Improving the performance of Invertible Bloom Lookup Tables

Invertible Bloom Lookup Tables (IBLTs) have been recently introduced as an extension of traditional Bloom filters. IBLTs store key-value pairs. Unlike traditional Bloom filters, IBLTs support both a lookup operation (given a key, return a value) and an operation that lists out all the key-value pairs stored. One issue with IBLTs is that there is a probability that a lookup operation will return “not found” for a key. In this paper, a technique to reduce this probability without affecting the storage requirement and only moderately increasing the search time is presented and evaluated. The results show that it can significantly reduce the probability of not returning a value that is actually stored in the IBLT. The overhead of the modified search procedure, compared to the standard IBLT search procedure, is small and has little impact on the average search time.     

Estimation of predictive accuracy in survival analysis using R and S-PLUS

When the purpose of a survival regression model is to predict future outcomes, the predictive accuracy of the model needs to be evaluated before practical application. Various measures of predictive accuracy have been proposed for survival data, none of which has been adopted as a standard, and their inclusion in statistical software is disregarded. We developed the surev library for R and S-PLUS, which includes functions for evaluating the predictive accuracy measures proposed by Schemper and Henderson. The library evaluates the predictive accuracy of parametric regression models and of Cox models. The predictive accuracy of the Cox model can be obtained also when time-dependent covariates are included because of non-proportional hazards or when using Bayesian model averaging. The use of the library is illustrated with examples based on a real data set.     

An efficient distributed algorithm for generating and updating multicast trees

As group applications are becoming widespread, efficient network utilization becomes a growing concern. Multicast transmission represents a necessary lower network service for the wide diffusion of new multimedia network applications. Multicast transmission may use network resources more efficiently than multiple point-to-point messages; however, creating optimal multicast trees (Steiner Tree Problem in networks) is prohibitively expensive. This paper proposes a distributed algorithm for the heuristic solution of the Steiner Tree Problem, allowing the construction of effective distribution trees using a coordination protocol among the network nodes. Furthermore, we propose a novel distributed technique for dynamically updating the multicast tree. The approach proposed has been implemented and extensively tested both in simulation, and on experimental networks. Performance evaluation indicates that the distributed algorithm performs as well as the centralized version, providing good levels of convergence time and communication complexity.     

ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.     

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.     

Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine

Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine.     

Cost‐Efficient Virtual Optical Network Embedding for Manageable Inter‐Data‐Center Connectivity

Network virtualization opens the door to novel infrastructure services offering connectivity and node manageability. In this letter, we focus on the cost‐efficient embedding of on‐demand virtual optical network requests for interconnecting geographically distributed data centers. We present a mixed integer linear programming formulation that introduces flexibility in the virtual‐physical node mapping to optimize the usage of the underlying physical resources. Illustrative results show that flexibility in the node mapping can reduce the number of add‐drop ports required to serve the offered demands by 40%.