Landslide susceptibility mapping at VAZ watershed (Iran) using an artificial neural network model: a comparison between multilayer perceptron (MLP) and radial basic function (RBF) algorithms

Landslide susceptibility and hazard assessments are the most important steps in landslide risk mapping. The main objective of this study was to investigate and compare the results of two artificial neural network (ANN) algorithms, i.e., multilayer perceptron (MLP) and radial basic function (RBF) for spatial prediction of landslide susceptibility in Vaz Watershed, Iran. At first, landslide locations were identified by aerial photographs and field surveys, and a total of 136 landside locations were constructed from various sources. Then the landslide inventory map was randomly split into a training dataset 70 % (95 landslide locations) for training the ANN model and the remaining 30 % (41 landslides locations) was used for validation purpose. Nine landslide conditioning factors such as slope, slope aspect, altitude, land use, lithology, distance from rivers, distance from roads, distance from faults, and rainfall were constructed in geographical information system. In this study, both MLP and RBF algorithms were used in artificial neural network model. The results showed that MLP with Broyden–Fletcher–Goldfarb–Shanno learning algorithm is more efficient than RBF in landslide susceptibility mapping for the study area. Finally the landslide susceptibility maps were validated using the validation data (i.e., 30 % landslide location data that was not used during the model construction) using area under the curve (AUC) method. The success rate curve showed that the area under the curve for RBF and MLP was 0.9085 (90.85 %) and 0.9193 (91.93 %) accuracy, respectively. Similarly, the validation result showed that the area under the curve for MLP and RBF models were 0.881 (88.1 %) and 0.8724 (87.24 %), respectively. The results of this study showed that landslide susceptibility mapping in the Vaz Watershed of Iran using the ANN approach is viable and can be used for land use planning

Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome

We report the isolation of the 5′ flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway