Context Information for Fast Cell Discovery in mm-wave 5G Networks

The exploitation of the mm-wave bands is one of the most promising solutions for 5G mobile radio networks. However, the use of mm-wave technologies in cellular networks is not straightforward due to mm-wave harsh propagation conditions that limit access availability. In order to overcome this obstacle, hybrid network architectures are being considered where mm-wave small cells can exploit an overlay coverage layer based on legacy technology. The additional mm-wave layer can also take advantage of a functional split between control and user plane, that allows to delegate most of the signaling functions to legacy base stations and to gather context information from users for resource optimization. However, mm-wave technology requires high gain antenna systems to compensate for high path loss and limited power, e.g., through the use of multiple antennas for high directivity. Directional transmissions must be also used for the cell discovery and synchronization process, and this can lead to a non-negligible delay due to the need to scan the cell area with multiple transmissions at different directions. In this paper, we propose to exploit the context information related to user position, provided by the separated control plane, to improve the cell discovery procedure and minimize delay. We investigate the fundamental trade-offs of the cell discovery process with directional antennas and the effects of the context information accuracy on its performance. Numerical results are provided to validate our observations.Comment: 6 pages, 8 figures, in Proceedings of European Wireless 201

Fast Cell Discovery in mm-wave 5G Networks with Context Information

The exploitation of mm-wave bands is one of the key-enabler for 5G mobile radio networks. However, the introduction of mm-wave technologies in cellular networks is not straightforward due to harsh propagation conditions that limit the mm-wave access availability. Mm-wave technologies require high-gain antenna systems to compensate for high path loss and limited power. As a consequence, directional transmissions must be used for cell discovery and synchronization processes: this can lead to a non-negligible access delay caused by the exploration of the cell area with multiple transmissions along different directions. The integration of mm-wave technologies and conventional wireless access networks with the objective of speeding up the cell search process requires new 5G network architectural solutions. Such architectures introduce a functional split between C-plane and U-plane, thereby guaranteeing the availability of a reliable signaling channel through conventional wireless technologies that provides the opportunity to collect useful context information from the network edge. In this article, we leverage the context information related to user positions to improve the directional cell discovery process. We investigate fundamental trade-offs of this process and the effects of the context information accuracy on the overall system performance. We also cope with obstacle obstructions in the cell area and propose an approach based on a geo-located context database where information gathered over time is stored to guide future searches. Analytic models and numerical results are provided to validate proposed strategies.Comment: 14 pages, submitted to IEEE Transaction on Mobile Computin

Sex-related differences in death control of somatic cells

In 2001, The United States Institute of Medicine (IOM) Committee on Understanding the Biology of Sex and Gender Differences concluded that ‘Sex…should be considered when designing and analysing studies in all areas and at all levels of biomedical and health-related research…’ and stated an apparent paradox i.e.: ‘every cell has a sex’ 1. Sex is defined as ‘the classification of living things, generally as male or female according to their reproductive organs and functions assigned by chromosomal complement’ whereas gender is defined as ‘a person's self representation as male or female, or how that person is responded to by social institutions based on the individual's gender presentation. Gender is rooted in biology and shaped by environment and experience’ 1. It is unchallenged that there are health differences between males and females and that social and cultural factors could contribute to the observed differences. Anyway, the sex-dependent differences also have a biological base which sometimes has not been deeply investigated. Scientists studying health differences between male and female aim to both considering social/cultural environment and investigating biological/molecular mechanisms different between sexes. Some experimental studies have elucidated important differences in cell death control 2. A sex disparity, in fact, has been shown both in the propensity to apoptosis and in the activation of the autophagic pathway. In the context of cell fate control, hormones represent important regulators of both apoptosis and autophagy. In the cardiovascular system, for example, oestrogens inhibit cardiomyocyte apoptosis by decreasing reactive oxygen species production and increasing intracellular antioxidants 3. Oestrogens may also indirectly control autophagy as they up-regulate urocortin 4, a neuropeptide hormone able to inhibiting autophagy in cardiomyocytes. Conversely, increasing evidence suggests possible adverse effects of androgens on the vasculature showing that androgens, as opposed to oestrogens, may worsen vascular dysfunction in men, thus contributing to sex-based differences in cardiovascular diseases 5. However, it is currently emerging that some cell death programs are differentially controlled by sex-related hormone-independent cellular genetics. Differences in cell death sensitivity in male and female may then occur in the absence of an hormonal context. This is not an immediately obvious finding; Penaloza C et al., 6 have shown that the apoptosis amount differs between the sexes in isolated embryonic cells exposed to similar conditions and this happens at embryonal stages where there are no hormonal influences. Previous studies had reported a sexual dimorphism in embryonic neuronal signal transduction pathways and consequently differences in cell survival 7. Death pathways in XX and XY cells have been poorly investigated as most studies have been performed on established cells lines often irrespective of their male or female origin. Recently, using freshly isolated cells from male and female individuals gave important information on sex disparity in cell fate control. Such sex specificity has been in part clarified thanks to cell culture models where sex steroids can be removed from the media. Even sex-related differences in caspase activation have been found to be independent on hormone exposure. More in detail, cell death occurring in cortical neurons after ischaemia proceeds predominantly via an apoptosis-inducing factor-dependent pathway (a caspase-independent pathway) in male neurons while proceeds via a cytochrome C-dependent pathway (a process mediated by caspase activation) in female neurons 8. In this context, a sex-specific microRNA expression after ischaemia has been described in in vivo studies. In particular, it has been demonstrated that microRNA-23a, by binding the mRNA of the caspase inhibitor named XIAP, induces its translational repression in females, leading to enhanced caspase signalling in the ischaemic female brain. This effect has been shown to be independent of circulating oestrogen levels 9. Sex differences in ischaemic brain injury and cerebrovascular regulation have been observed in clinical and experimental studies and an important determinant of such differences is also represented by the integrity of endothelial cells. In fact, endothelial function is improved in women compared with men, contributing to female cellular higher resistance after ischaemic brain injury. Gupta NC et al. 10 showed that female cerebrovascular endothelial cells express lower level of soluble epoxide hydrolase and consequently have higher levels of vasoprotective epoxyeicosatrienoic acids as compared with male endothelial cells. This study therefore presents a novel additional mechanism underlying differences between male and female cells in apoptotic response after oxygen-glucose deprivation, contributing to explain higher resistance observed in females as compared with males. This study remarks again that differences between male and female cells do not necessarily depend on the hormonal context but may be inherent the cells. We believe that this apparently paradoxical concept has not been sufficiently highlighted in the scientific literature. The present ‘Letter to the Editor’ therefore aims at underlining such an important issue which deserves more attention and discussion in the researchers' community. A practical consequence of sex-dependent discrepancies in cell death control is that cellular response to any stimulus or treatment, in any physiological or pathological context, may well depend on the sex of the cell line used; journals guidelines should therefore require authors to state in any case the sex of the cell lines used in any in vitro study. In addition, at least to some extent, sex-matched or sex-unmatched cell controls may be necessary in many experimental settings. In conclusion, sex-related differences in cell death mechanism may have strong implications for experimental studies and sexual dimorphism dependent on chromosomal rather than hormonal differences have important implications for planning preclinical studies and clinical interventions

c-Flip KO fibroblasts display lipid accumulation associated with endoplasmic reticulum stress

c-Flip proteins are well-known apoptosis modulators. They generally contribute to tissue homeostasis maintenance by inhibiting death-receptor-mediated cell death. In the present manuscript, we showthat c-Flip knock-out (KO) mouse embryonic fibroblasts (MEFs) kept in culture under starvation conditions gradually modify their phenotype and accumulate vacuoles, becoming progressively larger according to the duration of starvation. Large vacuoles are present in KO MEFs though not in WT MEFs, and are Oil Red-O positive, which indicates that they represent lipid droplets. Western blot experiments reveal that, unlikeWTMEFs, KOMEFs express high levels of the lipogenic transcription factor PPAR-γ. Lipid droplet accumulation was found to be associated with endoplasmic reticulum (ER) stress activation and autophagic modulation valuated by means of BIP increase, LC3 lipidation and AMP-activated protein kinase (AMPK) phosphorylation, and p62 accumulation. Interestingly, XBP-1, an ER stress-induced lipogenic transcription factor, was found to preferentially localize in the nucleus rather than in the cytoplasm of KO MEFs. These data demonstrate that, upon starvation, c-Flip affects lipid accumulation, ER stress and autophagy, thereby pointing to an important role of c-Flip in the adaptive response and ER stress response programs under both normal and pathological conditions

Adaptive Robust Traffic Engineering in Software Defined Networks

One of the key advantages of Software-Defined Networks (SDN) is the opportunity to integrate traffic engineering modules able to optimize network configuration according to traffic. Ideally, network should be dynamically reconfigured as traffic evolves, so as to achieve remarkable gains in the efficient use of resources with respect to traditional static approaches. Unfortunately, reconfigurations cannot be too frequent due to a number of reasons related to route stability, forwarding rules instantiation, individual flows dynamics, traffic monitoring overhead, etc. In this paper, we focus on the fundamental problem of deciding whether, when and how to reconfigure the network during traffic evolution. We propose a new approach to cluster relevant points in the multi-dimensional traffic space taking into account similarities in optimal routing and not only in traffic values. Moreover, to provide more flexibility to the online decisions on when applying a reconfiguration, we allow some overlap between clusters that can guarantee a good-quality routing regardless of the transition instant. We compare our algorithm with state-of-the-art approaches in realistic network scenarios. Results show that our method significantly reduces the number of reconfigurations with a negligible deviation of the network performance with respect to the continuous update of the network configuration.Comment: 10 pages, 8 figures, submitted to IFIP Networking 201

Microvascular alterations in hypertension and vascular aging

Hypertension and aging are characterized by vascular remodelling and stiffness as well as endothelial dysfunction. Endothelial function declines with age, since aging is associated with senescence of the endothelium due to increased rate of apoptosis and reduced regenerative capacity of the endothelium. Different phenotypes of hypertension have been described in younger and adult subjects with hypertension. In younger patients functional and structural alterations of resistance arteries occur as the earliest vascular alterations which have prognostic significance and may contribute to stiffness of large arteries through wave reflection. In individuals above age of 50 years as well as in subjects with long-lasting elevated blood pressure, vascular changes occur predominantly in conduit arteries which become stiffer. Activation of renin-angiotensin-aldosterone and endothelin systems plays a key role in endothelial dysfunction, vascular remodelling, and aging by inducing reactive oxygen species production, and promoting inflammation and cell growth

Cancer microenvironment and endoplasmic reticulum stress response

Different stressful conditions such as hypoxia, nutrient deprivation, pH changes, or reduced vascularization, potentially able to act as growth-limiting factors for tumor cells, activate the unfolded protein response (UPR). UPR is therefore involved in tumor growth and adaptation to severe environments and is generally cytoprotective in cancer. The present review describes the molecular mechanisms underlying UPR and able to promote survival and proliferation in cancer. The critical role of UPR activation in tumor growth promotion is discussed in detail for a few paradigmatic tumors such as prostate cancer and melanoma

Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of plasmodium falciparum

BACKGROUND: Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. RESULTS: This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca2+ levels. CONCLUSIONS: This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca2+ oscillations suggests a potential role of NAADP in regulating Ca2+ signalling of P. falciparum

Transfected poly(I:C) activates different dsRNA receptors leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells

Background: Castration-resistant prostate cancer (CRPC) is refractory to chemo-radiotherapy. Results: Transfection of the synthetic analog of dsRNA poly(I:C) simultaneously stimulates apoptosis and IFN- expression through different pathways in androgen-independent prostate cancer (PCa) cells. Conclusion: Dual parallel pathways triggered by distinct receptors activate direct and immunologically mediated antitumor effects in advanced PCa. Significance: The proapoptotic/immunoadjuvant poly(I:C)-Lipofectamine complex may offer new therapeutic insights into CRPC

Facing the Millimeter-wave Cell Discovery Challenge in 5G Networks with Context-awareness

The introduction of mm-wave technologies in the future 5G networks poses a rich set of network access challenges. We need new ways of dealing with legacy network functionalities to fully unleash their great potential, among them the cell discovery procedure is one of the most critical. In this article, we propose novel cell discovery algorithms enhanced by the context information available through a C-/Uplane- split heterogeneous network architecture. They rely on a geo-located context database to overcome the severe effects of obstacle blockages. Moreover, we investigate the coordination problem of multiple mm-wave base stations that jointly process user access requests. We show that optimizing the resource allocated to the discovery has a great importance in defining perceived latency and supported user request rate. We have performed complete and accurate numerical simulations to provide a clear overview of the main challenging aspects. Results show that the proposed solutions have an outstanding performance with respect to basic discovery approaches and can fully enable mm-wave cell discovery in 5G networks