Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Effects of compressibility and heat release on entrainment processes in mixing layers

Characteristics of the process of entrainment in plane mixing layers, and the changes with compressibility and heat release, were studied using temporal DNS with simultaneous fluid packet tracking. Convective Mach numbers of the simulations are 0.15, 0.7 and 1.1. The Reynolds number is quite high (between 11 000 and 37 000 based on layer width and velocity difference), and is above the mixing transition. The study agrees with recent findings in round jets: first, engulfed fluid volume and its growth rate are both very small compared with the volume of the turbulent region and its growth rate, respectively. Secondly, most often, the process occurs close to the turbulent-nonturbulent boundaries. A new finding is that both compressibility and heat release retard the entrainment process so that it takes an O(1) time for vorticity or scalar levels to grow even after growth has been initiated. This delay is manifested as the fall in mixing layer growth rates as compressibility and heat release levels increase.

Paluu paratiisiin : Polkuja hyvän ja pahan tuolle puolen Martti Lutherin ja Friedrich Nietzschen perinteissä

Tutkimukseni tarkoitus on paikallistaa polkuja hyvän ja pahan tuolle puolen. Tutkimukseni termit hyvä ja paha määrittyvät moraalisesti. Täten tutkimusaiheeni on ihmisen ja moraalin välinen suhde. Tutkin ihmisen moraalista olotilaa, siinä tapahtuvaa muutosta ja tämän muutoksen ehtoja. Tutkimuksellani on kaksi pääkysymystä: kuinka on mahdollista päästä hyvän ja pahan tuolle puolen ja miksi meidän tulisi siirtyä hyvän ja pahan tuolle puolen. Polut hyvän ja pahan tuolle puolen vievät myös etiikan tuolle puolen. Tutkimukseni pyrkii selvittämään mitä vikaa etiikassa on ja kuinka on mahdollista perustella toimintaa ilman etiikkaa. Tutkimukseni metodi on systemaattinen analyysi. Johdanto-osassa käsittelen yleisesti moraalia, sen vaikutuspiiriä ja niitä syitä, joiden vuoksi se täytyy hylätä. Tarkastelen myös etiikkaa ja selvitän sitä laajempaa kontekstia mihin se liittyy. Ensimmäisessä luvussa käsittelen Martti Lutherin teologiaa. Lutherilla moraalia edustaa Jumalan laki, jonka alaisuudesta kristitty pääsee vapaaksi kun Jeesus ottaa ristinkuolemassaan ihmisten synnin itselleen ja kärsii Jumalan lain mukaisen kuolemanrangaistuksen. Uskon yhteydessä Kristukseen kristitty kohoaa lain ulkopuolelle tekemään rakkauden tekoja. Toinen luku on omistettu Søren Kierkegaardin kristilliselle eksistentialismille. Kierkegaardin eksistenssitasojen filosofiassa uskonnollinen olemisen taso paljastuu korkeammaksi kuin eettinen. Tässä nousee tärkeäksi Kierkegaardin kirja Pelko ja vavistus. Kierkegaard tutkii Raamatun kertomusta Aabrahamista, jolle Jumala antaa käskyn uhrata oma poikansa Iisak. Kierkegaardille tarina on esimerkki eettistä korkeammasta ja sitä tilapäisesti vastustavasta olemisen tavasta. Kolmannessa luvussa käsittelen Dietrich Bonhoefferin teologiaa. Bonhoefferin mukaan Jeesus kutsuu ihmisiä seuraamaan häntä. Tämä on kutsu hyvän ja pahan tuolle puolen paratiisin viattomuuteen, joka rikkoo eettisyyden ihmisen ja Jeesuksen välillä. Neljännessä luvussa tarkastelen Friedrich Nietzschen filosofiaa ja pyrin ymmärtämään mitä hänen ohjelmansa hyvän ja pahan tuolle puolen tarkoittaa. Nietzschen vallantahdon filosofiassa moraali on heikkojen keino alistaa vahvat. Tarkastelen Nietzschen käsitystä moraalin synnystä ja sen haitallisuudesta ja pyrin selvittämään kuinka herrat elävät hyvän ja pahan tuolla puolen. Viidennessä luvussa tutkin Jaques Derridan grammatologiaa. Derridan mukaan teksti on suljettu tila, jonka ulkopuolelle on mahdoton päästä. Derrida sanoittaa kuitenkin sanoittamatonta tilattomuutta tekstin tuolla puolen. Tästä ei-paikasta käsin hypereettinen dekonstruktio purkaa perinteistä etiikkaa. Kuudennessa luvussa tarkastelen Mark C. Taylorin epä/teologiaa. Taylorille olotilan muutosta kuvaa termi harhautuminen , joka vie ihmisen lainsuojattomuuteen hyvän ja pahan tuolle puolen. Selvitän mitä harhautuminen tarkoittaa ja miten se liittyy Taylorin Jumalan kuoleman epä/teologiaan. Johtopäätösluvussa tuon esiin tutkimustuloksia, nostan esille joitain pääluvuissa esiintyviä teemoja ja vertaan tutkimuskohteitteni näkemyksiä toisiinsa. Lutherin ja Nietzschen perinteissä on paljon yhteistä, mutta pohjimmiltaan ne sotivat toisiaan vastaan. Hyvän ja pahan tuolle puolen johtaa kaksi polkua. Toinen niistä vie paratiisiin, toinen tuhoon.

Lattice vibrations and specific heat of zinc blende

The dispersion relations, frequency distribution function and specific heat of zinc blende have been calculated using Houston's method on (1) A short range force (S. R.) model of the type employed in diamond by Smith and (2) A long range model assuming an effective charge Ze on the ions. Since the elastic constant data on ZnS are not in agreement with one another the following values were used in these calculations: {Mathematical expression}. As compared to the results on the S. R. model, the Coulomb force causes 1. A splitting of the optical branches at (000) and a larger dispersion of these branches; 2. A rise in the acoustic frequency branches the effect being predominant in a transverse acoustic branch along [110]; 3. A bridging of the gap of forbidden frequencies in the S. R. model; 4. A reduction of the moments of the frequency distribution function and 5. A flattening of the Θ- T curve. By plotting (Θ/Θ0) vs. T., the experimental data of Martin and Clusius and Harteck are found to be in perfect coincidence with the curve for the short range model. The values of the elastic constants deduced from the ratio Θ0 (Theor)/Θ0 (Expt) agree with those of Prince and Wooster. This is surprising as several lines of evidence indicate that the bond in zinc blende is partly covalent and partly ionic. The conclusion is inescapable that the effective charge in ZnS is a function of the wave vector {Mathematical expression}.

Bilateral smoothing of gradient vector field and application to image segmentation

Medical image segmentation finds application in computer-aided diagnosis, computer-guided surgery, measuring tissue volumes, locating tumors, and pathologies. One approach to segmentation is to use active contours or snakes. Active contours start from an initialization (often manually specified) and are guided by image-dependent forces to the object boundary. Snakes may also be guided by gradient vector fields associated with an image. The first main result in this direction is that of Xu and Prince, who proposed the notion of gradient vector flow (GVF), which is computed iteratively. We propose a new formalism to compute the vector flow based on the notion of bilateral filtering of the gradient field associated with the edge map - we refer to it as the bilateral vector flow (BVF). The range kernel definition that we employ is different from the one employed in the standard Gaussian bilateral filter. The advantage of the BVF formalism is that smooth gradient vector flow fields with enhanced edge information can be computed noniteratively. The quality of image segmentation turned out to be on par with that obtained using the GVF and in some cases better than the GVF.

Electronic structure origin of conductivity and oxygen reduction activity changes in low-level Cr-substituted (La, Sr)MnO3

The electronic structure of the (La0.8Sr0.2)(0.98)Mn1-xCrxO3 model series (x = 0, 0.05, or 0.1) was measured using soft X-ray synchrotron radiation at room and elevated temperature. O K-edge near-edge X-ray absorption fine structure (NEXAFS) spectra showed that low-level chromium substitution of (La, Sr)MnO3 resulted in lowered hybridisation between O 2p orbitals and M 3d and M 4sp valance orbitals. Mn L-3-edge resonant photoemission spectroscopy measurements indicated lowered Mn 3d-O 2p hybridisation with chromium substitution. Deconvolution of O K-edge NEXAFS spectra took into account the effects of exchange and crystal field splitting and included a novel approach whereby the pre-peak region was described using the nominally filled t(2g) up arrow state. 10% chromium substitution resulted in a 0.17 eV lowering in the energy of the t(2g) up arrow state, which appears to provide an explanation for the 0.15 eV rise in activation energy for the oxygen reduction reaction, while decreased overlap between hybrid O 2p-Mn 3d states was in qualitative agreement with lowered electronic conductivity. An orbital-level understanding of the thermodynamically predicted solid oxide fuel cell cathode poisoning mechanism involving low-level chromium substitution on the B-site of (La, Sr)MnO3 is presented. (C) 2015 AIP Publishing LLC.

Fabrication and electrical characteristics of carbon nanotube-based microcathodes for use in a parallel electron-beam lithography system

The development of the Nanolith parallel electron-beam writing head was discussed. The fabrication and electrical characteristics of carbon nanotube-based microcathodes for use in the lithographic system were described. The microcathode exhibited a peak current of 10.5 μA at 48 V when operated with a duty cycle of 0.5 percent.

Experimental Investigation Of Influence Of Interfacial Tension On Convection Of Two-Layer Immiscible Liquid

Benard-Marangoni convections of two-layer fluids heated from the bottom are investigated experimentally with a particle imagine velocimetry. The flows are visualized from the side, and various velocity fields near the onset of convection, such as three-layer vortex convective patterns, are observed when the depth ratio varies in a wide range. A new classification of the convective patterns is proposed with more detail than in previous studies. The analysis of the results indicates that the interface tension greatly influences the motion intensities of the bottom and top layers. The dimensionless wave number increases with the Bond number when the motion in the top layer is not more intense than that in the bottom layer, which agrees with the theoretical prediction.

PICES-GLOBEC International Program on Climate Change and Carrying Capacity: Report of 2001 BASS/MODEL, MONITOR and REX Workshops, and the 2002 MODEL/REX Workshop

Table of Contents [pdf, 0.22 Mb] Executive Summary [pdf, 0.31 Mb] Report of the 2001 BASS/MODEL Workshop [pdf, 0.65 Mb] To review ecosystem models for the subarctic gyres Report of the 2001 MONITOR Workshop [pdf, 0.7 Mb] To review ecosystem models for the subarctic gyres Workshop presentations: Sonia D. Batten PICES Continuous Plankton Recorder pilot project Phillip R. Mundy GEM (Exxon Valdez Oil Spill Trustee Council`s "Gulf Ecosystem Monitoring" initiative) and U.S. GOOS plans in the North Pacific Ron McLaren and Brian O`Donnell A proposal for a North Pacific Action group of the international Data Buoy Cooperation Panel Gilberto Gaxiola-Castrol and Sila Najera-Martinez The Mexican oceanographic North Pacific program: IMECOCAL Sydney Levitus Building global ocean profile and plankton databases for scientific research Report of the 2001 REX Workshop [pdf, 1.73 Mb] On temporal variations in size-at-age for fish species in coastal areas around the Pacific Rim Workshop presentations: Brian J. Pyper, Randall M. Peterman, Michael F. Lapointe and Carl J. Walters [pdf, 0.33 Mb] Spatial patterns of covariation in size-at-age of British Columbia and Alaska sockeye salmon stocks and effects of abundance and ocean temperature R. Bruce MacFarlane, Steven Ralston, Chantell Royer and Elizabeth C. Norton [pdf, 0.4 Mb] Influences of the 1997-1998 El Niño and 1999 La Niña on juvenile Chinook salmon in the Gulf of the Farallones Olga S. Temnykh and Sergey L. Marchenko [pdf, 0.5 Mb] Variability of the pink salmon sizes in relation with abundance of Okhotsk Sea stocks Ludmila A. Chernoivanova, Alexander N. Vdoven and D.V. Antonenko [pdf, 0.3 Mb] The characteristic growth rate of herring in Peter the Great Bay (Japan/East Sea) Nikolay I. Naumenko [pdf, 0.5 Mb] Temporal variations in size-at-age of the western Bering Sea herring Evelyn D. Brown [pdf, 0.45 Mb] Effects of climate on Pacific herring, Clupea pallasii, in the northern Gulf of Alaska and Prince William Sound, Alaska Jake Schweigert, Fritz Funk, Ken Oda and Tom Moore [pdf, 0.6 Mb] Herring size-at-age variation in the North Pacific Ron W. Tanasichuk [pdf, 0.3 Mb] Implications of variation in euphausiid productivity for the growth, production and resilience of Pacific herring (Clupea pallasi) from the southwest coast of Vancouver Island Chikako Watanabe, Ahihiko Yatsu and Yoshiro Watanabe [pdf, 0.3 Mb] Changes in growth with fluctuation of chub mackerel abundance in the Pacific waters off central Japan from 1970 to 1997 Yoshiro Watanabe, Yoshiaki Hiyama, Chikako Watanabe and Shiro Takayana [pdf, 0.35 Mb] Inter-decadal fluctuations in length-at-age of Hokkaido-Sakhalin herring and Japanese sardine in the Sea of Japan Pavel A. Balykin and Alexander V. Buslov [pdf, 0.4 Mb] Long-term variability in length of walley pollock in the western Bering Sea and east Kamchtka Alexander A. Bonk [pdf, 0.4 Mb] Effect of population abundance increase on herring distribution in the western Bering Sea Sergey N. Tarasyuk [pdf, 0.4 Mb] Survival of yellowfin sole (Limanda aspera Pallas) in the northern part of the Tatar Strait (Sea of Japan) during the second half of the 20th century Report of the 2002 MODEL/REX Workshop [pdf, 1.2 Mb] To develop a marine ecosystem model of the North Pacific Ocean including pelagic fishes Summary and Overview [pdf, 0.4 Mb] Workshop presentations: Bernard A. Megrey, Kenny Rose, Francisco E. Werner, Robert A. Klumb and Douglas E. Hay [pdf, 0.47 Mb] A generalized fish bioenergetics/biomass model with an application to Pacific herring Robert A. Klumb [pdf, 0.34 Mb] Review of Clupeid biology with emphasis on energetics Douglas E. Hay [pdf, 0.47 Mb] Reflections of factors affecting size-at-age and strong year classes of herring in the North Pacific Shin-ichi Ito, Yutaka Kurita, Yoshioki Oozeki, Satoshi Suyama, Hiroya Sugisaki and Yongjin Tian [pdf, 0.34 Mb] Review for Pacific saury (Cololabis saira) study under the VENFISH project lexander V. Leonov and Gennady A. Kantakov [pdf, 0.34 Mb] Formalization of interactions between chemical and biological compartments in the mathematical model describing the transformation of nitrogen, phosphorus, silicon and carbon compounds Herring group report and model results [pdf, 0.34 Mb] Saury group report and model results [pdf, 0.46 Mb] Model experiments and hypotheses Recommendations [pdf, 0.4 Mb] Achievements and future steps Acknowledgements [pdf, 0.29 Mb] References [pdf, 0.32 Mb] Appendix 1. List of Participants [pdf, 0.32 Mb] Appendices 2-5. FORTRAN codes [pdf, 0.4 Mb] (Document pdf contains 182 pages)

PICES-GLOBEC International Program on Climate Change and Carrying Capacity: Report of the 1999 MONITOR and REX Workshops, and the 2000 MODEL Workshop on Lower Trophic Level Modelling

Table of Contents [pdf, 0.11 Mb] Executive Summary [pdf, 0.07 Mb] MODEL Task Team Workshop Report Final Report of the International Workshop to Develop a Prototype Lower Trophic Level Ecosystem Model for Comparison of Different Marine Ecosystems in the North Pacific [pdf, 11.64 Mb] Report of the 1999 MONITOR Task Team Workshop [pdf, 0.32 Mb] Report of the 1999 REX Task Team Workshop Herring and Euphausiid population dynamics Douglas E. Hay and Bruce McCarter Spatial, temporal and life-stage variation in herring diets in British Columbia [pdf, 0.10 Mb] Augustus J. Paul and J. M. Paul Over winter changes in herring from Prince William Sound, Alaska [pdf, 0.08 Mb] N. G. Chupisheva Qualitative texture characteristic of herring (Clupea pallasi pallasi) pre-larvae developed from the natural and artificial spawning-grounds in Severnaya Bay (Peter the Great Bay) [pdf, 0.07 Mb] Gordon A. McFarlane, Richard J. Beamish and Jake SchweigertPacific herring: Common factors have opposite impacts in adjacent ecosystems [pdf, 0.15 Mb] Tokimasa Kobayashi, Keizou Yabuki, Masayoshi Sasaki and Jun-Ichi Kodama Long-term fluctuation of the catch of Pacific herring in Northern Japan [pdf, 0.39 Mb] Jacqueline M. O’Connell Holocene fish remains from Saanich Inlet, British Columbia, Canada [pdf, 0.40 Mb] Elsa R. Ivshina and Irina Y. Bragina On relationship between crustacean zooplankton (Euphausiidae and Copepods) and Sakhalin-Hokkaido herring (Tatar Strait, Sea of Japan) [pdf, 0.14 Mb] Stein Kaartvbeedt Fish predation on krill and krill antipredator behaviour [pdf, 0.08 Mb] Nikolai I. Naumenko Euphausiids and western Bering Sea herring feeding [pdf, 0.07 Mb] David M. Checkley, Jr. Interactions Between Fish and Euphausiids and Potential Relations to Climate and Recruitment [pdf, 0.08 Mb] Vladimir I. Radchenko and Elena P. Dulepova Shall we expect the Korf-Karaginsky herring migrations into the offshore western Bering Sea? [pdf, 0.75 Mb] Young Shil Kang Euphausiids in the Korean waters and its relationship with major fish resources [pdf, 0.29 Mb] William T. Peterson, Leah Feinberg and Julie Keister Ecological Zonation of euphausiids off central Oregon [pdf, 0.11 Mb] Scott M. Rumsey Environmentally forced variability in larval development and stage-structure: Implications for the recruitment of Euphausia pacifica (Hansen) in the Southern California Bight [pdf, 3.26 Mb] Scott M. Rumsey Inverse modelling of developmental parameters in Euphausia pacifica: The relative importance of spawning history and environmental forcing to larval stage-frequency distributions [pdf, 98.79 Mb] Michio J. Kishi, Hitoshi Motono & Kohji Asahi An ecosystem model with zooplankton vertical migration focused on Oyashio region [pdf, 33.32 Mb] PICES-GLOBEC Implementation Panel on Climate Change and Carrying Capacity Program Executive Committee and Task Team List [pdf, 0.05 Mb] (Document pdf contains 142 pages)

Abbildungen zur naturgeschichte brasiliens : herausgegeben Von Maximilian, Prinzen Von Wied-Neuwied = Recueil de Planches coloriées d'animaux Du Brésil / publie par S.A.S. le Prince Maximilien de Wied-Neuwied

Abbildungen zur naturgeschichte brasiliens é uma magnífica obra publicada em fascículos, cada um deles contendo seis lâminas e seis folhas de texto. As estampas, coloridas, foram gravadas em metal e o texto explicativo apresenta-se em alemão e francês. As gravuras representam espécies da fauna brasileira identificadas pelo autor durante a expedição científica que, juntamente com os naturalistas Georg Freyreiss e Friedrich Sellow, empreendeu ao brasil entre 1815 e 1817. Segundo Borba de Moraes trata-se de edição "muito rara nos dias de hoje".