Magazine Media Challenges

Moderator: Samir Mr. Magazine ™ Husni, Founder and Director, Magazine Innovation Center Linda Thomas Brooks: President & CEO, MPA: The Association of Magazine Media James Hewes: President & CEO, FIPP Jerry Lynch: President, Magazine & Books Retail Association Michael Marchesano: Managing Director, Connectiv/SIIA/AM&

N-[(2-Chloro-3-quinol­yl)meth­yl]-4-fluoro­aniline

In the title compound, C16H12ClFN2, the dihedral angle between the quinoline ring system and the flourophenyl ring is 86.70 (4)°. In the crystal, mol­ecules are linked into chains along the a axis by N—H⋯N hydrogen bonds. In addition, C—H⋯π inter­actions involving the two benzene rings are observed

Radiation and Health Technology Laboratory Capabilities

The Radiological Standards and Calibrations Laboratory, a part of Pacific Northwest National Laboratory (PNNL)(a) performs calibrations and upholds reference standards necessary to maintain traceability to national standards. The facility supports U.S. Department of Energy (DOE) programs at the Hanford Site, programs sponsored by DOE Headquarters and other federal agencies, radiological protection programs at other DOE and commercial nuclear sites and research and characterization programs sponsored through the commercial sector. The laboratory is located in the 318 Building of the Hanford Site's 300 Area. The facility contains five major exposure rooms and several laboratories used for exposure work preparation, low-activity instrument calibrations, instrument performance evaluations, instrument maintenance, instrument design and fabrication work, thermoluminescent and radiochromic Dosimetry, and calibration of measurement and test equipment (M&TE). The major exposure facilities are a low-scatter room used for neutron and photon exposures, a source well room used for high-volume instrument calibration work, an x-ray facility used for energy response studies, a high-exposure facility used for high-rate photon calibration work, a beta standards laboratory used for beta energy response studies and beta reference calibrations and M&TE laboratories. Calibrations are routinely performed for personnel dosimeters, health physics instrumentation, photon and neutron transfer standards alpha, beta, and gamma field sources used throughout the Hanford Site, and a wide variety of M&TE. This report describes the standards and calibrations laboratory

Heat or Insulation: Behavioral Titration of Mouse Preference for Warmth or Access to a Nest

In laboratories, mice are housed at 20–24°C, which is below their lower critical temperature (≈30°C). This increased thermal stress has the potential to alter scientific outcomes. Nesting material should allow for improved behavioral thermoregulation and thus alleviate this thermal stress. Nesting behavior should change with temperature and material, and the choice between nesting or thermotaxis (movement in response to temperature) should also depend on the balance of these factors, such that mice titrate nesting material against temperature. Naïve CD-1, BALB/c, and C57BL/6 mice (36 male and 36 female/strain in groups of 3) were housed in a set of 2 connected cages, each maintained at a different temperature using a water bath. One cage in each set was 20°C (Nesting cage; NC) while the other was one of 6 temperatures (Temperature cage; TC: 20, 23, 26, 29, 32, or 35°C). The NC contained one of 6 nesting provisions (0, 2, 4, 6, 8, or 10g), changed daily. Food intake and nest scores were measured in both cages. As the difference in temperature between paired cages increased, feed consumption in NC increased. Nesting provision altered differences in nest scores between the 2 paired temperatures. Nest scores in NC increased with increasing provision. In addition, temperature pairings altered the difference in nest scores with the smallest difference between locations at 26°C and 29°C. Mice transferred material from NC to TC but the likelihood of transfer decreased with increasing provision. Overall, mice of different strains and sexes prefer temperatures between 26–29°C and the shift from thermotaxis to nest building is seen between 6 and 10 g of material. Our results suggest that under normal laboratory temperatures, mice should be provided with no less than 6 grams of nesting material, but up to 10 grams may be needed to alleviate thermal distress under typical temperatures

Response of the thermohaline circulation to cold climates

A coupled atmosphere-ocean-sea ice-land surface-ice sheet model of intermediate complexity, the so-called McGill Paleoclimate Model, is employed to study the response of the thermohaline circulation (THC) to various global climate coolings, which are realized by increasing the present-day planetary emissivity to various values. Generally, it is found that the response of the THC to global cooling is nonlinear: For a slightly cold climate the THC in the North Atlantic and the Pacific upwelling become intensified. For a very cold climate the THC in the North Atlantic may be weakened or even collapsed. The associated Pacific upwelling for a very cold climate also becomes weak when the THC is weakened, and intermediate deep water may form in the Pacific when the THC is collapsed. Some support for this nonlinear response is found in recent paleoceanographic data. The reduced atmospheric poleward moisture transport due to the global cooling is mainly responsible for the intensification of the THC in the North Atlantic for a slightly cold climate. For a very cold climate the global cooling may lead to a decrease of the meridional surface density gradient and an increase of the vertical density difference (lower layer density minus upper layer density) in the deep water formation region, which can weaken or shut down the THC. It is the temperature-dependent part of the density differences that is mainly responsible for the weakening or shutting down of the THC. The potential influence of surface temperature changes must be taken into account for a full understanding of the role of the THC in the climate system

Polymorphisms, Mutations, and Amplification of the EGFR Gene in Non-Small Cell Lung Cancers

Masaharu Nomura and colleagues examine the distribution ofEGFR polymorphisms in different populations and find differences that might explain different responses to tyrosine kinase inhibitors in lung cancer patients

Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

Introduction Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. Methods Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. Results Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors

Energy Reallocation to Breeding Performance through Improved Nest Building in Laboratory Mice.

Mice are housed at temperatures (20-26°C) that increase their basal metabolic rates and impose high energy demands to maintain core temperatures. Therefore, energy must be reallocated from other biological processes to increase heat production to offset heat loss. Supplying laboratory mice with nesting material may provide sufficient insulation to reduce heat loss and improve both feed conversion and breeding performance. Naïve C57BL/6, BALB/c, and CD-1breeding pairs were provided with bedding alone, or bedding supplemented with either 8g of Enviro-Dri, 8g of Nestlets, for 6 months. Mice provided with either nesting material built more dome-like nests than controls. Nesting material improved feed efficiency per pup weaned as well as pup weaning weight. The breeding index (pups weaned/dam/week) was higher when either nesting material was provided. Thus, the sparing of energy for thermoregulation of mice given additional nesting material may have been responsible for the improved breeding and growth of offspring

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci.We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)).We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.National Heart, Lung and Blood Institute R01-HL095393 R01-HL097163 P01-HL092870 RC2-HL101715 U01-HL089897 U01-HL089856 U01-HL108642 P50-HL089493

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary