bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Galaxy to Perform Large‐Scale Interactive Data Analyses
Authors: Taylor James , Schenck Ian , Blankenberg Dan , Nekrutenko Anton
Published: October 2007

While most experimental biologists know where to download genomic data, few have a concrete plan on how to analyze it. This situation can be corrected by: (1) providing unified portals serving genomic data and (2) building Web applications to allow flexible retrieval and on‐the‐fly analyses of the data. Powerful resources, such as the UCSC Genome Browser already address the first issue. The second issue, however, remains open. For example, how to find human protein‐coding exons with the highest density of single nucleotide polymorphisms (SNPs) and extract orthologous sequences from all sequenced mammals? Indeed, one can access all relevant data from the UCSC Genome Browser. But once the data is downloaded how would one deal with millions of SNPs and gigabytes of alignments? Galaxy (http://g2.bx.psu.edu) is designed specifically for that purpose. It amplifies the strengths of existing resources (such as UCSC Genome Browser) by allowing the user to access and, most importantly, analyze data within a single interface in an unprecedented number of ways. Curr. Protoc. Bioinform. 19:10.5.1‐10.5.25. © 2007 by John Wiley & Sons, Inc.
Defined, Feeder‐Independent Medium for Human Embryonic Stem Cell Culture
Authors: Ludwig Tenneille , A. Thomson James
Published: October 2007

The developmental potential of human ES cells makes them an important tool in developmental, pharmacological, and clinical research. For human ES cell technology to be fully exploited, however, culture efficiency must be improved, large‐scale culture enabled, and safety ensured. Traditional human ES cell culture systems have relied on serum products and mouse feeder layers, which limit the scale, present biological variability, and expose the cells to potential contaminants. Defined, feeder‐independent culture systems improve the safety and efficiency of ES cell technology, enabling translational research. The protocols herein are designed with the standard research laboratory in mind. They contain recipes for the formulation of mTeSR (a defined medium for human ES cell culture) and detailed protocols for the culture, transfer, and passage of cells grown in these feeder‐independent conditions. They provide a basis for routine feeder‐independent culture, and a starting point for additional optimization of culture conditions. Curr. Protoc. Stem Cell Biol. 2:1C.2.1‐1C.2.16. © 2007 by John Wiley & Sons, Inc.
Intelligent control using multiple models and neural networks
Authors: Fu Yue , Chai Tianyou , Yue Heng
Published: October 2007

Most adaptive control algorithms for nonlinear discrete time systems become invalid when the controlled systems have non‐minimum phase properties and large uncertainties. In this paper, an intelligent control method using multiple models and neural networks (NN) is developed to deal with those problems. The proposed control method includes a set of fixed controllers, a re‐initialized neural network (NN) adaptive controller and a free‐running NN adaptive controller. The bounded‐input‐bounded‐output (BIBO) stability and performance convergence of the system are guaranteed by the free‐running adaptive controller, while the multiple fixed controllers and the re‐initialized adaptive controller are used to improve the transient response. Simulation results are presented to demonstrate the effectiveness of the proposed method. Copyright © 2007 John Wiley & Sons, Ltd.
Utility of consecutive repeat HIT ELISA testing for heparin‐induced thrombocytopenia
Authors: Chan Maren , Malynn Elizabeth , Shaz Beth , Uhl Lynne
Published: October 2007

Heparin‐induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI‐PF4 enzyme‐linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0–0.132, medium = 0.133–0.267, and high = 0.268–0.399. A pretest clinical score was retrospectively determined using the “4T's” (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
The chromosome 9q subtelomere deletion syndrome
Authors: Stewart Douglas R. , Kleefstra Tjitske
Published: October 2007

The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative micro‐ or brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid‐face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down‐turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub‐microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haplo‐insufficiency of EHMT1, a gene whose protein product (Eu‐HMTase1) is a histone H3 Lys 9 (H3‐K9) methyltransferase. This was established by identification of three patients with features of the syndrome and either mutations or a balanced translocation in EHMT1. H3‐K9 histone methylation is restricted to the euchromatin of mammals and functions to silence individual genes. Deletion size does not correlate with the severity of the 9qSTDS since patients with mutations in EHMT1 are as severely affected as those with submicroscopic deletions. Patients clinically suspected of having the 9qSTDS but with normal subtelomere deletion testing by FISH or MLPA should be considered for detailed 9q MLPA analysis and/or sequencing of EHMT1. EHMT1 is another example in the growing list of genes responsible for brain development that appear to play a role in chromatin remodeling. Published 2007 Wiley‐Liss, Inc.
Cryptic telomere imbalance: A 15‐year update
Authors: Ledbetter David H. , Martin Christa Lese
Published: October 2007

It has been 15 years since we proposed that assays of telomere integrity might reveal cryptic translocations and deletions as a significant cause of mental retardation (MR) in patients with normal G‐banded karyotypes. Development of unique genomic probes adjacent to the subtelomeric repeats of each chromosome arm allowed multiplex FISH analyses that confirmed such cryptic telomeric imbalances in 3–6% of all unexplained MR. Although such “telomere FISH” analysis quickly became standard of care, limitations of this technology platform included a lack of information on the size and gene content of the deleted/duplicated segments and the failure to detect interstitial deletions not involving the most distal unique clone. The development of “molecular ruler” clone sets for every human telomere provided the foundation for accurate determination of size and gene content of each imbalance, as well as the detection of interstitial deletions within these regions. Array comparative genomic hybridization (aCGH) has emerged as a powerful technology to assess single copy changes (monosomy or trisomy) at targeted loci such as telomeres or across the whole genome. This technology now replaces multiplex FISH for the assessment of telomere integrity in unexplained MR and has the advantage of efficiently determining the size and gene content of the imbalance, as well as detecting interstitial deletions near telomeres or anywhere else in the genome covered by the array design. The application of aCGH in several studies of unexplained MR has confirmed that telomere imbalances are overrepresented compared to “average” chromosomal regions, although this is likely due to random chromosome breakage rather than specific molecular mechanisms associated with the genomic architecture of human telomeres. Telomere imbalances are significantly larger than initially envisioned (∼40% are >5 Mb in size), and indicate the analytic sensitivity of the G‐banded karyotype is much lower than previously thought. Finally, experience with smaller benign variants compared to larger pathogenic imbalances at telomeres serves as a model for approaching whole‐genome aCGH in a clinical setting. © 2007 Wiley‐Liss, Inc.
Engineering education in the Australian context
Authors: Bradley A. B. , Allen R. M.
Published: October 2007

This paper provides a background to the Higher Education System in Australia and in particular to the provision of undergraduate professional engineering degree programmes, often from the perspective of an accrediting body. The current issues impacting on the operating environment, as well as educational design and quality assurance approaches are discussed. Some of the key features and emerging innovations within the Australian engineering education system are reviewed. Copyright © 2007 Curtin University of Technology and John Wiley & Sons, Ltd.
Microwave‐Assisted Palladium‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Chlorides
Authors: Iwasaki Masayuki , Yorimitsu Hideki , Oshima Koichiro
Published: October 2007

Treatment of 1,4‐disubstituted 1,2,3‐triazoles with aryl chlorides in the presence of potassium carbonate under palladium catalysis and microwave irradiation at 250 °C for 15 min leads to arylation of the triazole at the 5‐position. A variety of functional groups, including ester and hydroxy groups, are compatible. The procedure is suitable for the regioselective preparation of trisubstituted triazoles. Microwave irradiation accelerates the reaction, thus allowing the rapid synthesis of trisubstituted triazoles, which are difficult to synthesize selectively.
Beanspruchungen in dicken Bodenplatten infolge des Abfließens der Hydratationswärme
Authors: Tue Nguyen Viet , Schlicke Dirk , Bödefeld Jörg
Published: October 2007

Als Grundlage für die Erstellung eines mechanisch fundierten Bemessungskonzeptes zur Begrenzung der Rissbreite infolge des Abfließens der Hydratationswärme in sehr dicken Betonbauteilen wurde ein Messprogramm im Zuge des Neubaus der Schleuse Sülfeld‐Süd durchgeführt. Primäres Ziel dieser Untersuchung war die Beschreibung der tatsächlichen Beanspruchung in dicken Betonbauteilen während der Betonerhärtung. Hierzu wurde die Zuverlässigkeit messtechnischer Größen durch eine Kompatibilitätsprüfung überprüft. Anschließend wurden die Messgrößen für die Verifikation eines 3D‐FE‐Modells verwendet. Neue Erkenntnisse zum Bauteilverhalten konnten gewonnen werden. In diesem Beitrag werden die wesentlichen Ergebnisse zusammenfassend erläutert.
Chirality and chemical processes: A few afterthoughts
Authors: Cintas Pedro
Published: October 2007

Chirality and chiral have become terms that pervade a wide range of disciplines in physical and life sciences. Although such terms are precisely defined, their use often engenders confusion and ambiguity. Perhaps, the most improper use of chirality, yet widely accepted, is related to its association with stereodynamics and physico‐chemical transformations, such as chiral discrimination, chiral resolution, chiral recognition, chiral synthesis, and so on. Even though this conceptual perversion has been highlighted by renowned stereochemists, it has become a recurring keyword and a hot message in modern literature. It is timely to renew the correct use and context in forums such as the present journal, adding further reflections that may help both beginners and practitioners. This short article is not intended to criticize or highlight errors, but rather to encourage a level of rigor and the use of statements, which should be universally correct. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Conformational Influence on the Type of Stabilization of Sulfur Radical Cations in Cyclic Peptides
Authors: Hug Gordon L. , Bobrowski Krzysztof , Pogocki Dariusz , Hörner Gerald , Marciniak Bronislaw
Published: October 2007

The free‐radical chemistry of two oxidized cyclic dipeptides is investigated using time‐resolved optical and conductivity detection. Two cyclic dipeptides, cyclo‐Gly‐L‐Met and cyclo‐D‐Met‐L‐Met, are synthesized and irradiated with nanosecond pulses of electrons, which initiate the oxidation of the methionine side chains with hydroxyl radicals from the radiolysis of water. The cyclic peptides are taken to be models for the interior of proteins where there are no terminal groups. This opens up the possibility that neighboring‐group effects can be studied directly between the initially formed sulfur radical cations and the heteroatoms associated with the peptide bonds. Such complexation of the sulfur radical cations is observed with the amide nitrogen atoms. In addition, intermolecular stabilization with the unoxidized sulfur atoms on separate cyclic dipeptide molecules is observed. Little or no intramolecular stabilization by the unoxidized sulfur in the neighboring methionine occurs in cyclo‐D‐Met‐L‐Met, in contrast to the previously observed intramolecular sulfur stabilization of the sulfur radical cation in the isomer cyclo‐L‐Met‐L‐Met. This contrasting behavior is rationalized by conformational differences in the two isomers as seen through molecular‐modeling simulations. The implications for the oxidation of the protein calmodulin, which contains multiple residues of methionine, are discussed as having analogous determining factors.
Cell‐microarray analysis of antigen‐specific B‐cells: Single cell analysis of antigen receptor expression and specificity
Authors: Tajiri Kazuto , Kishi Hiroyuki , Tokimitsu Yoshiharu , Kondo Sachiko , Ozawa Tatsuhiko , Kinoshita Koshi , Jin Aishun , Kadowaki Shinichi , Sugiyama Toshiro , Muraguchi Atsushi
Published: October 2007

The authors previously developed a cell‐microarray system that effectively detects antigen‐specific B‐cells by monitoring intracellular Ca2+ at single cell levels. Here they present a novel method to detect antigen‐specific B‐cells using cell‐microarray system. To detect antigen‐specific B‐cells, they arrayed live lymphocytes on a chip, stained cells with fluorescence‐labeled nonspecific proteins, and analyzed them with a fluorescence scanner to detect nonspecific protein binding to B‐cells. They then stained cells with fluorescence‐labeled antigen and analyzed them with the scanner. Cells stained with specific antigen, but not with nonspecific proteins, were determined as antigen‐specific B‐cells and harvested. Antibody cDNA was amplified from retrieved B‐cells by single‐cell RT‐PCR, inserted into expression vectors, and was examined for its specificity by ELISA. They could detect antigen‐specific B‐cells at a frequency of 0.01% in a model system using transgenic mice that express antibody to hen‐egg lysozyme on the surface of B‐cells. They applied this system to directly detect hepatitis B virus surface‐antigen (HBs‐Ag)‐specific B‐cells from peripheral blood in HBs‐Ag‐vaccinated volunteers and succeeded in producing HBs‐Ag‐specific monoclonal antibody. This novel system allows us to identify human antigen‐specific B‐cells of very low frequency and is a powerful tool to explore the candidates of antibody therapeutics. © 2007 International Society for Analytical Cytology
New Pyrimidylboronic Acids and Functionalized Heteroarylpyrimidines by Suzuki Cross‐Coupling Reactions
Authors: Clapham Kate M. , Smith Amy E. , Batsanov Andrei S. , McIntyre Laura , Pountney Adam , Bryce Martin R. , Tarbit Brian
Published: October 2007

We report the synthesis of 2‐chloro‐5‐pyrimidylboronic acid (6) and 2‐amino‐5‐pyrimidylboronic acid (8) by lithium–halogen exchange followed by reaction with triisopropylborate. Their reactivity with heteroaryl halides in Suzuki–Miyaura cross‐coupling reactions has been evaluated. New highly functionalized 5‐heteroarylpyrimidine derivatives 24–33 (heteroaryl = quinoline, pyridine, pyrimidine, pyrazine, thiophene, benzothiazole) have been obtained in synthetically useful yields. The X‐ray structure of 6 reveals extensive intermolecular O–H···N hydrogen bonding in the crystal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
One‐Pot Indium Iodide Mediated Synthesis of Chiral β‐Seleno Amides and Selenocysteine Derivatives by Ring‐Opening Reaction of 2‐Oxazolines
Authors: Braga Antonio L. , Vargas Fabrício , Galetto Fábio Z. , Paixão Márcio W. , Schwab Ricardo S. , Taube Paulo S.
Published: October 2007

A set of chiral β‐seleno amides were efficiently synthesized by a simple and efficient procedure involving a ring‐opening reaction of 2‐oxazoline with diorganyl dichalcogenides mediated by indium(I) iodide. As an application, the synthesis of selenocysteine derivatives was accomplished. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
System identification applied to long‐span cable‐supported bridges using seismic records
Authors: Siringoringo Dionysius M. , Fujino Yozo
Published: October 2007

This paper presents the application of system identification (SI) to long‐span cable‐supported bridges using seismic records. The SI method is based on the System Realization using Information Matrix (SRIM) that utilizes correlations between base motions and bridge accelerations to identify coefficient matrices of a state‐space model. Numerical simulations using a benchmark cable‐stayed bridge demonstrate the advantages of this method in dealing with multiple‐input multiple‐output (MIMO) data from relatively short seismic records. Important issues related to the effects of sensor arrangement, measurement noise, input inclusion, and the types of input with respect to identification results are also investigated. The method is applied to identify modal parameters of the Yokohama Bay Bridge, Rainbow Bridge, and Tsurumi Fairway Bridge using the records from the 2004 Chuetsu‐Niigata earthquake. Comparison of modal parameters with the results of ambient vibration tests, forced vibration tests, and analytical models are presented together with discussions regarding the effects of earthquake excitation amplitude on global and local structural modes. Copyright © 2007 John Wiley & Sons, Ltd.
Treating young people with eating disorders: transition from child mental health to specialist adult eating disorder services
Authors: Arcelus Jon , Bouman Walter P. , Morgan John. F.
Published: October 2007

Background

The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) of young people with eating disorders may pose a number of difficulties, including an inconsistent referral process and age boundaries.

Methods

We compared young adults referred to a specialist Adult Eating Disorders Service (AEDS) who had previous involvement with CAMHS for the treatment of their eating disorder with those who did not. Information regarding the socio‐demographic characteristics and eating disorders symptomatology of patients assessed by an AEDS over a 4‐year period was collected.

Results

Patients who had previous involvement with CAMHS (particularly the ones treated as in‐patients) presented with a lower self‐esteem and more maturity fears (MF) than those without previous involvement.

Conclusions

This study discusses the implication of these results in transitional arrangements between CAMHS and Adult services. It also highlights the need for heightened awareness of particular issues of self‐esteem and maturation in these patients moving between services. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
Dieting in Spanish adolescent girls
Authors: López‐Guimerà Gemma , Fauquet Jordi , Portell Mariona , Sánchez‐Carracedo David , Raich Rosa M.
Published: October 2007

This article examines the relation between dieting and non‐dieting adolescent girls and body mass index (BMI), eating attitudes and the influence of the aesthetic body shape model. Three hundred forty‐nine Spanish adolescent girls in their second year of secondary education were selected. The research design was a cross‐sectional ex post facto study and validated measures were used to assess the main variables. Fourteen per cent of the sample was on a diet. Of this group, 69% were overweight, 70% had disordered eating attitudes and 70% were influenced by the current aesthetic body shape model. In all situations, the scores for dieters were significantly higher than those for non‐dieters. Although there is not yet any clear consensus with regards to how adolescents interpret the term ‘diet’, the results indicate major differences between dieters and non‐dieters and that those who self‐report that they are on a diet present elements of the risk of developing eating and weight disorders. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
Eating disorders and concurrent psychopathology: a reconceptualisation of clinical need through Rasch analysis
Authors: Fletcher B. (C) , Kupshik G. A. , Uprichard S. , Shah S. , Nash A. S.
Published: October 2007

Therapies for anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS) take as their focus, perhaps of necessity, the eating disorder symptomatology. However, there is increasing evidence of comorbidity of psychopathological mechanisms (e.g. perfectionism, depression) with eating disorders which, left untreated, may diminish any therapeutic effects. Thus identifying the extent of comorbidity in an eating disorder population and assessing the relationship between psychopathological mechanisms and the eating disorder is important. Rasch analysis was applied to the findings from questionnaires (EDI‐2; SCL90‐R) completed by 105 female patients referred to an eating disorder unit. General psychopathology was found to be more indicative of ‘caseness’ than eating disorder psychopathology. In particular, interpersonal sensitivity, depression and mild interpersonal aspects of psychoticism emerged as important factors across eating disorders. The comorbidity of psychopathological mechanisms needs to be given consideration in the successful treatment of eating disorders. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
Diurnal fluctuations in glacier ice deformation: Haut Glacier d'Arolla, Switzerland
Authors: Mair Douglas , Hubbard Bryn , Nienow Peter , Willis Ian , Fischer Urs H.
Published: October 2007

Measurements of surface velocity, ice deformation (at 42 and 89% ice depth) and proglacial stream discharge were made at Haut Glacier d'Arolla, Switzerland, to determine diurnal patterns of variation in each. Data are analysed in order to understand better the relationship between hydraulically induced basal motion and glacier ice deformation over short timescales. The data suggest that hydraulically induced localized basal ‘slippery’ spots are created over diurnal cycles, causing enhanced basal motion and spatially variable glacier speed‐up. Our data indicate that daily glacier speed‐up is associated with reduced internal deformation over areas previously identified as slippery spots and increased deformation in areas located adjacent to or down‐glacier from slippery spots. We interpret this pattern in terms of a transfer of mechanical support for basal shear stress away from slippery spots to adjacent sticky areas, where the resulting stronger ice–bed coupling causes increased ice deformation near the bed. These patterns indicate that basal ice is subjected to stress regimes that are variable at a high spatial and temporal resolution. Such variations may be central to the creation of anomalous vertical velocity profiles measured above and down‐glacier of basal slippery zones, which have shown evidence for ‘plug flow’ and extrusion flow over annual timescales. Copyright © 2007 John Wiley & Sons, Ltd.
Identification of genes with abnormal expression changes in acute myeloid leukemia
Authors: Stirewalt Derek L. , Meshinchi Soheil , Kopecky Kenneth J. , Fan Wenhong , Pogosova‐Agadjanyan Era L. , Engel Julia H. , Cronk Michelle R. , Dorcy Kathleen Shannon , McQuary Amy R. , Hockenbery David , Wood Brent , Heimfeld Shelly , Radich Jerald P.
Published: October 2007

Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies. We hypothesized that microarray studies could identify previously unrecognized expression changes that occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets. To test this hypothesis, we compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients. Normal hematopoietic samples included CD34+ selected cells (N = 18), unselected bone marrows (N = 10), and unselected peripheral bloods (N = 10). Twenty genes displayed AML‐specific expression changes that were not found in the normal hematopoietic cells. Subsequent analyses using microarray data from 285 additional AML patients confirmed expression changes for 13 of the 20 genes. Seven genes (BIK, CCNA1, FUT4, IL3RA, HOMER3, JAG1, WT1) displayed increased expression in AML, while 6 genes (ALDHA1A, PELO, PLXNC1, PRUNE, SERPINB9, TRIB2) displayed decreased expression. Quantitative RT/PCR studies for the 7 over‐expressed genes were performed in an independent set of 9 normal and 21 pediatric AML samples. All 7 over‐expressed genes displayed an increased expression in the AML samples compared to normals. Three of the 7 over‐expressed genes (WT1, CCNA1, and IL3RA) have already been linked to leukemogenesis and/or AML prognosis, while little is known about the role of the other 4 over‐expressed genes in AML. Future studies will determine their potential role in leukemogenesis and their clinical significance. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2007 Wiley‐Liss, Inc.
Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia
Authors: Paulsson Kajsa , Horvat Andrea , Strömbeck Bodil , Nilsson Fredrik , Heldrup Jesper , Behrendtz Mikael , Forestier Erik , Andersson Anna , Fioretos Thoas , Johansson Bertil
Published: October 2007

Although it has been suggested that mutations of the FLT3, NRAS, KRAS, and PTPN11 genes are particularly frequent in high hyperdiploid (>50 chromosomes) pediatric acute lymphoblastic leukemias (ALLs), this has as yet not been confirmed in a large patient cohort. Furthermore, it is unknown whether mutations of these genes coexist in hyperdiploid cases. We performed mutation analyses of FLT3, NRAS, KRAS, and PTPN11 in a consecutive series of 78 high hyperdiploid ALLs. Twenty‐six (33%) of the cases harbored a mutation, comprising six activating point mutations and one internal tandem duplication of FLT3 (7/78 cases; 9.0%), eight codon 12, 13, or 61 NRAS mutations (8/78 cases; 10%), five codon 12 or 13 KRAS mutations (5/78 cases, 6.4%), and seven exon 3 or 13 PTPN11 mutations (7/78 cases; 9.0%). No association was seen between the presence of a mutation in FLT3, NRAS, KRAS, or PTPN11 and gender, age, white blood cell count, or relapse, suggesting that they do not confer a negative prognostic impact. Only one case harbored mutations in two different genes, suggesting that mutations of these four genes are generally mutually exclusive. In total, one third of the cases harbored a FLT3, NRAS, KRAS, or PTPN11 mutation, identifying the RTK‐RAS signaling pathway as a potential target for novel therapies of high hyperdiploid pediatric ALLs. © 2007 Wiley‐Liss, Inc.
The effect of CXCL1 on human fetal oligodendrocyte progenitor cells
Authors: Filipovic Radmila , Zecevic Nada
Published: October 2007

Chemokine CXCL1 is abundantly present in proliferative zones during brain development and in regions of remyelination, suggesting that it influences development of oligodendrocyte progenitors (OPC) in these regions. We studied in vitro the effects and possible mechanisms by which CXCL1 acts on human fetal OPC. In organotypic slice cultures of human fetal cortical ventricular/subventricular (VZ/SVZ) zones, blocking of CXCL1 signaling reduced significantly the proliferation of OPC. Moreover, exogenously added CXCL1 induced increase of OPC proliferation. Treatments of purified OPC cultures and cell depletion experiments demonstrated that this effect of CXCL1 was mainly indirect, mediated through astrocytes. We identified that CXCL1 acted through the extracellular signal regulated kinase (ERK1/2) pathway, activated primarily in astrocytes. In vitro, astrocytes stimulated with CXCL1 released several cytokines, but only the release of interleukin‐6 (IL‐6) was completely blocked by inhibition of ERK1/2 pathway. When released IL‐6 was neutralized in slices, a decrease in OPC proliferation was demonstrated, while addition of IL‐6 was able to return OPC proliferation in astrocyte‐depleted slices to the control level. These results suggest that in the human fetal brain CXCL1 promotes proliferation of early OPC, acting in part through an ERK1/2‐dependent pathway and release of IL‐6 from astrocytes. © 2007 Wiley‐Liss, Inc.
Lipopolysaccharide is a frequent and significant contaminant in microglia‐activating factors
Authors: Weinstein Jonathan R. , Swarts Sarah , Bishop Caroline , Hanisch Uwe‐Karsten , Möller Thomas
Published: October 2007

Lipopolysaccharide (LPS/endotoxin) is a potent immunologic stimulant. Many commercial‐grade reagents used in research are not screened for LPS contamination. LPS induces a wide spectrum of proinflammatory responses in microglia, the immune cells of the brain. Recent studies have demonstrated that a broad range of endogenous factors including plasma‐derived proteins and bioactive phospholipids can also activate microglia. However, few of these studies have reported either the LPS levels found in the preparations used or the effect of LPS inhibitors such as polymyxin B (PMX) on factor‐induced responses. Here, we used the Limulus amoebocyte lysate assay to screen a broad range of commercial‐ and pharmaceutical‐grade proteins, peptides, lipids, and inhibitors commonly used in microglia research for contamination with LPS. We then characterized the ability of PMX to alter a representative set of factor‐induced microglial activation parameters including surface antigen expression, metabolic activity/proliferation, and NO/cytokine/chemokine release in both the N9 microglial cell line and primary microglia. Significant levels of LPS contamination were detected in a number of commercial‐grade plasma/serum‐ and nonplasma/serum‐derived proteins, phospholipids, and synthetic peptide preparations, but not in pharmaceutical‐grade recombinant proteins or pharmacological inhibitors. PMX had a significant inhibitory effect on the microglia‐activating potential of a number of commercial‐, but not pharmaceutical‐grade, protein preparations. Novel PMX‐resistant responses to α2‐macroglobulin and albumin were incidentally observed. Our results indicate that LPS is a frequent and significant contaminant in commercial‐grade preparations of previously reported microglia‐activating factors. Careful attention to LPS levels and appropriate controls are necessary for future studies in the neuroinflammation field. © 2007 Wiley‐Liss, Inc.
Activation of CysLT receptors induces astrocyte proliferation and death after oxygen–glucose deprivation
Authors: Huang Xiao‐Jia , Zhang Wei‐Ping , Li Cheng‐Tan , Shi Wen‐Zhen , Fang San‐Hua , Lu Yun‐Bi , Chen Zhong , Wei Er‐Qing
Published: October 2007

We recently found that 5‐lipoxygenase (5‐LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT1 and CysLT2 receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5‐LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen‐glucose deprivation (OGD) followed by recovery to induce ischemic‐like injury in the cultured rat astrocytes. We found that 1‐h OGD did not injure astrocytes (sub‐lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4‐h OGD moderately injured the cells (moderate OGD) and led to death 24–72 h after recovery. Inhibition of phospholipase A2 and 5‐LOX attenuated both the proliferation and death. Sub‐lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5‐LOX inhibitors. Sub‐lethal OGD increased the expressions of CysLT1 receptor mRNA and protein, while moderate OGD induced the expression of CysLT2 receptor mRNA. Exogenously applied leukotriene D4 (LTD4) induced astrocyte proliferation at 1–10 nM and astrocyte death at 100–1,000 nM. The CysLT1 receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT2 receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD4 (100 nM) increased the expression of CysLT2 receptor mRNA. Thus, in vitro ischemia activates astrocyte 5‐LOX to produce CysLTs, and CysLTs result in CysLT1 receptor‐mediated proliferation and CysLT2 receptor‐mediated death. © 2007 Wiley‐Liss, Inc.
Primary care physicians' attitudes related to cognition enhancers in early dementia: a representative eight‐year follow‐up study in Lower Saxony, Germany
Authors: Maeck Lienhard , Haak Sebastian , Knoblauch Anita , Stoppe Gabriela
Published: October 2007

Objective

By means of a representative follow‐up survey, we investigated changes in family physicians' (FPs) attitudes towards cognition enhancers in early dementia during 1993 and 2001.

Methods

One hundred and twenty‐two FPs (response rate 71.8%) in Lower Saxony, Germany, were randomly assigned to one of two written case samples presenting a patient with cognitive decline suggestive of early Alzheimer's disease (DAT; case A: female patient vs case B: male patient). Using a structured face‐to‐face interview, they were asked to suggest their potential drug treatment. The results were compared to corresponding data from our previous survey in 1993.

Results

FPs' readiness to start antidementia drug treatment decreased from 70.4% in 1993 to 43.4% at follow‐up, although underlying DAT was significantly more frequently suggested (11.0% vs 26.2%, p < 0.05). Substances with questionable efficacy such as Piracetame were prescribed less frequently in 2001 whereas evidence‐based medication like cholinesterase inhibitors (ChEIs) failed to compensate for this drop. Compared to 1993, when 55.2% of FPs expected no therapeutic impact, at follow‐up, 75.4% expected slowdown of disease progression, stabilisation or improvement of symptoms (p < 0.05).

Conclusions

Our results demonstrate a significant decrease of therapeutic nihilism in primary care within eight years. However, in patients with suspicion of DAT, this is not reflected accordingly in potential treatment. Copyright © 2007 John Wiley & Sons, Ltd.
Diurnal and seasonal variations of sap flow of Caragana korshinskii in the arid desert region of north‐west China
Authors: Xia Guimin , Kang Shaozhong , Li Fusheng , Zhang Jianhua , Zhou Qingyun
Published: October 2007

The aim of this study was to obtain the diurnal and seasonal changes of trunk sap flow in desert‐living Caragana korshinskii so as to understand its water requirement and ecological significance. The experiment was carried out with 15‐year old Caragana korshinskii grown in north‐west China under natural conditions. Heat pulse sensors based on the heat compensation theory were applied to measure the trunk sap flow, and soil moisture content at 0–300 cm layer, using tube‐type time domain reflectometry (Tube‐TDR). The solar radiation, the maximum and minimum air temperatures, relative humidity, wind speed, wind direction and precipitation were measured at a standard automatic weather station. The diurnal and seasonal variations of sap flow rate, the sap velocity at different positions in the trunk and the sap flow rate under different weather conditions were analysed. And the correlation between the sap flow rate and the meteorological factors was also analysed. Results showed that the trunk sap flow varied regularly in the diurnal term and the sap flow velocity decreased with the probe‐inserted depth into the sapwood. Magnitude of sap flow changed considerably between sunny and rainy days. The order of the main meteorological factors affecting the sap flow rate of Caragana korshinskii shrubs were: vapour pressure deficit > solar radiation > air temperature > wind speed. The close correlation between daily sap flow rate and meteorological factors in the whole growing season can be used to estimate the transpiration of Caragana korshinskii. Copyright © 2007 John Wiley & Sons, Ltd.
Aquifer heterogeneity determination through the slope method
Authors: Şen Zekai , Wagdani Essam
Published: October 2007

In arid‐region wadis, groundwater storage lies within shallow Quaternary alluvium deposits, which are connected with the present‐day hydrological cycle and, therefore, are replenished due to occasional runoff and flash flood occurrences. The groundwater resources are precious in these environments; therefore, their potentiality must be assessed with care in the best manner. The aquifer potentiality is calculated after the storativity and transmissivity parameter estimations, which require rather long‐duration field tests with restrictive assumptions in the theoretical model developments, such as the homogeneity and isotropy.

It is the main purpose of this paper to expose the fundamentals of the slope‐matching procedure (SMP) and its application for short‐duration field tests in arid‐region aquifers. In this manner, the subsurface hydrogeological behaviours of the bored land pieces at and around the well locations are prospected in a detailed and refined manner. It is shown that in many cases the classical techniques are appropriate, inconvenient and inapplicable with conclusive reliable results and conclusions. The application of the SMP is presented for some aquifer tests from the central western part of the Kingdom of Saudi Arabia. Copyright © 2007 John Wiley & Sons, Ltd.
Water source characterization through spatiotemporal patterns of major, minor and trace element stream concentrations in a complex, mesoscale German catchment
Authors: Fröhlich Holger L. , Breuer Lutz , Frede Hans‐Georg , Huisman Johan A. , Vaché Kellie B.
Published: October 2007

The link between spatiotemporal patterns of stream water chemistry and catchment characteristics for the mesoscale Dill catchment (692 km2) in Germany is explored to assess the catchment scale controls on water quality and to characterize water sources. In order to record the spatiotemporal pattern, ‘snapshot sampling’ was applied during low, mean and high flow, including 73 nested sites throughout the catchment. Water samples were analysed for the elements Li, B, Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Rb, Sr, Mo, Ba, Pb and U using inductively‐coupled‐plasma mass spectrometry, and for electric conductivity and pH. Principle component analysis and hierarchical cluster analysis were used to find typical element associations and to group water samples according to their hydrochemical fingerprints. This revealed regional hydrochemical patterns of water quality which were subsequently related to catchment attributes to draw conclusions about the controls on stream chemistry. It was found that various lithologic signals and anthropogenic point source inputs controlled the base flow hydrochemistry. During increased flows, stream waters were diluted causing additional hydrochemical variability in response to heterogeneous precipitation inputs and differences in aquifer storage capacities. The hydrochemical patterns further displayed in‐stream mixing of waters. This implied, that stream waters could be apportioned to the identified water sources throughout the catchment. The basin‐wide hydrochemical variability has the potential to outrange the tracer signatures typically inferred in studies at the hillslope scale and is able to strongly influence the complexity of the catchment output. Both have to be considered for further catchment scale tracer and modelling work. Despite the likelihood of non‐conservative behaviour, the minor and trace elements enhanced the rather qualitative discrimination of the various groundwater types, as the major cations were strongly masked by point source inputs. Copyright © 2007 John Wiley & Sons, Ltd.
Solute movement through intact columns of cryoturbated Upper Chalk
Authors: Mahmood‐ul‐Hassan M. , Akhtar M. S. , Gregory P. J.
Published: October 2007

Cryoturbated Upper Chalk is a dichotomous porous medium wherein the intra‐fragment porosity provides water storage and the inter‐fragment porosity provides potential pathways for relatively rapid flow near saturation. Chloride tracer movement through 43 cm long and 45 cm diameter undisturbed chalk columns was studied at water application rates of 0·3, 1·0, and 1·5 cm h−1. Microscale heterogeneity in effluent was recorded using a grid collection system consisting of 98 funnel‐shaped cells each 3·5 cm in diameter. The total porosity of the columns was 0·47 ± 0·02 m3 m−3, approximately 13% of pores were ≥ 15 µm diameter, and the saturated hydraulic conductivity was 12·66 ± 1·31 m day−1. Although the column remained unsaturated during the leaching even at all application rates, proportionate flow through macropores increased as the application rate decreased. The number of dry cells (with 0 ml of effluent) increased as application rate decreased. Half of the leachate was collected from 15, 19 and 22 cells at 0·3, 1·0, 1·5 cm h−1 application rates respectively. Similar breakthrough curves (BTCs) were obtained at all three application rates when plotted as a function of cumulative drainage, but they were distinctly different when plotted as a function of time. The BTCs indicate that the columns have similar drainage requirement irrespective of application rates, as the rise to the maxima (C/Co) is almost similar. However, the time required to achieve that leaching requirement varies with application rates, and residence time was less in the case of a higher application rate. A two‐region convection–dispersion model was used to describe the BTCs and fitted well (r2 = 0·97–0·99). There was a linear relationship between dispersion coefficient and pore water velocity (correlation coefficient r = 0·95). The results demonstrate the microscale heterogeneity of hydrodynamic properties in the Upper Chalk. Copyright © 2007 John Wiley & Sons, Ltd.
Mapping detention basins and deriving their spatial attributes from airborne LiDAR data for hydrological applications
Authors: Liu Hongxing , Wang Lei
Published: October 2007

This paper presents a new technique for mapping detention basins and measuring their spatial attributes using high‐resolution airborne LiDAR (Light Detection and Ranging) data. An efficient least‐cost search algorithm is employed to identify surface depressions from a bare‐earth LiDAR digital elevation model (DEM). Surface depressions are automatically delineated into hydrological objects using the connected component identification and indexing algorithm. Various spatial attributes are derived for these hydrologic objects, including location, perimeter, surface area, depth, storage volume and shape properties. Based on spatial attributes, a rule‐based classifier is established to separate detention basins from other types of surface depressions. We have successfully applied our technique to an urban watershed in the Houston Metropolitan area, Texas. Detention basins at regional and residential subdivision levels are mapped out for the watershed, and measurements on the spatial attributes are derived for each detention basin. The quantitative information derived from LiDAR data provides a scientific basis for formulating an appropriate management plan for detention basins and for assessing their effects on flood control and storm water quality treatment. Copyright © 2007 John Wiley & Sons, Ltd.
A systematic approach to the input determination for neural network rainfall–runoff models
Authors: Lin Gwo‐Fong , Chen Guo‐Rong
Published: October 2007

Input determination has a great influence on the performance of artificial neural network (ANN) rainfall–runoff models. To improve the performance of ANN models, a systematic approach to the input determination for ANN models is proposed. In the proposed approach, the irrelevant inputs are removed. Then an adequate ANN model, which only includes highly relevant inputs, is constructed. Unlike the trial‐and‐error procedure, the proposed approach is more systematic and avoids unnecessary trials. To demonstrate the effectiveness of the proposed approach, an application to actual typhoon events is presented. The results show that the proposed ANN model, which is constructed by the proposed approach, has advantages over those obtained by the trial‐and‐error procedure. The proposed ANN model has a simpler architecture, needs less training time, and performs better. The proposed ANN model is recommended as an alternative to existing rainfall–runoff ANN models. Copyright © 2007 John Wiley & Sons, Ltd.
Glucocorticoid‐induced leucine zipper (GILZ) mediates glucocorticoid action and inhibits inflammatory cytokine‐induced COX‐2 expression
Authors: Yang Nianlan , Zhang Weixi , Shi Xing‐Ming
Published: October 2007

Cyclooxygenase‐2 (COX‐2) plays an important role in rheumatoid arthritis and therefore, has been a major target for anti‐arthritis therapies. The expression of COX‐2 is induced by inflammatory cytokines such as TNF‐α and IL‐1β, and inhibited by glucocorticoids. However, the molecular mechanisms underlying the anti‐inflammatory and immune suppressive actions of glucocorticoids are not well defined. Here we report that glucocorticoid‐induced leucine zipper (GILZ) mimics glucocorticoid action and inhibits inflammatory cytokine‐induced COX‐2 expression in bone marrow mesenchymal stem cells, the cells that have been recently implicated in the pathogenesis and progression of rheumatoid arthritis. Using a retrovirus‐mediated gene expression approach we demonstrate that overexpression of GILZ inhibits TNF‐α and IL‐1β‐induced COX‐2 mRNA and protein expression, and knockdown of GILZ by shRNA reduces glucocorticoid inhibition of cytokine‐induced COX‐2 expression. Consistent to these results, overexpression of GILZ also inhibits NF‐κB‐mediated COX‐2 promoter activity. Finally, we show that GILZ inhibits COX‐2 expression by blocking NF‐κB nuclear translocation. Our results suggest that GILZ is a key glucocorticoid effect mediator and that GILZ may have therapeutic value for novel anti‐inflammation therapies. J. Cell. Biochem. 103: 1760–1771, 2008. © 2007 Wiley‐Liss, Inc.