bluuebunny/crossref_metadata_2025 huggingface dataset:
Insufficient Autoantigen Presentation and Failure of Tolerance in a Mouse Model of Rheumatoid Arthritis
Authors: Perera Jason , Liu Xiao , Zhou Yuzhen , Joseph Nora E. , Meng Liping , Turner Jerrold R. , Huang Haochu
Published: July 2013

Objective

In the K/BxN mouse model of rheumatoid arthritis, T cells reactive for the self antigen glucose‐6‐phosphate isomerase (GPI) escape negative selection even though GPI expression is ubiquitous. We sought to determine whether insufficient GPI presentation could account for the failure of negative selection and for the development of arthritis.

Methods

To increase the antigen presentation of GPI, we generated transgenic mice expressing a membrane‐bound form of GPI (mGPI) and crossed them with K/BxN mice. A monoclonal antibody specific for the α‐chain of the KRN T cell receptor was generated to examine the fate of GPI‐specific T cells.

Results

The mGPI‐transgenic mice presented GPI more efficiently and showed a dramatic increase in negative selection and an inhibition of arthritis. Interestingly, thymic negative selection remained incomplete in these mice, and the escaped autoreactive T cells were anergic in the peripheral lymphoid organs, suggesting that enhanced antigen presentation also induces peripheral tolerance. Despite this apparent tolerance induction toward GPI, these mice developed a chronic wasting disease, characterized by colonic inflammation with epithelial dysplasia, as well as a dramatic reduction in Treg cells.

Conclusion

These data indicate that insufficient autoantigen expression or presentation results in defects of both central and peripheral tolerance in the K/BxN mice. Our findings also support the idea that insufficient autoantigen levels may underlie the development of autoimmunity.
Solution‐Mediated Phase Transformation of a Hydrate to its Anhydrous Form of Donepezil Hydrochloride
Authors: Liu T. , Wang B. , Dong W. , Gong J.
Published: July 2013

The solubility of form I (hydrate) and form III (anhydrous form) of donepezil hydrochloride (DHCl) in methanol/isopropyl ether mixtures was determined at different temperatures by a synthetic method with laser monitoring observation. The experimental data were correlated with the modified Apelblat equation. Dissolution enthalpy and entropy were predicted by this equation. The mechanisms involved in solution‐mediated transformation of a hydrate (form I) to its anhydrous form (form III) was investigated and characterized by in situ and offline measurement technologies, such as focused‐beam reflectance measurement (FBRM), powder X‐ray diffraction (PXRD), differential scanning calorimetry analysis (DSC), and moisture analyzer. The transformation involves nucleation of the metastable solid (form I), dissolution of the metastable solid, self‐recognition of the molecular units to nucleate a more stable solid phase (form III), and growth of the stable phase. The results indicate that the rate of transformation increases with increasing temperature and driving force.
Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions
Authors: Fang Kuan‐Min , Lin Tzu‐Chien , Chan Ti‐Chun , Ma Shi‐Zhang , Tzou Bo‐Cheng , Chang Wen‐Ruei , Liu Jun‐Jen , Chiou Shih‐Hwa , Yang Chung‐Shi , Tzeng Shun‐Fen
Published: July 2013

CD133 (Prominin‐1/AC133) is generally treated as a cell surface marker found on multipotent stem cells and tumor stem‐like cells, and its biological function remains debated. Genetically modified rat glioma cell lines were generated by lentiviral gene delivery of human CD133 into rat C6 glioma cells (hCD133+‐C6) or by infection of C6 cells with control lentivirus (mock‐C6). Stable hCD133 expression promoted the self‐renewal ability of C6‐formed spheres with an increase in the expression of the stemness markers, Bmi‐1 and SOX2. Akt phosphorylation, Notch‐1 activation, and Notch‐1 target gene expression (Hes‐1, Hey1 and Hey2) were increased in hCD133+‐C6 when compared to mock‐C6. The inhibition of Akt phosphorylation, Notch‐1 activation, and Hes‐1 in hCD133+‐C6 cells effectively suppressed their clonogenic ability, indicating that these factors are involved in expanding the growth of hCD133+‐C6. An elevated expression of GTPase‐activating protein 27 (Arhgap27) was detected in hCD133+‐C6. A decline in the invasion of hCD133+‐C6 by knockdown of Arhgap27 expression indicated the critical role of Arhgap27 in promoting cell migration of hCD133+‐C6. In vivo study further showed that hCD133+‐C6 formed aggressive tumors in vivo compared to mock‐C6. Exposure of hCD133+‐C6 to arsenic trioxide not only reduced Akt phosphorylation, Notch‐1 activation and Hes‐1 expression in vitro, but also inhibited their tumorigenicity in vivo. The results show that C6 glioma cells with stable hCD133 expression enhanced their stemness properties with increased Notch‐1/Hes‐1 signaling, Akt activation, and Arhgap27 action, which contribute to increased cell proliferation and migration of hCD133+‐C6 in vitro, as well as progressive tumor formation in vivo.
The new ESA satellite‐only gravity field model via the direct approach
Authors: Bruinsma Sean L. , Förste Christoph , Abrikosov Oleg , Marty Jean‐Charles , Rio Marie‐Helene , Mulet Sandrine , Bonvalot Sylvain
Published: July 2013

Reprocessed Gravity Field and Steady‐State Ocean Circulation Explorer (GOCE) gravity gradient data were combined with data from Laser Geodynamics Satellite (LAGEOS) 1/2 and Gravity Recovery and Climate Experiment (GRACE) to generate a satellite‐only gravity field model to degree 260 using the direct approach, named DIR‐R4. When compared to Earth Gravitational Model 2008 (EGM2008), it is more accurate at low to medium resolution thanks to GOCE and GRACE data. When compared to earlier releases of ESA GOCE models, it is more accurate at high degrees owing to the larger amount of data ingested. It is also slightly more accurate than ESA's fourth release of the time‐wise model (TIM‐R4), as demonstrated by GPS/leveling, orbit determination tests, and an oceanographic evaluation. According to the formal, probably too optimistic by a factor of 2–2.5, cumulated geoid (1.3 cm) and gravity anomaly (0.4 mGal) errors at 100 km resolution, the GOCE mission objectives have been reached.
Reliability of the steric and mass components of Mediterranean sea level as estimated from hydrographic gridded products
Authors: Jordà Gabriel , Gomis Damià
Published: July 2013

The steric component of Mediterranean sea level as obtained from different hydrographic gridded products is compared for the last decades. The widely used MEDATLAS2, ENACT/ENSEMBLES, ISHIIV6.7, and ISHIIV6.12 databases show large discrepancies, mainly derived from the halosteric component. The validation of the mass component against gravimetry data suggests that ENACT is slightly more accurate than the other data sets. Concerning long‐term trends, the thermosteric component computed down to the bottom for the period 1960–2000 ranges from −0.06 ± 0.12 to 0.09 ± 0.16 mm/yr. Halosteric trends are negative for all products, but the magnitude and spatial patterns provided by the four products are statistically inconsistent among them. This prevents giving consistent figures for the overall steric term and mass term. Conversely, the trend of the freshwater content of the Mediterranean basin can be estimated more accurately, ranging from 1.0 to 1.3 mm/yr for the period 1960–2000.
Earlier onset of the Indian monsoon in the late twentieth century: The role of anthropogenic aerosols
Authors: Bollasina Massimo A. , Ming Yi , Ramaswamy V.
Published: July 2013

The impact of the late twentieth century increase of anthropogenic aerosols on the Indian monsoon onset was investigated with a state‐of‐the‐art climate model with fully interactive aerosols and chemistry. We find that aerosols are likely responsible for the observed earlier onset, resulting in enhanced June precipitation over most of India. This shift is preceded by strong aerosol forcing over the Bay of Bengal and Indochina, mostly attributable to the direct effect, resulting in increased atmospheric stability that inhibits the monsoon migration in May. The adjusted atmospheric circulation leads to thermodynamic changes over the northwestern continental region, including increased surface temperature and near‐surface moist static energy, which support a stronger June flow and, facilitated by a relative warming of the Indian Ocean, a vigorous northwestward precipitation shift. These findings underscore the importance of dynamical feedbacks and of regional land‐surface processes for the aerosol‐monsoon link.
Impacts of changes in North Atlantic atmospheric circulation on particulate matter and human health in Europe
Authors: R. Pausata Francesco S. , Pozzoli Luca , Dingenen Rita Van , Vignati Elisabetta , Cavalli Fabrizia , Dentener Frank J.
Published: July 2013

In this study we use a global climate model to assess particulate matter (PM) variability induced by the North Atlantic Oscillation (NAO) in Europe during winter and the potential impact on human health of a future shift in the NAO mean state. Our study shows that extreme NAO phases in the 1990s modulated most of the interannual variability of winter PM concentrations in several European countries. Increased PM concentrations as a result of a positive shift in the mean winter NAO of one standard deviation would lead to about 5500 additional premature deaths in Mediterranean countries, compared to the simulated average PM health impact for the year 2000. In central‐northern Europe, instead, higher wind speed and increased PM removal by precipitation lead to negative PM concentration anomalies with associated health benefits. We suggest that the NAO index is a useful indicator for the role of interannual atmospheric variability on large‐scale pollution‐health impacts.
Interannual variability in tropospheric nitrous oxide
Authors: Thompson R. L. , Dlugokencky E. , Chevallier F. , Ciais P. , Dutton G. , Elkins J. W. , Langenfelds R. L. , Prinn R. G. , Weiss R. F. , Tohjima Y. , O'Doherty S. , Krummel P. B. , Fraser P. , Steele L. P.
Published: July 2013

Observations of tropospheric N2O mixing ratio show significant variability on interannual timescales (0.2 ppb, 1 standard deviation). We found that interannual variability in N2O is weakly correlated with that in CFC‐12 and SF6 for the northern extratropics and more strongly correlated for the southern extratropics, suggesting that interannual variability in all these species is influenced by large‐scale atmospheric circulation changes and, for SF6 in particular, interhemispheric transport. N2O interannual variability was not, however, correlated with polar lower stratospheric temperature, which is used as a proxy for stratosphere‐to‐troposphere transport in the extratropics. This suggests that stratosphere‐to‐troposphere transport is not a dominant factor in year‐to‐year variations in N2O growth rate. Instead, we found strong correlations of N2O interannual variability with the Multivariate ENSO Index. The climate variables, precipitation, soil moisture, and temperature were also found to be significantly correlated with N2O interannual variability, suggesting that climate‐driven changes in soil N2O flux may be important for variations in N2O growth rate.
Free cholesterol accumulation in hepatic stellate cells: Mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice
Authors: Tomita Kengo , Teratani Toshiaki , Suzuki Takahiro , Shimizu Motonori , Sato Hirokazu , Narimatsu Kazuyuki , Okada Yoshikiyo , Kurihara Chie , Irie Rie , Yokoyama Hirokazu , Shimamura Katsuyoshi , Usui Shingo , Ebinuma Hirotoshi , Saito Hidetsugu , Watanabe Chikako , Komoto Shunsuke , Kawaguchi Atsushi , Nagao Shigeaki , Sugiyama Kazuo , Hokari Ryota , Kanai Takanori , Miura Soichiro , Hibi Toshifumi
Published: July 2013

Although nonalcoholic steatohepatitis (NASH) is associated with hypercholesterolemia, the underlying mechanisms of this association have not been clarified. We aimed to elucidate the precise role of cholesterol in the pathophysiology of NASH. C57BL/6 mice were fed a control, high-cholesterol (HC), methionine-choline-deficient (MCD), or MCD+HC diet for 12 weeks or a control, HC, high-fat (HF), or HF+HC diet for 24 weeks. Increased cholesterol intake accelerated liver fibrosis in both the mouse models without affecting the degree of hepatocellular injury or Kupffer cell activation. The major causes of the accelerated liver fibrosis involved free cholesterol (FC) accumulation in hepatic stellate cells (HSCs), which increased Toll-like receptor 4 protein (TLR4) levels through suppression of the endosomal-lysosomal degradation pathway of TLR4, and thereby sensitized the cells to transforming growth factor (TGF)β-induced activation by down-regulating the expression of bone morphogenetic protein and activin membrane-bound inhibitor. Mammalian-cell cholesterol levels are regulated by way of a feedback mechanism mediated by sterol regulatory element-binding protein 2 (SREBP2), maintaining cellular cholesterol homeostasis. Nevertheless, HSCs were sensitive to FC accumulation because the high intracellular expression ratio of SREBP cleavage-activating protein (Scap) to insulin-induced gene (Insig) disrupted the SREBP2-mediated feedback regulation of cholesterol homeostasis in these cells. HSC activation subsequently enhanced the disruption of the feedback system by Insig-1 down-regulation. In addition, the suppression of peroxisome proliferator-activated receptor γ signaling accompanying HSC activation enhanced both SREBP2 and microRNA-33a signaling. Consequently, FC accumulation in HSCs increased and further sensitized these cells to TGFβ-induced activation in a vicious cycle, leading to exaggerated liver fibrosis in NASH.

Conclusion :

These characteristic mechanisms of FC accumulation in HSCs are potential targets to treat liver fibrosis in liver diseases including NASH.
M2 Kupffer cells promote M1 Kupffer cell apoptosis: A protective mechanism against alcoholic and nonalcoholic fatty liver disease
Authors: Wan Jinghong , Benkdane Merieme , Teixeira-Clerc Fatima , Bonnafous Stéphanie , Louvet Alexandre , Lafdil Fouad , Pecker Françoise , Tran Albert , Gual Philippe , Mallat Ariane , Lotersztajn Sophie , Pavoine Catherine
Published: July 2013

Alcoholic and nonalcoholic fatty liver disease (ALD and NAFLD) are the predominant causes of liver-related mortality in Western countries. We have shown that limiting classical (M1) Kupffer cell (KC) polarization reduces alcohol-induced liver injury. Herein, we investigated whether favoring alternatively activated M2 KCs may protect against ALD and NAFLD. Ongoing alcohol drinkers and morbidly obese patients, with minimal hepatic injury and steatosis, displayed higher hepatic expression of M2 genes, as compared to patients with more severe liver lesions; individuals with limited liver lesions showed negligible hepatocyte apoptosis but significant macrophage apoptosis. Experiments in mouse models of ALD or NAFLD further showed that BALB/c or resveratrol-treated mice fed alcohol or a high-fat diet displayed preponderant M2 KC polarization, M1 KC apoptosis, and resistance to hepatocyte steatosis and apoptosis, as compared to control C57BL6/J mice.

In vitro

experiments in isolated KC, peritoneal, and Raw264.7 macrophages demonstrated that M1 macrophage apoptosis was promoted by conditioned medium from macrophages polarized into an M2 phenotype by either interleukin (IL)4, resveratrol, or adiponectin. Mechanistically, IL10 released from M2 cells promoted M1 death, and anti-IL10 antibodies blunted the proapoptic effects of M2-conditioned media. IL10 secreted by M2 KCs promoted selective M1 death by a mechanism involving activation of arginase in high inducible nitric oxide synthase-expressing M1 KCs. In alcohol-exposed mice, neutralization of IL10 impaired M1 apoptosis.

Conclusion :

These data uncover a novel mechanism regulating the M1/M2 balance that relies on apoptotic effects of M2 KCs towards their M1 counterparts. They suggest that promoting M2-induced M1 KC apoptosis might prove a relevant strategy to limit alcohol- and high fat-induced inflammation and hepatocyte injury.
Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies
Authors: Turtoi Andrei , Blomme Arnaud , Debois Delphine , Somja Joan , Delvaux David , Patsos Georgios , Di Valentin Emmanuel , Peulen Olivier , Mutijima Eugène Nzaramba , De Pauw Edwin , Delvenne Philippe , Detry Olivier , Castronovo Vincent
Published: July 2013

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. (HEPATOLOGY 2014;59:924–934)
Microstructural Failure Mechanisms in the Human Proximal Femur for Sideways Fall Loading
Authors: Nawathe Shashank , Akhlaghpour Hosna , Bouxsein Mary L , Keaveny Tony M
Published: July 2013

The etiology of hip fractures remains unclear but might be elucidated by an improved understanding of the microstructural failure mechanisms of the human proximal femur during a sideways fall impact. In this context, we biomechanically tested 12 cadaver proximal femurs (aged 76 ± 10 years; 8 female, 4 male) to directly measure strength for a sideways fall and also performed micro-computed tomography (CT)-based, nonlinear finite element analysis of the same bones (82-micron-sized elements, ∼120 million elements per model) to estimate the amount and location of internal tissue-level failure (by ductile yielding) at initial structural failure of the femur. We found that the correlation between the directly measured yield strength of the femur and the finite element prediction was high (R2 = 0.94, p < 0.0001), supporting the validity of the finite element simulations of failure. In these simulations, the failure of just a tiny proportion of the bone tissue (1.5% to 6.4% across all bones) led to initial structural failure of the femur. The proportion of failed tissue, estimated by the finite element models, decreased with decreasing measured femoral strength (R2 = 0.88, p < 0.0001) and was more highly correlated with measured strength than any measure of bone volume, mass, or density. Volume-wise, trabecular failure occurred earlier and was more prominent than cortical failure in all femurs and dominated in the very weakest femurs. Femurs with low measured strength relative to their areal bone mineral density (BMD) (by dual-energy X-ray absorptiometry [DXA]) had a low proportion of trabecular bone compared with cortical bone in the femoral neck (p < 0.001), less failed tissue (p < 0.05), and low structural redundancy (p < 0.005). We conclude that initial failure of the femur during a sideways fall is associated with failure of just a tiny proportion of the bone tissue, failure of the trabecular tissue dominating in the very weakest femurs owing in part to a lack of structural redundancy. © 2014 American Society for Bone and Mineral Research.
Diet-Derived Phenolic Acids Regulate Osteoblast and Adipocyte Lineage Commitment and Differentiation in Young Mice
Authors: Chen Jin-Ran , Lazarenko Oxana P , Zhang Jian , Blackburn Michael L , Ronis Martin JJ , Badger Thomas M
Published: July 2013

A blueberry (BB)-supplemented diet has been previously shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and they were found in the serum of rats fed BB-containing diet. We conducted in vitro studies with PAs and demonstrated stimulation of osteoblast differentiation and proliferation. On the other hand, adipogenesis was inhibited. To more fully understand the mechanistic actions of PAs on bone formation, we administered hippuric acid, one of the major metabolites found in animal circulation after BB consumption, to prepubertal female mice for 2 weeks. We found that hippuric acid was able to stimulate bone-forming gene expression but suppress PPARγ expression, leading to increased bone mass dose-dependently. Cellular signaling studies further suggested that the skeletal effects of PAs appeared to be mediated through activation of G-protein-coupled receptor 109A and downstream p38 MAP kinase and osterix. In conclusion, PAs are capable of altering the mesenchymal stem cell differentiation program and merit investigation as potential dietary therapeutic alternatives to drugs for degenerative bone disorders. © 2014 American Society for Bone and Mineral Research.
Intravenous Treatment With Ibandronate Normalizes Bone Matrix Mineralization and Reduces Cortical Porosity After Two Years in Male Osteoporosis: A Paired Biopsy Study
Authors: Misof Barbara M , Patsch Janina M , Roschger Paul , Muschitz Christian , Gamsjaeger Sonja , Paschalis Eleftherios P , Prokop Eva , Klaushofer Klaus , Pietschmann Peter , Resch Heinrich
Published: July 2013

The spectrum of therapeutic options and the amount of clinical trials for male osteoporosis (mOP) is lower than those for postmenopausal osteoporosis. Therefore, we examined the effects of 24 months of ibandronate (IBN) treatment (3 mg/3 mL intravenously every 3 months) on bone material quality in 19 subjects with mOP within an open-label, single-center, prospective phase III study (Eudract number 2006-006692-20). Patients (median age [25th, 75th percentiles] 53.0 [44.5; 57.0] years) were included if they had low bone mineral density (BMD) and/or at least one low trauma fracture and no secondary cause of osteoporosis. The primary endpoint was to evaluate IBN effects on cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) of paired transiliacal bone biopsies (baseline, 24 months). Secondary endpoints included changes in areal bone mineral density (BMD by dual-energy X-ray absorptiometry [DXA]) and serum markers of bone turnover including type I collagen peptides CrossLaps (CTX), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC). At baseline, cancellous bone matrix mineralization from mOP was lower than published reference data (mean degree of mineralization Cn.CaMean −1.8%, p < 0.01). IBN treatment increased calcium concentrations versus baseline (Cn.CaMean +2.4%, Ct.CaMean, +3.0% both p < 0.01), and reduced heterogeneity of mineralization (Cn.CaWidth −14%, p = 0.044; Ct.CaWidth, −16%, p = 0.001), leading to cancellous BMDD within normal range. IBN treatment was associated with a decrease in porosity of mineralized cortical tissue (−25%, p = 0.01); increases in BMD at the lumbar spine, the femoral neck, and the total hip (+3.3%, +1.9%, and +5.6%, respectively, p ≤ 0.01); and reductions in CTX (−37.5%), P1NP (−44.4%), and OC (−36.3%, all p < 0.01). Our BMDD findings are in line with the reduction of bone turnover markers and the increase in BMD by IBN in our patients and suggest that the latter mainly reflects the increase in matrix mineralization and the reduction of cortical porosity in this cohort with mOP. © 2014 American Society for Bone and Mineral Research.
Simultaneous observations of precipitating radiation belt electrons and ring current ions associated with the plasmaspheric plume
Authors: Yuan Zhigang , Li Ming , Xiong Ying , Li Haimeng , Zhou Meng , Wang Dedong , Huang Shiyong , Deng Xiaohua , Wang Jingfang
Published: July 2013

The wave‐particle interactions and associated precipitation of energetic ions/electrons play an important role in the coupling between the inner magnetosphere and the ionosphere. In this paper, we present characteristics of precipitating ring current (RC) ions/electrons and precipitating radiation belt electrons associated with wave‐particle interactions in the plasmaspheric plume in the main phase of a geomagnetic storm during 8–9 May 2001. With observations of the NOAA 16 satellite, within the anisotropic zone, the peak of precipitating RC electron flux was equatorward to that of precipitating RC proton flux in a plasmaspheric plume recognized by the IMAGE and LANL‐91/94 satellites. An enhancement of precipitating flux for >3 MeV electrons was simultaneously observed by NOAA 16 with the increase of precipitating RC proton flux within the anisotropic zone. Theoretical calculations of pitch angle diffusion coefficients for RC protons and for radiation belt electrons caused by electromagnetic ion cyclotron (EMIC) waves demonstrated that precipitating flux enhancements of RC protons and >3 MeV radiation belt electrons are a result of EMIC wave‐particle interactions in the plasmaspheric plume. Our result suggests that EMIC waves in the plasmaspheric plume can scatter not only RC ions but also radiation belt electrons into the loss cone, which cause the loss of the RC ions and radiation belt electrons.
Spectroscopic diagnostics of laboratory air plasmas as a benchmark for spectral rotational (gas) temperature determination in TLEs
Authors: Parra‐Rojas F. C. , Passas M. , Carrasco E. , Luque A. , Tanarro I. , Simek M. , Gordillo‐Vázquez F. J.
Published: July 2013

We have studied laboratory low pressure (0.1 mbar ≤ p ≤2 mbar) glow air discharges by optical emission spectroscopy to discuss several spectroscopic techniques that could be implemented by field spectrographs, depending on the available spectral resolution, to experimentally quantify the gas temperature associated to transient luminous events (TLEs) occurring at different altitudes including blue jets, giant blue jets, and sprites. Laboratory air plasmas have been analyzed from the near UV (300 nm) to the near IR (1060 nm) with high (up to 0.01 nm) and low (2 nm) spectral resolution commercial grating spectrographs and by an in‐house intensified CCD grating spectrograph that we have recently developed for TLE spectral diagnostic surveys with ≃0.45 nm spectral resolution. We discuss the results of lab tests and comment on the convenience of using one or another technique for rotational (gas) temperature determination depending on the altitude and available spectral resolution. Moreover, we compare available low resolution (3 nm ≤Δλ≤7 nm) N2 1PG field recorded sprite spectra at 53 km (≃1 mbar), and resulting vibrational distribution function, with 1 mbar laboratory glow discharge spectrum (Δλ=2 nm) and synthetic sprite spectra from models. We found that while the relative population of N2(B3Πg,v=2−7) in sprites and laboratory produced air glow plasmas are similar, the N2(B3Πg,v=1) vibrational level in sprites is more efficiently populated (in agreement with model predictions) than in laboratory air glow plasmas at similar pressures.
Pulsating auroral electron flux modulations in the equatorial magnetosphere
Authors: Jaynes A. N. , Lessard M. R. , Rodriguez J. V. , Donovan E. , Loto'aniu T. M. , Rychert K.
Published: July 2013

In this study, we present the first in situ continuous measurements of electron flux modulations in the near‐equatorial magnetosphere correlated with pulsating aurora (PA) observations. The contested conjecture that the source of these electrons originates near the equator, made decades ago using sounding rocket data, has now been confirmed using this data. We compared the frequencies of equatorial electron flux pulsations and PA luminosity fluctuations at their ionospheric footprint, using simultaneous satellite‐ and ground‐based data from GOES 13 and Time History of Events and Macroscale Interactions during Substorms (THEMIS) instrumentation. Observations of PA were obtained on 15 March 2008 using a THEMIS All‐Sky Imager (ASI) located in northern Canada. The field line footprint of the geostationary GOES 13 satellite, mapped down to the ionosphere at ∼100 km, falls within the field‐of‐view of the ASI. We examined electron flux data from the Magnetospheric Electron Detector (MAGED) on GOES 13, in the energy range of 30 to 50 keV, by computing an array of the correlation coefficients between the pixel luminosity for each individual pixel of the ASI images and the flux measurements at the satellite. The results reveal a direct correlation between diffuse luminosity fluctuation periods near the ground and particle pulsation periods. The time variance between the two data sets was examined in order to explore the validity of the equatorial source region premise. The resulting time lag of < 1 s in the PA measurements is consistent with this claim. We also report on a preliminary quantification of the loss cone using the MAGED telescope response functions.
Characteristics of penetration electric fields to the equatorial ionosphere during southward and northward IMF turnings
Authors: Bhaskar Ankush , Vichare Geeta
Published: July 2013

The signatures of abrupt turnings of the vertical component of the interplanetary magnetic field (IMF), Bz, can be seen at equatorial latitudes through the prompt transmission of high‐latitude electric fields to the lower latitudes, called as prompt penetration electric field (PPE). The present work studies the signatures of PPE in daytime equatorial electrojet (EEJ) index derived in the Indian sector during 2001–2005. The signatures are observed in polar (PCN index) and equatorial (EEJ index) ionosphere almost instantaneously (<1 min). The communication time of 12±6 min is observed between bow shock nose and the equatorial ionosphere, and it is found to have inverse relationship with radial component of solar wind velocity during southward and northward Bz turnings which might indicate magnetosphere crossing time scale by solar wind. Ionospheric reconfiguration time during southward turnings shows inverse relationship with solar wind flow in contrast to northward turnings with “no relationship,” indicating differences in underlying physical mechanisms during both turnings. We observe no local time dependence (within 06–18 h) in conductivity‐corrected EEJ signatures associated with Bz turnings. Regression analysis between conductivity‐corrected EEJ and interplanetary electric field shows higher efficiency during northward turnings. However, further analysis investigating the effect of actual orientation of Bz indicates that the magnitude of northward Bz does not have influence on the ionospheric signatures. It is noticed that the response signatures are mainly controlled by the magnitudes of southward Bz. Thus, the present study signifies the role of inner magnetospheric shielding electric field in addition to ceasing of convection during northward turnings.
Responses of Earth's radiation belts to solar wind dynamic pressure variations in 2002 analyzed using multisatellite data and Kalman filtering
Authors: Ni Binbin , Shprits Yuri Y. , Friedel Reiner H. W. , Thorne Richard M. , Daae Marianne , Chen Yue
Published: July 2013

It has been difficult to establish a definitive causal link between radiation belt electron dropouts and solar wind dynamic pressure, due to adiabatic effects and observations limited to a single location in space at one time. Here we reconstruct the radial profiles of radiation belt electron phase space density (PSD) for the entire year of 2002 (solar maximum), based on a combination of the VERB radial diffusion model and data assimilation of the sparse observations from six satellites including GEO1989, GEO1990, LANL‐97A, LANL‐01A, GPSns33, and POLAR, to perform a statistical analysis of the potential relationship between electron PSD dropout and solar wind dynamic pressure variation. We capture 59 electron PSD dropout events, 81% associated with solar wind dynamic pressure sudden jumps (i.e., pulses) or modest increase, consistent with the results of Shprits et al. (2012) for the period of 1990–1991. With the continuous availability of high quality solar wind data in 2002, we further identify 41 pressure pulses and determine that 68% of them are associated with electron PSD dropouts. We also identify 49 pressure enhancements, 41% of which are associated with electron PSD dropouts. Our results support that gradual or sharp enhancements in solar wind dynamic pressure can play an important role in producing electron PSD dropouts, owing to inward intrusion of the magnetopause that enhances the loss to the magnetopause and outward radial diffusion. But we conclusively demonstrate that solar wind dynamic pressure pulses and enhancements are neither a necessary nor a sufficient condition for the formation of electron PSD dropouts, which suggests that some other mechanism(s), which remains mysterious, is required to explain electron PSD dropout occurrences without pressure pulse or modest pressure increase. For the first time, we also perform a quantitative comparison of conjunctions between electron PSD reanalysis results and satellite PSD data, which indicates a tolerable and reasonable error in assimilated PSD within a factor of 5. Differences in assimilated PSD and satellite PSD have a potential for use to evaluate the ignored processes in the physical model and to estimate the errors associated with satellite measurements.
Direct top‐down estimates of biomass burning CO emissions using TES and MOPITT versus bottom‐up GFED inventory
Authors: Pechony Olga , Shindell Drew T. , Faluvegi Greg
Published: July 2013

In this study, we utilize near‐simultaneous observations from two sets of multiple satellite sensors to segregate Tropospheric Emission Spectrometer (TES) and Measurements of Pollution in the Troposphere (MOPITT) CO observations over active fire sources from those made over clear background. Hence, we obtain direct estimates of biomass burning CO emissions without invoking inverse modeling as in traditional top‐down methods. We find considerable differences between Global Fire Emissions Database (GFED) versions 2.1 and 3.1 and satellite‐based emission estimates in many regions. Both inventories appear to greatly underestimate South and Southeast Asia emissions, for example. On global scales, however, CO emissions in both inventories and in the MOPITT‐based analysis agree reasonably well, with the largest bias (30%) found in the Northern Hemisphere spring. In the Southern Hemisphere, there is a one‐month shift between the GFED and MOPITT‐based fire emissions peak. Afternoon tropical fire emissions retrieved from TES are about two times higher than the morning MOPITT retrievals. This appears to be both a real difference due to the diurnal fire activity variations, and a bias due to the scarcity of TES data.
The role of coherent flow structures in the sensible heat fluxes of an Alaskan boreal forest
Authors: Starkenburg Derek , Fochesatto Gilberto J. , Prakash Anupma , Cristóbal Jordi , Gens Rudiger , Kane Douglas L.
Published: July 2013

Accelerations in the flow over forests generate coherent structures which locally enhance updrafts and downdrafts, forcing rapid exchanges of energy and matter. Here, observations of the turbulent flow are made in a highly heterogeneous black spruce boreal forest in Fairbanks, Alaska at ~2.6 h (12 m) and ~0.6 h (3 m), where h is the mean canopy height of 4.7 m. Wavelet analysis is used to detect coherent structures. The sonic temperature and wind data cover 864 half‐hour periods spanning winter, spring, and summer. When mean global statistics of structures are analyzed at the two levels independently, results are similar to other studies. Specifically, an average of eight structures occurs per period, their mean duration is 85 s, and their mean heat flux contribution is 48%. However, this analysis suggests that 31% of the structures detected at 2.6 h, and 13% at 0.6 h, may be influenced by wave‐like flow organization. Remarkably, less than 25% of the structures detected occur synchronously in the subcanopy and above canopy levels, which speaks robustly to the lack of flow interaction within only nine vertical meters of the forest.
Modified MALDI MS fatty acid profiling for bacterial identification
Authors: Voorhees Kent J. , Jensen Kirk R. , McAlpin Casey R. , Rees Jon C. , Cody Robert , Ubukata Masaaki , Cox Christopher R.
Published: July 2013

Bacterial fatty acid profiling is a well‐established technique for bacterial identification. Ten bacteria were analyzed using both positive‐ and negative‐ion modes with a modified matrix‐assisted laser desorption ionization mass spectrometry (MALDI MS) approach using CaO as a matrix replacement (metal oxide laser ionization MS (MOLI MS)). The results show that reproducible lipid cleavage similar to thermal in situ tetramethyl ammonium hydroxide saponification/derivatization had occurred. Principal component analysis showed that replicates from each organism grouped in a unique space. Cross validation (CV) of spectra from both ionization modes resulted in greater than 94% validation of the data. When CV results were compared for the two ionization modes, negative‐ion data produced a superior outcome. MOLI MS provides clinicians a rapid, reproducible and cost‐effective bacterial diagnostic tool. Copyright © 2013 John Wiley & Sons, Ltd.
The ornithine effect in peptide cation dissociation
Authors: McGee William M. , McLuckey Scott A.
Published: July 2013

Facile cleavage C‐terminal to ornithine residues in gas phase peptides has been observed and termed the ornithine effect. Peptides containing internal or C‐terminal ornithine residues, which are formed from deguanidination of arginine in solution, were fragmented to produce either a y‐ion or water loss, respectively, and the complementary b‐ion. The fragmentation patterns of several peptides containing arginine were compared to those of the ornithine analogues. Conversion of arginine to ornithine results in a decrease of the gas phase proton affinity of the residue, thereby increasing the mobility of the ionizing proton. This alteration allows the nucleophilic amine to facilitate a neighboring group reaction to induce a cleavage of the adjacent amide bond. The selective cleavage at the ornithine residue is proposed to result from the highly favorable generation of a six‐membered lactam ring. The ornithine effect was compared with the well‐known proline and aspartic acid effects in peptide fragmentation using angiotensin II, DRVYIHPF and the ornithine analogue, DOVYIHPF. Under conditions favorable to either the aspartic acid (i.e. singly protonated peptide) or proline effect (i.e. doubly protonated peptide), the ornithine effect was consistently observed to be the more favorable fragmentation pathway. The highly selective nature of the ornithine effect opens up the possibility for conversion of arginine to ornithine residues to induce selective cleavages in polypeptide ions. Such an approach may complement strategies that seek to generate non‐selective cleavages of the related peptides. Copyright © 2013 John Wiley & Sons, Ltd.
Sodiation as a tool for enhancing the diagnostic value of MALDI‐TOF/TOF‐MS spectra of complex astaxanthin ester mixtures from Haematococcus pluvialis
Authors: Weesepoel Yannick , Vincken Jean‐Paul , Pop Raluca Maria , Liu Kun , Gruppen Harry
Published: July 2013

The microalga Haematococcus pluvialis produces the pigment astaxanthin mainly in esterified form with a multitude of fatty acids, which results in a complex mixture of carotenol mono‐ and diesters. For rapid fingerprinting of these esters, matrix‐assisted laser desorption ionization time of flight mass spectrometry (MALDI‐TOF/TOF‐MS) might be an alternative to traditional chromatographic separation combined with MS. Investigation of ionization and fragmentation of astaxanthin mono‐ and diester palmitate standards in MALDI‐TOF/TOF‐MS showed that sodium adduct parent masses [M + Na]+ gave much simpler MS2 spectra than radical / protonated [M]+● / [M + H]+ parents. [M + Na]+ fragments yielded diagnostic polyene‐specific eliminations and fatty acid neutral losses, whereas [M]+● / [M + H]+ fragmentation resulted in a multitude of non‐diagnostic daughters. For diesters, a benzonium fragment, formed by polyene elimination, was required for identification of the second fatty acid attached to the astaxanthin backbone. Parents were forced into [M + Na]+ ionization by addition of sodium acetate, and best signal‐to‐noise ratios were obtained in the 0.1 to 1.0 mM range. This method was applied to fingerprinting astaxanthin esters in a crude H. pluvialis extract. Prior to MALDI‐TOF/TOF‐MS, the extract was fractionated by normal phase Flash chromatography to obtain fractions enriched in mono‐ and diesters and to remove pheophytin a, which compromised monoester signals. All 12 types of all‐trans esterified esters found in LC were identified with MALDI‐TOF/TOF‐MS, with the exception of two minor monoesters. Copyright © 2013 John Wiley & Sons, Ltd.
Stepwise optimization approach for improving LC‐MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design
Authors: Kostić Nađa , Dotsikas Yannis , Malenović Anđelija , Stojanović Biljana Jančić , Rakić Tijana , Ivanović Darko , Medenica Mirjana
Published: July 2013

In this article, a step‐by‐step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate‐mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal‐to‐noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC‐MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vigabatrin, pregabalin and gabapentin, respectively, while for signal‐to‐noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time‐segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0 ng ml−1–10.0 × 103 ng ml−1). Copyright © 2013 John Wiley & Sons, Ltd.
Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres
Authors: Sonnet Corinne , Simpson C. LaShan , Olabisi Ronke M. , Sullivan Kayleigh , Lazard ZaWaunyka , Gugala Zbigniew , Peroni John F. , Weh J. Michael , Davis Alan R. , West Jennifer L. , Olmsted‐Davis Elizabeth A.
Published: July 2013

Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic “carrier” cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm‐long femur defect in a rat model occurs in under 3 weeks, through secretion of 100‐fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2–3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1597–1604, 2013
Tibiofemoral centroid velocity correlates more consistently with cartilage damage than does contact path length in two ovine models of stifle injury
Authors: Beveridge Jillian E. , Heard Bryan J. , Shrive Nigel G. , Frank Cyril B.
Published: July 2013

Anterior cruciate ligament (ACL) rupture and/or meniscal injury are known risk factors for post‐traumatic osteoarthritis. We tested the hypothesis that increasingly abnormal tibiofemoral centroid path lengths and velocities would correlate with the severity of cartilage damage in injured sheep. Six sheep underwent combined ACL/medial collateral ligament transection (ACL/MCLx), five complete lateral meniscectomy (Mx), and four sham arthrotomy (Sham). Weighted centroids were used to estimate in vivo tibiofemoral cartilage contact path length during stance and the velocity of relative motion. Cartilage morphology was graded at dissection. Ligament transection significantly elongated plateau centroid path lengths and velocities, whereas condyle paths and velocities were reduced. Differences between plateau and femoral velocities (relative centroid velocity) were increased up to 10‐fold over baseline values in the medial compartment. Reductions in Mx lateral compartment paths were significantly different from ACL/MCLx paths, but not relative to baseline or Sham values. Importantly, only centroid velocities consistently correlated with cartilage damage in either injury model, suggesting that while path length is valuable in detecting changes in the envelope of joint motion, it may average out meaningful peaks in the rate of relative motion that more closely relate to the mechanisms that might be damaging articular cartilage in these models. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1745–1756, 2013