Evaluation of the performance of tests for spatial randomness on prostate cancer data

Background: Spatial global clustering tests can be used to evaluate the geographical distribution of health outcomes. The power of several of these tests has been evaluated and compared using simulated data, but their performance using real unadjusted data and data adjusted for individual- and area-level covariates has not been reported previously. We evaluated data on prostate cancer histologic tumor grade and stage of disease at diagnosis for incident cases of prostate cancer reported to the Maryland Cancer Registry during 1992–1997. We analyzed unadjusted data as well as expected counts from models that were adjusted for individual- level covariates (race, age and year of diagnosis) and area-level covariates (census block group median household income and a county-level socioeconomic index). We chose 3 spatial clustering tests that are commonly used to evaluate the geographic distribution of disease: Cuzick-Edwards' k-NN (k-Nearest Neighbors) test, Moran's I and Tango's MEET (Maximized Excess Events Test). Results: For both grade and stage at diagnosis, we found that Cuzick-Edwards' k-NN and Moran's I were very sensitive to the percent of population parameter selected. For stage at diagnosis, all three tests showed that the models with individual- and area-level adjustments reduced clustering the most, but did not reduce it entirely. Conclusion: Based on this specific example, results suggest that these tests provide useful tools for evaluating spatial clustering of disease characteristics, both before and after consideration of covariates

Combining Electrochemical Nitrate Reduction and Anammox for Treatment of Nitrate-Rich Wastewater: A Short Review

Treatment of nitrate-rich wastewater is important but challenging for the conventional biological denitrification process. Here, we propose combining the electrochemical reduction and anaerobic ammonium oxidation (anammox) processes together for treatment of nitrate-rich wastewater. This article reviews the mechanism and current research status of electrochemical reduction of nitrate to ammonium as well as the mechanism and applicability of the anammox process. This article discusses the principles, superiorities, and challenges of this combined process. The feasibility of the combined process depends on the efficiency of electrochemical nitrate reduction to ammonium and the conditions in the anammox process to use the reduced ammonium as the substrate to achieve deep nitrogen removal. The article provides a feasible strategy for using the electrochemical reduction and anammox combined process to treat nitrate-rich wastewater

Carbon nanotubes adhesion and nanomechanical behavior from peeling force spectroscopy

Applications based on Single Walled Carbon Nanotube (SWNT) are good example of the great need to continuously develop metrology methods in the field of nanotechnology. Contact and interface properties are key parameters that determine the efficiency of SWNT functionalized nanomaterials and nanodevices. In this work we have taken advantage of a good control of the SWNT growth processes at an atomic force microscope (AFM) tip apex and the use of a low noise (1E-13 m/rtHz) AFM to investigate the mechanical behavior of a SWNT touching a surface. By simultaneously recording static and dynamic properties of SWNT, we show that the contact corresponds to a peeling geometry, and extract quantities such as adhesion energy per unit length, curvature and bending rigidity of the nanotube. A complete picture of the local shape of the SWNT and its mechanical behavior is provided

The Effects of DLEU1 Gene Expression in Burkitt Lymphoma (BL): Potential Mechanism of Chemoimmunotherapy Resistance in BL

Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines. Furthermore, NSG mice xenografted with DLEU1 knockdown BL cells had significantly shortened survival (p \u3c 0.05 and p \u3c 0.005), whereas those xenografted with DLEU1 overexpressing BL cells had significantly improved survival (p \u3c 0.05 and p \u3c 0.0001), following treatment with rituximab and/or cyclophosphamide. These data suggest that DLEU1 may in part function as a tumor suppressor gene and confer chemoimmunotherapy resistance in children and adolescents with BL

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

A Magnetic Bead-Integrated Chip for the Large Scale Manufacture of Normalized esiRNAs

The chemically-synthesized siRNA duplex has become a powerful and widely used tool for RNAi loss-of-function studies, but suffers from a high off-target effect problem. Recently, endoribonulease-prepared siRNA (esiRNA) has been shown to be an attractive alternative due to its lower off-target effect and cost effectiveness. However, the current manufacturing method for esiRNA is complicated, mainly in regards to purification and normalization on a large-scale level. In this study, we present a magnetic bead-integrated chip that can immobilize amplification or transcription products on beads and accomplish transcription, digestion, normalization and purification in a robust and convenient manner. This chip is equipped to manufacture ready-to-use esiRNAs on a large-scale level. Silencing specificity and efficiency of these esiRNAs were validated at the transcriptional, translational and functional levels. Manufacture of several normalized esiRNAs in a single well, including those silencing PARP1 and BRCA1, was successfully achieved, and the esiRNAs were subsequently utilized to effectively investigate their synergistic effect on cell viability. A small esiRNA library targeting 68 tyrosine kinase genes was constructed for a loss-of-function study, and four genes were identified in regulating the migration capability of Hela cells. We believe that this approach provides a more robust and cost-effective choice for manufacturing esiRNAs than current approaches, and therefore these heterogeneous RNA strands may have utility in most intensive and extensive applications

Reliability analysis of the Ahringer Caenorhabditis elegans RNAi feeding library: a guide for genome-wide screens

<p>Abstract</p> <p>Background</p> <p>The Ahringer <it>C. elegans </it>RNAi feeding library prepared by cloning genomic DNA fragments has been widely used in genome-wide analysis of gene function. However, the library has not been thoroughly validated by direct sequencing, and there are potential errors, including: 1) mis-annotation (the clone with the retired gene name should be remapped to the actual target gene); 2) nonspecific PCR amplification; 3) cross-RNAi; 4) mis-operation such as sample loading error, <it>etc</it>.</p> <p>Results</p> <p>Here we performed a reliability analysis on the Ahringer <it>C. elegans </it>RNAi feeding library, which contains 16,256 bacterial strains, using a bioinformatics approach. Results demonstrated that most (98.3%) of the bacterial strains in the library are reliable. However, we also found that 2,851 (17.54%) bacterial strains need to be re-annotated even they are reliable. Most of these bacterial strains are the clones having the retired gene names. Besides, 28 strains are grouped into unreliable category and 226 strains are marginal because of probably expressing unrelated double-stranded RNAs (dsRNAs). The accuracy of the prediction was further confirmed by direct sequencing analysis of 496 bacterial strains. Finally, a freely accessible database named CelRNAi (<url>http://biocompute.bmi.ac.cn/CelRNAi/</url>) was developed as a valuable complement resource for the feeding RNAi library by providing the predicted information on all bacterial strains. Moreover, submission of the direct sequencing result or any other annotations for the bacterial strains to the database are allowed and will be integrated into the CelRNAi database to improve the accuracy of the library. In addition, we provide five candidate primer sets for each of the unreliable and marginal bacterial strains for users to construct an alternative vector for their own RNAi studies.</p> <p>Conclusions</p> <p>Because of the potential unreliability of the Ahringer <it>C. elegans </it>RNAi feeding library, we strongly suggest the user examine the reliability information of the bacterial strains in the CelRNAi database before performing RNAi experiments, as well as the post-RNAi experiment analysis.</p