National Foreclosure Mitigation Counseling Program Evaluation: Final Report, Rounds 3 Through 5

The Urban Institute completed a four-year evaluation of Rounds 3 through 5 of the National Foreclosure Mitigation Counseling (NFMC) program. Using a representative NFMC sample of 137,000 loans and a comparison non-NFMC sample of 103,000 loans, the Urban Institute was able to employ robust statistical techniques to isolate the impact of NFMC counseling on loan performance through June 2013.The final evaluation of Rounds 3 through 5 conducted by Urban Institute indicates that the NFMC program continues to have positive effects for homeowners participating in the program Counseled homeowners were more likely to cure a serious delinquency or foreclosure with a modification or other type cure, stay current after obtaining a cure, and for NFMC clients who cured a serious delinquency, avoid foreclosure altogether

The mixmaster universe: A chaotic Farey tale

When gravitational fields are at their strongest, the evolution of spacetime is thought to be highly erratic. Over the past decade debate has raged over whether this evolution can be classified as chaotic. The debate has centered on the homogeneous but anisotropic mixmaster universe. A definite resolution has been lacking as the techniques used to study the mixmaster dynamics yield observer dependent answers. Here we resolve the conflict by using observer independent, fractal methods. We prove the mixmaster universe is chaotic by exposing the fractal strange repellor that characterizes the dynamics. The repellor is laid bare in both the 6-dimensional minisuperspace of the full Einstein equations, and in a 2-dimensional discretisation of the dynamics. The chaos is encoded in a special set of numbers that form the irrational Farey tree. We quantify the chaos by calculating the strange repellor's Lyapunov dimension, topological entropy and multifractal dimensions. As all of these quantities are coordinate, or gauge independent, there is no longer any ambiguity--the mixmaster universe is indeed chaotic.Comment: 45 pages, RevTeX, 19 Figures included, submitted to PR

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Acoustics and oceanographic observations collected during the QPE Experiment by Research Vessels OR1, OR2 and OR3 in the East China Sea in the Summer of 2009

This document describes data, sensors, and other useful information pertaining to the ONR sponsored QPE field program to quantify, predict and exploit uncertainty in observations and prediction of sound propagation. This experiment was a joint operation between Taiwanese and U.S. researchers to measure and assess uncertainty of predictions of acoustic transmission loss and ambient noise, and to observe the physical oceanography and geology that are necessary to improve their predictability. This work was performed over the continental shelf and slope northeast of Taiwan at two sites: one that was a relatively flat, homogeneous shelf region and a more complex geological site just shoreward of the shelfbreak that was influenced by the proximity of the Kuroshio Current. Environmental moorings and ADCP moorings were deployed and a shipboard SeaSoar vehicle was used to measure environmental spatial structure. In addition, multiple bottom moored receivers and a horizontal hydrophone array were deployed to sample transmission loss from a mobile source and ambient noise. The acoustic sensors, environmental sensors, shipboard resources, and experiment design, and their data, are presented and described in this technical report.Funding was provided by the Office of Naval Research under Contract No. N00014-08-1-076

Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease compared to non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to Crohn’s disease etiology in this population, most notably at NOD2, in which three causal, uncommon, and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes which showed significantly greater association to Crohn’s disease in the Ashkenazi Jewish population compared to a non-Jewish population (145 haplotypes and no haplotypes with P-value < 10−3, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established Crohn’s disease loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare Crohn’s disease-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association

Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K/Akt Pathway in Gliomas

Glioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes.In the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU)-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results.In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

The climate sensitivity of Norway spruce [Picea abies (L.) Karst.] in the southeastern European Alps

Tree ring chronologies were developed from trees growing at two sites in Slovenia which differed in their ecological and climatological characteristics. Ring width, maximum latewood density, annual height increment and latewood cellulose carbon isotope composition were developed at both sites and time-series verified against instrumental climate data over the period (AD 1960–AD 2002). Ring width sensitivity to summer temperature is site-dependent, with contrasting responses at alpine and lowland sites. Maximum density responds to September temperatures, suggesting lignification after cell division has ended for the season. Stable carbon isotopes have great potential, responding to summer temperature at oth alpine and lowland stands. Height increment appears relatively insensitive to climate, and is likely to be dominated by local stand dynamics

Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3b, LC3B, Atg4, Atg5/12, Atg.7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1-1- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. © 2008 Chen et al