ATG proteins mediate efferocytosis and suppress inflammation in mammary involution.

Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1(+/-) and Atg7-deficient mammary epithelial cells (MECs) produced 'competent' apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment. Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance

Hydrological Parameter Estimations from a Conservative Tracer Test with Variable-Density Effects at the Boise Hydrogeophysical Research Site

Reliable predictions of groundwater flow and solute transport require an estimation of the detailed distribution of the parameters (e.g., hydraulic conductivity, effective porosity) controlling these processes. However, such parameters are difficult to estimate because of the inaccessibility and complexity of the subsurface. In this regard, developments in parameter estimation techniques and investigations of field experiments are still challenging and necessary to improve our understanding and the prediction of hydrological processes. Here we analyze a conservative tracer test conducted at the Boise Hydrogeophysical Research Site in 2001 in a heterogeneous unconfined fluvial aquifer. Some relevant characteristics of this test include: variable-density (sinking) effects because of the injection concentration of the bromide tracer, the relatively small size of the experiment, and the availability of various sources of geophysical and hydrological information. The information contained in this experiment is evaluated through several parameter estimation approaches, including a grid-search-based strategy, stochastic simulation of hydrological property distributions, and deterministic inversion using regularization and pilot-point techniques. Doing this allows us to investigate hydraulic conductivity and effective porosity distributions and to compare the effects of assumptions from several methods and parameterizations. Our results provide new insights into the understanding of variable-density transport processes and the hydrological relevance of incorporating various sources of information in parameter estimation approaches. Among others, the variable-density effect and the effective porosity distribution, as well as their coupling with the hydraulic conductivity structure, are seen to be significant in the transport process. The results also show that assumed prior information can strongly influence the estimated distributions of hydrological properties

Voice, plumage and natural history of Anthony's Nightjar (Caprimulgus anthonyi)

This is the published version. Copyright Central Ornithology Publication Offic

Implementation of an Online Database for Chemical Propulsion Systems

The Johns Hopkins University, Chemical Propulsion Information Analysis Center (CPIAC) has been working closely with NASA Goddard Space Flight Center (GSFC); NASA Marshall Space Flight Center (MSFC); the University of Alabama at Huntsville (UAH); The Johns Hopkins University, Applied Physics Laboratory (APL); and NASA Jet Propulsion Laboratory (JPL) to capture satellite and spacecraft propulsion system information for an online database tool. The Spacecraft Chemical Propulsion Database (SCPD) is a new online central repository containing general and detailed system and component information on a variety of spacecraft propulsion systems. This paper only uses data that have been approved for public release with unlimited distribution. The data, supporting documentation, and ability to produce reports on demand, enable a researcher using SCPD to compare spacecraft easily, generate information for trade studies and mass estimates, and learn from the experiences of others through what has already been done. This paper outlines the layout and advantages of SCPD, including a simple example application with a few chemical propulsion systems from various NASA spacecraft

Increased bit rate direct modulation AMO-OFDM transmission by optical injection using monolithically integrated lasers

Experimental and simulation work, presented in this letter, demonstrates for the first time how the monolithic integration of two single-mode lasers in a master-slave configuration, can substantially increase the achievable bit rate of a direct modulation adaptively modulated optical orthogonal frequency-division multiplexing (AMO-OFDM) system. The Levin-Campello algorithm is applied to select the OFDM bit and power loading scheme used for each system configuration. Improvement in terms of data throughput due to injection is measured for several transmission distances with the improvement in performance presented in terms of error vector magnitude per OFDM subcarrier

Financial Development, Structure and Growth : New Data, Method and Results

The existing weight of evidence suggests that financial structure (the classification of a financial system as bank-based versus market-based) is irrelevant for economic growth. This contradicts the common belief that the institutional structure of a financial system matters. We re-examine this issue using a novel dataset covering 69 countries over 1989-2011 in a Bayesian framework. Our results are conformable to the belief - a market-based system is relevant - with sizable economic effects for the high-income but not for the middle-and-low-income countries. Our findings provide a counterexample to the weight of evidence. We also identify a regime shift in 2008.JEL Classification Codes: G0, O4, O16http://www.grips.ac.jp/list/jp/facultyinfo/leon_gonzalez_roberto

Simulation of a ship advancing in floating ice floes

The effect of global warming is inducing sea ice retreat and transforming the Arctic into a navigable ocean. The melted ice cover can result in an environment where pancake-shaped ice floes are floating on sea surface; however, the effect of such an ice condition on ship performance has yet to be understood. This work develops a numerical model to predict the ship resistance in this typical case. Building on a traditional computational model for predicting ship hydrodynamics in open ocean, the Discrete Element Method is incorporated to include ice floes, so as to achieve ship-wave-ice coupling; thus, the simulation innovatively considers the influence of fluid flow on the interaction process. Following validation against experiments, the proposed model has been shown capable of accurately predicting ship resistance in pancake ice condition. Subsequently, the relationship of the resistance with ship speed, ice concentration and floe size is investigated

The BBC, Austerity and Broadcasting the 1948 Olympic Games

Based on original archive research, including papers held in the BBC Written Archives Centre, and interviews with those involved, this paper analyses the historical importance for the BBC of the 1948 Games as the first publicly televised Olympics. In particular, the paper addresses the management of operations by the Head of Outside Broadcasting at the BBC, Seymour Joly de Lotbiniere. De Lotbiniere had been an important figure in the development of outside broadcasting commentaries during the inter-war period and was given the task of organising the radio and television coverage of the London Games in 1948. The paper examines the technical, operational and ideological issues raised by the event for the BBC and its legacy for the development of live televised outside broadcasts from sport. The analysis suggests the BBC’s ability to host international broadcasters became a matter of prestige and its forays into television a sign of its emerging post-War modernity

Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype

BACKGROUND: MMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early lineage markers and many myoepithelial cells. The occurrence of tumors is accelerated in experiments that activate FGF proto-oncogenes or remove the tumor suppressor genes Pten or P53, implying that secondary oncogenic events are required for progression from mammary hyperplasia to carcinoma. It is not known, however, which oncogenic pathways contribute to Wnt1-induced tumorigenesis – further experimental manipulation of these mice is needed. Secondary events also appear to be required for mammary tumorigenesis in MMTV-Neu transgenic mice because the transgene in the tumors usually contains an acquired mutation that activates the Neu protein-tyrosine kinase. METHODS: cDNA or DNA from the mammary glands and mammary tumors from MMTV-Wnt1, MMTV-Wnt1/p53(-/-), MMTV-Neu transgenic mice, and newly generated MMTV-Wnt1/MMTV-Neu bitransgenic mice, was sequenced to seek activating mutations in H-Ras, K-Ras, and N-Ras genes, or in the MMTV-Neu transgene. In addition, tumors from bitransgenic animals were examined to determine the cellular phenotype. RESULTS: We found activating mutations at codons 12, 13, and 61 of H-Ras in just over half of the mammary tumors in MMTV-Wnt1 transgenic mice, and we confirmed the high frequency of activating mutations of Neu in tumors in MMTV-Neu transgenic mice. Tumors appeared earlier in bitransgenic MMTV-Wnt1/MMTV-Neu mice, but no Ras or MMTV-Neu mutations were found in these tumors, which were phenotypically similar to those arising in MMTV-Wnt1 mice. In addition, no Ras mutations were found in the mammary tumors that arise in MMTV-Wnt1 transgenic mice lacking an intact P53 gene. CONCLUSIONS: Tumorigenic properties of cells undergoing functionally significant secondary mutations in H-Ras or the MMTV-Neu transgene allow selection of those cells in MMTV-Wnt1 and MMTV-Neu transgenic mice, respectively. Alternative sources of oncogenic potential, such as a second transgenic oncogene or deficiency of a tumor suppressor gene, can obviate the selective power of those secondary mutations. These observations are consistent with the notion that somatic evolution of mouse mammary tumors is influenced by the specific nature of the inherited cancer-promoting genotype