bluuebunny/crossref_metadata_2025_split huggingface dataset:
β‐Lactam‐Synthon‐Interceded, Facile, One‐Pot, Diastereoselective Synthesis of Functionalized Tetra/Octahydroisoquinolone Derivatives
Authors: Raj Raghu , Mehra Vishu , Singh Pardeep , Kumar Vipan , Bhargava Gaurav , Mahajan Mohinder P. , Handa Sachin , Slaughter LeGrande M. 
Published: March 2011

AbstractThe convenient and facile synthesis of tetra/octahydroisoquinolones has been developed and validated by using inter/intramolecular amidolysis of racemic N‐aryl‐β‐lactams followed by intramolecular iodocyclization protocols. Thesingle‐pot synthetic version of the desired conversion was successfully developed. The single‐pot synthesis of tetrahydro‐4H‐isoquinoline‐1,3‐diones invariably resulted in aromatic electrophilic iodination rather than the desired iodocyclization in cases where N‐phenyl‐2‐azetidinones were employed as the synthetic precursors.
Cancer biomarker discovery: Opportunities and pitfalls in analytical methods
Authors: Issaq Haleem J. , Waybright Timothy J. , Veenstra Timothy D. 
Published: March 2011

AbstractMany diseases result in specific and characteristic changes in the chemical and biochemical profiles of biological fluids and tissues prior to development of clinical symptoms. These changes are often useful diagnostic and prognostic biomarkers. Identifying biomarkers that can be used for the early detection of cancer will result in more efficient treatments, reduction in suffering, and lower mortality rates. An ideal screening test should be non‐invasive with high sensitivity and specificity. Proteomic and metabolomic analyses of biological samples can reveal changes in abundance levels of metabolites and proteins that when validated and confirmed through clinical trials can function as clinical tests for early detection, diagnosis, monitoring disease progression, and predicting therapeutic response. While the past decade has seen great advancements in proteomics and metabolomics research producing potential biomarkers for cancer, most of the identified biomarkers have failed to replace existing clinical tests. To become a clinically approved test, a potential biomarker should be confirmed and validated using hundreds of specimens and should be reproducible, specific, and sensitive. A search of the scientific and medical literature indicates that many studies report the discovery of potential biomarkers without proper validation and/or they do not meet the above criteria. In this manuscript, we will discuss the successes and the pitfalls of biomarker research and comment on study and experimental design, which in most cases is lacking, resulting in suboptimal biomarkers.
Concurrent use of finite element and finite volume methods for shallow water flows in locally 1‐D channel networks
Authors: Unami K. , Alam A. H. M. Badiul 
Published: March 2011

SUMMARYA numerical model is developed for shallow water equation in locally 1‐D channel networks. The model concurrently uses the standard Galerkin finite element method for the continuity equation and the finite volume method with an upwind scheme for the momentum equation. The surface gradient method is consistently employed. A minimum treatment is given for channel junctions so that application to multiply connected channels do not require any special consideration The model is capable of computing different types of transcritical flows, wet and dry flows, and flows with complex source terms. Standardized test problems and laboratory experimental data are used for verifying the model. Applicability of the models is validated in a multiply connected channel network draining hydromorphic farmlands located in a West African savanna, and Manning's roughness coefficient is identified, so that the steady solution is consistent with field observations. Unsteady simulation demonstrates that the model is capable of stably reproducing shifts of hydraulic jumps in flows of sub‐millimeter water depths. Copyright © 2011 John Wiley & Sons, Ltd.
Multivariate GARCH Models with Correlation Clustering
Authors: So Mike K. P. , Yip Iris W. H. 
Published: March 2011

ABSTRACTA new clustered correlation multivariate generalized autoregressive conditional heteroskedasticity (CC‐MGARCH) model that allows conditional correlations to form clusters is proposed. This model generalizes the time‐varying correlation structure of Tse and Tsui (2002, Journal of Business and Economic Statistics 20: 351–361) by classifying the correlations among the series into groups. To estimate the proposed model, Markov chain Monte Carlo methods are adopted. Two efficient sampling schemes for drawing discrete indicators are also developed. Simulations show that these efficient sampling schemes can lead to substantial savings in computation time in Monte Carlo procedures involving discrete indicators. Empirical examples using stock market and exchange rate data are presented in which two‐cluster and three‐cluster models are selected using posterior probabilities. This implies that the conditional correlation equation is likely to be governed by more than one set of decaying parameters. Copyright © 2011 John Wiley & Sons, Ltd.
Predictors of outcome of pharmacological and psychological treatment of late‐life panic disorder with agoraphobia
Authors: Hendriks Gert‐Jan , Keijsers Ger P. J. , Kampman Mirjam , Hoogduin Cees A. L. , Oude Voshaar Richard C. 
Published: March 2011

ObjectiveThis study aims to evaluate the differential predictive values of age, age of onset and duration of illness on paroxetine and cognitive‐behavioural therapy (CBT) outcome in late‐life panic disorder with agoraphobia.MethodPatients 60 years and older with a confirmed diagnosis of panic disorder with agoraphobia (n = 49) were randomly assigned to paroxetine (40 mg/day) treatment, individual CBT or a waiting‐list control condition. Multiple regression analyses were conducted per treatment arm with post‐treatment avoidance behaviour and agoraphobic cognitions as the dependent variables.ResultsHigher age at onset and shorter duration of illness were predictors of superior outcomes following CBT, although these variables did not influence the treatment effects of paroxetine.ConclusionsIn late‐life agoraphobic panic disorder, chronological age has no impact on treatment modality outcome. In older patients with a late disease onset or shorter duration of illness, CBT is to be preferred over paroxetine, whereas paroxetine might be the treatment of choice for older people with an early onset and short duration of illness. Copyright © 2011 John Wiley & Sons, Ltd.
Modeling sharp wave‐ripple complexes through a CA3‐CA1 network model with chemical synapses
Authors: Taxidis Jiannis , Coombes Stephen , Mason Robert , Owen Markus R. 
Published: March 2011

AbstractThe hippocampus, and particularly the CA3 and CA1 areas, exhibit a variety of oscillatory rhythms that span frequencies from the slow theta range (4–10 Hz) up to fast ripples (˜200 Hz). Various computational models of different complexities have been developed in an effort to simulate such population oscillations. Nevertheless the mechanism that underlies the so called Sharp Wave‐Ripple complex (SPWR), observed in extracellular recordings in CA1, still remains elusive. We present here, the combination of two simple but realistic models of the rat CA3 and CA1 areas, connected together in a feedforward scheme mimicking Schaffer collaterals. Both network models are computationally simple one‐dimensional arrays of excitatory and inhibitory populations interacting only via fast chemical synapses. Connectivity schemes and postsynaptic potentials are based on physiological data, yielding a realistic network topology. The CA3 model exhibits quasi‐synchronous population bursts, which give rise to sharp wave‐like deep depolarizations in the CA1 dendritic layer accompanied by transient field oscillations at ∼150–200 Hz in the somatic layer. The frequency and synchrony of these oscillations is based on interneuronal activity and fast‐decaying recurrent inhibition in CA1. Pyramidal cell spikes are sparse and come from a subset of cells receiving stronger than average excitatory input from CA3. The model is shown to accurately reproduce a large number of basic characteristics of SPWRs and yields a new mechanism for the generation of ripples, offering an interpretation to a range of neurophysiological observations, such as the ripple disruption by halothane and the selective firing of pyramidal cells during ripples, which may have implications for memory consolidation during SPWRs. © 2011 Wiley Periodicals, Inc.
NMR‐based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid
Authors: He Cui‐Cui , Dai Yun‐Qing , Hui Rong‐Rong , Hua Jia , Chen Hong‐Juan , Luo Qiao‐Yun , Li Jian‐Xin 
Published: March 2011

ABSTRACTCimicifugae Rhizoma, a well‐known botanical dietary supplement, has been the subject of intense interest due to its potential application for alleviating menopausal symptom. Although there are clinic data that the Cimicifuga extract should have hepatotoxicity, no evidence on the main chemical components has been reported. Cimicidol‐3‐O‐β ‐d‐xyloside (CX) is one of the main triterpenoids of the rhizome. This work studies the toxicological effects of CX after oral administration (50 mg kg−1 per day) over a 7‐day period in female SD rats using metabonomic analyses of 1H NMR spectra of urine, serum and liver tissue extracts. Histopathological studies of liver and analyses of blood biochemical parameter, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine revealed that CX had no negative impacts on liver and kidney. However, the metabolic signature of 1H NMR‐based urinalysis of daily samples displayed an increment in the levels of taurine, trimethylamine‐N‐oxide (TMAO), betaine and acetate. Elevated serum levels of creatinine, glucose, alanine, TMAO and betaine and lower levels of lactate were observed. Metabolic profiling on aqueous soluble extracts of liver showed simultaneously increases in succinate, glycogen, choline, glycerophosphorylcholine, TMAO and betaine levels and reduction in valine, glucose and lactate levels. Nevertheless, no changes in any metabonomic level were found in lipid‐soluble extracts of liver. These findings indicate that CX has a slight toxicity in liver and kidney via disturbance of the metabolisms of energy and amino acids. The present study provides a reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype
Authors: Jemtland Rune , Holden Marit , Reppe Sjur , Olstad Ole K , Reinholt Finn P , Gautvik Vigdis T , Refvem Hilde , Frigessi Arnoldo , Houston Brian , Gautvik Kaare M 
Published: March 2011

Abstract
Genome-wide gene expressions in bone biopsies from patients with postmenopausal osteoporosis and healthy controls were profiled, to identify osteoporosis candidate genes. All osteoporotic patients (n = 27) in an unbiased cohort of Norwegian women presented with bone mineral density (BMD) T-scores of less than −2.5 SD and one or more confirmed low-energy fracture(s). A validation group (n = 18) had clinical and laboratory parameters intermediate to the control (n = 39) and osteoporosis groups. RNA from iliac crest bone biopsies were analyzed by Affymetrix microarrays and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Differentially expressed genes in osteoporosis versus control groups were identified using the Bayesian ANOVA for microarrays (BAMarray) method, whereas the R-package Limma (Linear Models for Microarray Data) was used to determine whether these transcripts were explained by disease, age, body mass index (BMI), or combinations thereof. Laboratory tests showed normal ranges for the cohort. A total of 609 transcripts were differentially expressed in osteoporotic patients relative to controls; 256 transcripts were confirmed for disease when controlling for age or BMI. Most of the osteoporosis susceptibility genes (80%) also were confirmed to be regulated in the same direction in the validation group. Furthermore, 217 of 256 transcripts were correlated with BMD (adjusted for age and BMI) at various skeletal sites (|r| &gt; 0.2, p &lt; .05). Among the most distinctly expressed genes were Wnt antagonists DKK1 and SOST, the transcription factor SOX4, and the bone matrix proteins MMP13 and MEPE, all reduced in osteoporosis versus control groups. Our results identify potential osteoporosis susceptibility candidate genes adjusted for confounding factors (ie, age and BMI) with or without a significant correlation with BMD. © 2011 American Society for Bone and Mineral Research
Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation
Authors: Rodova Marianna , Lu Qinghua , Li Ye , Woodbury Brent G , Crist Jamie D , Gardner Brian M , Yost John G , Zhong Xiao-bo , Anderson H Clarke , Wang Jinxi 
Published: March 2011

Abstract
The development of disease-modifying pharmacologic therapy for osteoarthritis (OA) currently faces major obstacles largely because the regulatory mechanisms for the function of adult articular chondrocytes remain unclear. We previously demonstrated that lack of Nfat1, one of the nuclear factor of activated T cells (NFAT) transcription factors, causes OA-like changes in adult mice. This study aimed to identify whether Nfat1 specifically regulates adult articular chondrocyte function and its age-dependent regulatory mechanism using both Nfat1-deficient and wild-type mice. Deletion of Nfat1 did not induce OA-like articular chondrocyte dysfunction (e.g., overexpression of proinflammatory cytokines and matrix-degrading proteinases) until the adult stage. RNAi-mediated Nfat1 knockdown caused dysfunction of wild-type adult articular chondrocytes. Nfat1 expression in wild-type articular chondrocytes was low in the embryonic but high in the adult stage. Chromatin immunoprecipitation assays demonstrated that an increase in Nfat1 expression in articular chondrocytes was associated with increased H3K4me2 (a histone modification linked to transcriptional activation), whereas a decrease in Nfat1 expression in articular chondrocytes was correlated with increased H3K9me2 (a histone modification linked to transcriptional repression). Knockdown of lysine-specific demethylase-1 (Lsd1) in embryonic articular chondrocytes upregulated Nfat1 expression concomitant with increased H3K4me2 at the Nfat1 promoter. Knockdown of Jmjc-containing histone demethylase-2a (Jhdm2a) in 6-month articular chondrocytes downregulated Nfat1 expression concomitant with increased H3K9me2 at the Nfat1 promoter. These results suggest that Nfat1 is an essential transcriptional regulator of chondrocyte homeostasis in adult articular cartilage. Age-dependent Nfat1 expression in articular chondrocytes is regulated by dynamic histone methylation, one of the epigenetic mechanisms that regulate gene transcription. © 2011 American Society for Bone and Mineral Research
Evaluation of nonbiomedical and biomedical grade alginates for the transplantation of genetically modified articular chondrocytes to cartilage defects in a large animal model in vivo
Authors: Heiligenstein Susanne , Cucchiarini Magali , Laschke Matthias W. , Bohle Rainer M. , Kohn Dieter , Menger Michael D. , Madry Henning 
Published: March 2011

AbstractBackgroundGenetically modified chondrocytes embedded in alginate improve cartilage repair in experimental models, and alginates are clinically used for articular chondrocyte transplantation. In the present study, we tested the hypothesis that the alginate system allows for sustained transgene expression in cartilage defects in a preclinical large animal model in vivo.MethodsPrimary cultures of ovine articular chondrocytes were transfected with the Photinus pyralis luc or the Escherichia coli lacZ genes in monolayer culture in vitro using eight different nonviral compounds. Optimally transfected chondrocytes were encapsulated in spheres composed of nonbiomedical or biomedical grade alginates for evaluation of luciferase expression, cell numbers and viabilities in vitro. Transfected chondrocytes encapsulated in spheres comprised of the different alginates were then implanted into osteochondral defects in the knee joints of sheep to examine the profiles of transgene expression in vivo.ResultsOvine articular chondrocytes were efficiently transfected with FuGENE 6. Transgene expression was detectable after encapsulation in the alginates over 21 days in vitro. Transplantation of genetically modified chondrocytes to cartilage defects in vivo resulted in maximal transgene expression on day 1 after transfection, with a decrease by day 21, the longest time point evaluated. Remarkably, the reduction in luciferase activity was less pronounced when biomedical grade alginates were employed, compared to nonbiomedical grade alginates, suggesting that such alginates might be better suited to support elevated transgene expression after transplantation of genetically modified chondrocytes.ConclusionsThis approach may be of value to study the effects of potential therapeutic genes upon cartilage repair in a clinically relevant setting. Copyright © 2011 John Wiley & Sons, Ltd.
Cytokine expression in muscle following traumatic injury
Authors: Jackson Wesley M. , Aragon Amber B. , Onodera Jun , Koehler Steven M. , Ji Youngmi , Bulken‐Hoover Jamie D. , Vogler Jared A. , Tuan Rocky S. , Nesti Leon J. 
Published: March 2011

AbstractHeterotopic ossification (HO) occurs at a high frequency in severe orthopaedic extremity injuries; however, the etiology of traumatic HO is virtually unknown. Osteogenic progenitor cells have previously been identified within traumatized muscle. Although the signaling mechanisms that lead to this dysregulated differentiation pathway have not been identified, it is assumed that inflammation and fibrosis, which contribute to an osteoinductive environment, are necessary for the development of HO. The hypothesis of this study was that cytokines related to chronic inflammation, fibrogenesis, and osteogenesis become up‐regulated following severe muscle trauma where HO forms. Classification of these cytokines by their differential expression relative to control muscle will provide guidance for further study of the mechanisms leading to HO. Real‐time RT‐PCR analysis revealed no significant up‐regulation of cytokines typically associated with HO (e.g., BMP‐4, as observed in the genetic form of HO, fibrodysplasia ossificans progressiva). Instead, the cytokine gene expression profile associated with the traumatized muscle included up‐regulation of cytokines associated with osteogenesis and fibrosis (i.e., BMP‐1 and TGF‐β1). Using immunohistochemistry, these cytokines were localized to fibroproliferative lesions, which have previously been implicated in HO. This study identifies other cell and tissue‐level interactions in traumatized muscle that should be investigated further to better define the etiology of HO. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1613–1620, 2011.
In‐Vivo knee kinematics in rotationally unconstrained total knee arthroplasty
Authors: Catani Fabio , Belvedere Claudio , Ensini Andrea , Feliciangeli Alessandro , Giannini Sandro , Leardini Alberto 
Published: March 2011

AbstractTotal knee replacement designs claim characteristic kinematic performance that is rarely assessed in patients. In the present study, in vivo kinematics of a new prosthesis design was measured during activities of daily living. This design is posterior stabilized for which spine–cam interaction coordinates free axial rotation throughout the flexion–extension arc by means of a single radius of curvature for the femoral condyles in the sagittal and frontal planes. Fifteen knees were implanted with this prosthesis, and 3D video‐fluoroscopic analysis was performed at 6‐month follow‐up for three motor tasks. The average range of flexion was 70.1° (range: 60.1–80.2°) during stair‐climbing, 74.7° (64.6–84.8°) during chair‐rising, and 64.1° (52.9–74.3°) during step‐up. The corresponding average rotation on the tibial base‐plate of the lines between the medial and lateral contact points was 9.4° (4.0–22.4°), 11.4° (4.6–22.7°), and 11.3° (5.1–18.0°), respectively. The pivot point for these lines was found mostly in the central area of the base‐plate. Nearly physiological range of axial rotation can be achieved at the replaced knee during activities of daily living. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1484–1490, 2011
TRENDS IN RECOVERY OF MEDITERRANEAN SOIL CHEMICAL PROPERTIES AND MICROBIAL ACTIVITIES AFTER INFREQUENT AND FREQUENT WILDFIRES
Authors: Guénon R. , Vennetier M. , Dupuy N. , Roussos S. , Pailler A. , Gros R. 
Published: March 2011

ABSTRACTSince the 1970s, increase in fire frequency has been observed in all European Mediterranean regions. The objectives of this study were (1) to determine the effects of wildfire frequency on the recovery at short‐ and long‐term of soil chemical and microbial properties and (2) to identify the mechanisms underlying the recovery of these sites properties. Soils from 17 plots (Maures mountains range, Var, France) were classified into 5 wildfire regimes (i.e. not burned since at least 57 years ago, infrequently and frequently burned‐with time since fire between 4 and 17 years). Soil samples from these plots were analysed for their nutrient content, chemical functions of soil organic matter (SOM) using FT‐MIR spectroscopy and microbial mineralising activities. Our results showed that the frequent wildfire regime slowed down the recovery in the short term of SOM spectroscopic properties and nutrient availability. Both low quantity and low quality (i.e. high percentage of aromatic and phenolic organic forms) of soil organic matter were found to be related to soil microbial recovery at 4 years after frequent wildfires. The frequent wildfires improved the recovery in net nitrification and nitrate content, leading to an increase in catabolic evenness and a recovery in microbial C‐substrate utilisation profiles between 4 and 17 years. However, frequent wildfires slowed down the recovery of hydrolytic enzyme pool (i.e. FDA hydrolases) and phenol oxidase activity, both involved in soil C cycling. Overall, our observations suggest that 4 fires in 50 years is a threshold beyond which soil quality may be endangered. Copyright © 2011 John Wiley & Sons, Ltd.
On the tamagawa number conjecture for hecke characters
Authors: Bars Francesc 
Published: March 2011

AbstractIn this paper, we prove the weak p‐part of the Tamagawa number conjecture in all non‐critical cases for the motives associated to Hecke characters of the form $\varphi ^a\overline{\varphi }^b$ where φ is the Hecke character of a CM elliptic curve E defined over an imaginary quadratic field K, under certain restrictions which originate mainly from the Iwasawa theory of imaginary quadratic fields. © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim