The Fueling and Evolution of AGN: Internal and External Triggers

In this chapter, I review the fueling and evolution of active galactic nuclei (AGN) under the influence of internal and external triggers, namely intrinsic properties of host galaxies (morphological or Hubble type, color, presence of bars and other non-axisymmetric features, etc) and external factors such as environment and interactions. The most daunting challenge in fueling AGN is arguably the angular momentum problem as even matter located at a radius of a few hundred pc must lose more than 99.99 % of its specific angular momentum before it is fit for consumption by a BH. I review mass accretion rates, angular momentum requirements, the effectiveness of different fueling mechanisms, and the growth and mass density of black BHs at different epochs. I discuss connections between the nuclear and larger-scale properties of AGN, both locally and at intermediate redshifts, outlining some recent results from the GEMS and GOODS HST surveys.Comment: Invited Review Chapter to appear in LNP Volume on "AGN Physics on All Scales", Chapter 6, in press. 40 pages, 12 figures. Typo in Eq 5 correcte

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay). RESULTS: Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001). CONCLUSION: Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia

Measurement of event-shape observables in Z→ℓ+ℓ− events in pp collisions at √ s=7 TeV with the ATLAS detector at the LHC

Event-shape observables measured using charged particles in inclusive $Z$-boson events are presented, using the electron and muon decay modes of the $Z$ bosons. The measurements are based on an integrated luminosity of $1.1 {\rm fb}^{-1}$ of proton--proton collisions recorded by the ATLAS detector at the LHC at a centre-of-mass energy $\sqrt{s}=7$ TeV. Charged-particle distributions, excluding the lepton--antilepton pair from the $Z$-boson decay, are measured in different ranges of transverse momentum of the $Z$ boson. Distributions include multiplicity, scalar sum of transverse momenta, beam thrust, transverse thrust, spherocity, and $\mathcal{F}$-parameter, which are in particular sensitive to properties of the underlying event at small values of the $Z$-boson transverse momentum. The Sherpa event generator shows larger deviations from the measured observables than Pythia8 and Herwig7. Typically, all three Monte Carlo generators provide predictions that are in better agreement with the data at high $Z$-boson transverse momenta than at low $Z$-boson transverse momenta and for the observables that are less sensitive to the number of charged particles in the event.Comment: 36 pages plus author list + cover page (54 pages total), 14 figures, 4 tables, submitted to EPJC, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2014-0

Using structural MRI to identify bipolar disorders - 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data

Binding agents for low-salt, low-fat, restructured beef roasts: connective tissue or gelatin

Connective tissue, from the outside of three major chuck muscles, was evaluated for binding properties when incorporated either raw or following preheating into precooked, restructured beef. Food-grade gelatin was also evaluated as a binding agent. Adding 10% raw or preheated connective tissue increased (P<.05) instrumentally measured tensile strength and reduced (P<.05) juiciness perception. One percent gelatin reduced (P<.05) cook yields and increased (P<.05) tensile strength but not to the degree of 10% raw or preheated connective tissue. Preheating had minimal effects on improving connective tissue utility. Based on the improvement in bind and cook yields, use of connective tissue as a binder is feasible in manufacturing low-salt, precooked, restructured beef

Binding agents for low-salt, low-fat, restructured beef roasts: fish surimi and beef heart or skeletal muscle

Five percent fish surimi, unwashed or washed ground beef, and washed or unwashed beef hearts were evaluated in precooked, chunked and formed, restructured beef roasts to determine if they would increase bind in low-salt (0.2% NaCl) product. An industry-like product with 1.0% NaCl and 5% unwashed ground beef was prepared, as well as a product with 0.2% NaCl and no binder. Roasts without binder were comparable in texture and integrity to those prepared with binding agents. Washing ground heart improved the sensory traits, texture measured instrumentally, and oxidative stability of the resulting products. Color was more stable for roasts containing ground heart. Roasts with 1.0% NaCl were firmer (P<.05) and had greater tensile strength (P<.05) than all other treatments. Adding salt increased binding more than adding binders, even though acceptable products could be made with minimal salt. Using binders with or without washing is not recommended, unless processors want to expand use of beef hearts

Polyvinylchloride-packaged loin strip steaks from vacuum-packaged beef strip loins decontaminated with lactic acid and stored for up to 126 days

Aerobic plate counts (APCs), presence/ absence of Listeria monocytogenes and Salmonella spp., and visual color evaluations were used to determine the microbiological and display quality of steaks fabricated from beef strip loins sprayed with lactic acid (1.5% v/v) or water before, after, o r both before and after vacuum storage (14, 28, 56, 84, or 126 days) at either 30E or 36EF compared to nonsprayed or nonstored controls. Lactic acid applied pre- and poststorage (126 days) at 30EF reduced APCs of steak s up to 2 log (99%). L. monocytogenes and Salmonella spp. were absent from all steaks. Lactic acid caused slightly more rapid color deterioration, resulting in slightly shorter display-life for steaks

Decontamination of beef carcasses and subprimal cuts

Lactic acid sprays effectively reduce the microbial load on both carcasses and subprimal cuts. Lactic acid decontamination of subprimals appears to carry through to retail cuts during display. Because of recontamination during fabrication, treating subprimals may be more effective than treating carcasses. This information will allow us to identify the most critical control points at which to employ decontamination practices designed to reduce the incidence of pathogenic bacteria and extend shelf life