bluuebunny/crossref_metadata_2025 huggingface dataset:
A preliminary disease severity score for juvenile systemic sclerosis
Authors: La Torre Francesco , Martini Giorgia , Russo Ricardo , Katsicas Maria Marta , Corona Fabrizia , Calcagno Giuseppina , Falcini Fernanda , Vittadello Fabio , Zulian Francesco
Published: August 2012

Objective

To develop a preliminary disease severity score for juvenile systemic sclerosis (SSc).

Methods

We conducted an evidence‐ and consensus‐based study that included the following 5 phases: 1) prospective collection of data regarding the demographic and clinical characteristics of patients with diffuse juvenile SSc who were followed up for at least 4 years or until death; 2) blinded evaluation of the disease course profiles of these patients by experts in juvenile SSc, so that patient profiles with a defined clinical course could be used as the gold standard for the score validation phase; 3) definition of candidate severity indices to be included in potential scores; 4) selection of the pediatric severity score with the best statistical performance, as determined by its ability to classify individual patients as having improvement or worsening of disease compared with baseline values or the previous evaluation; 5) validation of the efficiency of the selected score in patients with a mild, moderate, or severe disease course and comparison with the Medsger severity score for adults with SSc.

Results

Thirty‐five patients classified as having a mild (n = 17), moderate (n = 10), or severe (n = 8) disease course entered the study. The selected pediatric SSc score, defined as the Juvenile Systemic Sclerosis Severity Score (J4S), included indices of 9 organ systems each scored on a scale of 0–4. To weight the importance of the involvement of different organ systems, a coefficient of severity was introduced. Compared with the modified Medsger severity score, the J4S performed significantly better in detecting change in severity, both in patients with a moderate disease course (0.89 versus 0.52) and in patients with a severe disease course (0.82 versus 0.75).

Conclusion

The J4S is a valid instrument to assess disease severity in juvenile SSc.
Brief Report: Association of HLA–DRB1*0101/*0405 with susceptibility to anti–melanoma differentiation–associated gene 5 antibody–positive dermatomyositis in the Japanese population
Authors: Gono Takahisa , Kawaguchi Yasushi , Kuwana Masataka , Sugiura Tomoko , Furuya Takefumi , Takagi Kae , Ichida Hisae , Katsumata Yasuhiro , Hanaoka Masanori , Ota Yuko , Yamanaka Hisashi
Published: August 2012

Objective

The complication of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) is associated with anti–aminoacyl–transfer RNA synthetase (anti‐aaRS) antibody or anti–melanoma differentiation–associated gene 5 (anti–MDA‐5) antibody positivity. Anti–MDA‐5 antibody is associated with clinically amyopathic DM and fatal outcome due to rapidly progressive ILD in Asian populations. The association between genetic factors and anti–MDA‐5 antibody–positive DM is unclear. This study was undertaken to investigate the HLA–DRB1 genotype in patients with anti–MDA‐5 antibody–positive DM.

Methods

We examined genetic differences among 17 patients with anti–MDA‐5 antibody–positive DM, 33 patients with anti‐aaRS antibody–positive PM/DM, 33 patients with PM/DM without anti‐aaRS antibody or ILD, and 265 healthy controls.

Results

The frequencies of HLA–DRB1*0101 and DRB1*0405 were 29% and 71%, respectively, in patients with anti–MDA‐5 antibody–positive DM, which were higher than the frequencies in healthy controls (10% and 25%, respectively). Among the 17 patients with anti–MDA‐5 antibody–positive DM, 16 (94%) harbored either the DRB1*0101 or DRB1*0405 allele. The combined frequency of the DRB1*0101 allele and the DRB1*0405 allele was significantly higher in patients with anti–MDA‐5 antibody–positive DM than in patients with PM/DM without anti‐aaRS antibody or ILD, with an odds ratio (OR) of 42.7 (95% confidence interval [95% CI] 4.9–370.2) (P = 1.1 × 10−5), or in patients with anti‐aaRS antibody–positive PM/DM (OR 13.3 [95% CI 1.6–112.6], P = 4.5 × 10−3).

Conclusion

Our findings indicate that HLA–DRB1*0101/*0405 is associated with susceptibility to anti–MDA‐5 antibody–positive DM in the Japanese population.
Macrophage activation syndrome in children with systemic lupus erythematosus and children with juvenile idiopathic arthritis
Authors: Bennett Tellen D. , Fluchel Mark , Hersh Aimee O. , Hayward Kristen N. , Hersh Adam L. , Brogan Thomas V. , Srivastava Rajendu , Stone Bryan L. , Korgenski E. Kent , Mundorff Michael B. , Casper T. Charles , Bratton Susan L.
Published: August 2012

Objective

To describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA).

Methods

We performed a retrospective cohort study using data recorded in the Pediatric Health Information System (PHIS) database from October 1, 2006 to September 30, 2010. Participants had International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality (for the index admission). Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use.

Results

A total of 121 children at 28 children's hospitals met the inclusion criteria, including 19 children with SLE and 102 children with JIA. The index admission mortality rate was 7% (8 of 121 patients). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had a similar mortality rate (6% versus 11%, respectively; exact P = 0.6). More patients with SLE than those with JIA received ICU care (63% versus 27%; P = 0.002), received mechanical ventilation (53% versus 21%; P = 0.003), and had cardiovascular dysfunction (47% versus 23% received inotrope/vasopressor therapy; P = 0.02). Children with SLE and those with JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil, and more children with JIA received interleukin‐1 antagonists.

Conclusion

Organ system dysfunction is common in children with rheumatic diseases complicated by MAS, and more organ system support is required in children with underlying SLE than in children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease.
Brief Report: Enrichment of associations in genes with fibrosis, apoptosis, and innate immunity functions with cardiac manifestations of neonatal lupus
Authors: Ramos Paula S. , Marion Miranda C. , Langefeld Carl D. ,   the International Consortium on Systemic Lupus Erythematosus Genetics, Buyon Jill P. , Clancy Robert M.
Published: August 2012

Objective

The proposed pathogenesis of the cardiac manifestations of neonatal lupus (cardiac‐NL) involves maternal autoantibodies to the RNPs SSA/Ro and SSB/La, enhanced by as‐yet‐unknown factors that likely involve dysregulation of both inflammatory and fibrotic fetal responses. This study was designed to improve the power to detect specific associations in genes with candidate biologic functions.

Methods

Using data from our genome‐wide association study of 116 Caucasian children with cardiac‐NL and 3,351 Caucasian controls, we tested for enrichment of single‐nucleotide polymorphism (SNP) associations in genes with candidate biologic functions related to fibrosis, immune function, apoptosis, T cell function, cell infiltration, innate immune cell function, interferon, Toll‐like receptors, and calcium channels. After linkage disequilibrium pruning and exclusion of the extended HLA region, a total of 15,103 SNPs in 3,068 genes remained.

Results

A highly significant enrichment of P values was observed for genes related to fibrosis (P = 2.27 × 10−9), apoptosis (P = 7.67 × 10−7), and innate immune cell (P = 2.53 × 10−6), immune (P = 5.01 × 10−4), T cell (P = 2.23 × 10−4), and interferon functions (P = 1.64 × 10−3). The most significant non‐HLA associations included the sialyltransferase gene ST8SIA2 (rs1487982; odds ratio 2.20 [95% confidence interval 1.52–3.19], P = 3.37 × 10−5), the integrin gene ITGA1 (rs2432143; odds ratio 2.31 [95% confidence interval 1.54–3.45], P = 4.54 × 10−5), and the complement regulator gene CSMD1 (rs7002001; odds ratio 2.41 [95% confidence interval 1.57–3.72], P = 6.33 × 10−5).

Conclusion

This study identified novel candidate genes associated with cardiac‐NL and highlights the value of studying this cohort for advancing knowledge regarding the genetic etiology of this syndrome. Identification of causal alleles is expected to provide critical insight into the molecular mechanisms responsible for linking maternal autoantibodies to cardiac scarring in these fetuses/neonates.
Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C‐terminus
Authors: Struglics André , Lohmander L. Stefan , Last Karena , Akikusa Jonathan , Allen Roger , Fosang Amanda J.
Published: August 2012

Objective

To investigate aggrecan degradation in juvenile idiopathic arthritis (JIA).

Methods

The pattern and abundance of aggrecan fragments in synovial fluid (SF) aspirates from JIA patients were analyzed and compared with aggrecan fragments in SF from patients with other arthritides, children with knee injury, and a knee‐healthy reference group. Concentrations of sulfated glycosaminoglycan (sGAG) in SF were measured by Alcian blue precipitation assay. Aggrecan fragments were purified by dissociative CsCl density‐gradient centrifugation, deglycosylated, and analyzed by Western blot using antibodies specific for either aggrecanase‐derived ARGS, SELE, and KEEE neoepitopes or the aggrecan G3 domain.

Results

The concentration of sGAG in SF from patients with JIA was significantly lower compared with that in SF from patients with osteoarthritis (OA) (P < 0.001), patients with juvenile knee injury (P = 0.006), and knee‐healthy controls (P = 0.022). Western blot analysis revealed KEEE, SELE, and G3 fragments generated by aggrecanase cleavage in the chondroitin sulfate–rich region of aggrecan in patients with JIA. The pattern of aggrecan fragments in JIA patients was not identical to that in pooled OA SF, although there were notable similarities. Surprisingly, aggrecanase‐derived ARGS fragments were barely detectable in JIA SF, in marked contrast to levels in OA SF.

Conclusion

Aggrecanases appear to cleave minimally in the interglobular domain of aggrecan in JIA patients despite robust levels of cleavage in the chondroitin sulfate–rich region. These results suggest that in JIA, unlike other arthritides, aggrecanase cleavage in the aggrecan interglobular domain might not be a major pathogenic event.
Distribution of CYP2C9*13 allele in the Chinese Han and the long‐range haplotype containing CYP2C9*13 and CYP2C19*2
Authors: Si Dayong , Wang Juan , Zhang Yifan , Zhong Dafang , Zhou Hui
Published: August 2012

Cytochrome P450 2C9 (CYP2C9) and CYP2C19, located in tandem on chromosome 10q23–24, are known as genetically polymorphic. CYP2C9*13 is an important CYP2C9 variant in Asian populations, and is correlated with the reduced plasma clearance of some clinically important drugs. In this research, the allele frequency of CYP2C9*13 was determined to be 0.42% (95% CI of 0.17% to 0.86%) in 839 Chinese Han, male subjects. All detected subjects with CYP2C9*13 carry the CYP2C19*2 allele, too. Sequencing results infer the CYP2C9*13 haplotype, which contains eight linked SNPs, originates from the CYP2C9*1B haplotype group. CYP2C9*1B has been reported to be linked with CYP2C19*2. These indicate a long‐range haplotype containing the CYP2C9*13 and CYP2C19*2 mutation, which means most CYP2C9*13 carriers will carry the CYP2C19*2 allele and the six SNPs of the CYP2C9*1B haplotype group, and may have more reduced intrinsic clearance of drugs such as phenytoin, tolbutamide and chlorpropamide that are metabolized by both CYP2C9 and CYP2C19. Copyright © 2012 John Wiley & Sons, Ltd.
Current status of drug screening and disease modelling in human pluripotent stem cells
Authors: Rajamohan Divya , Matsa Elena , Kalra Spandan , Crutchley James , Patel Asha , George Vinoj , Denning Chris
Published: August 2012

The emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overcome to fully realise the potential of hPSCs. Details are provided for all disease‐specific human induced pluripotent stem cell lines spanning a dozen dysfunctional organ systems. Phenotype and pharmacology have been examined in only 17 of 63 lines, primarily those that model neurological and cardiac conditions. Drug screening is most advanced in hPSC‐cardiomyocytes. Responses for almost 60 agents include examples of how careful tests in hPSC‐cardiomyocytes have improved on existing in vitro assays, and how these cells have been integrated into high throughput imaging and electrophysiology industrial platforms. Such successes will provide an incentive to overcome bottlenecks in hPSC technology such as improving cell maturity and industrial scalability whilst reducing cost.
Cumulative disease progression models for cross‐sectional data: A review and comparison
Authors: Hainke Katrin , Rahnenführer Jörg , Fried Roland
Published: August 2012

A better understanding of disease progression is beneficial for early diagnosis and appropriate individual therapy. Many different approaches for statistical modelling of cumulative disease progression have been proposed in the literature, including simple path models up to complex restricted Bayesian networks. Important fields of application are diseases such as cancer and HIV. Tumour progression is measured by means of chromosome aberrations, whereas people infected with HIV develop drug resistances because of genetic changes of the HI‐virus. These two very different diseases have typical courses of disease progression, which can be modelled partly by consecutive and partly by independent steps.

This paper gives an overview of the different progression models and points out their advantages and drawbacks. Different models are compared via simulations to analyse how they work if some of their assumptions are violated. In a simulation study, we evaluate how models perform in terms of fitting induced multivariate probability distributions and topological relationships. We often find that the true model class used for generating data is outperformed by either a less or a more complex model class. The more flexible conjunctive Bayesian networks can be used to fit oncogenetic trees, whereas mixtures of oncogenetic trees with three tree components can be well fitted by mixture models with only two tree components.
Proline dehydrogenase (oxidase) in cancer
Authors: Liu Wei , Phang James M.
Published: August 2012

Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the proline degradative pathway, plays a special role in tumorigenesis and tumor development. Proline metabolism catalyzed by PRODH/POX is closely linked with the tricarboxylic acid (TCA) cycle and urea cycle. The proline cycle formed by the interconversion of proline and Δ1‐pyrroline‐5‐carboxylate (P5C) between mitochondria and cytosol interlocks with pentose phosphate pathway. Importantly, by catalyzing proline to P5C, PRODH/POX donates electrons into the electron transport chain to generate ROS or ATP. In earlier studies, we found that PRODH/POX functions as a tumor suppressor to initiate apoptosis, inhibit tumor growth, and block the cell cycle, all by ROS signaling. It also suppresses hypoxia inducible factor signaling by increasing α‐ketoglutarate. During tumor progression, PRODH/POX is under the control of various tumor‐associated factors, such as tumor suppressor p53, inflammatory factor peroxisome proliferator‐activated receptor gamma (PPARγ), onco‐miRNA miR‐23b*, and oncogenic transcription factor c‐MYC. Recent studies revealed the two‐sided features of PRODH/POX‐mediated regulation. Under metabolic stress such as oxygen and glucose deprivation, PRODH/POX can be induced to serve as a tumor survival factor through ATP production or ROS‐induced autophagy. The paradoxical roles of PRODH/POX can be understood considering the temporal and spatial context of the tumor. Further studies will provide additional insights into this protein and on its metabolic effects in tumors, which may lead to new therapeutic strategies. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Evaluation of density and distribution of CART‐immunoreactive structures in gastrointestinal tract of hypertensive rats
Authors: Kasacka Irena , Piotrowska Żaneta
Published: August 2012

The prevalence of CART (cocaine‐ and amphetamine‐regulated transcript) throughout the organism, multiplicity of functions fulfilled by that peptide, and the collected evidence confirming CART contribution to blood pressure regulation prompted us to undertake the research aiming to identify, localize, and assess changes in CART‐immunopositive structures of the gastrointestinal tract (GI tract) of rats with renovascular hypertension. The two‐kidney one‐clip model of arterial hypertension was used to evaluate the location and density of CART‐containing structures in the stomach (cardia, fundus, and pylorus), duodenum, jejunum, ileum, and colon of hypertensive rats. The study was carried out on the GI tract of 20 rats. Ten rats were subjected to the renal artery clipping procedure and after a 6‐week period each of them developed stable hypertension. An immunohistochemical localization of CART was performed on paraffin GI tract sections from all the study animals. CART was detected in the extensive population of neurons, particularly within the myenteric plexuses all along the GI tract, and also in neuroendocrine cells, being especially numerous in the stomach and a few in the small intestine. The hypertension significantly increased the density of CART‐positive structures in the rat GI tract. The differences between the hypertensive rats and the control animals concerned not only the density of CART‐immunoreactive structures but also the staining intensity. As this study provides novel findings, we are planning further molecular examinations to better understand the impact of hypertension on the functioning and activity of CART in the GI tract. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Stepping stones in DNA sequencing
Authors: Stranneheim Henrik , Lundeberg Joakim
Published: August 2012

In recent years there have been tremendous advances in our ability to rapidly and cost‐effectively sequence DNA. This has revolutionized the fields of genetics and biology, leading to a deeper understanding of the molecular events in life processes. The rapid technological advances have enormously expanded sequencing opportunities and applications, but also imposed strains and challenges on steps prior to sequencing and in the downstream process of handling and analysis of these massive amounts of sequence data. Traditionally, sequencing has been limited to small DNA fragments of approximately one thousand bases (derived from the organism's genome) due to issues in maintaining a high sequence quality and accuracy for longer read lengths. Although many technological breakthroughs have been made, currently the commercially available massively parallel sequencing methods have not been able to resolve this issue. However, recent announcements in nanopore sequencing hold the promise of removing this read‐length limitation, enabling sequencing of larger intact DNA fragments. The ability to sequence longer intact DNA with high accuracy is a major stepping stone towards greatly simplifying the downstream analysis and increasing the power of sequencing compared to today. This review covers some of the technical advances in sequencing that have opened up new frontiers in genomics.
HDAC8 substrates: Histones and beyond
Authors: Wolfson Noah A. , Pitcairn Carol Ann , Fierke Carol A.
Published: August 2012

The lysine deacetylase family of enzymes (HDACs) was first demonstrated to catalyze deacetylation of acetyllysine residues on histones. In subsequent years, HDACs have been shown to recognize a large pool of acetylated nonhistone proteins as substrates. Recently, thousands of acetylated proteins have been discovered, yet in most cases, the HDAC that catalyzes deacetylation in vivo has not been identified. This gap has created the need for better in vivo, in vitro, and in silico approaches for determining HDAC substrates. While HDAC8 is the best kinetically and structurally characterized HDAC, few efficient substrates have yet been substantiated in vivo. In this review, we delineate factors that may be important for determining HDAC8 substrate recognition and catalytic activity, including structure, complex formation, and post‐translational modifications. This summary provides insight into the challenges of identifying in vivo substrates for HDAC8, and provides a good vantage point for understanding the variables important for predicting HDAC substrate recognition. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 112–126, 2013.
Effect of detergents on the thermal behavior of elastin‐like polypeptides
Authors: Thapa Arjun , Han Wei , Simons Robin H. , Chilkoti Ashutosh , Chi Eva Y. , López Gabriel P.
Published: August 2012

Elastin‐like polypeptide (ELP) fusions have been designed to allow large‐scale, nonchromatographic purification of many soluble proteins by using the inverse transition cycling (ITC) method; however, the sensitivity of the aqueous lower critical solubility phase transition temperature (Tt) of ELPs to the addition of cosolutes, including detergents, may be a potential hindrance in purification of proteins with surface hydrophobicity in such a manner. To identify detergents that are known to solubilize such proteins (e.g., membrane proteins) and that have little effect on the Tt of the ELP, we screened a number of detergents with respect to their effects on the Tt and secondary structures of a model ELP (denoted here as ELP180). We found that mild detergents (e.g., n‐dodecyl‐β‐D‐maltoside, Triton‐X100, and 3‐[(3‐cholamidopropyl) dimethylamino]‐1‐propanesulfonate) do not alter the phase transition behavior or structure (as probed by circular dichroism) of ELP180. This result is in contrast to previous studies that showed a strong effect of other detergents (e.g., sodium dodecylsulfate) on the Tt of ELPs. Our results clearly indicate that mild detergents do not preclude ITC‐based separation of ELPs, and thus that ELP fusions may prove to be useful in the purification of detergent‐solubilized recombinant hydrophobic proteins, including membrane proteins, which are otherwise notoriously difficult to extract and purify by conventional separation methods (e.g., chromatography). © 2012 Wiley Periodicals, Inc.
Structural and dynamical properties of KTS‐disintegrins: A comparison between Obtustatin and Lebestatin
Authors: Daidone Isabella , Aschi Massimiliano , Patamia Maria , Bozzi Argante , Petruzzelli Raffaele
Published: August 2012

Obtustatin and Lebestatin are lysine‐threonine‐serine (KTS)‐disintegrins, which are a family of low molecular weight polypeptides present in many viperidae venoms and are potent and specific inhibitors of collagen‐binding integrins. The integrin binding loop, harboring the 21KTS23 motif, and the C‐terminal tail are known to be responsible for the selective binding to the α1β1 integrin. Despite a very high sequence homology (only two mutations are present in Lebestatin relative to Obtustatin, namely R24L and S38L), Lebestatin exhibits a higher inhibitory effect than Obtustatin on cell adhesion and cell migration to collagens I and IV. Here we show, by means of molecular dynamics simulations of the two polypeptides in aqueous solution, that Lebestatin possesses a higher flexibility of the C‐terminal tail and a greater solvent accessibility of the integrin binding loop than Obtustatin. It may be hypothesized that these properties may contribute to the higher binding‐affinity of Lebestatin to its biological partner. © 2012 Wiley Periodicals, Inc.
Enzymatic Glycosylation of Small Molecules: Challenging Substrates Require Tailored Catalysts
Authors: Desmet Tom , Soetaert Wim , Bojarová Pavla , Křen Vladimir , Dijkhuizen Lubbert , Eastwick‐Field Vanessa , Schiller Alexander
Published: August 2012

Glycosylation can significantly improve the physicochemical and biological properties of small molecules like vitamins, antibiotics, flavors, and fragrances. The chemical synthesis of glycosides is, however, far from trivial and involves multistep routes that generate lots of waste. In this review, biocatalytic alternatives are presented that offer both stricter specificities and higher yields. The advantages and disadvantages of different enzyme classes are discussed and illustrated with a number of recent examples. Progress in the field of enzyme engineering and screening are expected to result in new applications of biocatalytic glycosylation reactions in various industrial sectors.
Absolute Configuration and Enantiodifferentiation of a Hemicryptophane Incorporating an Azaphosphatrane Moiety
Authors: Payet Elina , Dimitrov‐Raytchev Pascal , Chatelet Bastien , Guy Laure , Grass Stephane , Lacour Jerome , Dutasta Jean‐Pierre , Martinez Alexandre
Published: August 2012

The hemicryptophane racemate (±)‐M-1, P-1 was optically resolved by semipreparative HPLC on Chiralpak IC column. The absolute configuration of each isolated enantiomer was established from the analysis of their electronic circular dichroism spectra. Enantiodifferentiation of the chiral cationic cage (±)‐M-1, P-1 was evidenced in solution using Δ‐TRISPHAT as chiral solvating agent, and the diastereomeric associations were observed in 1H and 31P NMR spectra. Chirality 24:1077–1081, 2012. © 2012 Wiley Periodicals, Inc.
Mass transfer around prolate spheroidal drops in an extensional flow
Authors: Favelukis Moshe , Lavrenteva Olga M.
Published: August 2012

Mass transfer in the continuous phase around a small eccentricity prolate spheroidal drop in an axisymmetric extensional creeping flow and at large Peclet numbers was investigated theoretically. The results show that, at very short times, the total quantity of solute transferred to or from the drop represents, at O(Ca1), mass transfer by diffusion only around a sphere. For long times, or at steady‐state, the total quantity of solute transferred is, at O(Ca1), slightly smaller than that of a spherical drop, and it decreases with an increase of the capillary number or the viscosity ratio. © 2012 Canadian Society for Chemical Engineering
Imputation for statistical inference with coarse data
Authors: Kim Jae Kwang , Hong Minki
Published: August 2012

Coarse data is a general type of incomplete data that includes grouped data, censored data, and missing data. The likelihood‐based estimation approach with coarse data is challenging because the likelihood function is in integral form. The Monte Carlo EM algorithm of Wei & Tanner [Wei & Tanner (1990).Journal of the American Statistical Association, 85, 699–704] is adapted to compute the maximum likelihood estimator in the presence of coarse data. Stochastic coarse data is also covered and the computation can be implemented using the parametric fractional imputation method proposed by Kim [Kim (2011).Biometrika, 98, 119–132]. Results from a limited simulation study are presented. The proposed method is also applied to the Korean Longitudinal Study of Aging (KLoSA).The Canadian Journal of Statistics40: 604–618; 2012 © 2012 Statistical Society of Canada
Potential Retention and Release Capacity of Phosphorus in the Newly Formed Wetland Soils from the Yellow River Delta, China
Authors: Sun Junna , Xu Gang , Shao Hongbo , Xu Shaohui
Published: August 2012

There are few researches on the characteristics of phosphorus (P) in the newly born wetland soils from Yellow River Delta of China. Meanwhile, whether the wetland soils can protect the aquatic ecosystem from excessive P input or not and the risk of P release from the soils to the water quality have generated considerable interests. Through isothermal batch static equilibrium sorption experiments followed by six subsequent extraction steps, the present study assessed the variations in P sorption and desorption properties of the newly born wetland soils in Yellow River Delta. It is found that the P sorption isotherms were nonlinear and the amount of P sorption reached a steady state as P initial concentration added increased in the studied soils. Though the capacity of P retention differed strongly among the studied zone, the soils can protect the aquatic ecosystem from excessive P input to a certain extent degree. From the desorption experiments, it is found that the newly sorbed P was easily desorbed in higher initial added concentration and the desorption P significantly decreased with successive extraction in all samples. The release of P from soil proposed a significant contribution to the water quality and eutrophication of coastal zone. Correlation and regression analyses showed that the amorphous and free Fe/Al oxides, correlated with clay content in the studied soils, were the crucial chemical factors ascribed to the soil P retention and release capacity.
Expression of kisspeptins in the brain and pituitary of the european sea bass (Dicentrarchus labrax)
Authors: Escobar Sebastián , Felip Alicia , Gueguen Marie‐Madeleine , Zanuy Silvia , Carrillo Manuel , Kah Olivier , Servili Arianna
Published: August 2012

Kisspeptins are now considered key players in the neuroendocrine control of puberty and reproduction, at least in mammals. Most teleosts have two kiss genes, kiss1 and kiss2, but their sites of expression are still poorly documented. As a first step in investigating the role of kisspeptins in the European sea bass, a perciform fish, we studied the distribution of kiss1 and kiss2‐expressing cells in the brain of males and females undergoing their first sexual maturation. Animals were examined at early and late in the reproductive season. We also examined the putative expression of estrogen receptors in kiss‐expressing cells and, finally, we investigated whether kisspeptins are expressed in the pituitary gland. We show that kiss1‐expressing cells were consistently detected in the habenula and, in mature males and females, in the rostral mediobasal hypothalamus. In both sexes, kiss2‐expressing cells were consistently detected at the level of the preoptic area, but the main kiss2 mRNA‐positive population was observed in the dorsal hypothalamus, above and under the lateral recess. No obvious sexual differences in kiss1 and kiss2 mRNA expression were detected. Additional studies based on confocal imaging clearly showed that most kiss1 mRNA‐containing cells of the mediobasal hypothalamus strongly express ERα and slightly express ERβ2. At the pituitary level, both sexes exhibited kiss1 mRNA expression in most FSHβ‐positive cells and never in LHβ‐positive cells. J. Comp. Neurol. 521:933–948, 2013. © 2012 Wiley Periodicals, Inc.
Stat3 defines three populations of müller glia and is required for initiating maximal müller glia proliferation in the regenerating zebrafish retina
Authors: Nelson Craig M. , Gorsuch Ryne A. , Bailey Travis J. , Ackerman Kristin M. , Kassen Sean C. , Hyde David R.
Published: August 2012

We analyzed the role of Stat3, Ascl1a, and Lin28a in Müller glia reentry into the cell cycle following damage to the zebrafish retina. Immunohistochemical analysis was employed to determine the temporal and spatial expression of Stat3 and Ascl1a proteins following rod and cone photoreceptor cell apoptosis. Stat3 expression was observed in all Müller glia, whereas Ascl1a expression was restricted to only the mitotic Müller glia. Knockdown of Stat3 protein expression did not affect photoreceptor apoptosis, but significantly reduced, without abolishing, the number of proliferating Ascl1a‐positive Müller glia. Knockdown of Ascl1a protein also did not change the extent of photoreceptor apoptosis, but did yield significantly fewer Müller glia that reentered the cell cycle relative to the stat3 morphant and significantly decreased the number and intensity of Stat3‐expressing Müller glia. Finally, introduction of lin28a morpholinos resulted in decreased Müller glia expression of Stat3 and Ascl1a, significantly reducing the number of proliferating Müller glia. Thus, there are three populations of Müller glia in the light‐damaged zebrafish retina: 1) Stat3‐expressing Ascl1a‐nonexpressing nonproliferating (quiescent) Müller glia; 2) Stat3‐dependent Ascl1a‐dependent proliferating Müller glia; and 3) Stat3‐independent Ascl1a‐dependent proliferating Müller glia. Whereas Ascl1a and Lin28a are required for Müller glia proliferation, Stat3 is necessary for the maximal number of Müller glia to proliferate during regeneration of the damaged zebrafish retina. J. Comp. Neurol. 520:4294–4311, 2012. © 2012 Wiley Periodicals, Inc.
Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly
Authors: Heinze Stanley , Florman Jeremy , Asokaraj Surainder , el Jundi Basil , Reppert Steven M.
Published: August 2012

Each fall, eastern North American monarch butterflies in their northern range undergo a long‐distance migration south to their overwintering grounds in Mexico. Migrants use a time‐compensated sun compass to determine directionality during the migration. This compass system uses information extracted from sun‐derived skylight cues that is compensated for time of day and ultimately transformed into the appropriate motor commands. The central complex (CX) is likely the site of the actual sun compass, because neurons in this brain region are tuned to specific skylight cues. To help illuminate the neural basis of sun compass navigation, we examined the neuronal composition of the CX and its associated brain regions. We generated a standardized version of the sun compass neuropils, providing reference volumes, as well as a common frame of reference for the registration of neuron morphologies. Volumetric comparisons between migratory and nonmigratory monarchs substantiated the proposed involvement of the CX and related brain areas in migratory behavior. Through registration of more than 55 neurons of 34 cell types, we were able to delineate the major input pathways to the CX, output pathways, and intrinsic neurons. Comparison of these neural elements with those of other species, especially the desert locust, revealed a surprising degree of conservation. From these interspecies data, we have established key components of a conserved core network of the CX, likely complemented by species‐specific neurons, which together may comprise the neural substrates underlying the computations performed by the CX. J. Comp. Neurol. 521:267–298, 2013. © 2012 Wiley Periodicals, Inc.
The Influence of H2O Content in Solvents {Water + Carbinol} and {Water + Ethanol} on the Deposition Mechanism of AZO Films Synthesized by Cold‐wall AACVD
Authors: Zhao Lin , Qin Xiu Juan , Shao Guang Jie , Wang Na
Published: August 2012

Using binary mixtures {x water + (1‐x) carbinol} and {x water + (1‐x) ethanol} as solvents for the precursor solutions, Al‐doped ZnO films are synthesized by cold‐wall, aerosol‐assisted (AA)CVD. The behavior of aerosol droplets influenced by H2O content in the precursor solution is discussed. It is found that as H2O content increases, the coagulation of the droplets is promoted by an increase in both the surface tension of the precursor solution and initial droplet mass. The coagulation reduces the amount of usable reactants that deposit on the substrate. As a result, the film thickness decreases with the increase in surface tension of the precursor solution and initial droplet mass. Transmittances in the visible range are also reduced by those micrometer‐sized grains that precipitate from large coagulate droplets. Film cannot be synthesized once the surface tension of the precursor solution exceeds 25.00 × 10−3 N · m−1 and the initial droplet mass exceeds 4.474 × 10−15 kg in both systems {x water + (1‐x) carbinol} and {x water + (1‐x) ethanol}.
Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance
Authors: Fritz T. , Caidahl K. , Krook A. , Lundström P. , Mashili F. , Osler M. , Szekeres F. L. M. , Östenson C. G. , Wändell P. , Zierath J. R.
Published: August 2012

Background

Physical activity remains a valuable prevention for metabolic disease. The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation.

Methods

We included 213 individuals, aged 60 ± 5.3 years and with body mass index (BMI) of 30.2 ± 3.8 kg/m2; of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4‐month period. Dietary habits were unaltered. BMI, waist circumference, blood pressure, glucose tolerance, clinical chemistry, maximal oxygen uptake (peak VO2) and self‐reported physical activity (questionnaire) were assessed at the time of inclusion and after 4 months. The participants in the exercise‐intervention group kept a walking diary.

Results

In the NGT exercise group, self‐reported physical activity increased markedly, and body weight (−2.0 ± 3.8 kg), BMI (−0.8 ± 1.4 kg/m2) and waist circumference (−4.9 ± 4.4 cm) (mean ± SD) decreased. Exercise power output (12.9 ± 9.9 W) and peak VO2 (2.7 ± 2.8 mL/kg/min) increased in the IGT exercise group. More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise.

Conclusions

Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health‐promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation. Copyright © 2012 John Wiley & Sons, Ltd.
Testing transpiration controls by quantifying spatial variability along a boreal black spruce forest drainage gradient
Authors: Angstmann Julia L. , Ewers Brent E. , Barber Jarrett , Kwon Hyojung
Published: August 2012

One of the biggest challenges in predicting ecohydrologic fluxes is scaling from easily measured variables to more difficult, often emergent patterns and processes. This is especially true in spatially heterogeneous systems such as black spruce (Picea mariana)‐dominated boreal forests containing excessive and low soil moisture conditions. Traditional hypotheses suggest that transpiration is controlled by hydraulic responses to vapor pressure deficit (D) and soil moisture; however, these may potentially be misinformed because of omission of soil drainage gradients. Thus, we predict that 1) spatial heterogeneity in tree transpiration along a soil drainage gradient is positively correlated withD, 2) sap flux (JS) and leaf‐level transpiration (EL) are higher and whole‐tree transpiration (EC) lower in the poorly drained than well‐drained stands, and 3) spatial heterogeneity ofECis regulated primarily by tree‐related covariates such as sapwood and leaf area and secondarily by environmental covariates including peat and moss depth. With the use of 122 black spruce sap flux measurements, the range of autocorrelation (inverse of spatial variation) decreased from 20 m at lowD(<0.7 kPa) to 2 m at middayDvalues (>0.9 kPa).JSandELwere significantly greater andECless in poorly drained than well‐drained stands; controlled primarily by tree‐related covariates (sapwood and leaf area) representing long‐term growth conditions and secondarily by soil moisture and spatially sampledDreflecting shorter‐term environmental variation. Quantification of spatial heterogeneity informs predictive models of the distance at which homogeneity can no longer be assumed and will improve mechanistic predictions of transpiration at multiple spatial scales. Copyright © 2012 John Wiley & Sons, Ltd.
Studies of the Electronic Properties of N‐Heterocyclic Carbene Ligands in the Context of Homogeneous Catalysis and Bioorganometallic Chemistry
Authors: Kumar Anuj , Ghosh Prasenjit
Published: August 2012

N‐heterocyclic carbenes (NHCs) have been dominating the world of homogeneous catalysis in an unprecedented manner in the last two decades. Understanding the underlying reasons behind catalysis with NHC ligands has thus become of significant interest. Subscribing to this view, we strive to identify the key attributes of N‐heterocyclic carbene ligands through a combination of experimental and computational studies. Rational catalyst design, by appropriate functionalization of N‐heterocyclic carbene ligands to investigate their utility in a host of catalytically relevant transformations of interest to contemporary organic synthesis, is thus central to our efforts. From this perspective, a variety of C–C and C–N bond forming reactions, namely, the Suzuki–Miyaura, Sonogashira, and Hiyama cross‐couplings, the base‐free Michael additions, the alkene and alkyne hydroaminations, the formation of β‐enaminones from 1,3‐dicarbonyl compounds and primary amines, and the environmentally important ring‐opening polymerizations (ROP) of L‐lactides, which produce biodegradable polylactide polymers from renewable resources, have been studied. The metal–carbene interaction in these catalysts has been probed with the aid of computational studies, which suggest that strong σ‐donor N‐heterocyclic carbene ligands bind tightly to the metal center and thereby impart the much needed stability to these catalysts. Even going beyond catalysis, we investigated the potential of N‐heterocyclic carbene complexes in biomedical applications particularly for their antimicrobial and anticancer properties.
Pseudo‐Polymorphism in a Conformationally Rigid Copper Helicate – Structural Studies of a Shape‐Awkward System
Authors: Martinez Belmonte Marta , Price Daniel J.
Published: August 2012

The coordination of copper(II) by the acyclic polydentate ligand ethylene‐1,2‐bisoxamate [(oeo)4–] results in the formation of an anionic dinuclear double‐stranded helicate, [Cu2(oeo)2]4–. The potassium salt of this large, chiral, approximately spherical, D2 symmetric and highly charged complex molecular anion is found to crystallise in five different hydrated forms; a trihydrate 6a, a tetrahydrate 6b, a tetrahemihydrate 6c, a pentahydrate 6d and an approximate heptahydrate 6e. All of these forms crystallise from solution under similar conditions. Together this large anion and the relatively small K+ cation provide something of a shape‐awkward system, as evidenced by the high degree of pseudo‐polymorphism. X‐ray structural analysis of 6a–e reveals much similarity in the order, symmetry and packing of the anions, but great irregularity and disorder in the packing of the K+ counterions and water of crystallisation. The structures are further complicated by a Cu nonstoichiometry. Although 6e has a 100 % Cu site occupancy, 6a and 6c have site occupancies less than 100 % and contain both [Cu2(oeo)2]4– and [Cu(Hoeo)2]4– complex ions as a solid solution. In 6b and 6d, where the Cu site occupancy is below 50 %, the compound comprises [Cu(Hoeo)2]4– and [(H2oeo)2]4– units distributed over the same site. It is a remarkable feature of this system that hydrogen bond interactions between pairs of the protonated acyclic ligands result in a dimeric structure, which has the same shape, charge and structure as that of the copper complex of the fully deprotonated ligand. So similar are the [Cu2(oeo)2]4–, [Cu(Hoeo)2]4– and [(H2oeo)2]4– components that they are undifferentiated in the crystal structures, and the solid solutions that they form can be viewed as molecular alloys.
Total Synthesis of (+)‐Seimatopolide A
Authors: Raji Reddy Chada , Rao Nagavaram Narsimha , Reddy Motatipally Damoder
Published: August 2012

The first enantioselective total synthesis of a polyhydroxylated macrolide, (+)‐seimatopolide A, was achieved. The key reactions, Sharpless asymmetric dihydroxylation, Yamaguchi esterification, and ring‐closing metathesis, provided easy access to the target molecule from L‐aspartic acid. Further, the absolute stereochemistry of the natural product has also been revised.
One‐dimensional Model of Oxygen Transport Impedance Accounting for Convection Perpendicular to the Electrode
Authors: Mainka J. , Maranzana G. , Thomas A. , Dillet J. , Didierjean S. , Lottin O.
Published: August 2012

A one‐dimensional (1D) model of oxygen transport in the diffusion media of proton exchange membrane fuel cells (PEMFC) is presented, which considers convection perpendicular to the electrode in addition to diffusion. The resulting analytical expression of the convecto‐diffusive impedance is obtained using a convection–diffusion equation instead of a diffusion equation in the case of classical Warburg impedance. The main hypothesis of the model is that the convective flux is generated by the evacuation of water produced at the cathode which flows through the porous media in vapor phase. This allows the expression of the convective flux velocity as a function of the current density and of the water transport coefficient α (the fraction of water being evacuated at the cathode outlet). The resulting 1D oxygen transport impedance neglects processes occurring in the direction parallel to the electrode that could have a significant impact on the cell impedance, like gas consumption or concentration oscillations induced by the measuring signal. However, it enables us to estimate the impact of convection perpendicular to the electrode on PEMFC impedance spectra and to determine in which conditions the approximation of a purely diffusive oxygen transport is valid. Experimental observations confirm the numerical results.
Effect of Anode off‐gas Recycling on Reforming of Natural Gas for Solid Oxide Fuel Cell Systems
Authors: Halinen M. , Thomann O. , Kiviaho J.
Published: August 2012

The effect of anode off‐gas recycling (AOGR) on the characteristic performance of a natural gas reformer equipped with a precious metal catalyst is investigated experimentally. The reformer is operated both with synthetic AOGR gas and in steam reforming (SR) conditions. The characteristic performance in SR and AOGR mode are compared with equilibrium, and it is found that equilibrium is more readily achieved in AOGR mode. The reformer is used for extended periods of time (100–1,000 h) in conditions where carbon formation is thermodynamically possible to measure any changes in characteristic performance. No significant change in the performance is observed due to carbon formation or catalyst deactivation. The reformer could be successfully implemented in a 10 kW SOFC system with an anode off‐gas recycling loop.