Fall Migration of Ringed Seals (Phoca hispida) through the Beaufort and Chukchi Seas, 2001–02

In a study examining the range, distribution, and habitat use of the ringed seal, Phoca hispida, in Canada’s Western Arctic, eight ringed seals were live-captured, instrumented with satellite-linked (SLTDR-16) transmitters, and released at Cape Parry, Northwest Territories, Canada, on 17 – 19 September 2001 and 7 – 8 September 2002. Locations accepted by the filtering process were received from seven of the eight tagged seals (5 subadults, 1 adult female, 1 pup) over periods ranging from 35 to 207 days (mean 99 d, SD 66). Mean rates of travel were 0.91 m/s (SE 0.011, n = 7) in the Canadian Beaufort Sea, 0.92 m/s (SE 0.014, n = 7) offshore of Alaska’s North Slope, and 0.79 m/s (SE 0.008, n = 5) in the Chukchi Sea. On average, the seals took 32 days (range 19 – 56 d) to migrate between Cape Parry and Point Barrow, almost always remaining within 100 km of shore and over the continental shelf or slope, and covering an average migration distance of 2138 km. Dive depths for all groupings were mainly in the 4 – 80 m range (adult female: 63 – 73%; subadults: 54 – 73%; pup: 64 – 82%), with only the adult female diving deeper than 80 m on occasion, mainly in the Canadian Beaufort Sea (15.1% of her dives). The subadults and pup dove mainly for more than 1 to 5 min (60% and 55%, respectively), while a large proportion of the adult female’s dives were longer (34% for > 1 to 5 min; 31% for > 5 to 8 min; 5.4% for > 8 min). The tracks of the westward migrating seals revealed a routing through three political jurisdictions (including oil and gas industry lease areas in all three) over a period of about two months. This pattern highlights the importance of cooperation between the United States, Canada, and Russia in managing this species.Du 17 au 19 septembre 2001 et les 7 et 8 septembre 2002, dans le cadre d’une étude portant sur le parcours, la répartition et l’utilisation de l’habitat du phoque annelé, Phoca hispida, dans l’ouest de l’Arctique canadien, huit phoques annelés ont été capturés en vie, dotés de transmetteurs en liaison avec un satellite (SLTDR-16), puis relâchés au cap Parry, dans les Territoires du Nord-Ouest, au Canada. Des emplacements acceptés par filtrage ont été reçus de la part de sept des huit phoques marqués (5 préreproducteurs, 1 femelle adulte, 1 jeune) sur des périodes variant entre 35 et 207 jours (moyenne 99 d, SD 66). Les taux de déplacement moyens étaient de 0,91 m/s (SE 0,011; n = 7) dans la mer canadienne de Beaufort, de 0,92 m/s (SE 0,014; n = 7) au large du versant nord de l’Alaska et de 0,79 m/s (SE 0,008; n = 5) dans la mer des Tchouktches. En moyenne, la migration des phoques entre le cap Parry et la pointe Barrow durait 32 jours (écart de 19 à 56 d), et les phoques restaient presque toujours en-dedans de 100 km de la côte et au-dessus de la pente ou du plateau continental. Ils couvraient en moyenne une distance de migration de 2 138 km. La profondeur des plongées de tous les groupements variait entre 4 et 80 m (femelle adulte : 63 % à 73 %; préreproducteurs : 54 % à 73 %; jeune : 64 % à 82 %), et seulement la femelle adulte plongeait à plus de 80 m de profondeur à l’occasion, surtout dans la mer canadienne de Beaufort (15,1 % de ses plongées). Les prérepro­ducteurs et le jeune phoque étaient principalement en plongée pendant plus de 1 à 5 min (60 % et 55 %, respectivement), tandis qu’une grande proportion des plongées de la femelle adulte durait plus longtemps (34 % pour > 1 à 5 min; 31 % pour > 5 à 8 min; 5,4 % pour > 8 min). Les pistes des phoques en migration vers l’ouest révélaient des itinéraires passant par trois compétences politiques (comprenant des concessions de l’industrie pétrolière et gazière dans les trois cas) sur une période d’environ deux mois. Cette tendance fait ressortir l’importance d’une collaboration entre les États-Unis, le Canada et la Russie en matière de gestion de cette espèce

PkANN - I. Non-linear matter power spectrum interpolation through artificial neural networks

We investigate the interpolation of power spectra of matter fluctuations using Artificial Neural Network (PkANN). We present a new approach to confront small-scale non-linearities in the power spectrum of matter fluctuations. This ever-present and pernicious uncertainty is often the Achilles' heel in cosmological studies and must be reduced if we are to see the advent of precision cosmology in the late-time Universe. We show that an optimally trained artificial neural network (ANN), when presented with a set of cosmological parameters (Omega_m h^2, Omega_b h^2, n_s, w_0, sigma_8, m_nu and redshift z), can provide a worst-case error <=1 per cent (for z<=2) fit to the non-linear matter power spectrum deduced through N-body simulations, for modes up to k<=0.7 h/Mpc. Our power spectrum interpolator is accurate over the entire parameter space. This is a significant improvement over some of the current matter power spectrum calculators. In this paper, we detail how an accurate interpolation of the matter power spectrum is achievable with only a sparsely sampled grid of cosmological parameters. Unlike large-scale N-body simulations which are computationally expensive and/or infeasible, a well-trained ANN can be an extremely quick and reliable tool in interpreting cosmological observations and parameter estimation. This paper is the first in a series. In this method paper, we generate the non-linear matter power spectra using HaloFit and use them as mock observations to train the ANN. This work sets the foundation for Paper II, where a suite of N-body simulations will be used to compute the non-linear matter power spectra at sub-per cent accuracy, in the quasi-non-linear regime 0.1 h/Mpc <= k <= 0.9 h/Mpc. A trained ANN based on this N-body suite will be released for the scientific community.Comment: 12 pages, 9 figures, 2 tables, updated to match version accepted by MNRA

Seasonal Movements and Diving of Ringed Seals, Pusa hispida, in the Western Canadian Arctic, 1999–2001 and 2010–11

Satellite-linked time-depth recorders were deployed on 17 ringed seals in early summer in 1999, 2000, and 2010, near the Inuvialuit community of Ulukhaktok, Northwest Territories, Canada. The main objective was to investigate movements and diving behaviour of ringed seals in the Prince Albert Sound (PAS) and eastern Amundsen Gulf (EAG) regions in relation to season, sex, and age-class. Tags performed well on 16 of 17 tagged seals, with average tracking periods of 256 d (SD 69, range: 134 – 352). Adult and subadult ringed seals traveled considerable distances throughout the open water period (mean = 5844 km, range = 1232 – 9473 km), using vast home ranges during this season, shown with 90 Percent Volume Contours (90 PVC) averaging 122 854 km2 for subadults, 76 658 km2 for adult females, and 21 649 km2 for adult males. Overall, adults spent 69.5% of the observed open water days in foraging/resident mode and 22.8% in traveling mode. The majority (75%) of total observed foraging/resident time was spent in PAS and EAG. Eleven of 12 adults made forays outside EAG and PAS to distant areas, including Prince of Wales Strait (7 seals), Viscount Melville Sound (6), Minto Inlet (4), western Amundsen Gulf (4), and six other zones. During open water season, subadults spent 36.8% traveling and 51.4% foraging/ resident, also mainly in EAG and PAS (61%), but they all traveled to distant zones, eight in total. During winter, all tagged adult females, five of seven adult males, and three of four subadults returned to PAS and EAG to occupy winter home ranges that were on average 15% of the size of the open water home range (mean winter ranges = 1299 km2 for adult males, 3599 km2 for adult females, and 30 499 km2 for subadults). The mean size of the winter home ranges varied by as much as a factor of 10 among the three winters examined. Seal movements were most restricted during the winters with extensive fast ice (1999 – 2000 and 2010 – 11) and least restricted during the winter (2000 – 01) when fast ice did not form in EAG. In winter, adult females made more long, deep dives than either adult males or subadults.Des enregistreurs de profondeur temporelle en liaison avec un satellite ont été déployés sur 17 phoques annelés au début des étés 1999, 2000 et 2010 près de la collectivité inuvialuite d’Ulukhaktok, dans les Territoires du Nord-Ouest, au Canada. L’objectif principal consistait à étudier les déplacements et les comportements de plongée des phoques annelés des régions du détroit de Prince-Albert (DPA) et de la partie est du golfe Amundsen (EGA) en fonction de la saison, du sexe et de la classe d’âge. Les étiquettes ont donné des résultats valables dans le cas de 16 des 17 phoques étiquetés, les périodes moyennes de pistage ayant atteint 256 jours (SD 69, étendue : 134 – 352). Les phoques annelés adultes et jeunes adultes parcouraient des distances considérables pendant la période des eaux libres (moyenne = 5 844 km, étendue = 1 232 – 9 473 km), dans de vastes domaines vitaux au cours de la saison. Les pourcentages du volume des contours de 90 (90 PVC) s’établissaient en moyenne à 122 854 km2 pour les jeunes adultes, à 76 658 km2 pour les femelles adultes et à 21 649 km2 pour les mâles adultes. Dans l’ensemble, les adultes ont passé 69,5 % des journées observées en eaux libres en mode d’alimentation et de résidence, et 22,8 % en mode de déplacement. La majorité (75 %) du temps total observé en mode d’alimentation et de résidence était dans le DPA et l’EGA. Onze adultes sur 12 se sont aventurés en dehors du DPA et de l’EGA pour atteindre des endroits éloignés, dont le détroit du Prince-de-Galles (7 phoques), le détroit du Vicomte de Melville (6), l’anse Mintot (4), l’ouest du golfe Amundsen (4) et six autres zones. Pendant la saison des eaux libres, les jeunes adultes ont passé 36,8 % du temps en mode de déplacement et 51,4 % du temps en mode d’alimentation ou de résidence, également principalement dans le DPG et l’EGA (61 %), mais ils se sont tous rendus dans des zones éloignées, huit en tout. Durant l’hiver, toutes les femelles adultes étiquetées, cinq mâles adultes sur sept et trois jeunes adultes sur quatre sont revenus dans le DPA et l’EGA pour occuper des domaines vitaux hivernaux qui correspondaient, en moyenne, à 15 % de la taille du domaine vital en eaux libres (étendues moyennes des domaines hivernaux = 1 299 km2 pour les mâles adultes, 3 599 km2 pour les femelles adultes et 30 499 km2 pour les jeunes adultes). La taille moyenne des domaines vitaux hivernaux a varié en fonction d’un facteur de 10 au cours des trois hivers à l’étude. Le déplacement des phoques était plus restreint pendant les hivers où la glace était rapide (1999-2000 et 2010-2011) et moins restreint pendant l’hiver (2000-2001) où la glace rapide ne s’est pas formée dans l’EGA. L’hiver, les femelles adultes faisaient plus de plongées longues et profondes que les mâles adultes ou les jeunes adultes

2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase

Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described.National Human Genome Research Institute (U.S.) (Molecular Libraries Initiative of the NIH Roadmap for Medical Research

A Drosophila Model of HPV E6-Induced Malignancy Reveals Essential Roles for Magi and the Insulin Receptor

We would like to thank Drs. Vivian Budnik, Herbert Jäckle, Larry Reiter, Andreas Wodarz, for generously providing reagents, the Bloomington Drosophila Stock Center, and the Confocal facility at University of Oklahoma (supported by a Major Research Instrumentation grant DBI-1126578 from the National Science Foundation to B. Zhang, R. Hewes, B. Holt, D. McCauley, and M. Nanny) for the use of the confocal microscope. We also thank Dr. David McCauley and Dr. Randall Hewes for discussions and sharing equipment. We thank the Developmental Studies Hybridoma Bank (University of Iowa, Department of Biology, Iowa City) for antibodies.Author Summary Human papillomaviruses (HPV) are the causative agents of cervical cancer, one of the leading causes of cancer death in women worldwide. The E6 oncoprotein encoded by HPV has been implicated in the progression of primary tumors to metastatic disease and we have developed a new model in the fruit fly (Drosophila melanogaster) to study the cellular effects of E6. The E6 protein recruits an E3 ubiquitin ligase (UBE3A) to induce the degradation of a number of cellular proteins, including members of the MAGUK family of scaffolding proteins that control the structure and polarity of epithelial cells: Dlg, Scribble and Magi. Expression of E6 and human UBE3A in the wing and eye of Drosophila disrupted these tissues. Similar to human cells we found that Drosophila Magi was a major E6 degradation target and that overexpression of Magi rescued the tissue disruption. However, Drosophila p53 was not degraded by E6/UBE3A, making our fly model potentially useful for studying the p53-independent activities of the E6+UBE3A complex. When we paired E6 expression with oncogenic proteins, including activated Ras, we observed that epithelia were transformed into mesechymal-like cells that left the epithelium and spread through the body. As a test of the potential of our system, we carried out a pilot genetic screen and identified the insulin receptor as a strong modulator of the E6-mediated disruption of Drosophila tissues. Therefore, we have developed a new system and approach to help us better understand the mechanisms that underlie how HPV infection leads to cell transformation and cancer.Yeshttp://www.plospathogens.org/static/editorial#pee

Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315

Substituted pyrimidine inhibitors of the Clk and Dyrk kinases have been developed, exploring structure-activity relationships around four different chemotypes. The most potent compounds have low-nanomolar inhibitory activity against Clk1, Clk2, Clk4, Dyrk1A and Dyrk1B. Kinome scans with 442 kinases using agents representing three of the chemotypes show these inhibitors to be highly selective for the Clk and Dyrk families. Further off-target pharmacological evaluation with ML315, the most selective agent, supports this conclusion

Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses

Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys[superscript 358]. This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys[superscript 358] to Ser[superscript 358] oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.National Institutes of Health (U.S.) (R03MH085679)National Institutes of Health (U.S.) (1P30CA147882)Burroughs Wellcome FundDamon Runyon Cancer Research FoundationSmith Family FoundationStarr Cancer Consortiu

Bayesian analysis of weak gravitational lensing and Sunyaev-Zel'dovich data for six galaxy clusters

We present an analysis of observations made with the Arcminute Microkelvin Imager (AMI) and the Canada-France-Hawaii Telescope (CFHT) of six galaxy clusters in a redshift range of 0.16--0.41. The cluster gas is modelled using the Sunyaev--Zel'dovich (SZ) data provided by AMI, while the total mass is modelled using the lensing data from the CFHT. In this paper, we: i) find very good agreement between SZ measurements (assuming large-scale virialisation and a gas-fraction prior) and lensing measurements of the total cluster masses out to r_200; ii) perform the first multiple-component weak-lensing analysis of A115; iii) confirm the unusual separation between the gas and mass components in A1914; iv) jointly analyse the SZ and lensing data for the relaxed cluster A611, confirming our use of a simulation-derived mass-temperature relation for parameterizing measurements of the SZ effect.Comment: 22 pages, 12 figures, 12 tables, published by MNRA