings and traffic patterns, showcase the effects of the new 5G-V2X features on the sidelink resource allocation performance and provide some insights into possible ways to further improve Mode 2 performance

Toward 6G Vehicle-to-Everything Sidelink: Nonorthogonal Multiple Access in the Autonomous Mode

The cellular vehicle-to-everything (C-V2X) sidelink technology, specified in the long-term evolution (LTE) and further improved in the 5G new radio (NR) standards to facilitate direct data exchange between vehicles, will play a crucial role in revolutionizing transportation systems. However, the demand for very high reliability and ultralow latency services especially challenges the sidelink resource allocation mechanism when performed by distributed vehicles, in the so-called autonomous mode. One of the major causes of ­performance degradation is the resource allocation mechanism, which was designed for orthogonal multiple access (OMA) and can generate interference and collisions under high load conditions. In this context, here we argue in favor of the use of non-OMA (NOMA) as a game changer for the sidelink in the upcoming 6G V2X, and the purpose of this article is to provide a reference for further intriguing studies in the field. Additionally, the gain achievable over conventional allocation schemes by enabling NOMA through the use of successive interference cancelation (SIC) at the receiver is measured through realistic simulations conducted when considering the latest C-V2X specifications

Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection

A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, "cytokines storm", that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)". The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo

Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease

Evaluation of a Gel Containing a Propionibacterium Extract in an In Vivo Model of Wound Healing

Inappropriate wound healing (WH) management can cause significant comorbidities, especially in patients affected by chronic and metabolic diseases, such as diabetes. WH involves several different, partially overlapping processes, including hemostasis, inflammation, cell proliferation, and remodeling. Oxidative stress in WH contributes to WH impairment because of the overexpression of radical oxygen species (ROS) and nitrogen species (RNS). This study aimed to evaluate the in vitro antioxidative action of a gel containing a Propionibacterium extract (Emorsan (R) Gel) and assess its skin re-epithelialization properties in a mouse model of WH. The scavenging effects of the bacterial extract were assessed in vitro through the ABTS and DPPH assays and in L-929 murine fibroblasts. The effects of the Emorsan (R) Gel were studied in vivo in a murine model of WH. After WH induction, mice were treated daily with vehicle or Emorsan (R) Gel for 6 or 12 days. According to the in vitro tests, the Propionibacterium extract exerted an inhibitory effect on ROS and RNS, consequently leading to the reduction in malondialdehyde (MDA) and nitrite levels. Before proceeding with the in vivo study, the Emorsan (R) Gel was verified to be unabsorbed. Therefore, the observed effects could be ascribed to a local action. The results obtained in vivo showed that through local reduction of oxidative stress and inflammation (IL-1 beta, TNF-alpha), the Emorsan (R) Gel significantly reduced the infiltration of mast cells into the injured wound, leading to the amelioration of symptoms such as itch and skin irritation. Therefore, the Emorsan (R) Gel improved the speed and percentage of wound area closure by improving the tissue remodeling process, prompting vascular-endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta production and reducing the expression of adhesion molecules. Emorsan (R) Gel, by its ability to inhibit free radicals, could reduce local inflammation and oxidative stress, thus enhancing the speed of wound healing

Self-paced reaching after stroke: a quantitative assessment of longitudinal and directional sensitivity using the H-Man planar robot for upper limb neurorehabilitation

Technology aided measures offer a sensitive, accurate and time-efficient approach for the assessment of sensorimotor function after neurological insult compared to standard clinical assessments. This study investigated the sensitivity of robotic measures to capture differences in planar reaching movements as a function of neurological status (stroke, healthy), direction (front, ipsilateral, contralateral), movement segment (outbound, inbound), and time (baseline, post-training, 2-week follow-up) using a planar, two-degrees of freedom, robotic-manipulator (H-Man). Twelve chronic stroke (age: 55 ± 10.0 years, 5 female, 7 male, time since stroke: 11.2 ± 6.0 months) and nine aged-matched healthy participants (age: 53 ± 4.3 years, 5 female, 4 male) participated in this study. Both healthy and stroke participants performed planar reaching movements in contralateral, ipsilateral and front directions with the H-Man, and the robotic measures, spectral arc length (SAL), normalized time to peak velocities (TpeakN), and root-mean square error (RMSE) were evaluated. Healthy participants went through a one-off session of assessment to investigate the baseline. Stroke participants completed a 2-week intensive robotic training plus standard arm therapy (8 × 90 min sessions). Motor function for stroke participants was evaluated prior to training (baseline, week-0), immediately following training (post-training, week-2), and 2-weeks after training (follow-up, week-4) using robotic assessment and the clinical measures Fugl-Meyer Assessment (FMA), Activity-Research-Arm Test (ARAT), and grip-strength. Robotic assessments were able to capture differences due to neurological status, movement direction, and movement segment. Movements performed by stroke participants were less-smooth, featured longer TpeakN, and larger RMSE values, compared to healthy controls. Significant movement direction differences were observed, with improved reaching performance for the front, compared to ipsilateral and contralateral movement directions. There were group differences depending on movement segment. Outbound reaching movements were smoother and featured longer TpeakN values than inbound movements for control participants, whereas SAL, TpeakN, and RMSE values were similar regardless of movement segment for stroke patients. Significant change in performance was observed between initial and post-assessments using H-Man in stroke participants, compared to conventional scales which showed no significant difference. Results of the study indicate the potential of H-Man as a sensitive tool for tracking changes in performance compared to ordinal scales (i.e., FM, ARAT)

Exploring efficient seamless handover in VANET systems using network dwell time

Vehicular ad hoc networks are a long-term solution contributing significantly towards intelligent transport systems (ITS) in providing access to critical life-safety applications and services. Although vehicular ad hoc networks are attracting greater commercial interest, current research has not adequately captured the real-world constraints in vehicular ad hoc network handover techniques. Therefore, in order to have the best practice for vehicular ad hoc network services, it is necessary to have seamless connectivity for optimal coverage and ideal channel utilisation. Due to the high velocity of vehicles and smaller coverage distances, there are serious challenges in providing seamless handover from one roadside unit (RSU) to another. Though other research efforts have looked at many issues in vehicular ad hoc networks (VANETs), very few research work have looked at handover issues. Most literature assume that handover does not take a significant time and does not affect the overall VANET operation. In our previous work, we started to investigate these issues. This journal provides a more comprehensive analysis involving the beacon frequency, the size of beacon and the velocity of the vehicle. We used some of the concepts of Y-Comm architecture such as network dwell time (NDT), time before handover (TBH) and exit time (ET) to provide a framework to investigate handover issues. Further simulation studies were used to investigate the relation between beaconing, velocity and the network dwell time. Our results show that there is a need to understand the cumulative effect of beaconing in addition to the probability of successful reception as well as how these probability distributions are affected by the velocity of the vehicle. This provides more insight into how to support life critical applications using proactive handover techniques

Influence of MLH1 on colon cancer sensitivity to poly(ADP-ribose) polymerase inhibitor combined with irinotecan

Poly(ADP-ribose) polymerase inhibitors (PARPi) are currently evaluated in clinical trials in combination with topoisomerase I (Top1) inhibitors against a variety of cancers, including colon carcinoma. Since the mismatch repair component MLH1 is defective in 10-15% of colorectal cancers we have investigated whether MLH1 affects response to the Top1 inhibitor irinotecan, alone or in combination with PARPi. To this end, the colon cancer cell lines HCT116, carrying MLH1 mutations on chromosome 3 and HCT116 in which the wildtype MLH1 gene was replaced via chromosomal transfer (HCT116+3) or by transfection of the corresponding MLH1 cDNA (HCT116 1-2) were used. HCT116 cells or HCT116+3 cells stably silenced for PARP-1 expression were also analysed. The results of in vitro and in vivo experiments indicated that MLH1, together with low levels of Top1, contributed to colon cancer resistance to irinotecan. In the MLH1-proficient cells SN-38, the active metabolite of irinotecan, induced lower levels of DNA damage than in MLH1-deficient cells, as shown by the weaker induction of γ-H2AX and p53 phosphorylation. The presence of MLH1 contributed to induce of prompt Chk1 phosphorylation, restoring G2/M cell cycle checkpoint and repair of DNA damage. On the contrary, in the absence of MLH1, HCT116 cells showed minor Chk1 phosphorylation and underwent apoptosis. Remarkably, inhibition of PARP function by PARPi or by PARP-1 gene silencing always increased the antitumor activity of irinotecan, even in the presence of low PARP-1 expression