GA SAKe : forecasting landslide activations by a genetic-algorithms-based hydrological model

Abstract. GASAKe is a new hydrological model aimed at forecasting the triggering of landslides. The model is based on genetic algorithms and allows one to obtain thresholds for the prediction of slope failures using dates of landslide activations and rainfall series. It can be applied to either single landslides or a set of similar slope movements in a homogeneous environment. Calibration of the model provides families of optimal, discretized solutions (kernels) that maximize the fitness function. Starting from the kernels, the corresponding mobility functions (i.e., the predictive tools) can be obtained through convolution with the rain series. The base time of the kernel is related to the magnitude of the considered slope movement, as well as to the hydro-geological complexity of the site. Generally, shorter base times are expected for shallow slope instabilities compared to larger-scale phenomena. Once validated, the model can be applied to estimate the timing of future landslide activations in the same study area, by employing measured or forecasted rainfall series. Examples of application of GASAKe to a medium-size slope movement (the Uncino landslide at San Fili, in Calabria, southern Italy) and to a set of shallow landslides (in the Sorrento Peninsula, Campania, southern Italy) are discussed. In both cases, a successful calibration of the model has been achieved, despite unavoidable uncertainties concerning the dates of occurrence of the slope movements. In particular, for the Sorrento Peninsula case, a fitness of 0.81 has been obtained by calibrating the model against 10 dates of landslide activation; in the Uncino case, a fitness of 1 (i.e., neither missing nor false alarms) has been achieved using five activations. As for temporal validation, the experiments performed by considering further dates of activation have also proved satisfactory. In view of early-warning applications for civil protection, the capability of the model to simulate the occurrences of the Uncino landslide has been tested by means of a progressive, self-adaptive procedure. Finally, a sensitivity analysis has been performed by taking into account the main parameters of the model. The obtained results are quite promising, given the high performance of the model against different types of slope instabilities characterized by several historical activations. Nevertheless, further refinements are still needed for application to landslide risk mitigation within early-warning and decision-support systems

Use of observed ice crystal sizes and shapes to calculate mean-scattering properties and multispectral radiances: CEPEX April 4, 1993, case study

During the Central Equatorial Pacific Experiment, ice crystal sizes and shapes were measured in an outflow anvil. A habit (i.e., column, bullet rosette, Koch fractal polycrystal, sphere) was assigned to each particle using a self-organized neural network based on simulations of how the maximum particle dimension and area ratio varied for random orientations of these crystals. Average ice crystal size and shape distributions were calculated for 25 km long segments at six altitudes using measurements from a two-dimensional cloud probe for crystals larger than 90 μm and a parameterization for smaller crystals based on measurements from the Video Ice Particle Sampler (VIPS). Mean-scattering properties were determined by weighting the size and shape dependent single-scattering properties computed with ray-tracing algorithms according to scattering cross-section. Reflectances at 0.664, 0.875, 1.621, and 2.142 μm were then calculated using a Monte Carlo radiative transfer routine. Although these reflectances agree reasonably with those measured by the MODIS airborne simulator (MAS) above the anvil, uncertainties in cloud base and system evolution prevent a determination of whether ray-tracing or anomalous diffraction theory better predict reflectance. The calculated reflectances are as sensitive to the numbers and shapes of crystals smaller than 90 μm as to those of larger crystals. The calculated reflectances were insensitive to the classification scheme (i.e., neural network, discriminator analysis, and previously used classification scheme) for assigning particle shape to observed crystals. However, the reflectances significantly depended on assumed particle shape

Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients

Tissue engineering-based bone graft is an emerging viable treatment modality to repair and regenerate tissues damaged as a result of diseases or injuries. The structure and composition of scaffolds should modulate the classical osteogenic pathways in human stem cells. The osteoinductivity properties of the hydroxylapatite-collagen hybrid scaffold named Coll/Pro Osteon 200 were investigated in an in vitro model of human adipose mesenchymal stem cells (hASCs), whereas the clinical evaluation was carried out in maxillofacial patients. Differentially expressed genes (DEGs) induced by the scaffold were analyzed using the Osteogenesis RT2 PCR Array. The osteoinductivity potential of the scaffold was also investigated by studying the alkaline phosphatase (ALP) activity, matrix mineralization, osteocalcin (OCN), and CLEC3B expression protein. Fifty patients who underwent zygomatic augmentation and bimaxillary osteotomy were evaluated clinically, radiologically, and histologically during a 3-year follow-up. Among DEGs, osteogenesis-related genes, including BMP1/2, ALP, BGLAP, SP7, RUNX2, SPP1, and EGFR, which play important roles in osteogenesis, were found to be upregulated. The genes to cartilage condensation SOX9, BMPR1B, and osteoclast cells TNFSF11 were detected upregulated at every time point of the investigation. This scaffold has a high osteoinductivity revealed by the matrix mineralization, ALP activity, OCN, and CLEC3B expression proteins. Clinical evaluation evidences that the biomaterial promotes bone regrowth. Histological results of biopsy specimens from patients showed prominent ossification. Experimental data using the Coll/Pro Osteon 200 indicate that clinical evaluation of bone regrowth in patients, after scaffold implantation, was supported by DEGs implicated in skeletal development as shown in "in vitro" experiments with hASCs

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies

A History of Chagas Disease Transmission, Control, and Re-Emergence in Peri-Rural La Joya, Peru

The historically rural problem of Chagas disease is increasing in urban areas in Latin America. Peri-rural development may play a critical role in the urbanization of Chagas disease and other parasitic infections. We conducted a cross-sectional study in an urbanizing rural area in southern Peru, and we encountered a complex history of Chagas disease in this peri-rural environment. Specifically, we discovered: (1) long-standing parasite transmission leading to substantial burden of infection; (2) interruption in parasite transmission resulting from an undocumented insecticide application campaign; (3) relatively rapid re-emergence of parasite-infected vector insects resulting from an unsustained control campaign; (4) extensive migration among peri-rural inhabitants. Long-standing parasite infection in peri-rural areas with highly mobile populations provides a plausible mechanism for the expansion of parasite transmission to nearby urban centers. Lack of commitment to control campaigns in peri-rural areas may have unforeseen and undesired consequences for nearby urban centers. Novel methods and perspectives are needed to address the complexities of human migration and erratic interventions

The RIP140 Gene Is a Transcriptional Target of E2F1

RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases

Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

<p>Abstract</p> <p>Background</p> <p>Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored.</p> <p>Results</p> <p>In this study, we examined the effects of <it>in vitro </it>exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis.</p> <p>Conclusions</p> <p>This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.</p

A Factor Graph Nested Effects Model To Identify Networks from Genetic Perturbations

Complex phenotypes such as the transformation of a normal population of cells into cancerous tissue result from a series of molecular triggers gone awry. We describe a method that searches for a genetic network consistent with expression changes observed under the knock-down of a set of genes that share a common role in the cell, such as a disease phenotype. The method extends the Nested Effects Model of Markowetz et al. (2005) by using a probabilistic factor graph to search for a network representing interactions among these silenced genes. The method also expands the network by attaching new genes at specific downstream points, providing candidates for subsequent perturbations to further characterize the pathway. We investigated an extension provided by the factor graph approach in which the model distinguishes between inhibitory and stimulatory interactions. We found that the extension yielded significant improvements in recovering the structure of simulated and Saccharomyces cerevisae networks. We applied the approach to discover a signaling network among genes involved in a human colon cancer cell invasiveness pathway. The method predicts several genes with new roles in the invasiveness process. We knocked down two genes identified by our approach and found that both knock-downs produce loss of invasive potential in a colon cancer cell line. Nested effects models may be a powerful tool for inferring regulatory connections and genes that operate in normal and disease-related processes

Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers

We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy (ADT) synergizes with ionizing radiation (IR). Using a model of castration-resistant prostate cancer, we show that second-generation antiandrogen therapy results in downregulation of DNA repair genes. Next, we demonstrate that primary prostate cancers display a significant spectrum of AR transcriptional output which correlates with expression of a set of DNA repair genes. Employing RNA-seq and ChIP-seq, we define which of these DNA repair genes are both induced by androgen and represent direct AR targets. We establish that prostate cancer cells treated with IR plus androgen demonstrate enhanced DNA repair and decreased DNA damage and furthermore that antiandrogen treatment causes increased DNA damage and decreased clonogenic survival. Finally, we demonstrate that antiandrogen treatment results in decreased classical non-homologous end joining