bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival in dementia and predictors of mortality: a review
Authors: Todd Stephen , Barr Stephen , Roberts Mark , Passmore A Peter 
Published: March 2013

ObjectiveDementia is an important cause of mortality and, with the ageing population and increasing prevalence of dementia, reliable data on prognosis and survival will be of interest to patients and caregivers as well as providers and commissioners of health and social care. A review of the literature was undertaken to determine the rates of survival in dementia and Alzheimer's disease (AD) and to identify factors that are or are not predictive of mortality in dementia and AD.MethodsRelevant articles on mortality in dementia were identified following a search of several electronic databases from 1990 to September 2012. Inclusion criteria were reports on prospective community or clinic based cohorts published in English since 1990, to reflect more recent recognition of possible predictors.ResultsMedian survival time from age of onset of dementia ranges from 3.3 to 11.7 years, with most studies in the 7 to 10‐year period. Median survival time from age of disease diagnosis ranges from 3.2 to 6.6 years for dementia or AD cohorts as a whole. Age was consistently reported as a predictor of mortality, with male gender a less consistent predictor. Increased disease severity and functional impairment were often associated with mortality.ConclusionsSubstantial heterogeneity in the design of included studies limits the ability to prognosticate for individual patients. However, it is clear that dementia and AD are associated with significant mortality. Reasons for the increased mortality are not established. Copyright © 2013 John Wiley & Sons, Ltd.
From groundwater abstraction to vegetative response in fen ecosystems
Authors: Johansen Ole Munch , Jensen Jacob Birk , Pedersen Morten Lauge 
Published: March 2013

AbstractHydrological effects of groundwater abstraction near a Danish river valley have been assessed by integrated hydrological modelling. The study site contains groundwater‐dependent terrestrial ecosystems in terms of fen and spring habitats that are highly dependent on regional and local scale hydrology. Fens are rare and threatened worldwide due to pressures from agriculture, to lack of appropriate management and to altered catchment hydrology. A solid foundation for hydrological modelling was established based on intensive monitoring at the site, combined with full‐scale pumping tests in the area. A regional groundwater model was used to describe the dynamics in groundwater recharge and the large‐scale discharge to streams. A local grid refinement approach was then applied in a detailed assessment of damage in order to balance the computational effort and the need for a high spatial resolution. A considerable flow reduction in the natural spring was monitored during a full‐scale pumping test while no significant effects on the water table in the fen habitats were observed. A modelled abstraction scenario predicted a lowering of 2–3 cm in the centre of the main fen area during summer periods. The predicted change in water table conditions in the fen habitat is compared to the variability found in 35 Danish fens, and the ecological response is discussed based on statistical water‐level vegetation relations. The results provide a rare quantitative foundation for decision making in relation to management of groundwater‐dependent terrestrial ecosystems. Copyright © 2013 John Wiley & Sons, Ltd.
A SYSTEM DYNAMICS APPROACH TO MODEL REHABILITATION OF IRRIGATION NETWORKS CASE STUDY: QAZVIN IRRIGATION NETWORK, IRAN
Authors: Vaez Tehrani Mahsa , Monem Mohammad Javad , Bagheri Ali 
Published: March 2013

ABSTRACTAssessment of irrigation networks shows that their utility is less than what is expected because of poor performance. Poor performance of irrigation networks is partly due to their aged condition, which requires rehabilitation. Rehabilitation of irrigation systems is commonly practised on a basis lacking integration; thus they have not led to considerable improvement. Integration requires a systemic approach and system dynamics methodology provides a practical tool to implement integration in a complex system such as an irrigation system. Using system dynamics modelling, the paper intends to evaluate several rehabilitation policies in the Qazvin Irrigation Network, in mid‐northern Iran, and then the effects of policies on performance elements (efficiency) will be investigated.The main elements that affect network utility are considered to be efficiency, adequacy, equity, flexibility and stability in water delivery. Three policies for network rehabilitation are considered to be: fixing the crop area, decreasing drawdown of groundwater, and increasing investment in renovation projects. The results show that all of these three policies improve system utility; however, the ‘fixing the crop area' policy showed a better improvement. Copyright © 2013 John Wiley & Sons, Ltd.
TESTS OF EQUAL FORECAST ACCURACY FOR OVERLAPPING MODELS
Authors: Clark Todd E. , Mccracken Michael W. 
Published: March 2013

SUMMARYThis paper examines the asymptotic and finite‐sample properties of tests of equal forecast accuracy when the models being compared are overlapping in the sense of Vuong (Econometrica 1989; 57: 307–333). Two models are overlapping when the true model contains just a subset of variables common to the larger sets of variables included in the competing forecasting models. We consider an out‐of‐sample version of the two‐step testing procedure recommended by Vuong but also show that an exact one‐step procedure is sometimes applicable. When the models are overlapping, we provide a simple‐to‐use fixed‐regressor wild bootstrap that can be used to conduct valid inference. Monte Carlo simulations generally support the theoretical results: the two‐step procedure is conservative, while the one‐step procedure can be accurately sized when appropriate. We conclude with an empirical application comparing the predictive content of credit spreads to growth in real stock prices for forecasting US real gross domestic product growth. Copyright © 2013 John Wiley & Sons, Ltd.
Targeted disruption of leucine-rich repeat kinase 1 but not leucine-rich repeat kinase 2 in mice causes severe osteopetrosis
Authors: Xing Weirong , Liu Jeff , Cheng Shaohong , Vogel Peter , Mohan Subburaman , Brommage Robert 
Published: March 2013

ABSTRACT

To assess the roles of Lrrk1 and Lrrk2, we examined skeletal phenotypes in Lrrk1 and Lrrk2 knockout (KO) mice. Lrrk1 KO mice exhibit severe osteopetrosis caused by dysfunction of multinucleated osteoclasts, reduced bone resorption in endocortical and trabecular regions, and increased bone mineralization. Lrrk1 KO mice have lifelong accumulation of bone and respond normally to the anabolic actions of teriparatide treatment, but are resistant to ovariectomy-induced bone boss. Precursors derived from Lrrk1 KO mice differentiate into multinucleated cells in response to macrophage colony-stimulating factor (M-CSF)/receptor activator of NF-κB ligand (RANKL) treatment, but these cells fail to form peripheral sealing zones and ruffled borders, and fail to resorb bone. The phosphorylation of cellular Rous sarcoma oncogene (c-Src) at Tyr-527 is significantly elevated whereas at Tyr-416 is decreased in Lrrk1-deficient osteoclasts. The defective osteoclast function is partially rescued by overexpression of the constitutively active form of Y527F c-Src. Immunoprecipitation assays in osteoclasts detected a physical interaction of Lrrk1 with C-terminal Src kinase (Csk). Lrrk2 KO mice do not show obvious bone phenotypes. Precursors derived from Lrrk2 KO mice differentiate into functional multinucleated osteoclasts. Our finding of osteopetrosis in Lrrk1 KO mice provides convincing evidence that Lrrk1 plays a critical role in negative regulation of bone mass in part through modulating the c-Src signaling pathway in mice.
p130Cas, Crk-Associated Substrate, Plays Important Roles in Osteoclastic Bone Resorption
Authors: Nagai Yoshie , Osawa Kenji , Fukushima Hidefumi , Tamura Yukihiko , Aoki Kazuhiro , Ohya Keiichi , Yasuda Hisataka , Hikiji Hisako , Takahashi Mariko , Seta Yuji , Seo Sachiko , Kurokawa Mineo , Kato Shigeaki , Honda Hiroaki , Nakamura Ichiro , Maki Kenshi , Jimi Eijiro 
Published: March 2013

ABSTRACT

p130Cas, Crk-associated substrate (Cas), is an adaptor/scaffold protein that plays a central role in actin cytoskeletal reorganization. We previously reported that p130Cas is not tyrosine-phosphorylated in osteoclasts derived from Src-deficient mice, which are congenitally osteopetrotic, suggesting that p130Cas serves as a downstream molecule of c-Src and is involved in osteoclastic bone resorption. However, the physiological role of p130Cas in osteoclasts has not yet been confirmed because the p130Cas-deficient mice displayed embryonic lethality. Osteoclast-specific p130Cas conditional knockout (p130CasΔOCL–) mice exhibit a high bone mass phenotype caused by defect in multinucleation and cytoskeleton organization causing bone resorption deficiency. Bone marrow cells from p130CasΔOCL– mice were able to differentiate into osteoclasts and wild-type cells in vitro. However, osteoclasts from p130CasΔOCL– mice failed to form actin rings and resorb pits on dentine slices. Although the initial events of osteoclast attachment, such as β3-integrin or Src phosphorylation, were intact, the Rac1 activity that organizes the actin cytoskeleton was reduced, and its distribution was disrupted in p130CasΔOCL– osteoclasts. Dedicator of cytokinesis 5 (Dock5), a Rho family guanine nucleotide exchanger, failed to associate with Src or Pyk2 in osteoclasts in the absence of p130Cas. These results strongly indicate that p130Cas plays pivotal roles in osteoclastic bone resorption. © 2013 American Society for Bone and Mineral Research.
Atomic force microscopy: High resolution dynamic imaging of cellular and molecular structure in health and disease
Authors: Taatjes Douglas J. , Quinn Anthony S. , Rand Jacob H. , Jena Bhanu P. 
Published: March 2013

AbstractThe atomic force microscope (AFM), invented in 1986, and a member of the scanning probe family of microscopes, offers the unprecedented ability to image biological samples unfixed and in a hydrated environment at high resolution. This opens the possibility to investigate biological mechanisms temporally in a heretofore unattainable resolution. We have used AFM to investigate: (1) fundamental issues in cell biology (secretion) and, (2) the pathological basis of a human thrombotic disease, the antiphospholipid syndrome (APS). These studies have incorporated the imaging of live cells at nanometer resolution, leading to discovery of the “porosome,” the universal secretory portal in cells, and a molecular understanding of membrane fusion from imaging the interaction and assembly of proteins between opposing lipid membranes. Similarly, the development of an in vitro simulacrum for investigating the molecular interactions between proteins and lipids has helped define an etiological explanation for APS. The prime importance of AFM in the success of these investigations will be presented in this manuscript, as well as a discussion of the limitations of this technique for the study of biomedical samples. J. Cell. Physiol. 228: 1949–1955, 2013. © 2013 Wiley Periodicals, Inc.
Hemophagocytosis‐mediated keratinization in oral carcinoma in situ and squamous cell carcinoma: A possible histopathogenesis of keratin pearls
Authors: Al‐Eryani Kamal , Cheng Jun , Abé Tatsuya , Yamazaki Manabu , Maruyama Satoshi , Tsuneki Masayuki , Essa Ahmed , Babkair Hamzah , Saku Takashi 
Published: March 2013

AbstractAlthough the histopathogenetic process of keratin pearls is still poorly understood, acceleration of keratinization in squamous cell carcinoma (SCC) cells may represent one possible therapeutic avenue. Based on our histopathological observations, we have hypothesized that SCC cells are keratinized by phagocytosis of extravasated erythrocytes. To confirm this hypothesis, we firstly examined immature keratin pearls in oral carcinoma in situ (CIS) and mature ones in SCC by immunohistochemistry. Concentric dyskeratotic cells in CIS keratin pearls became positive for keratin (K) 10, K17, heme oxygenase‐1 (HO‐1), or protease activated receptor‐2 (PAR‐2), a candidate regulator for hemophagocytosis. When ZK‐1 cells, an SCC cell system, were incubated with human peripheral blood erythrocytes, or with crude and purified hemoglobins (Hbs), their erythro‐hemophagocytotic activities were confirmed by immunofluorescence. Immunofluorescence signals for K10, K17, and HO‐1 were enhanced due to hemophagocytosis in time‐dependent manners. mRNA expression levels for the three molecules were most enhanced by purified Hb, followed by crude Hb and erythrocytes. K17/K10 mRNA expression levels were more elevated when PAR‐2 was activated in ZK‐1 cells. The results indicated that immature and mature keratin pearls in CIS and SCC were generated by oxidative stresses derived from erythro‐hemophagocytosis, which might mediate HO‐1 expression and be regulated by PAR‐2. Thus, hemorrhage from the rupture of blood vessels can be one of the triggers for keratin pearl formation in oral CIS and SCC. J. Cell. Physiol. 228: 1977–1988, 2013. © 2013 Wiley Periodicals, Inc.
Opposite roles of myocardin and atrogin‐1 in L6 myoblast differentiation
Authors: Jiang Yulan , Singh Pavneet , Yin Hao , Zhou Yi‐Xia , Gui Yu , Wang Da‐Zhi , Zheng Xi‐Long ,   Smooth Muscle Research Group,   Libin Cardiovascular Institute of Alberta
Published: March 2013

AbstractL6 rat myoblasts undergo differentiation and myotube formation when cultured in medium containing a low‐concentration of serum, but the underlying mechanism is not well understood. The role of atrogin‐1, an E3 ligase with well‐characterized roles in muscle atrophy, has not been defined in muscle differentiation. Myocardin is a coactivator of serum response factor (SRF), which together promotes smooth muscle differentiation. Myocardin is transiently expressed in skeletal muscle progenitor cells with inhibitory effects on the expression of myogenin and muscle differentiation. It remains unknown whether myocardin, which undergoes ubiquitination degradation, plays a role in L6 cell differentiation. The current study aimed to investigate the potential roles of myocardin and atrogin‐1 in differentiation of L6 cells. As reported by many others, shifting to medium containing 2% serum induced myotube formation of L6 cells. Differentiation was accompanied by up‐regulation of atrogin‐1 and down‐regulation of myocardin, suggesting that both may be involved in muscle differentiation. As expected, over‐expression of atrogin‐1 stimulated the expression of troponin T and myogenin and differentiation of the L6 myoblasts. Co‐expression of myocardin with atrogin‐1 inhibited atrogin‐1‐induced myogenin expression. Over‐expression of atrogin‐1 decreased myocardin protein level, albeit without affecting its mRNA level. Small‐interfering RNA‐mediated knockdown of atrogin‐1 increased myocardin protein. Consistently, ectopic expression of myocardin inhibited myogenic differentiation. Unexpectedly, myocardin decreased the expression of atrogin‐1 without involving Foxo1. Taken together, our results have demonstrated that atrogin‐1 plays a positive role in skeletal muscle differentiation through down‐regulation of myocardin. J. Cell. Physiol. 228: 1989–1995, 2013. © 2013 Wiley Periodicals, Inc.
Acetaminophen attenuates doxorubicin‐induced cardiac fibrosis via osteopontin and GATA4 regulation: Reduction of oxidant levels
Authors: Schunke Kathryn J. , Coyle Luke , Merrill Gary F. , Denhardt David T. 
Published: March 2013

AbstractIt is well documented in animal and human studies that therapy with the anti‐cancer drug doxorubicin (DOX) induces fibrosis, cardiac dysfunction, and cell death. The most widely accepted mechanism of cardiac injury is through production of reactive oxygen species (ROS), which cause mitochondrial damage, sarcomere structural alterations, and altered gene expression in myocytes and fibroblasts. Here we investigated the effects of acetaminophen (APAP, N‐acetyl‐para‐aminophenol) on DOX‐induced cardiac injury and fibrosis in the presence or absence of osteopontin (OPN). H9c2 rat heart‐derived embryonic myoblasts were exposed to increasing concentrations of DOX ± APAP; cell viability, oxidative stress, and OPN transcript levels were analyzed. We found a dose‐dependent decrease in cell viability and a corresponding increase in intracellular oxidants at the tested concentrations of DOX. These effects were attenuated in the presence of APAP. RT‐PCR analysis revealed a small increase in OPN transcript levels in response to DOX, which was suppressed by APAP. When male 10–12‐week‐old mice (OPN+/+ or OPN−/−) were given weekly injections of DOX ± APAP for 4 weeks there was substantial cardiac fibrosis in OPN+/+ and, to a lesser extent, in OPN−/− mice. In both groups, APAP decreased fibrosis to near baseline levels. Activity of the pro‐survival GATA4 transcription factor was diminished by DOX in both mouse genotypes, but retained baseline activity in the presence of APAP. These effects were mediated, in part, by the ability of APAP, acting as an anti‐inflammatory agent, to decrease intracellular ROS levels, consequently diminishing the injury‐induced increase in OPN levels. J. Cell. Physiol. 228: 2006–2014, 2013. © 2013 Wiley Periodicals, Inc.
Network analysis of endogenous gene expression profiles after polyethyleneimine‐mediated DNA delivery
Authors: Martin Timothy M. , Plautz Sarah A. , Pannier Angela K. 
Published: March 2013

AbstractBackgroundDNA delivery systems, which transport exogenous DNA to cells, have applications that include gene therapy, tissue engineering and medical devices. Although the cationic nonviral DNA carrier polyethyleneimine (PEI) has been widely studied, the molecular factors and pathways underlying PEI‐mediated DNA transfer remain largely unknown, preventing the design of more efficient delivery systems.MethodsHEK 293 T cells were treated with polyplexes formed with PEI and pEGFPLuc encoding for green fluorescent protein (GFP). Transfected cells expressing GFP were flow‐separated from treated, untransfected cells. Gene expression profiles were obtained using Affymetrix HG‐U133 2.0 microarrays and differentially expressed genes were identified using R/Bioconductor. Gene network analysis using EGAN (exploratory gene association network) bioinformatics tools was then used to find interaction among genes and enriched gene ontology (GO) terms related to transfection. Genes identified by this method were perturbed using pharmacologic activators or inhibitors to assess their effect on DNA transfer.ResultsMicroarray analysis comparing transfected cells to untransfected cells revealed 215 genes to be differentially expressed, with the majority enriched to GO processes including metabolism, response to stimulus, cell cycle, biological regulation and cellular component organization or biogenesis pathways. Gene network analysis revealed a coordinated induction of RAP1A, SCG5, PGAP1, ATF3 and NEB genes implicated in cell stress, cell cycle and cytoskeletal processes. Altering pathways with pharmacologic agents confirmed the potential role of RAP1A, SCG5 and ATF3 in transfection.ConclusionsMicroarray and gene network analyses of the sorted, transfected cell population can identify potential mediators of transfection, providing a basis for the design of improved delivery systems. Copyright © 2013 John Wiley & Sons, Ltd.
TECHNICAL EFFICIENCY IN AFRICAN AGRICULTURE: IS IT CATCHING UP OR LAGGING BEHIND?
Authors: Mugera A. , Ojede A. 
Published: March 2013

AbstractThis article uses recent advances in data envelopment analysis, bootstrap data envelopment analysis, to investigate whether technical efficiency in the agricultural sector of 33 African countries improved (catching up) for the period 1966–2001. We also investigate whether there is evidence of efficiency catching‐up within the five regions of Central, Eastern, Western, Northern and Southern Africa. Overall, the results show no evidence for efficiency catching‐up in the entire sample. However, efficiency differed across countries and regions with evidence of catching‐up within the East African countries. Our analyses point to the need for policies that improve technological uptake in African agriculture. Copyright © 2013 John Wiley & Sons, Ltd.
An improved synthesis of 1′‐[18F]fluoroethyl‐β‐d‐lactose ([18F]‐FEL) for positron emission tomography imaging of pancreatic cancer
Authors: Turkman Nashaat , Gelovani Juri G. , Alauddin Mian M. 
Published: March 2013

IntroductionEarlier, we reported syntheses of ethyl‐β‐d‐galactopyranosyl‐(1,4′)‐2′‐deoxy‐2′‐[18F]fluoro‐β‐d‐glucopyranoside (Et‐[18F]FDL) and 1′‐[18F]fluoroethyl‐β‐d‐lactose ([18F]‐FEL) for positron emission tomography (PET) of pancreatic carcinoma. Et‐[18F]FDL requires a precursor, which involves 11 steps to synthesize and produces overall low yields. Synthesis of precursors for [18F]‐FEL requires four steps, but those precursors produced low radiochemical yields. Here, we report new precursors and an improved synthesis of [18F]‐FEL.MethodTwo precursors, 1′‐(methanesulfonyl)ethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐β‐d‐lactose 2a and 1′‐(p‐nitrophenyl‐sulfonyl)ethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐β‐d‐lactose 2b, were synthesized from lactose in four steps. Radiofluorination reactions were performed using K18F/kryptofix and the crude product [18F]‐3 was purified by HPLC. Basic hydrolysis of [18F]‐3 produced 1′‐[18F]fluoroethyl‐β‐d‐lactose [18F]‐4, which was neutralized, diluted with saline, filtered on a 0.22‐µm filter, and analyzed by radio‐TLC.ResultsThe average radiochemical yields of [18F]‐4 (d. c.) from 2a and 2b were 21% (n = 6) and 65% (n = 6), respectively, with >99% radiochemical purity and specific activity of 55.5 GBq/µmol. Synthesis time was 90–95 min from the end of bombardment.ConclusionAn improved synthesis of [18F]FEL has been achieved in high yields, with high purity and specific activity. Precursor 2b with this method should be applicable for high yield automated production in a commercial synthesis module for clinical application.