Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

Ceramic Foam For Molten metal Filtration

In this study, ceramic foam filters were used for the inductrial filtration of aluminum. Results are compared with laboratory experiments which are in good agreement with trajectory analyses of deep bed filtration for the early stage of filtration. The correlations between structural characteristics of the filter media, filtration parameters and filter efficiency are given. In addition, the most important parameters for the industrial use of filters are discussed.

     

Information diffusion in distributed OSN: The impact of trusted relationships

Distributed Online Social Networks (DOSN) are a valid alternative to OSN based on peer-to-peer communications. Without centralised data management, DOSN must provide the users with higher level of control over their personal information and privacy. Thus, users may wish to restrict their personal network to a limited set of peers, depending on the level of trust with them. This means that the effective social network (used for information exchange) may be a subset of the complete social network, and may present different structural patterns, which could limit information diffusion. In this paper, we estimate the capability of DOSN to diffuse content based on trust between social peers. To have a realistic representation of a OSN friendship graph, we consider a large-scale Facebook network, from which we estimate the trust level between friends. Then, we consider only social links above a certain threshold of trust, and we analyse the potential capability of the resulting graph to spread information through several structural indices. We test four possible thresholds, coinciding with the definition of personal social circles derived from sociology and anthropology. The results show that limiting the network to “active social contacts” leads to a graph with high network connectivity, where the nodes are still well-connected to each other, thus information can potentially cover a large number of nodes with respect to the original graph. On the other hand, the coverage drops for more restrictive assumptions. Nevertheless the re-insertion of a single excluded friend for each user is sufficient to obtain good coverage (i.e., always higher than 40 %) even in the most restricted graphs. We also analyse the potential capability of the network to spread information (i.e., network spreadability), studying the properties of the social paths between any pairs of users in the graph, which represent the effective channels traversed by information. The value of contact frequency between pairs of users determines a decay of trust along the path (the higher the contact frequency the lower the decay), and a consequent decay in the level of trustworthiness of information traversing the path. We show that selecting the link to re-insert in the network with probability proportional to its level of trust is the best re-insertion strategy, as it leads to the best connectivity/spreadability combination.     

Energy efficient and reliable data delivery in urban sensing applications: A performance analysis

Urban sensing is an emerging application field for Wireless Sensor Networks (WSNs), where a number of static sensors is sparsely deployed in an urban area to collect environmental information. Data sensed by each sensor are, then, opportunistically transmitted to Mobile Nodes (MNs) that happen to be in contact. In the considered scenario, communications between MNs and sensors require paradigms with a minimal synchronization between devices, extremely fast and energy efficient, especially at the sensor side. To deal with the above issues, in [1] we proposed a hybrid protocol for data delivery from sensors to MNs, named Hybrid Adaptive Interleaved Data Protocol (HI). By combining Erasure Coding (EC) with an Automatic Repeat reQuest (ARQ) scheme, the proposed protocol maximizes the reliability of communications while minimizing the energy consumed by sensors. In this paper, we present an in-depth analysis of the HI performance. We provide an analytical evaluation by defining a flexible model to derive the probability of data delivery and exploiting it to investigate the performance over a wide range of parameters. Moreover, we perform an experimental study to evaluate the HI effectiveness on real sensor platforms. Specifically, we analyze the impact of resource constraints imposed by sensors on data delivery and provide a careful characterization of its actual consumption of resources.     

Driving business performance: innovation complementarities and persistence patterns

Complementarities between technological and non-technological innovation are crucial determinants of firm performance. Although innovation complementarity has been extensively tested in the empirical literature, it has not been analysed in conjunction with innovation persistence. This fact is mainly due to the lack of data sets able to provide adequate longitudinal information. The capacities to develop market-oriented behaviour and introduce new organisational innovations, together with technological innovation, are the drivers of a firm’s productivity and profitability. We find that these activities complement technological innovation and that their impact is greater when they persist over time, thus introducing a more general concept of innovation persistence. We present an empirical model based on a large new panel of Italian manufacturing firms covering the period 2000–2012 which enables us to determine the precise impacts of a firm’s innovative attitude, in a broad definition that incorporates non-technological innovation and persistence, on its productivity and profitability.     

Providing the right stuff: feeding children with chronic renal failure

The progressive loss of renal function in children with chronic renal failure (CRF) has a negative influence on their nutritional status and statural growth. Supportive therapies with 1-25 dihydroxy-vitamin D3, recombinant erythropoietin and growth hormone have significantly improved the biochemical and clinical features but the success of these therapies is largely related to an appropriate diet, with adequate protein/caloric intakes. Children more than adults have minimal protein requirements to avoid malnutrition and growth impairment FAO/WHO and RDA recommendations save as guidelines for a correct diet in children with CRF. Following these allowances leads to a "normoproteic" diet, with a protein intake which is often half the unrestricted one in Western European countries, but which is still likely to be not enough to protect against renal deterioration. Indeed the European Study Group for Nutritional Treatment of CRF in children failed to show a significant effect of diet on the mean decline of glomerular filtration rate over two years.     

Blind maximum likelihood estimation of traffic matrices under long-range dependent traffic

A new method, based on the maximum likelihood principle, through the numerical Expectation–Maximization algorithm, is proposed to estimate traffic matrices when traffic exhibits long-range dependence. The methods proposed so far in the literature do not account for long-range dependence. The method proposed in the present paper also provides an estimate of the Hurst parameter. Simulation results show that: (i) the estimate of the traffic matrix is more efficient than those obtained via existing techniques; (ii) the estimation error of the traffic matrix is lower for larger values of the true traffic intensity; (iii) the estimate of the Hurst parameter is slightly negatively biased.