A comparison of computational approaches for maximum likelihood estimation of the Dirichlet parameters on high-dimensional data

Likelihood estimates of the Dirichlet distribution parameters can be obtained only through numerical algorithms. Such algorithms can provide estimates outside the correct range for the parameters and/or can require a large amount of iterations to reach convergence. These problems can be aggravated if good starting values are not provided. In this paper we discuss several approaches that can partially avoid these problems providing a good trade-off between efficiency and stability. The performances of these approaches are compared on high-dimensional real and simulated data

A comparison of computational approaches for maximum likelihood estimation of the Dirichlet parameters on high-dimensional data

Likelihood estimates of the Dirichlet distribution parameters can be obtained only through numerical algorithms. Such algorithms can provide estimates outside the correct range for the parameters and/or can require a large amount of iterations to reach convergence. These problems can be aggravated if good starting values are not provided. In this paper we discuss several approaches that can partially avoid these problems providing a good trade-off between efficiency and stability. The performances of these approaches are compared on high-dimensional real and simulated data.Peer Reviewe

Nonparametric Estimation for accelerated life testing under imperfect repair.

This paper considers nonparametric estimation of lifetime distribution of a system subject to imperfect repair, based on data from constant stress accelerated life tests. By assuming as time transformation function relating stress to lifetime, a version of the inverse power law, a method of estimating the lifetime distribution at use condition stress has been recently proposed by Diana and Giordan. This method, based on the Brown-Proschan imperfect repair model, is nonparametric in that it does not make any assumptions about the underlying distribution of life length. Some simulations to understand if accelerated life tests can be used instead of normal tests evaluate the behaviour of the test procedure

Short‐term biogeomorphology of a gravel‐bed river: Integrating remote sensing with hydraulic modelling and field analysis

In recent decades, fluvial geomorphology and ecohydraulic research have extensively used field observations, remote sensing or hydrodynamic modelling to understand river systems. This study presents an innovative approach that combines field surveys, Light Detection and Ranging (LiDAR)-based topographical and biomass analyses and model-derived hydro-morphodynamic geostatistics to examine short-term bio-geomorphological changes in the wandering gravel-bed Orco River in Italy. Our primary hypothesis is that hydro-morphological variables can be robust descriptors for riparian vegetation distribution. From a geomorphological perspective, our study con-firms the prevalent wandering behaviour of the Orco River. Moreover, we identified a widening trend in braiding and anabranching sections, particularly downstream.This is evident because of hotspots of flood-induced morphological reactivation and the redistribution of sediments from the riverbed to lateral bars, resulting in a multi-thread pattern. Our analysis reveals a net increase in biomass during the observation period despite frequent flood disturbances. We attributed it to two opposing bio-geomorphological dynamics: the reduced flow disturbance in some regions due to flood-induced geomorphological changes and the self-healing of lateral connectivity through river wandering. Such a net increase indicates that transitional rivers store carbon in the form of vegetation biomass due to their short-term morphological instability and the different timescales between vegetation and morphological adjustments. Finally, we supported our initial hypothesis with three key findings: (i) a signature of vegetation not just on topography but also on hydro-morphological conditions, summarised by inundation probability; (ii) the lower variance in vertical topographical changes in vegetated areas compared with bare ones; and (iii) the introduction of a new parameter, named inundation viscosity, derived from the product of mean bed shear stress and average inundation duration, as a discriminating factor for colonisation conditions. These results underscore the value of our comprehensive approach

A new procedure for an effective management of geo-hydrological risks across the "Sentiero Verde-Azzurro" trail, Cinque Terre National Park, Liguria (North-Western Italy)

In recent years, Cinque Terre National Park, one of the most famous UNESCO sites in Italy, experienced a significant increase in tourist visits. This unique landscape is the result of the rough morphology of a small coastal basin with a very steep slope and a long-term human impact, mainly represented by anthropic terraces. This setting promotes the activation of numerous geo-hydrological instabilities, primarily related to heavy rainfall events that often affect this area. Currently, the main challenge for the administrators of Cinque Terre National Park is the correct maintenance of this environment along with the functional management of the hiking trail to ensure the safety of tourists. The definition of a methodology for effective management is mandatory for the sustainable administration of this unique site. We implement a new codified procedure based on the combined use of the Operative Monography and the Survey Form, focusing on the "Sentiero Verde-Azzurro" trail, for a proper description of the known landslides affecting the trail and the identification of damage and/or landslides activated by critical meteorological events. This guarantees effective geo-hydrological risk management, which is also applicable to other similar sites in a unique environmental and cultural heritage site such as Cinque Terre Park

The use of unmanned aerial vehicles (UAVs) for engineering geology applications

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Protein microarray analysis of aberrant signaling pathways in Acute Myeloid Leukemia to predict the patients responsiveness to PI3K/Akt/mTOR inhibitors

Mapping of deregulated kinases and protein signalling networks within tumors can provide a means to stratify patients with shared biological characteristics to the most optimal treatment, and identify drug targets. In particular, the PI3K/AKT/mTOR signaling pathways are frequently activated in blast cells from patients with acute myelogenous leukemia (AML), a neoplastic disorder characterized by the accumulation of genetically altered myelogenous cells displaying deregulated intracellular signalling pathways and aggressive clinical behavior with poor prognosis. Using Reverse Phase Protein Microarrays (RPMA), we have analyzed the phosphorylated epitopes of signal pathway proteins of 81 peripheral blood and bone marrow specimens with newly diagnosed AML. Patients are diagnosed according to blast content, FAB classification and cytogenetic analysis. Samples are enriched for leukemic cells by performing Ficoll separation to yield a mononuclear fraction with >60% blast cells. The objective of the study was to predict the sensitivity of each patient to PI3K/Akt/mTor inhibitors, to avoid unnecessary and toxic ineffective treatment of non-responsive patients. To this goal, fresh blast cells were grown for 16 h untreated or treated with phase I or phase II mTor or Akt inhibitors either alone or in combination. Remarkably, by unsupervised hierarchical clustering a strong phosphorylation/activity of most of the sampled members of the PI3K/Akt/mTOR pathway was observed in 70% of samples from AML patients. This confirms that this pathway might indeed represent a pharmacological target in many patients. Moreover, treatment with the above inhibitors had no effect on the phosphorylation of other selected targets, demonstrating the specificity of the above results (more than one different inhibitor was used to avoid off-target effects). More importantly, by the use of the above drugs, we have been able to discriminate within the “high pAkt” population a PI3K/Akt/mTOR inhibitor-responsive group of patients and a PI3K/Akt/mTOR inhibitor non-responsive group. In addition, our data indicate that the Akt pathway is hyper-activated in M4, M5 patients, compared to M0, M2 patients, and that a strong activation of most upstream and downstream Akt effectors correlates with an over-expression of the c-kit receptor (CD117). We believe these data are important because they, have the potential to define a profile for the personalized administration of targeted drugs

Functional Protein Network Activation Mapping Reveals New Potential Molecular Drug Targets for Poor Prognosis Pediatric BCP-ALL

Background: In spite of leukemia therapy improvements obtained over the last decades, therapy is not yet effective in all cases. Current approaches in Acute Lymphoblastic Leukemia (ALL) research focus on identifying new molecular targets to improve outcome for patients with a dismal prognosis. In this light phosphoproteomics seems to hold great promise for the identification of proteins suitable for targeted therapy. Methodology/Principal Findings: We employed Reverse Phase Protein Microarrays to identify aberrantly activated proteins in 118 pediatric B-cell precursor (BCP)-ALL patients. Signal transduction pathways were assayed for activation/expression status of 92 key signalling proteins. We observed an increased activation/expression of several pathways involved in cell proliferation in poor clinical prognosis patients. MLL-rearranged tumours revealed BCL-2 hyperphosphorylation through AMPK activation, which indicates that AMPK could provide a functional role in inhibiting apoptosis in MLL-rearranged patients, and could be considered as a new potential therapeutic target. Second, in patients with poor clinical response to prednisone we observed the up-modulation of LCK activity with respect to patients with good response. This tyrosine-kinase can be down-modulated with clinically used inhibitors, thus modulating LCK activity could be considered for further studies as a new additional therapy for prednisone-resistant patients. Further we also found an association between high levels of CYCLIN E and relapse incidence. Moreover, CYCLIN E is more expressed in early relapsed patients, who usually show an unfavourable prognosis. Conclusions/Significance: We conclude that functional protein pathway activation mapping revealed specific deranged signalling networks in BCP-ALL that could be potentially modulated to produce a better clinical outcome for patients resistant to standard-of-care therapies