Optimization of two-dimensional NMR by matched accumulation

It is well known that in the time-domain acquisition of NMR data, signal-to-noise (S/N) improves as the square root of the number of transients accumulated. However, the amplitude of the measured signal varies during the time of detection, having a functional form dependent on the coherence detected. Matching the time spent signal averaging to the expected amplitude of the signal observed should also improve the detected signal-to-noise. Following this reasoning, Barna et al. (J Magn. Reson.75, 384, 1987) demonstrated the utility of exponential sampling in one- and two-dimensional NMR, using maximum-entropy methods to analyze the data. It is proposed here that for two-dimensional experiments the exponential sampling be replaced by exponential averaging. The data thus collected can be analyzed by standard fast-Fourier-transform routines. We demonstrate the utility of exponential averaging in 2D NOESY spectra of the protein ubiquitin, in which an enhanced SIN is observed. It is also shown that the method acquires delayed double-quantum-filtered COSY without phase distortion.

Uso eficiente del nitrógeno por 16 líneas de sorgo en Nicaragua

El nitrógeno es uno de los factores que limita la producción del sorgo por su alta demanda y alto costo del fertilizante. Con el objetivo de evaluar distintos materiales de sorgo en Nicaragua, un experimento con 14 líneas de sorgo de ICRISAT, Jocoro de El Salvador y el testigo local Pinolero-1, se plantaron a cero y 37 kg N/ha en seis ambientes. Los ambientes eran combinaciones de localidad/año incluidos; El Plantel 2003 y 2004, CEO-Posoltega 2003 y 2004, y Tisma y San Isidro en 2004. Se utilizo un diseño de bloques completos al azar, los tratamientos se aleatorizaron en las parcelas. La línea se ubico en la parcela grande y el nivel de nitrógeno en las subparcelas. El rendi- miento de grano, rastrojo, concentración de N y extracción por grano y rastrojo, y el uso eficiente del N por grano y biomasa fueron deter- minados. Sin aplicación de N, ninguna línea de sorgo rindió mejor que Pinolero-1, mientras ICSVLM-93079 produjo 0.7 tm/ha más en grano con aplicación de N. Pinolero-1 obtuvo el uso eficiente de N más alto con 46 kg grano y 121 kg biomasa por unidad de N aplicado. ICSVLM-93079 presento la respuesta más alta en rendimiento con 35 kg N/ha. La aplicación de N aumentó el rendimiento de grano en 0.8 tm/ha y de rastrojo en 1.9 tm/ha. Los programas de mejoramiento de sorgo en Nicaragua, deben incluir ICSVLM-93079 para aumentar rendimiento de grano. Los productores deben usar el fertilizante N para aumentar rendimientos de grano y de rastrojo.

Evaluación del rendimiento de sorgo variedad CNIA-INTA bajo distintas fuentes de suministro del nitrógeno

Dada la importancia del cultivo de sorgo para pequeños y medianos productores nicaragüenses y su utilización para la producción de grano, la Universidad Nacional Agraria y el Programa INTSORMIL, desde el año 2000 evaluaron distintos materiales de sorgo. Después de tres años de resultados, se seleccionó la variedad CNIA-INTA por su buen rendimiento de grano para ser sometido a niveles bajos de fertilización (práctica del pequeño productor) y a un método alternativo que incluyen el uso de abono verde (Vigna radiata L.), como fuente de N. Con este propósito tres ensayos se establecieron en el ciclo de postrera del 2004. El primero en Tisma, Departamento de Masaya, el segundo en el Centro Experimental de Occidente (CEO) en el Municipio de Posoltega, departamento de Chinandega y el tercero en San Ramón, Matagalpa, en la Comunidad Guadalupe, ubicada a 1 O km. de la cabecera departamental. Se utilizó un diseño de bloques completos al azar (BCA), con cuatro repeticiones. Cada parcela constituida de siete surcos de cinco m de largo, separados a 0.60 m. Se utilizaron los cuatro surcos centrales como parcela útil para muestreos de las variables a evaluar. El análisis de varianza mostró diferencias altamente significativas entre localidades y tratamientos y para localidad x tratamiento para el rendimiento de grano (RG). Los tratamientos urea (toda) a la siembra (6 078 kg ha·1 ) y Mungo (5 655 kg ha·1 ) fueron estadísticamente iguales y ambos se diferenciaron del tratamiento urea fraccionada (4 488 kg ha·1 ). Entre localidades, Tisma obtuvo el mayor rendimiento con 7,259 kg .¡ superior al obtenido en el CEO, con 3 933 kg ha·1• No se encontraron diferencias entre tratamientos en el peso de mil granos y rendimiento de biomasa (RB), sin embargo, en San Ramón se obtuvo elmayor peso (26.74 g) y el menor en CEO (23.78 g). La forma de suministrar nitrógeno no tuvo efecto sobre la materia seca producida, sin embargo, el tratamiento con mungo, superó ligeramente a la biomasa producida con fertilización química. El mismo comportamiento se obtuvo para esta variable entre localidades. Se obtuvo interacción positiva entre localidad x tratamiento, siendo en Tisma donde se alcanzan los mayores rendimientos cuando se aplica el N 30 días después de la siembra (dds). El uso de mungo, presentó el segundo mejor rendimiento en las dos localidades antes mencionadas.

Proceedings of the Second PICES Workshop on the Okhotsk Sea and Adjacent Areas [Nemuro, Japan, November 9-12, 1998]

Table of Contents [pdf, 0.01 Mb] Preface [pdf, 0.01 Mb] Masaaki Aota Long-term tendencies of sea ice concentration and air temperature in the Okhotsk Sea coast of Hokkaido [pdf, 0.05 Mb] Hajime Ito & Miki Yoshioka Geography of the seasonally ice covered seas [pdf, 0.5 Mb] George V. Shevchenko & Victor F. Putov On wind and tide induced sea-ice drift on the northeastern shelf of Sakhalin Island (analysis of radar data) [pdf, 0.96 Mb] Boris S. Dyakov, A.A. Nikitin, L. S. Muktepavel & T.A. Shatilina Variability of the Japan and Okhotsk Seas ice cover depending on geopotential field H500 over the Far-Eastern region [pdf, 0.10 Mb] Aleksandr G. Petrov & Nikolay A. Rykov Intermediate cold layer and ice cover in the Sea of Okhotsk [pdf, 0.37 Mb] Vladimir Ponomarev, Olga Trusenkova, Elena Ustinova & Dmitry Kaplunenko Interannual variations of oceanographic and meteorological characteristics in the Sea of Okhotsk [pdf, 0.16 Mb] George V. Shevchenko & Akie Kato Seasonal and interannual changes of atmospheric pressure, air and water temperature in the area of the Kuril Ridge [pdf, 0.13 Mb] George V. Shevchenko & Vladimir Yu. Saveliev Spatial variability of the wind field in the area of the Kuril Islands [pdf, 0.15 Mb] Alexander L. Figurkin & Igor A. Zhigalov Seasonal variability and specifity of the oceanological conditions in the northern Okhotsk Sea in 1997 [pdf, 1.04 Mb] Igor A. Zhabin Ventilation of the upper portion of the intermediate water in the Okhotsk Sea [pdf, 0.80 Mb] Vladimir A. Luchin & Alexander L. Figurkin Oceanographic conditions over the Kashevarov Bank [pdf, 0.61 Mb] Toshiyuki Awaji, Tomohiro Nakamura, Takaki Hatayama, Kazunori Akimoto & Takatoshi Takizawa Tidal exchange through the Kuril Straits [pdf, 2.01 Mb] Tomohiro Nakamura, Toshiyuki Awaji, Takaki Hatayama, Kazunori Akimoto, Takatoshi Takizawa & Masao Fukasawa Vertical mixing induced by tidally generated internal waves in the Kuril Straits [pdf, 0.83 Mb] Katsuro Katsumata & Ichiro Yasuda Water exchange between the Okhotsk Sea and the North Pacific Ocean estimated by simple models [pdf, 0.97 Mb] Konstantin A. Rogachev Oyashio west path culmination as the consequence of a rapid thermohaline transition in the Pacific Subarctic [pdf, 0.22 Mb] Yasuhiro Kawasaki On the year-to-year change in subarctic water characteristics around the Kuril Islands [pdf, 0.39 Mb] Alexander L. Figurkin & Evgeniy E. Ovsyannikov Influence of oceanological conditions of the West Kamchatka shelf waters on spawning grounds and on pollock egg distribution [pdf, 0.97 Mb] Igor E. Kochergin & Alexander A. Bogdanovsky Transport and turbulence characteristics for the northeastern Sakhalin shelf conditions [pdf, 0.08 Mb] Igor E. Kochergin, Alexander A. Bogdanovsky, Valentina D. Budaeva, Vyacheslav G. Makarov, Vasily F. Mishukov, S.N. Ovsienko, Victor F. Putov, L.A. Reitsema, J.W. Sciallabba, O.O. Sergucheva & P.V. Yarosh Modeling of oil spills for the shelf conditions of northeastern Sakhalin [pdf, 0.32 Mb] Valentina D. Budaeva & Vyacheslav G. Makarov A peculiar water regime of currents in the area of eastern Sakhalin shelf [pdf, 0.66 Mb] Nikolay A. Rykov The oceanographic databases on the Sakhalin shelf [pdf, 0.27 Mb] Akifumi Nakata, Iori Tanaka, Hiroki Yagi, Tomomi Watanabe, Gennady A. Kantakov & Andrew D. Samatov Formation of high-density water (over 26.8 sigma-t) near the La Perouse Strait (the Soya Strait) [pdf, 0.09 Mb] Minoru Odamaki & Kouji Iwamoto Currents and tidal observations by Hydrographic Department of Maritime Safety Agency, off the Okhotsk coast of Hokkaido [pdf, 0.16 Mb] Yasushi Fukamachi, Genta Mizuta, Kay I. Ohshima, Motoyo Itoh, Masaaki Wakatsuchi & Masaaki Aota Mooring measurements off Shiretoko Peninsula, Hokkaido in 1997-1998 [pdf, 0.19 Mb] Mikhail A. Danchenkov, David Aubrey & Stephen C. Riser Oceanographic features of the La Perouse Strait [pdf, 0.91 Mb] Iori Tanaka & Akifumi Nakata Results of direct current measurements in the La Perouse Strait (the Soya Strait), 1995-1998 [pdf, 0.06 Mb] Gennady A. Kantakov & George V. Shevchenko In situ observations of Tsushima and West-Sakhalin currents near La Perouse (Soya) Strait [pdf, 0.79 Mb] Irina Y. Bragina Geographical and biological characteristics of the net zooplankton in the southwestern part of the Sea of Okhotsk during 1987-1996 [pdf, 0.27 Mb] List of corresponding authors [pdf, 0.01 Mb] (Document pdf contains 193 pages)

Proceedings of the Workshop on the Okhotsk Sea and Adjacent Areas [Vladivostok, June 1995]

I REPORT OF THE PICES WORKSHOP ON THE OKHOTSK SEA AND ADJACENT AREAS (pdf, 0.1 Mb) 1. Outline of the workshop 2. Summary reports from sessions 3. Recommendations of the workshop 4. Acknowledgments II SCIENTIFIC PAPERS SUBMITTED FROM SESSIONS 1. Physical Oceanography Sessions (pdf, 4 Mb) A. Circulation and water mass structure of the Okhotsk Sea and Northwestern Pacific Valentina D. Budaeva & Vyacheslav G. Makarov Seasonal variability of the pycnocline in La Perouse Strait and Aniva Gulf Valentina D. Budaeva & Vyacheslav G. Makarov Modeling of the typical water circulations in the La Perouse Strait and Aniva Gulf region Nina A. Dashko, Sergey M. Varlamov, Young-Ho Han & Young-Seup Kim Anticyclogenesis over the Okhotsk Sea and its influence on weather Boris S. Dyakov, Alexander A. Nikitin & Vadim P. Pavlychev Research of water structure and dynamics in the Okhotsk Sea and adjacent Pacific Howard J. Freeland, Alexander S. Bychkov, C.S. Wong, Frank A. Whitney & Gennady I. Yurasov The Ohkotsk Sea component of Pacific Intermediate Water Emil E. Herbeck, Anatoly I. Alexanin, Igor A. Gontcharenko, Igor I. Gorin, Yury V. Naumkin & Yury G. Proshjants Some experience of the satellite environmental support of marine expeditions at the Far East Seas Alexander A. Karnaukhov The tidal influence on the Sakhalin shelf hydrology Yasuhiro Kawasaki On the formation process of the subsurface mixed water around the Central Kuril Islands Lloyd D. Keigwin Northwest Pacific paleohydrography Talgat R. Kilmatov Physical mechanisms for the North Pacific Intermediate Water formation Vladimir A. Luchin Water masses in the Okhotsk Sea Andrey V. Martynov, Elena N. Golubeva & Victor I. Kuzin Numerical experiments with finite element model of the Okhotsk Sea circulation Nikolay A. Maximenko, Anatoly I. Kharlamov & Raissa I. Gouskina Structure of Intermediate Water layer in the Northwest Pacific Nikolay A. Maximenko & Andrey Yu. Shcherbina Fine-structure of the North Pacific Intermediate Water layer Renat D. Medjitov & Boris I. Reznikov An experimental study of water transport through the Straits of Okhotsk Sea by electromagnetic method Valentina V. Moroz Oceanological zoning of the Kuril Islands area in the spring-summer period Yutaka Nagata Note on the salinity balance in the Okhotsk Sea Alexander D. Nelezin Variability of the Kuroshio Front in 1965-1991 Vladimir I. Ponomarev, Evgeny P. Varlaty & Mikhail Yu. Cheranyev An experimental study of currents in the near-Kuril region of the Pacific Ocean and in the Okhotsk Sea Stephen C. Riser, Gennady I. Yurasov & Mark J. Warner Hydrographic and tracer measurements of the water mass structure and transport in the Okhotsk Sea in early spring Konstantin A. Rogachev & Andrey V. Verkhunov Circulation and water mass structure in the southern Okhotsk Sea, as observed in summer, 1994 Lynne D. Talley North Pacific Intermediate Water formation and the role of the Okhotsk Sea Anatoly S. Vasiliev & Fedor F. Khrapchenkov Seasonal variability of integral water circulation in the Okhotsk Sea B. Sea ice and its relation to circulation and climate V.P. Gavrilo, G.A. Lebedev & A.P. Polyakov Acoustic methods in sea ice dynamics studies Nina M. Pestereva & Larisa A. Starodubtseva The role of the Far-East atmospheric circulation in the formation of the ice cover in the Okhotsk Sea Yoshihiko Sekine Anomalous Oyashio intrusion and its teleconnection with Subarctic North Pacific circulation, sea ice of the Okhotsk Sea and air temperature of the northern Asian continent C. Waves and tides Vladimir A. Luchin Characteristics of the tidal motions in the Kuril Straits George V. Shevtchenko On seasonal variability of tidal constants in the northwestern part of the Okhotsk Sea D. Physical oceanography of the Japan Sea/East Sea Mikhail A. Danchenkov, Kuh Kim, Igor A. Goncharenko & Young-Gyu Kim A “chimney” of cold salt waters near Vladivostok Christopher N.K. Mooers & Hee Sook Kang Preliminary results from a numerical circulation model of the Japan Sea Lev P. Yakunin Influence of ice production on the deep water formation in the Japan Sea 2. Fisheries and Biology Sessions (pdf, 2.8 Mb) A. Communities of the Okhotsk Sea and adjacent waters: composition, structure and dynamics Lubov A. Balkonskaya Exogenous succession of the southwestern Sakhalin algal communities Tatyana A. Belan, Yelena V. Oleynik, Alexander V. Tkalin & Tat’yana S. Lishavskaya Characteristics of pelagic and benthic communities on the North Sakhalin Island shelf Lev N. Bocharov & Vladimir K. Ozyorin Fishery and oceanographic database of Okhotsk Sea Victor V. Lapko Interannual dynamics of the epipelagic ichthyocen structure in the Okhotsk Sea Valentina I. Lapshina Quantitative seasonal and year-to-year changes of phytoplankton in the Okhotsk Sea and off Kuril area of the Pacific Lyudmila N. Luchsheva Biological productivity in anomalous mercury conditions (northern part of Okhotsk Sea) Inna A. Nemirovskaya Origin of hydrocarbons in the ecosystems of coastal region of the Okhotsk Sea Tatyana A. Shatilina Elements of the Pacific South Kuril area ecosystem Vyacheslav P. Shuntov & Yelena P. Dulepova Biota of the Okhotsk Sea: Structure of communities, the interannual dynamics and current status B. Abundance, distribution, dynamics of the common fishes of the Okhotsk Sea Yuri P. Diakov Influence of some abiotic factors on spatial population dynamics of the West Kamchatka flounders (Pleuronectidae) Gordon A. McFarlane, Richard J. Beamish & Larisa M. Zverkova An examination of age estimates of walleye pollock (Theragra chalcogramma) from the Sea of Okhotsk using the burnt otolith method and implications for stock assessment and management Larisa P. Nikolenko Migration of Greenland turbot (Reinhardtius hippoglossoides) in the Okhotsk Sea Galina M. Pushnikova Fisheries impact on the Sakhalin-Hokkaido herring population Vidar G. Wespestad Is pollock overfished? C. Salmon of the Okhotsk Sea: biology, abundance and stock identification Vladimir A. Belyaev, Alexander Yu. Zhigalin Epipelagic Far Eastern sardine of the Okhotsk Sea Yuri E. Bregman, Victor V. Pushnikov, Lyudmila G. Sedova & Vladimir Ph. Ivanov A preliminary report on stock status and productive capacity of horsehair crab Erimacrus isenbeckii (Brandt) in the South Kuril Strait Natalia T. Dolganova Mezoplankton distribution in the West Japan Sea Vladimir V. Efremov, Richard L. Wilmot, Christine M. Kondzela, Natalia V. Varnavskaya, Sharon L. Hawkins & Maria E. Malinina Application of pink and chum salmon genetic baseline to fishery management Vyacheslav N. Ivankov & Valentina V. Andreyeva Strategy for culture, breeding and numerous dynamics of Sakhalin salmon populations Alla M. Kovalevskaya, Natalia I. Savelyeva & Dmitry M. Polyakov Primary production in Sakhalin shelf waters Tatyana N. Krupnova Some reasons for resource reduction of Laminaria japonica (Primorye region) Lyudmila N. Luchsheva & Anatoliy I. Botsul Mercury in bottom sediments of the northeastern Okhotsk Sea Pavel A. Luk’yanov, Natalia I. Belogortseva, Alexander A. Bulgakov, Alexander A. Kurika & Olga D. Novikova Lectins and glycosidases from marine macro and micro-organisms of Japan and Okhotsk Seas Boris A. Malyarchuk, Olga A. Radchenko, Miroslava V. Derenko, Andrey G. Lapinski & Leonid L. Solovenchuk PCR-fingerprinting of mitochondrial genome of chum salmon, Oncorhynchus keta Alexander A. Mikheev Chaos and relaxation in dynamics of the pink salmon (Oncorhynchus gorbuscha) returns for two regions Yuri A. Mitrofanov & Larisa N. Lesnikova Fish-culture of Pacific Salmons increases the number of heredity defects Larisa P. Nikolenko Abundance of young halibut along the West Kamchatka shelf in 1982-1992 Sergey A. Nizyaev Living conditions of golden king crab Lithodes aequispina in the Okhotsk Sea and near the Kuril Islands Ludmila A. Pozdnyakova & Alla V. Silina Settlements of Japanese scallop in Reid Pallada Bay (Sea of Japan) Galina M. Pushnikova Features of the Southwest Okhotsk Sea herring Vladimir I. Radchenko & Igor I. Glebov Present state of the Okhotsk herring stock and fisheries outlook Alla V. Silina & Ida I. Ovsyannikova Distribution of the barnacle Balanus rostratus eurostratus near the coasts of Primorye (Sea of Japan) Galina I. Victorovskaya Dependence of urchin Strongylocentrotus intermedius reproduction on water temperature Anatoly F. Volkov, Alexander Y. Efimkin & Valery I. Chuchukalo Feeding habits of Pacific salmon in the Sea of Okhotsk and in the Pacific waters of Kuril Islands in summer 1993 Larisa M. Zverkova & Georgy A. Oktyabrsky Okhotsk Sea walleye pollock stock status Tatyana N. Zvyagintseva, Elena V. Sundukova, Natalia M. Shevchenko & Ludmila A. Elyakova Water soluble polysaccharides of some Far-Eastern seaweeds 3. Biodiversity Program (pdf, 0.2 Mb) A. Biodiversity of island ecosystems and seasides of the North Pacific Larissa A. Gayko Productivity of Japanese scallop Patinopecten yessoensis (IAY) culture in Posieta Bay (Sea of Japan) III APPENDICES 1. List of acronyms 2. List of participants (Document pdf contains 431 pages)

The Little Ice Age: glacier variations and climate since AD 1250 [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): During the past hundred years, mountain glaciers throughout the world have retreated significantly from moraines built during the previous several centuries. In the 1930s, Francois Matthes of the U.S. Geological Survey concluded that the moraines represent the greatest advances of glaciers since the end of the last glacial age, some 10,000 years earlier, and informally referred to this late Holocene interval of expanded ice cover as the Little Ice Age.

Discovery of Main-Belt Comet P/2006 VW139 by Pan-STARRS 1

The main-belt asteroid (300163) 2006 VW139 (later designated P/2006 VW139) was discovered to exhibit comet-like activity by the Pan-STARRS1 (PS1) survey telescope using automated point-spread-function analyses performed by PS1's Moving Object Processing System. Deep follow-up observations show both a short (~10'') antisolar dust tail and a longer (~60'') dust trail aligned with the object's orbit plane, similar to the morphology observed for another main-belt comet (MBC), P/2010 R2 (La Sagra), and other well-established comets, implying the action of a long-lived, sublimation-driven emission event. Photometry showing the brightness of the near-nucleus coma remaining constant over ~30 days provides further evidence for this object's cometary nature, suggesting it is in fact an MBC, and not a disrupted asteroid. A spectroscopic search for CN emission was unsuccessful, though we find an upper limit CN production rate of Q CN 100 Myr, while a search for a potential asteroid family around the object reveals a cluster of 24 asteroids within a cutoff distance of 68 m s-1. At 70 m s-1, this cluster merges with the Themis family, suggesting that it could be similar to the Beagle family to which another MBC, 133P/Elst-Pizarro, belongs.

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

New susceptibility Loci associated with kidney disease in type 1 diabetes

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P?=?1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P?=?2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P?=?2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein-protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

An investigation of Mode I and Mode II fracture toughness enhancement using aligned carbon nanotubes forests at the crack interface

A novel approach for introducing aligned multi-walled carbon nanotubes (MWCNTs) in a carbon-fibre composite pre-impregnated (prepreg) laminate, to improve the through-thickness fracture toughness, is presented. Carbon nanotube (CNT) 'forests' were grown on a silicon substrate with a thermal oxide layer, using a chemical vapour deposition (CVD) process. The forests were then transferred to a pre-cured laminate interface, using a combination of pressure and heat, while maintaining through-thickness CNT alignment. Standard Mode I and four-point bend end-notched flexure Mode II tests were undertaken on a set of specimens and compared with pristine specimens. Mode I fracture toughness for T700/M21 laminates was improved by an average of 31% while for T700/SE84LV specimens, an improvement of 61% was observed. Only T700/M21 specimens were tested in Mode II which yielded an average fracture toughness improvement of 161%. Scanning Electron Microscopy (SEM) showed good wetting of the CNT forest as well as evidence of penetration of the forest into the adjacent plies. © 2013 Elsevier Ltd.

New methods in Biomass Depolymerisation: Catalytic Hydrogenolysis of Barks

Hydrogenolysis of bark from three different species of tree using heterogeneous platinum group metal catalysts produces two major product streams. Aromatic substituted guaiacols are produced from lignin and the lignin-like regions of suberin and a range of saturated fatty acids and alcohols, including a,?-functionalised species, are produced from the polyester regions of suberin. Control experiments demonstrate clear advantages of catalytic hydrogenolysis over base hydrolysis, both in terms of conversion and product selectivity.

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]​-​based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores.

Field-Isolated Genotypes of Mycobacterium bovis Vary in Virulence and Influence Case Pathology but Do Not Affect Outbreak Size

Strains of many infectious agents differ in fundamental epidemiological parameters including transmissibility, virulence and pathology. We investigated whether genotypes of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) differ significantly in transmissibility and virulence, combining data from a nine-year survey of the genetic structure of the M. bovis population in Northern Ireland with detailed records of the cattle population during the same period. We used the size of herd breakdowns as a proxy measure of transmissibility and the proportion of skin test positive animals (reactors) that were visibly lesioned as a measure of virulence. Average breakdown size increased with herd size and varied depending on the manner of detection (routine herd testing or tracing of infectious contacts) but we found no significant variation among M. bovis genotypes in breakdown size once these factors had been accounted for. However breakdowns due to some genotypes had a greater proportion of lesioned reactors than others, indicating that there may be variation in virulence among genotypes. These findings indicate that the current bTB control programme may be detecting infected herds sufficiently quickly so that differences in virulence are not manifested in terms of outbreak sizes. We also investigated whether pathology of infected cattle varied according to M. bovis genotype, analysing the distribution of lesions recorded at post mortem inspection. We concentrated on the proportion of cases lesioned in the lower respiratory tract, which can indicate the relative importance of the respiratory and alimentary routes of infection. The distribution of lesions varied among genotypes and with cattle age and there were also subtle differences among breeds. Age and breed differences may be related to differences in susceptibility and husbandry, but reasons for variation in lesion distribution among genotypes require further investigation. © 2013 Wright et al.

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test.