Intent-based management and orchestration of heterogeneous openflow/IoT SDN domains

One of the main challenges in delivering end-toend service chains across multiple Software Defined Networking (SDN) and Network Function Virtualization (NFV) domains is to achieve unified management and orchestration functions. A very critical aspect is the definition of an open, vendoragnostic, and interoperable northbound interface (NBI) that should be as abstracted as possible from domain-specific data and control plane technologies. In this paper we propose a reference architecture and an intent-based NBI for end-to-end service orchestration across multiple technological domains. In particular, we consider the use case of an Internet of Things (IoT) infrastructure deployment and the corresponding cloudbased data collection, processing, and publishing services with quality differentiation.We also report the experimental validation of the proposed architecture over a heterogeneous OpenFlow/IoT SDN test bed

Topografia di Atene. Sviluppo urbano e monumenti dalle origini al III secolo d.C., Tomo 5: Lexicon Topographicum Urbis Athenarum ad ἄστυ pertinens adiecto indice tomorum I-IV

Lessico topografico dell'area urbana di Aten

Hypoxanthine Derivatives in Experimental Infections

In vivo treatment with parenterally administered hypoxanthine derivatives, notably ST 789, was able to protect cyclophosphamide-immunosuppressed mice against experimental infections with both bacterial and fungal pathogens. However, the mechanisms accounting for these effects of hypoxanthine derivatives remain to be fully established. In fact, only the treatment with ST 789 resulted in a clear enhancement of the primary antibody production as well as macrophage phagocytic activity, whereas T lymphocyte responsiveness to mitogens and both macrophage- and natural killer-dependent cytotoxicity were not significantly affected. These data, together with the recently shown ability of ST 789 to increase interleukin-6 production, suggest that monocyte/macrophages are likely to be the main cellular target of the immunomodulating activity of ST 789. Finally, in the presentln vivo study, hypoxanthine derivatives did not enhance the mean survival time of tumour-bearing immunosuppressed mice

E2F1 germline copy number variations and melanoma susceptibility

Melanoma is an aggressive type of skin cancer whose aetiology remains elusive as both environmental and genetic factors can contribute to its development. Recent studies have demonstrated the existence of multiple copies of E2F1 gene in melanoma specimens which could explain the deregulated E2F1 activity in this type of cancer. This finding suggests a key role for this transcription factor in the malignant transformation of melanocytes. Therefore, E2F1 has been considered as a potential therapeutic target for this form of skin cancer. Since germline copy number variations (CNVs) have been associated with increased susceptibility to different types of cancer, the aim of our study was to assess germline E2F1 CNV in melanoma patients. However, CNVs not necessarily lead to gene dosage imbalance, hence, further factors, in association with CNVs, could contribute to clinical manifestations. Considering that heat stress has been hypothesised as a contributing factor to skin cancer, we also investigated the effect of heat stress on E2F1 expression

Detection of Cholesterol and its Oxidized Derivatives in Human Sperm Membranes through a Fast and Reliable LC-MS Method

The trafficking of membrane cholesterol (Chol) in mammals represents key processes in cells function, particularly in sperm physiology since Chol removal is strictly associated with motility gain. Moreover, the involvement of oxidized Chol derivatives, known as oxysterols, has been recently summoned in the regulation of sperm function. The study of sterols dynamic in human sperm is largely hampered by the low sample availability and the inadequate sensitivity of current methods based on chromatographic techniques. In this study we aimed to develop a robust and reliable method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the sperm levels of Chol and major oxysterols 7\u3b2-OH-Cholesterol (7\u3b2 -OHC) and 7-keto-Cholesterol (7-KC). In particular, by finely tuning the reverse-phase chromatography parameters, the unambiguous identification of Chol, 7\u3b2 -OHC and 7-KC in biological samples was allowed on the bases of their different retention times, accurate m/z determination and natural isotope abundance pattern. Finally, by applying the method on real sperm samples from 12 semen donors, we documented that normozoospermic subjects (total sperm count >39 7 106 cells/ejaculate) showed an underrepresentation of all steroids compared to subjects with oligozoospermia (total sperm count 64 39 7 106 cells/ejaculate; respectively P=0.048 for Chol, P=0.006 for 7\u3b2-OHC and P=0.001 for 7-KC). These preliminary data suggest further investigation about the impact of disorders of the spermatogenic process on the composition and function of the sperm membrane

Uncarboxylated Osteocalcin Stimulates 25-Hydroxy Vitamin D Production in Leydig Cell Line Through a GPRC6a-Dependent Pathway

Recent studies disclosed a cross talk between testis and bone. By the action of LH, Leydig cells are able to modulate bone metabolism through testosterone and insulin-like factor 3. Moreover, LH modulates the Leydig expression of CYP2R1, the key enzyme involved in vitamin D (Vit D) 25-hydroxylation. However, pathways regulating CYP2R1 expression have been poorly investigated. The cross talk from the bone to the testis of the vitamin D 25-hydroxylase CYP2R1 involves osteocalcin (OC), which is produced by the osteoblasts and stimulates the production of testosterone by the Leydig cells through its putative receptor GPRC6A, a cation-sensing G-protein-coupled receptor. The aim of this study was to investigate the possible action of OC on CYP2R1 expression and 25-hydroxy Vit D (25-OH Vit D) production in a mouse Leydig cell line (MA-10). After confirmation of the expression of GPRC6A by MA-10, we found that stimulation with either human chorionic gonadotropin or uncarboxylated-OC (ucOC) increases CYP2R1 protein expression in a dose-dependent manner and, in turn, increases the release of 25-OH Vit D in culture medium. This effect was abolished by receptor blockade with, respectively, anti-LH receptor and anti-GPRC6A antibodies. Moreover, both agonists converged to phosphorylation of Erk1/2 by a likely differential action on second messengers. Human chorionic gonadotropin induced slow "tonic" increase of intercellular calcium and accumulation of cAMP, whereas ucOC mainly induced phasic increase of cell calcium. Supporting these findings, we found that serum ucOC positively correlated with 25-OH Vit D levels in 40 overweight male patients and 21 controls. Altogether, our results suggest that OC contributes with LH to 25-OH Vit D production by Leydig cells

Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A

The undercarboxylated form of osteocalcin (ucOC) regulates male fertility and energy metabolism, acting through theGprotein-coupled receptor (GPRC)6A, thus forming anewpancreas-bone-testis axis. Recently, GPRC6A has also been suggested to mediate the nongenomic responses of free testosterone (T). However, these data did not consider the physiological scenario,wherecirculating T is mainly bound to sex hormone-binding globulin (SHBG) and only a small percentage circulates freely in the blood. Here, by the use of computational modelling, we document the existence of similar structural moieties between ucOC and SHBG that are predicted to bind to GPRC6A at docking analysis. This hypothesis of competition was assessed by binding experiments on human embryonic kidney-293 cells transfected with human GPRC6A gene. Unliganded SHBG specifically bound the membrane of human embryonic kidney-293 cells transfected with GPRC6A and was displaced by ucOC when coincubated at 100-fold molar excess. Furthermore, specific downstream Erk1/2 phosphorylation after stimulation of GPRC6A with ucOC was significantly blunted by 100- fold molar excess of unliganded SHBG. Intriguingly previous incubation with unliganded SHBG, followed by incubation with T, induced Erk1/2 phosphorylation in a dose-dependent manner. Neither binding nor stimulating activities were shown for SHBG saturated with T. Experiments on mutation constructs ofGPRC6Astrengthened the hypothesis of acommonbinding site ofucOCand SHBG. Given the role of GPRC6A on energy metabolism, these data agree with epidemiological association between SHBG levels and insulin sensitivity, suggest GPRC6A as a likely SHBG receptor, and add bases for the possible regulation of androgen activity in a nonsteroidal manner