bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted Junctional Membrane Complexes and Hyperactive Ryanodine Receptors After Acute Junctophilin Knockdown in Mice
Authors: van Oort Ralph J. , Garbino Alejandro , Wang Wei , Dixit Sayali S. , Landstrom Andrew P. , Gaur Namit , De Almeida Angela C. , Skapura Darlene G. , Rudy Yoram , Burns Alan R. , Ackerman Michael J. , Wehrens Xander H.T. 
Published: February 2011

Background—

Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca
2+
channels and Ca
2+
release channels on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss of junctional membrane complexes and embryonic lethality in germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role in junctional membrane complex formation and the Ca
2+
-induced Ca
2+
release process in the heart. Our recent work demonstrated loss-of-function mutations in JPH2 in patients with hypertrophic cardiomyopathy.

Methods and Results—
To elucidate the role of JPH2 in the heart, we developed a novel approach to conditionally reduce JPH2 protein levels using RNA interference. Cardiac-specific JPH2 knockdown resulted in impaired cardiac contractility, which caused heart failure and increased mortality. JPH2 deficiency resulted in loss of excitation-contraction coupling gain, precipitated by a reduction in the number of junctional membrane complexes and increased variability in the plasmalemma–sarcoplasmic reticulum distance.

Conclusions—

Loss of JPH2 had profound effects on Ca
2+
release channel inactivation, suggesting a novel functional role for JPH2 in regulating intracellular Ca
2+
release channels in cardiac myocytes. Thus, our novel approach of cardiac-specific short hairpin RNA–mediated knockdown of junctophilin-2 has uncovered a critical role for junctophilin in intracellular Ca
2+
release in the heart.
Stochastic Averaging of Idealized Climate Models
Authors: Monahan Adam H. , Culina Joel 
Published: February 2011

AbstractVariability in the climate system involves interactions across a broad range of scales in space and time. While models of slow “climate” variability may not explicitly account for fast “weather” processes, the dynamical influence of these unresolved scales cannot generally be ignored. Perspectives from statistical physics indicate that if the scale separation between slow and fast scales is sufficiently large, deterministic parameterizations are appropriate, while for smaller scale separations the parameterizations should be nondeterministic. The method of “stochastic averaging” provides a framework for the reduction of coupled fast–slow systems into an effective dynamics of the slow variables. This study describes the hierarchy of approximations associated with stochastic averaging and applies this reduction methodology to two idealized models: a Stommel-type model of the meridional overturning circulation and a model of coupled atmosphere–ocean boundary layers. Finally, stochastic averaging is compared to other stochastic reduction strategies that have been applied to climate models.
Evaluation of the HOMME Dynamical Core in the Aquaplanet Configuration of NCAR CAM4: Rainfall
Authors: Mishra Saroj K. , Taylor Mark A. , Nair Ramachandran D. , Lauritzen Peter H. , Tufo Henry M. , Tribbia Joseph J. 
Published: February 2011

Abstract
The NCAR Community Climate System Model, version 4 (CCSM4), includes a new dynamical core option based on NCAR’s High-Order Method Modeling Environment (HOMME). HOMME is a petascale-capable high-order element-based conservative dynamical core developed on the cubed-sphere grid. Initial simulations have been completed in an aquaplanet configuration of the Community Atmosphere Model, version 4 (CAM4), the atmospheric component of CCSM4. The authors examined the results of this simulation and assessed its fidelity in simulating rainfall, which is one of the most important components of the earth’s climate system. For this they compared the results from two other dynamical cores of CAM4: the finite volume (FV) and Eulerian (EUL).
Instantaneous features of rainfall in HOMME are similar to FV and EUL. Similar to EUL and FV, HOMME simulates a single-peak intertropical convergence zone (ITCZ) over the equator. The strength of the ITCZ is found to be almost the same in HOMME and EUL but more in FV. It is observed that in HOMME and EUL, there is higher surface evaporation, which supplies more moisture to the deep tropics and gives more rainfall over the ITCZ. The altitude of maximum precipitation is found to be at almost the same level in all three dynamical cores. The eastward propagation of rainfall bands is organized and more prominent in FV and HOMME than in EUL. The phase speed of the eastward propagation in HOMME is found to be higher than in FV. The results show that, in general, the rainfall simulated by HOMME falls in a regime between that of FV and EUL. Hence, they conclude that the key aspects of rainfall simulation with HOMME falls into an acceptable range, as compared to the existing dynamical cores used in the model.
Evaluation of MERRA Land Surface Estimates in Preparation for the Soil Moisture Active Passive Mission
Authors: Yi Yonghong , Kimball John S. , Jones Lucas A. , Reichle Rolf H. , McDonald Kyle C. 
Published: February 2011

Abstract
The authors evaluated several land surface variables from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) product that are important for global ecological and hydrological studies, including daily maximum (Tmax) and minimum (Tmin) surface air temperatures, atmosphere vapor pressure deficit (VPD), incident solar radiation (SWrad), and surface soil moisture. The MERRA results were evaluated against in situ measurements, similar global products derived from satellite microwave [the Advanced Microwave Scanning Radiometer for Earth Observing System (EOS) (AMSR-E)] remote sensing and earlier generation atmospheric analysis [Goddard Earth Observing System version 4 (GEOS-4)] products. Relative to GEOS-4, MERRA is generally warmer (~0.5°C for Tmin and Tmax) and drier (~50 Pa for VPD) for low- and middle-latitude regions (&lt;50°N) associated with reduced cloudiness and increased SWrad. MERRA and AMSR-E temperatures show relatively large differences (&gt;3°C) in mountainous areas, tropical forest, and desert regions. Surface soil moisture estimates from MERRA (0–2-cm depth) and two AMSR-E products (~0–1-cm depth) are moderately correlated (R ~ 0.4) for middle-latitude regions with low to moderate vegetation biomass. The MERRA derived surface soil moisture also corresponds favorably with in situ observations (R = 0.53 ± 0.01, p &lt; 0.001) in the midlatitudes, where its accuracy is directly proportional to the quality of MERRA precipitation. In the high latitudes, MERRA shows inconsistent soil moisture seasonal dynamics relative to in situ observations. The study’s results suggest that satellite microwave remote sensing may contribute to improved reanalysis accuracy where surface meteorological observations are sparse and in cold land regions subject to seasonal freeze–thaw transitions. The upcoming NASA Soil Moisture Active Passive (SMAP) mission is expected to improve MERRA-type reanalysis accuracy by providing accurate global mapping of freeze–thaw state and surface soil moisture with 2–3-day temporal fidelity and enhanced (≤9 km) spatial resolution.
A Model Study of the Salish Sea Estuarine Circulation*
Authors: Sutherland David A. , MacCready Parker , Banas Neil S. , Smedstad Lucy F. 
Published: February 2011

Abstract
A realistic hindcast simulation of the Salish Sea, which encompasses the estuarine systems of Puget Sound, the Strait of Juan de Fuca, and the Strait of Georgia, is described for the year 2006. The model shows moderate skill when compared against hydrographic, velocity, and sea surface height observations over tidal and subtidal time scales. Analysis of the velocity and salinity fields allows the structure and variability of the exchange flow to be estimated for the first time from the shelf into the farthest reaches of Puget Sound. This study utilizes the total exchange flow formalism that calculates volume transports and salt fluxes in an isohaline framework, which is then compared to previous estimates of exchange flow in the region. From this analysis, residence time distributions are estimated for Puget Sound and its major basins and are found to be markedly shorter than previous estimates. The difference arises from the ability of the model and the isohaline method for flux calculations to more accurately estimate the exchange flow. In addition, evidence is found to support the previously observed spring–neap modulation of stratification at the Admiralty Inlet sill. However, the exchange flow calculated increases at spring tides, exactly opposite to the conclusion reached from an Eulerian average of observations.
COSMIC Radio Occultation Processing: Cross-Center Comparison and Validation
Authors: Gorbunov Michael E. , Shmakov A. V. , Leroy Stephen S. , Lauritsen Kent B. 
Published: February 2011

Abstract
A radio occultation data processing system (OCC) was developed for numerical weather prediction and climate benchmarking. The data processing algorithms use the well-established Fourier integral operator–based methods, which ensure a high accuracy of retrievals. The system as a whole, or in its parts, is currently used at the Global Navigation Satellite System Receiver for Atmospheric Sounding (GRAS) Satellite Application Facility at the Danish Meteorological Institute, German Weather Service, and Wegener Center for Climate and Global Change. A statistical comparison of the inversions of the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) data by the system herein, University Corporation for Atmospheric Research (UCAR) data products, and ECMWF analyses is presented. Forty days of 2007 and 2008 were processed (from 5 days in the middle of each season) for the comparison of OCC and ECMWF, and 20 days of April 2009 were processed for the comparison of OCC, UCAR, and ECMWF. The OCC and UCAR inversions are consistent. For the tropics, the systematic difference between OCC and UCAR in the retrieved refractivity in the 2–30-km height interval does not exceed 0.1%; in particular, in the 9–25-km interval it does not exceed 0.03%. Below 1 km in the tropics the OCC – UCAR bias reaches 0.2%, which is explained by different cutoff and filtering schemes implemented in the two systems. The structure of the systematic OCC – ECMWF difference below 4 km changes in 2007, 2008, and 2009, which is explained by changes in the ECMWF analyses and assimilation schemes. It is estimated that in the 4–30-km height range the OCC occultation processing system obtains refractivities with a bias not exceeding 0.2%. The random error ranges from 0.3%–0.5% in the upper troposphere–lower stratosphere to about 2% below 4 km. The estimate of the bias below 4 km can currently be done with an accuracy of 0.5%–1% resulting from the structural uncertainty of the radio occultation (RO) data reflecting the insufficient knowledge of the atmospheric small-scale structures and instrumental errors. The OCC – UCAR bias is below the level of the structural uncertainty.
Non-invasive cerebral oximetry monitoring during cardiopulmonary bypass in congenital cardiac surgery: a starting point
Authors: Quarti A. , Manfrini F. , Oggianu A. , D'Orfeo F. , Genova S. , Silvano R. , Pozzi M. 
Published: February 2011

Introduction: Non-invasive cerebral monitoring with the INVOS cerebral oximeter is an accepted good indicator of cerebral metabolism. In recent years, it has been used in the monitoring of patients who underwent cardiac surgery. Herein, we describe the INVOS trend during cardiopulmonary bypass (CPB) in a cohort of patients operated in our institution for congenital heart disease. Patients and methods: Between December 2009 and March 2010, 40 patients (mean age 8.4 years; range 11 days-60 years) underwent cardiac surgical procedures using CPB. Values of INVOS cerebral parameter, pH, oxygen saturation, and CO2 level were collected pre CPB, during cooling, re-warming and weaning, and post CPB. INVOS parameters were evaluated according to CPB priming, age and preoperative oxygen saturation. Results: Patients were divided according to CPB priming (haematic vs clear), age (≤1 vs >1 year of age) and oxygen saturation (≤92% vs >92%). During the operations, the trend demonstrated a reduction in INVOS value at the institution of CPB and a further reduction during the cooling phase in all groups.This has been correlated to the loss of pulsatile flow. However, the value recovered during re-warming, weaning and CPB discontinuation. Cyanotic patients presented a lower cerebral oximetry compared to acyanotic patients during the whole CPB period. Between age and priming groups, we noticed a statistical difference in cerebral oximetry, with a lower value in the younger patients and in the haematic priming group. This might be interrelated because all patients younger than 1 year old always received haematic CPB priming. Conclusions: We demonstrated that cerebral oximetry decreases with the loss of pulsatile flow regardless of the mean arterial pressure and, furthermore, is not directly related to the haematocrit value in patients with reduced pulmonary blood flow.
CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia
Authors: Makishima Hideki , Jankowska Anna M. , McDevitt Michael A. , O'Keefe Christine , Dujardin Simon , Cazzolli Heather , Przychodzen Bartlomiej , Prince Courtney , Nicoll John , Siddaiah Harish , Shaik Mohammed , Szpurka Hadrian , Hsi Eric , Advani Anjali , Paquette Ronald , Maciejewski Jaroslaw P. 
Published: February 2011

AbstractProgression of chronic myelogenous leukemia (CML) to accelerated (AP) and blast phase (BP) is because of secondary molecular events, as well as additional cytogenetic abnormalities. On the basis of the detection of JAK2, CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations in myelodysplastic/myeloproliferative neoplasms, we hypothesized that they may also contribute to progression in CML. We screened these genes for mutations in 54 cases with CML (14 with chronic phase, 14 with AP, 20 with myeloid, and 6 with nonmyeloid BP). We identified 1 CBLB and 2 TET2 mutations in AP, and 1 CBL, 1 CBLB, 4 TET2, 2 ASXL1, and 2 IDH family mutations in myeloid BP. However, none of these mutations were found in chronic phase. No cases with JAK2V617F mutations were found. In 2 cases, TET2 mutations were found concomitant with CBLB mutations. By single nucleotide polymorphism arrays, uniparental disomy on chromosome 5q, 8q, 11p, and 17p was found in AP and BP but not involving 4q24 (TET2) or 11q23 (CBL). Microdeletions on chromosomes 17q11.2 and 21q22.12 involved tumor associated genes NF1 and RUNX1, respectively. Our results indicate that CBL family, TET2, ASXL1, and IDH family mutations and additional cryptic karyotypic abnormalities can occur in advanced phase CML.
Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy
Authors: Ibrahim Amr R. , Eliasson Lina , Apperley Jane F. , Milojkovic Dragana , Bua Marco , Szydlo Richard , Mahon Francois-Xavier , Kozlowski Kasia , Paliompeis Christos , Foroni Letizia , Khorashad Jamshid S. , Bazeos Alex , Molimard Mathieu , Reid Alistair , Rezvani Katayoun , Gerrard Gareth , Goldman John , Marin David 
Published: February 2011

Abstract
We studied the relation between adherence to imatinib measured with microelectronic monitoring systems and the probabilities of losing a complete cytogenetic response (CCyR) and of imatinib failure in 87 CCyR chronic myeloid leukemia patients receiving long-term therapy. We included in our analysis the most relevant prognostic factors described to date. On multivariate analysis, the adherence rate and having failed to achieve a major molecular response were the only independent predictors for loss of CCyR and discontinuation of imatinib therapy. The 23 patients with an adherence rate less than or equal to 85% had a higher probability of losing their CCyR at 2 years (26.8% vs 1.5%, P = .0002) and a lower probability of remaining on imatinib (64.5% vs 90.6%, P = .006) than the 64 patients with an adherence rate more than 85%. In summary, we have shown that poor adherence is the principal factor contributing to the loss of cytogenetic responses and treatment failure in patients on long-term therapy.
Different role of CD73 in leukocyte trafficking via blood and lymph vessels
Authors: Ålgars Annika , Karikoski Marika , Yegutkin Gennady G. , Stoitzner Patrizia , Niemelä Jussi , Salmi Marko , Jalkanen Sirpa 
Published: February 2011

AbstractCD73 is involved in the extracellular ATP metabolism by dephosphorylating extracellular AMP to adenosine and thus regulating permeability of the blood vessels and leukocyte traffic into the tissues. It is also present on lymphatic vessels where its distribution and function have not been characterized. We found that CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. The extracellular nucleotide metabolism on lymphatic endothelium differs from that on blood vessel endothelium as lymphatic endothelium has lower NTPDase and higher ecto-5′-nucleotidase/CD73 activity than blood vascular endothelium. In knockout mice, the lack of CD73 on lymphocytes decreases migration of lymphocytes to the draining lymph nodes more than 50% while CD73-deficient lymph vessels mediate lymphocyte trafficking as efficiently as the wild-type lymphatics. Thus, although endothelial CD73 is important for permeability and leukocyte extravasation in blood vessels, it does not have a role in these functions on lymphatics. Instead, lymphocyte CD73 is intimately involved in lymphocyte migration via afferent lymphatic vessels.
PIAS1 interacts with FLASH and enhances its co-activation of c-Myb
Authors: Alm-Kristiansen Anne Hege , Lorenzo Petra I , Molværsmyr Ann-Kristin , Matre Vilborg , Ledsaak Marit , Sæther Thomas , Gabrielsen Odd S 
Published: February 2011

Abstract

Background
FLASH is a huge nuclear protein involved in various cellular functions such as apoptosis signalling, NF-κB activation, S-phase regulation, processing of histone pre-mRNAs, and co-regulation of transcription. Recently, we identified FLASH as a co-activator of the transcription factor c-Myb and found FLASH to be tightly associated with active transcription foci. As a huge multifunctional protein, FLASH is expected to have many interaction partners, some which may shed light on its function as a transcriptional regulator.

Results
To find additional FLASH-associated proteins, we performed a yeast two-hybrid (Y2H) screening with FLASH as bait and identified the SUMO E3 ligase PIAS1 as an interaction partner. The association appears to involve two distinct interaction surfaces in FLASH. We verified the interaction by Y2H-mating, GST pulldowns, co-IP and ChIP. FLASH and PIAS1 were found to co-localize in nuclear speckles. Functional assays revealed that PIAS1 enhances the intrinsic transcriptional activity of FLASH in a RING finger-dependent manner. Furthermore, PIAS1 also augments the specific activity of c-Myb, and cooperates with FLASH to further co-activate c-Myb. The three proteins, FLASH, PIAS1, and c-Myb, are all co-localized with active RNA polymerase II foci, resembling transcription factories.

Conclusions
We conclude that PIAS1 is a common partner for two cancer-related nuclear factors, c-Myb and FLASH. Our results point to a functional cooperation between FLASH and PIAS1 in the enhancement of c-Myb activity in active nuclear foci.
Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production
Authors: Amjadi Fatemehsadat , Javanmard Shaghaygh Haghjooy , Zarkesh-Esfahani Hamid , Khazaei Majid , Narimani Manijeh 
Published: February 2011

Abstract

Background
Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Obesity increases the expression of leptin, a multifunctional peptide produced predominantly by adipocytes which may promote tumor growth. Several recently experiments have suggested that the tumors growth is in need of endothelial progenitor cell (EPC) dependent generation of new blood vessels.
Our objectives in the present study were to examine the effects of leptin on melanoma growth, circulating EPCs number and plasma levels of nitric oxide metabolites (NOx).

Methods
2 × 106 B16F10 melanoma cells were injected to thirty two C57BL6 mice subcutaneously. The mice were randomly divided into 4 groups (n = 8) in 8th day. Two groups were received twice daily intraperitoneal(i.p) injections of either PBS or recombinant murine leptin (1 μg/g initial body weight). Two groups were received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed.

Results
The tumor weight, EPC numbers and NOx level in leptin, PBS, 9F8, and IgG group were (3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2,1.7 ± 0.3 g), (222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26/ml of blood), and (22.47 ± 5.5, 12.30 ± 1.5, 6.26 ± 0.84, 15.75 ± 6.3 μmol/L) respectively. Tumors weight and size, circulating EPC numbers and plasma levels of NOx were significantly more in the leptin than 9f8 and both control groups (p < 0.05). The plasma concentration of NOx significantly decreased in 9f8 treated mice compare to control group (p < 0.05).

Conclusions
In conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.
The implementation of a system for managing analytical quality in networked laboratories
Authors: Jassam Nuthar , Lindsay Chris , Harrison Kevin , Thompson Douglas , Bosomworth Mike P , Barth Julian H 
Published: February 2011

Background In a network of laboratories analytical variability between instruments, even of the same type, may exist for reasons beyond the control of laboratory staff. Controlling variability is a prerequisite for the application of shared reference ranges and for ensuring the transferability of patient test results. Controlling variability requires a robust, non-conventional quality system to detect poor performance of analysers that are geographically distant. Essential to this quality system is a set of well-defined quality specifications. Methods The approach used in our study started with (1) selection of a model for quality specifications based on biological variation; the ‘three-level model’ (TLM) was selected on the basis of its flexibility to accommodate various levels of analytical performance; (2) determination of the performance characteristics of the 71 analytes measured in core biochemistry in terms of imprecision and bias; (3) defining quality requirements in the form of imprecision, bias and total error for 71 analytes measured routinely in core biochemistry; and (4) developing software to assist a consistent wide application of the quality specifications and to monitor analytical indices to the common quality specifications. Results In this paper we describe how we have implemented this model across our network. Forty-six of the 71 analytes in our core laboratory repertoire were allocated to the TLM. We were able to demonstrate equivalence of results on all analysers, for 42 out of 46 analytes allocated to this model. Conclusions We propose that other networked laboratories should investigate the suitability of this quality system for use in their network.