The interior structure of rotating black holes 1. Concise derivation

This paper presents a concise derivation of a new set of solutions for the interior structure of accreting, rotating black holes. The solutions are conformally stationary, axisymmetric, and conformally separable. Hyper-relativistic counter-streaming between freely-falling collisionless ingoing and outgoing streams leads to mass inflation at the inner horizon, followed by collapse. The solutions fail at an exponentially tiny radius, where the rotational motion of the streams becomes comparable to their radial motion. The papers provide a fully nonlinear, dynamical solution for the interior structure of a rotating black hole from just above the inner horizon inward, down to a tiny scale.Comment: Version 1: 8 pages, 3 figures. Version 2: Extensively revised to emphasize the derivation of the solution rather than the solution itself. 11 pages, 4 figures. Version 3: Minor changes to match published version. Mathematica notebook available at http://jila.colorado.edu/~ajsh/rotatinginflationary/rotatinginflationary.n

Linearized self-forces for branes

We compute the regularized force density and renormalized action due to fields of external origin coupled to a brane of arbitrary dimension in a spacetime of any dimension. Specifically, we consider forces generated by gravitational, dilatonic and generalized antisymmetric form-fields. The force density is regularized using a recently developed gradient operator. For the case of a Nambu--Goto brane, we show that the regularization leads to a renormalization of the tension, which is seen to be the same in both approaches. We discuss the specific couplings which lead to cancellation of the self-force in this case.Comment: 15 page

Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis

We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking the steroid responsiveness observed in patients with SSNS. The p.H310Y variant also disrupted binding of clavesin-1 to α-tocopherol transfer protein, resulting in increased reactive oxygen species (ROS) accumulation in CLVS1-deficient podocytes. Treatment of CLVS1-knockout or homozygous H310Y-knockin podocytes with pharmacological ROS inhibitors restored viability to control levels. Taken together, these data identify CLVS1 as a candidate gene for SSNS, provide insight into therapeutic effects of corticosteroids on podocyte cellular dynamics, and add to the growing evidence of the importance of endocytosis and oxidative stress regulation to podocyte function

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia

BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. METHODS: To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. RESULTS: Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPβ target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. CONCLUSIONS: These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting.R01 AR060217 - NIAMS NIH HHS; R01 AR060209 - NIAMS NIH HHS; T32 HD043730 - NICHD NIH HHS; R00 HL098453 - NHLBI NIH HHS; R00HL098453 - NHLBI NIH HHS; R01AR060209 - NIAMS NIH HHS; R01AR060217 - NIAMS NIH HH

Hot spots policing of small geographic areas effects on crime

Background In recent years, crime scholars and practitioners have pointed to the potential benefits of focusing crime prevention efforts on crime places. A number of studies suggest that there is significant clustering of crime in small places, or “hot spots,” that generate half of all criminal events. Researchers have argued that many crime problems can be reduced more efficiently if police officers focused their attention to these deviant places. The appeal of focusing limited resources on a small number of high-activity crime places is straightforward. If crime can be prevented at these hot spots, then citywide crime totals could be reduced. Objectives To assess the effects of focused police crime prevention interventions at crime hot spots. The review also examined whether focused police actions at specific locations result in crime displacement (i.e., crime moving around the corner) or diffusion (i.e., crime reduction in surrounding areas) of crime control benefits. Search Methods A keyword search was performed on 15 abstract databases. Bibliographies of past narrative and empirical reviews of literature that examined the effectiveness of police crime control programs were reviewed and forward searches for works that cited seminal hot spots policing studies were performed. Bibliographies of past completed Campbell systematic reviews of police crime prevention efforts were reviewed and hand searches of leading journals in the field were completed. Experts in the field were consulted and relevant citations were obtained. Selection Criteria To be eligible for this review, interventions used to control crime hot spots were limited to police-led prevention efforts. Suitable police-led crime prevention efforts included traditional tactics such as directed patrol and heightened levels of traffic enforcement as well as alternative strategies such as aggressive disorder enforcement and problem-oriented policing. Studies that used randomized controlled experimental or quasiexperimental designs were selected. The units of analysis were limited to crime hot spots or high-activity crime “places” rather than larger areas such as neighborhoods. The control group in each study received routine levels of traditional police crime prevention tactics. Data Collection and Analysis Sixty-five studies containing 78 tests of hot spots policing interventions were identified and full narratives of these studies were reported. Twenty-seven of the selected studies used randomized experimental designs and 38 used quasiexperimental designs. A formal meta-analysis was conducted to determine the crime prevention effects in the eligible studies. Random effects models were used to calculate mean effect sizes. Results Sixty-two of 78 tests of hot spots policing interventions reported noteworthy crime and disorder reductions. The meta-analysis of key reported outcome measures revealed a small statistically significant mean effect size favoring the effects of hot spots policing in reducing crime outcomes at treatment places relative to control places. The effect was smaller for randomized designs but still statistically significant and positive. When displacement and diffusion effects were measured, a diffusion of crime prevention benefits was associated with hot spots policing. Authors\u27 Conclusions The extant evaluation research suggests that hot spots policing is an effective crime prevention strategy. The research also suggests that focusing police efforts on high-activity crime places does not inevitably lead to crime displacement; rather, crime control benefits may diffuse into the areas immediately surrounding the targeted locations

Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown

CSO and CARMA Observations of L1157. II. Chemical Complexity in the Shocked Outflow

L1157, a molecular dark cloud with an embedded Class 0 protostar possessing a bipolar outflow, is an excellent source for studying shock chemistry, including grain-surface chemistry prior to shocks, and post-shock, gas-phase processing. The L1157-B1 and B2 positions experienced shocks at an estimated ~2000 and 4000 years ago, respectively. Prior to these shock events, temperatures were too low for most complex organic molecules to undergo thermal desorption. Thus, the shocks should have liberated these molecules from the ice grain-surfaces en masse, evidenced by prior observations of SiO and multiple grain mantle species commonly associated with shocks. Grain species, such as OCS, CH3OH, and HNCO, all peak at different positions relative to species that are preferably formed in higher velocity shocks or repeatedly-shocked material, such as SiO and HCN. Here, we present high spatial resolution (~3") maps of CH3OH, HNCO, HCN, and HCO+ in the southern portion of the outflow containing B1 and B2, as observed with CARMA. The HNCO maps are the first interferometric observations of this species in L1157. The maps show distinct differences in the chemistry within the various shocked regions in L1157B. This is further supported through constraints of the molecular abundances using the non-LTE code RADEX (Van der Tak et al. 2007). We find the east/west chemical differentiation in C2 may be explained by the contrast of the shock's interaction with either cold, pristine material or warm, previously-shocked gas, as seen in enhanced HCN abundances. In addition, the enhancement of the HNCO abundance toward the the older shock, B2, suggests the importance of high-temperature O-chemistry in shocked regions.Comment: Accepted for publication in the Astrophysical Journa

CSO and CARMA Observations of L1157. I. A Deep Search for Hydroxylamine (NH2_2OH)

A deep search for the potential glycine precursor hydroxylamine (NH$_2$OH) using the Caltech Submillimeter Observatory (CSO) at $\lambda = 1.3$ mm and the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at $\lambda = 3$ mm is presented toward the molecular outflow L1157, targeting the B1 and B2 shocked regions. We report non-detections of NH$_2$OH in both sources. We a perform non-LTE analysis of CH$_3$OH observed in our CSO spectra to derive kinetic temperatures and densities in the shocked regions. Using these parameters, we derive upper limit column densities of NH$_2$OH of $\leq1.4 \times 10^{13}$~cm$^{-2}$ and $\leq1.5 \times 10^{13}$~cm$^{-2}$ toward the B1 and B2 shocks, respectively, and upper limit relative abundances of $N_{NH_2OH}/N_{H_2} \leq1.4 \times 10^{-8}$ and $\leq1.5 \times 10^{-8}$, respectively.Comment: Accepted in the Astrophysical Journa