bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of conditional null alleles for APP and APLP2
Authors: Mallm Jan‐Philipp , Tschäpe Jakob‐Andreas , Hick Meike , Filippov Mikhail A. , Müller Ulrike C.
Published: February 2010

Proteolytical cleavage of the β‐amyloid precursor protein (APP) generates β‐amyloid, which is deposited in the brains of patients suffering from Alzheimer's disease (AD). Despite the well‐established key role of APP for AD pathogenesis, the physiological function of APP and its close homologues APLP1 and APLP2 remains poorly understood. Previously, we generated APP–/– mice that proved viable, whereas APP–/–APLP2–/– mice and triple knockouts died shortly after birth, likely due to deficits of neuromuscular synaptic transmission. Here, we generated conditional knockout alleles for both APP and APLP2 in which the promoter and exon1 were flanked by loxP sites. No differences in expression were detectable between wt and floxed alleles, whereas null alleles were obtained upon crossing with Cre‐transgenic deleter mice. These mice will now allow for tissue and time‐point controlled knockout of both genes. genesis 48:200–206, 2010. © 2010 Wiley‐Liss, Inc.
Complement C5a regulates IL‐17 by affecting the crosstalk between DC and γδ T cells in CLP‐induced sepsis
Authors: Xu Ruonan , Wang Renxi , Han Gencheng , Wang Jianan , Chen Guojiang , Wang Liyan , Li Xia , Guo Renfeng , Shen Beifen , Li Yan
Published: February 2010

Complement 5a (C5a) and Interleukin‐17 (IL‐17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL‐17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)‐induced sepsis and decreased IL‐17 expression in vivo. IL‐17 was secreted mainly by γδ T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL‐17 secretion by γδ T cells. Dendritic cells (DC) were found to act as a “bridge” between C5a and γδ T cells in a mechanism involving IL‐6 and transforming growth factor β (TGF‐β). These results imply that C5a affects the crosstalk between DC and γδ T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL‐17.
Axisymmetric stagnation flow obliquely impinging on a moving circular cylinder with uniform transpiration
Authors: Rahimi Asghar B. , Esmaeilpour M.
Published: February 2010

Laminar stagnation flow, axisymmetrically yet obliquely impinging on a moving circular cylinder, is formulated as an exact solution of the Navier–Stokes equations. Axial velocity is time‐dependent, whereas the surface transpiration is uniform and steady. The impinging free stream is steady with a strain rate k̄. The governing parameters are the stagnation‐flow Reynolds number Re=k̄a2/2ν, and the dimensionless transpiration S=U0/k̄a. An exact solution is obtained by reducing the Navier–Stokes equations to a system of differential equations governed by Reynolds number and the dimensionless wall transpiration rate, S. The system of Boundary Value Problems is then solved by the shooting method and by deploying a finite difference scheme as a semi‐similar solution. The results are presented for velocity similarity functions, axial shear stress and stream functions for a variety of cases. Shear stresses in all cases increase with the increase in Reynolds number and suction rate. The effect of different parameters on the deflection of viscous stagnation circle is also determined. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical simulation of the flow around a porous covering square cylinder in a channel via lattice Boltzmann method
Authors: Rong F. M. , Guo Z. L. , Lu J. H. , Shi B. C.
Published: February 2010

In this paper, a detailed investigation on the flow past a porous covering cylinder is presented through the lattice Boltzmann method. The Brinkman‐Forchheimer‐extended Darcy model is adopted for the entire flow field with the solid, fluid, and porous medium. The effects of several parameters, such as porous layer thickness, Darcy number, porosity, and Reynolds number on flow field are discussed. Compared with the case of a solid cylinder, the present work shows that the porous layer may play an important role on the flow, the lift and drag force exerted on the cylinder. The numerical results indicate that the maximal drag coefficient Cd and maximal amplitude of lift coefficient Cl exist at certain Darcy number which is in the range of 10−6–10−2. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical analysis of axisymmetric and planar sudden expansion flows for laminar regime
Authors: Dağtekin İhsan , Ünsal Mazhar
Published: February 2010

In this study, the Navier–Stokes equations are solved numerically for axisymmetric and planar sudden expansion flows. The flow is considered laminar and steady state, and the fluid is incompressible. Finite difference equations are obtained using a control volume method in a non‐staggered grid arrangement, and solved by line‐by‐line TDMA technique using the SIMPLEM (SIMPLEM‐Modified) algorithm. Calculations are performed for higher expansion ratios, β, ranging from 1.5 to 10 and Reynolds numbers from 0.1 to 500. Results are presented in terms of streamlines, relative eddy intensity, location of the eddy center, and the eddy reattachment length depending on Re number and β values for both axisymmetric and planar sudden expansions. It is aimed to provide a picture of the effects of high values of expansion ratio and Reynolds number on the sudden expansion flow. As a result, it is found that the flow characteristics keep their structure for both higher expansion ratios and higher Reynolds numbers. Further, correlations were developed for the nondimensional eddy reattachment length, location of the eddy center and the relative eddy intensity, which have agreeable results to the computed results available from the literature. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical Investigation into Thermofluidic and Electrochemical Characteristics of Tubular‐type SOFC
Authors: Kuo J.‐K.
Published: February 2010

Three‐dimensional simulations based on a multi‐physics model are performed to examine the thermofluidic and electrochemical characteristics of a tubular, anode‐supported solid oxide fuel cell (SOFC). The simulations focus on the local transport characteristics of the cathode and anode gases and the distribution of the temperature field within the fuel cell. In addition, the electrochemical properties of the SOFC are systematically examined for a representative range of inlet gas temperatures and pressures. The validity of the numerical model is confirmed by comparing the results obtained for the correlation between the power density and the current density with the experimental results presented in the literature. Overall, the present results show that the performance of the tubular SOFC is significantly improved under pressurised conditions and a higher operating temperature.
TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer
Authors: Okada Toshiyuki , Suehiro Yutaka , Ueno Koji , Mitomori Shoko , Kaneko Sayaka , Nishioka Mitsuaki , Okayama Naoko , Sakai Kouhei , Higaki Shingo , Hazama Shoichi , Hirata Hiroshi , Sakaida Isao , Oka Masaaki , Hinoda Yuji
Published: February 2010

Although growing evidence demonstrates that TWIST1 is an interesting tumor biomarker, little is known about the clinical significance of TWIST1 expression and TWIST1 methylation in human primary colorectal cancer. In this study, we examined the association of TWIST1 expression and TWIST1 methylation with clinicopathologic features in human primary colorectal tumors. Primary colorectal cancer (CRC) specimens from 319 patients, corresponding normal colorectal nontumorous mucosa from 251 patients with cancer, and colorectal adenomas from 189 patients were used. Methylation and expression levels of TWIST1 were compared with clinicopathologic features. The TWIST1 methylation level was higher in colorectal adenoma and cancer than in normal colorectal mucosa. Elevated TWIST1 mRNA expression in normal colorectal mucosa in patients with CRC as well as in primary CRC specimens was associated with unfavorable outcomes. There was no correlation between TWIST1 methylation and TWIST1 expression. Our results suggest that TWIST1 methylation may be a useful biomarker for screening colorectal tumors. In addition, TWIST1 mRNA expression is a possible molecular marker for predicting the outcome in patients with CRC. Confirmatory studies using independent data sets are needed to confirm our findings. © 2010 Wiley‐Liss, Inc.
Melatonergic regulation of hemolymph sugar levels in the freshwater edible crab, Oziotelphusa senex senex
Authors: Sainath S.B. , Reddy P. Sreenivasula
Published: February 2010

In this study, the hyperglycemic effect of melatonin in the freshwater edible crab, Oziotelphusa senex senex, is investigated. Injection of melatonin induced hyperglycemia in a dose‐dependent manner. Administration of melatonin produced hyperglycemia in both intact and eyestalk‐ablated crabs. Bilateral eyestalk ablation resulted in significant increase in the total carbohydrates and glycogen levels with a significant decrease in phosphorylase activity in the hepatopancreas and muscle of the crabs. Injection of melatonin resulted in significant decrease in the total carbohydrate and glycogen levels, with an increase in phosphorylase activity in hepatopancreas and muscle of both intact and eyestalk‐ablated crabs. From the results, it is hypothesized that melatonin‐induced hyperglycemia in the crab, O. senex senex, is not mediated by eyestalk hyperglycemic hormone. J. Exp. Zool. 313A:201–208, 2010. © 2010 Wiley‐Liss, Inc.
Dendritic cells lentivirally engineered to overexpress interleukin‐10 inhibit contact hypersensitivity responses, despite their partial activation induced by transduction‐associated physical stress
Authors: Besche Verena , Wiechmann Nadine , Castor Timo , Trojandt Stefanie , Höhn Yvonne , Kunkel Hanna , Grez Manuel , Grabbe Stephan , Reske‐Kunz Angelika B. , Bros Matthias
Published: February 2010

Background

Dendritic cells (DCs) constitute an attractive target for immunotherapeutic approaches. Because DCs are largely refractory to transfection with plasmid DNA, several viral transduction protocols were established. The potential side‐effects of lentiviral transduction on the phenotype and activation state of DCs left unstimulated after transduction have not been assessed. There is a need to analyse these parameters as a result of the requirement of using DCs with a low activation state for therapeutic strategies intended to induce tolerance.

Methods

Lentivirally‐transduced bone marrow (BM)‐derived DCs (LV‐DCs) in comparison with mock‐transduced (Mock‐DCs) and untreated DCs were analysed with regard to the induction of maturation processes on the RNA, protein and functional level. BM‐DCs engineered to overexpress interleukin (IL)‐10 were analysed for therapeutic potential in a mouse model of allergic contact dermatitis.

Results

Compared with untreated DCs, Mock‐DCs and LV‐DCs displayed an altered gene expression signature. Mock‐DCs induced a stronger T cell proliferative response than untreated DCs. LV‐DCs did not further augment the T cell proliferative response, but induced a slightly different T cell cytokine pattern compared to Mock‐DCs. Accordingly, the gene promoter of the DC maturation marker fascin mediated efficient expression of the model transgene IL‐10 in unstimulated‐transduced BM‐DCs. Nevertheless, IL‐10 overexpressing BM‐DCs exerted tolerogenic activity and efficiently inhibited the contact hypersensitivity response in previously hapten‐sensitized mice.

Conclusions

Lentiviral transduction of BM‐DCs results in their partial activation. Nevertheless, the transduction of these DCs with a vector encoding the immunomodulatory cytokine IL‐10 rendered them tolerogenic. Thus, lentivirally‐transduced DCs expressing immunomodulatory molecules represent a promising tool for induction of tolerance. Copyright © 2010 John Wiley & Sons, Ltd.
Indian summer monsoon during the last two millennia
Authors: Anderson David M. , Baulcomb Corinne K. , Duvivier Alice K. , Gupta Anil K.
Published: February 2010

The monsoon is a large‐scale feature of the tropical atmospheric circulation, affecting people and economies in the world's most densely populated regions. Future trends due to natural variability and human‐induced climate changes are uncertain. Palaeoclimate records can improve our understanding of monsoon dynamics and thereby reduce this uncertainty. Palaeoclimate records have revealed a dramatic decrease in the Asian summer monsoon since the early Holocene maximum 9 ka BP. Here we focus on the last 2 ka, where some records indicate an increasing trend in the summer monsoon. Analysing Globigerina bulloides upwelling records from the Arabian Sea, we find the weakest monsoon occurred 1500 a BP, with an increasing trend towards the present. Copyright © 2010 John Wiley & Sons, Ltd.
Annually resolved events of Younger Dryas glaciation in Lochaber (Glen Roy and Glen Spean), western Scottish Highlands
Authors: Palmer Adrian P. , Rose James , Lowe J. John , MacLeod Alison
Published: February 2010

This paper presents the results of micromorphological analysis of laminated sediments that accumulated in ice‐dammed lakes in Lochaber (Glen Roy and vicinity) during the Younger Dryas (Loch Lomond) Stadial. These lakes were responsible for the formation of the famous ‘Parallel Roads of Glen Roy’ (Agassiz, 1840), prominent shorelines cut into the valley sides of Glen Roy and adjacent valleys. Annually deposited (varved) layers, which can be distinguished from other rhythmites by micromorphological examination, have enabled the construction of a varve chronology which underpins the glacial history of the region, the duration of the lake stands and rates of ice margin advance and retreat. The lake system existed for a total of 515 a. During a rise in lake levels, the lowermost (260 m), middle (325 m) and highest (350 m) lakes existed for minimal periods of 191, 112 and 116 a, respectively, and the fall of lake levels from 350 m to 260 m took 95 years. Ice advance rates of between 13.4 and 41.9 m a−1 are inferred, while ice retreat is estimated to have been ∼38.5 m a−1. A provisional correlation between the Lochaber varve and GRIP ice core records suggests that the lakes started to form at ca. 12 165 a BP, in turn implying that the Loch Lomond Readvance limits in this area were not achieved until late in the Younger Dryas interval, a conclusion which does not accord with that based on numerical model simulations. Copyright © 2010 John Wiley & Sons, Ltd.
Farmers' perception of treated paper mill effluent irrigation
Authors: Rekha P. N. , Ambujam N. K.
Published: February 2010

The utilization of treated paper mill effluents for irrigation offers many benefits such as conservation of water resources, conversion of barren land into irrigated area, addition of nutrients to the soil and plant and above all the reduction of pollution of inland water bodies. However, the utility of this effluent irrigation programme depends mainly on farmers' acceptability, adoption and management of the scheme. Knowledge about the farmers' perception is thus very much imperative for further advocacy of the effluent irrigation programme. The determinants of farmers' perception of treated paper mill effluent irrigation is a pre‐requisite for the formulation of better programmes and strategies for the support of an unobstructed adoption and for the long‐term sustainability of effluent irrigation schemes. The present study was conducted to assess the farmers' perception and the determinants that influence the adoption of treated paper mill effluent irrigation by interviewing a random sample of 120 farmers, using a well‐structured interview schedule in paper mill effluent irrigated area in Tamil Nadu in India. The study revealed that there exists positive significant correlation between the perception and the characteristics of the farmers viz. educational status, farm size, annual income, mass media exposure, innovativeness and risk orientation. The response analysis of the perception revealed that treated paper mill effluent as alternative assured supply of irrigation water, conversion of elevated dry lands to irrigated land, changing of cropping pattern to sugarcane, increase in socioeconomic status of the farmers, incentives and technical inputs by the paper mill authorities and above all farmers' participation in planning, implementation and management of the effluent irrigation schemes influenced the farmers to form positive perception. Copyright © 2010 John Wiley & Sons, Ltd.
Evaluation of a technical revegetation action performed on foredunes at Devesa de la Albufera, Valencia, Spain
Authors: Escaray F. J. , Rosique F. J. C. , Scambato A. A. , Bilenca D. , Carrasco P. , Matarredona A. V. , Ruiz O. A. , Menéndez A. B.
Published: February 2010

We have evaluated the level of restoration achieved by a technical revegetation action carried out on reconstructed foredunes at the Devesa de la Albufera and compared this level with that achieved by spontaneous succession. Foredunes 1, 3, 6 and 20 y old since revegetated (1, 3, 6 and 20 y, respectively) were considered as spatially separated stages representing a successional trend in the development of the restored plant community. Lower and similar levels of diversity (richness andH´ and Pielou´s indexes) and coverage, respectively, were found on dunes corresponding to the oldest stage of technical revegetation compared with that of the reference site. Diversity and coverage parameters increased during the first 6 y of the technical succession and decreased after 20 y of revegetation. Moreover, that increase was quite obvious as early as 3 y after the onset of revegetation. Results also showed that the Devesa de la Albufera has its own capacity for revegetation. According to the Jaccard and Sørensen indexes, these dunes were more similar to the reference than those from the 20 y old site. Beyond the current functionality of the revegetated sites, it is concluded that the natural and aesthetic values may be restored at the Valencian Devesa de la Albufera. Copyright © 2010 John Wiley & Sons, Ltd.
Manipulation of glycemic response with isomaltulose in a milk‐based drink does not affect cognitive performance in healthy adults
Authors: Dye Louise , Gilsenan Mary B. , Quadt Frits , Martens Vanessa E. G. , Bot Arjen , Lasikiewicz Nicola , Camidge Diana , Croden Fiona , Lawton Clare
Published: February 2010

Previous research suggests that glucoregulation and nutrient interventions, which alter circulating glucose, impact cognitive function. To examine the effect of modulating glycemic response using isomaltulose on cognitive function 24 healthy male adult participants consumed energy and macronutrient‐matched milk‐based drinks containing 50 g isomaltulose, 50 g sucrose or a water control in a counterbalanced within‐subject design. Interstitial glucose was measured continuously in 12 subjects and all provided 9 capillary measures on each test day. A 30‐min cognitive test battery was administered before and twice (+35 and +115 min) after drink ingestion. Immediate, delayed, recognition, verbal and working memory, and psychomotor performance were assessed. Glycemic profiles induced by the drinks differed significantly during the first but not the second post‐drink test battery. Neither administration of the sucrose nor isomaltulose drinks produced consistent effects on verbal or working memory, or psychomotor performance. This study used isomaltulose as an investigative tool to lower glycemic response. Importantly, it demonstrates a lack of effect of modulating glucose on cognitive performance based on reliable, continuously measured glycemia. It refutes the hypothesis that glycemia is associated with cognitive performance and questions the suggestion that isomaltulose has an effect on cognitive performance.
Biological effects on granulosa cells of hydroxylated and methylated resveratrol analogues
Authors: Basini Giuseppina , Tringali Corrado , Baioni Laura , Bussolati Simona , Spatafora Carmela , Grasselli Francesca
Published: February 2010

Several resveratrol analogues have been designed to improve bioactivity: among these polymethoxystilbenes appear to be particularly promising. The present study was set up to investigate the biological functions of polymethoxystilbenes 2 and 3, recently found in our lab as antiangiogenic agents, on a well‐defined swine granulosa cell model. Proliferative activity and effects on steroidogenesis were evaluated, as well as the effect on granulosa cell vascular endothelial growth factor (VEGF) production, since these cells in basic conditions synthesize the main proangiogenic peptide. Moreover, we considered the effect of these two resveratrol analogues on granulosa cell redox status. Analogue 3 inhibited granulosa cell growth, while it stimulated steroidogenesis. A similar effect was displayed by 2 on estradiol 17β production and cell proliferation at the highest concentration tested. On the other hand, at the same dosage 2 decreased progesterone levels. Both analogues inhibited VEGF output. Granulosa cell redox status was unaffected by resveratrol analogue 2 while the highest concentration of 3 stimulated free radicals generation and scavenging enzyme activities. The overall results indicate that analogue 3 is the more powerful compound, thus suggesting that a slight modification in the structure markedly increases effectiveness. These data could be useful to develop more active resveratrol analogues for therapeutic use.
Protein template effect on hydrotalcite morphology
Authors: Sommer Alicia E. , Fetter Geolar , Bosch Pedro , Novelo Omar
Published: February 2010

Layered double hydroxides (LDHs), hydrotalcite‐like compounds, or hydrotalcites are porous materials, which may be used in catalysis, biomedicine, or adsorption as they may work as anion exchangers or drug deliverers. The morphology of hydrotalcites determines their use: in catalysis or in adsorption, reagents and gases have to reach as much surface as possible; in biomedicine, drugs have to be encapsulated and delivered later on. In this work, we synthesize hydrotalcites in presence of protein templates (egg white and yolk) and under two crystallization conditions (conventional and microwave). The obtained materials are hydrotalcites whose morphologies correspond to platelets organized as sand roses. Depending on the template and the preparation procedure, the amount of platelets can be increased. This feature is explained through the template effect of egg components. The resulting materials are promising adsorbers. Copyright © 2010 John Wiley & Sons, Ltd.
A reliable and efficient method for total rna isolation from various members of spurge family (Euphorbiaceae)
Authors: Xu Jia , Aileni Mahender , Abbagani Sadanandam , Zhang Peng
Published: February 2010

Introduction – It is prerequisite and crucial to extract RNA with high quality and integrity in order to carry out molecular biology studies in any plant species of a family. Euphorbiaceae members are known for high levels of their waxes, oils with polysaccharides, polyphenolics and secondary metabolites. These conditions are recognised to interfere unfavourably with various methodologies of RNA isolation.

Objective – To develop a simple, rapid and reproducible cetyltrimethylamonium bromide (CTAB)‐based protocol, to reduce the time and cost of extraction without reducing quality and yield of RNA extracted from various recalcitrant Euphorbiaceae member plant tissues such as from tree leaves (Hevea brasilensis), woody shrubs leaves (Ricinus communis, Jatropha curcas, Manihot esculenta) and storage root tissue (M. esculenta).

Methodology – Simple modifications and fast steps were introduced to the original CTAB protocol. All centrifugation steps were carried out at 4°C at 12000  rpm for 10  min, the sample weight was decreased and usage of spermidine and LiCl was omitted, reducing incubation time prior to RNA precipitation. This rapid CTAB protocol was compared with various RNA isolation methods intended for use with plants rich in polysaccharides and secondary metabolites.

Results – The procedure can be completed within 2  h and many samples can be processed at the same time. RNA of high quality could be isolated from all the tissues of species that we tried. The isolated RNA from different species served as a robust template for RT‐PCR analysis.

Conclusion – The study has shown that the improvement of a CTAB‐based protocol allows the rapid isolation of high‐quality RNA from various recalcitrant Euphorbiaceae members. Copyright © 2010 John Wiley & Sons, Ltd.
Simultaneous determination of four iridoid and secoiridoid glycosides and comparative analysis of Radix Gentianae Macrophyllae and their related substitutes by HPLC
Authors: Cao Xiao‐Yan , Wang Zhe‐Zhi
Published: February 2010

Introduction – Radix Gentianae Macrophyllae, a traditional Chinese medicine, has been frequently used to dispel rheumatism and ease pain. There are four species of Gentiana (G. macrophylla, G. straminea, G. dahurica and G. crassicaulis) recorded as herbal drugs in the Chinese Pharmacopoeia and two other Gentiana species (G. officinalis and G. siphonantha) are often used as substitutes. Currently, the LC fingerprint comparison among different species and evidence for the equivalent application of these herbs are lacking.

Objective – To develop an HPLC method for the simultaneous determination of four iridoid and secoiridoid glycosides and a comparative study of six species of Gentiana.

Methodology – HPLC analysis was performed on a C18 column (Phenomenex, 150 × 4.6  mm, 5  µm particle size) with gradient elution using 0.4% aqueous phosphoric acid and methanol at 242  nm.

Results – The proposed method was precise, accurate and sensitive enough for simultaneous quantitative evaluation of four iridoid and secoiridoid glycosides (loganic acid, swertiamarin, gentiopicroside and sweroside) in the six species of Gentiana. Contents of the four marker compounds varied from each other even among the samples from the same species and the LC chromatograms of the six species of Gentiana showed high similarities.

Conslusion – The close similarity of LC chromatograms and chemical composition of the four genuine Gentiana species explain their popular usage as Radix Gentianae Macrophyllae in Chinese medicine. By comparing the four genuine Gentiana species, it is suggested that the two substitutes could be used as Radix Gentianae Macrophyllae to relieve the scarcity of resources. Copyright © 2010 John Wiley & Sons, Ltd.
Validation of claims‐based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially‐insured population
Authors: Wahl Peter M. , Rodgers Keith , Schneeweiss Sebastian , Gage Brian F. , Butler Javed , Wilmer Charles , Nash Marshall , Esper Gregory , Gitlin Norman , Osborn Neal , Short Louise J. , Bohn Rhonda L.
Published: February 2010

Purpose

To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially‐insured US population.

Methods

These validation studies were part of a larger study examining the risk of MI, ischemic stroke, and severe UGI bleeds in patients receiving a new prescription of selective cyclooxygenase (COX)‐2 inhibitors (coxibs) and non‐over‐the‐counter (OTC) non‐steroidal anti‐inflammatory drugs (NSAIDs), between 1 July 2002 and 30 September 2004. Patients from the study cohort and other health plan members from the HealthCore Integrated Research DatabaseSM (HIRD) experiencing these events were selected for these studies. The positive predictive value (PPV) of each of the claims code algorithms, using medical chart review as the gold standard, was calculated.

Results

Two hundred charts per event were abstracted. The PPV for MI was 88.4% (177/200; 95%CI, 83.2–92.5%); PPV for ischemic stroke was 87.4% (175/200; 95%CI, 82.0–91.7%); PPV for severe UGI bleed was 56.5% (109/193; 95%CI, 49.2–63.6%). Refining the ischemic stroke claims algorithm resulted in a PPV of 95.5% (95%CI, 91.0–98.2%); refining the claims algorithm for severe UGI bleed resulted in a PPV of 87.8% (95%CI, 78.7–94.0%).

Conclusion

The results suggest that, for certain adverse events, claims data can serve as the basis for pharmacoepidemiology research and drug safety surveillance in the US. Copyright © 2010 John Wiley & Sons, Ltd.
Virtual Expert Mass Spectrometrist: iTRAQ tool for database‐dependent search, quantitation and result storage
Authors: Rodríguez‐Suárez Eva , Gubb Ewa , Alzueta Itziar Frades , Falcón‐Pérez Juan Manuel , Amorim António , Elortza Felix , Matthiesen Rune
Published: February 2010

A frequent goal of MS‐based proteomics experiments nowadays is to quantify changes in the abundance of proteins across several biological samples. The iTRAQ labeling method is a powerful technique; when combined with LC coupled to MS/MS it allows relative quantitation of up to eight different samples simultaneously. Despite the usefulness of iTRAQ current software solutions have limited functionality and require the combined use of several software programs for analysis of the data from different MS vendors. We developed an integrated tool, now available in the virtual expert mass spectrometrist (VEMS) program, for database‐dependent search of MS/MS spectra, quantitation and database storage for iTRAQ‐labeled samples. VEMS also provides useful alternative report types for large‐scale quantitative experiments. The implemented statistical algorithms build on quantitative algorithms previously used in proposed iTRAQ tools as described in detail herein. We propose a new algorithm, which provides more accurate peptide ratios for data that show an intensity‐dependent saturation. The accuracy of the proposed iTRAQ algorithm and the performance of VEMS are demonstrated by comparing results from VEMS, MASCOT and PEAKS Q obtained by analyzing data from a reference mixture of six proteins. Users can download VEMS and test data from “http://www.portugene.com/software.html”.
A comparative proteomic analysis of HepG2 cells incubated by S(−) and R(+) enantiomers of anti‐coagulating drug warfarin
Authors: Bai Jing , Sadrolodabaee Laleh , Ching Chi Bun , Chowbay Balram , Ning Chen Wei
Published: February 2010

Warfarin is a commonly prescribed oral anti‐coagulant with narrow therapeutic index. It interferes with vitamin K cycle to achieve anti‐coagulating effects. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported that the intracellular protein profile in HepG2 cells incubated with S(−) and R(+) warfarin, using iTRAQ‐coupled 2‐D LC‐MS/MS. In samples incubated with S(−) and R(+) warfarin alone, the multi‐task protein Protein SET showed significant elevation in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In cells incubated with individual enantiomers of warfarin in the presence of vitamin K, protein disulfide isomerase A3 which is known as a glucose‐regulated protein, in cells incubated with S(−) warfarin was found to be down‐regulated compared to those incubated with R(+) warfarin. In addition, Protein DJ‐1 and 14‐3‐3 Proteinσ were down‐regulated in cells incubated with either S(−) or R(+) warfarin regardless of the presence of vitamin K. Our results indicated that Protein DJ‐1 may act as an enzyme for expression of essential enzymes in vitamin K cycle. Taken together, our findings provided molecular evidence on a comprehensive protein profile on warfarin–cell interaction, which may shed new lights on future improvement of warfarin therapy.
Social outcomes of long‐term survivors of adolescent cancer
Authors: Dieluweit Ute , Debatin Klaus‐Michael , Grabow Desiree , Kaatsch Peter , Peter Richard , Seitz Diana C. M. , Goldbeck Lutz
Published: February 2010

Objectives: The study investigates psychosexual and family outcomes among German long‐term survivors of adolescent cancer.

Methods: Survivors of cancer during adolescence (n=820; age at onset of disease: M=15.8 years, SD=0.9, age at follow‐up: M=30.4, SD=6.0 years) completed questionnaires on their family life and their psychosexual and autonomy development. Outcomes were compared to an age‐matched sample (German Socio‐Economic Panel, G‐SOEP, n=820, age: M=30.4, SD=6.7 years) from the general population and to a control group of adults without cancer (n=1027, age: M=31.5, SD=7.0 years).

Results: Compared to controls of the same sex, female survivors had achieved fewer developmental milestones in their psychosexual development such as having their first boyfriend, or reached these milestones later, and reported a significantly stronger desire for children. Male survivors were more likely to live with their parents when compared to same sex controls. Equivalent proportions of survivors and persons in the G‐SOEP were living in a long‐term relationship; however, survivors were less likely to have ever married or had children. At first marriage and at the birth of their first child, survivors were significantly older compared to the G‐SOEP. About 14.5% of survivors reported cancer‐related infertility.

Conclusions: Survivors of adolescent cancer experience some social late effects of the disease in adulthood, such as a delayed social development as well as substantial differences in their family life and living conditions compared to healthy peers. Copyright © 2010 John Wiley & Sons, Ltd.
An MSE‐reduced estimator for the response proportion in a two‐stage clinical trial
Authors: Li Qizhai
Published: February 2010

Two‐stage design is very useful in clinical trials for evaluating the validity of a specific treatment regimen. When the second stage is allowed to continue, the method used to estimate the response rate based on the results of both stages is critical for the subsequent design. The often‐used sample proportion has an evident upward bias. However, the maximum likelihood estimator or the moment estimator tends to underestimate the response rate. A mean‐square error weighted estimator is considered here; its performance is thoroughly investigated via Simon's optimal and minimax designs and Shuster's design. Compared with the sample proportion, the proposed method has a smaller bias, and compared with the maximum likelihood estimator, the proposed method has a smaller mean‐square error. Copyright © 2010 John Wiley & Sons, Ltd.
Process and recyclability analyses of innovative bio‐composite for tray
Authors: Bras Julien , Mendez José Alberto , Krouit Mohammed , Lopez Joan Pere , Pelach Maria‐Angels , Belgacem Naceur
Published: February 2010

The originality of the present study is to give complete and pragmatic information associated with the preparation of a totally bio‐based composite. It covers the most relevant investigations from analyses of the fibres used as reinforcing elements to the final product acquisition and its recyclability analyses. This study is destined for packaging areas. It demonstrates the three‐dimensional formation processes with these new kinds of bio‐composites, as well as the recyclable features related to the prepared materials. Thus, several processing parameters were studied and a final tray was prepared. The addition of the fibres gives rise to an increase of the tray stiffness, when a flexible biopolymer is used as a matrix. The prepared bio‐composites were recycled several times (10 recycling cycles) and found that they maintain their most relevant characteristics. Thus, such bio‐composites can be reused several times. All these data, including a prototype sample prepared as a demonstrator, support the innovative and sustainable character of the packaging materials described. Copyright © 2010 John Wiley & Sons, Ltd.
Investigation on the magnesium segregation in low‐magnesium aluminium alloys
Authors: Guillot J. , Valle N. , Maitre E. , Verdier S. , Migeon H.‐N.
Published: February 2010

This paper studies the magnesium migration phenomenon during annealing in 8xxx series alloy with magnesium bulk content in the range of 20–240 ppm. X‐ray photoelectron spectroscopy and dynamic secondary ion mass spectrometry are used to determine the Mg surface concentration and distribution in the aluminium oxide layer depending on the magnesium bulk concentration and the annealing duration. Copyright © 2010 John Wiley & Sons, Ltd.
Software Cartography: thematic software visualization with consistent layout
Authors: Kuhn Adrian , Erni David , Loretan Peter , Nierstrasz Oscar
Published: February 2010

Software visualizations can provide a concise overview of a complex software system. Unfortunately, as software has no physical shape, there is no ‘natural’ mapping of software to a two‐dimensional space. As a consequence most visualizations tend to use a layout in which position and distance have no meaning, and consequently layout typically diverges from one visualization to another. We propose an approach to consistent layout for software visualization, calledSoftware Cartography, in which the position of a software artifact reflects itsvocabulary, and distance corresponds to similarity of vocabulary. We use Latent Semantic Indexing (LSI) to map software artifacts to a vector space, and then use Multidimensional Scaling (MDS) to map this vector space down to two dimensions. The resulting consistent layout allows us to develop a variety of thematicsoftware mapsthat express very different aspects of software while making it easy to compare them. The approach is especially suitable for comparing views of evolving software, as the vocabulary of software artifacts tends to be stable over time. We present a prototype implementation of Software Cartography, and illustrate its use with practical examples from numerous open‐source case studies. Copyright © 2010 John Wiley & Sons, Ltd.
Special issue: Los Angeles Tall Buildings Structural Design Council
Authors: Cochran Brian L. , Hart Gary C.
Published: February 2010

This issue is the 2009 Special Issue of the journal developed by the Los Angeles Tall Buildings Design Council. The papers noted in this issue are all exceptional papers selected by the council.
Connecting high school physics experiences, outcome expectations, physics identity, and physics career choice: A gender study
Authors: Hazari Zahra , Sonnert Gerhard , Sadler Philip M. , Shanahan Marie‐Claire
Published: February 2010

This study explores how students' physics identities are shaped by their experiences in high school physics classes and by their career outcome expectations. The theoretical framework focuses on physics identity and includes the dimensions of student performance, competence, recognition by others, and interest. Drawing data from the Persistence Research in Science and Engineering (PRiSE) project, which surveyed college English students nationally about their backgrounds, high school science experiences, and science attitudes, the study uses multiple regression to examine the responses of 3,829 students from 34 randomly selected US colleges/universities. Confirming the salience of the identity dimension for young persons' occupational plans, the measure for students' physics identity used in this study was found to strongly predict their intended choice of a physics career. Physics identity, in turn, was found to correlate positively with a desire for an intrinsically fulfilling career and negatively with a desire for personal/family time and opportunities to work with others. Physics identity was also positively predicted by several high school physics characteristics/experiences such as a focus on conceptual understanding, real‐world/contextual connections, students answering questions or making comments, students teaching classmates, and having an encouraging teacher. Even though equally beneficial for both genders, females reported experiencing a conceptual focus and real‐world/contextual connections less frequently. The explicit discussion of under‐representation of women in science was positively related to physics identity for female students but had no impact for male students. Surprisingly, several experiences that were hypothesized to be important for females' physics identity were found to be non‐significant including having female scientist guest speakers, discussion of women scientists' work, and the frequency of group work. This study exemplifies a useful theoretical framework based on identity, which can be employed to further examine persistence in science, and illustrates possible avenues for change in high school physics teaching. © 2010 Wiley Periodicals, Inc. J Res Sci Teach 47: 978–1003, 2010
Assessing impacts of climate change: an editorial essay
Authors: Carter Timothy R.
Published: February 2010

This article is categorized under:

Assessing Impacts of Climate Change > Evaluating Future Impacts of Climate Change
Climate, History, Society, Culture: an editorial essay
Authors: Fleming James Rodger
Published: February 2010

This article is categorized under:

Climate, History, Society, Culture > Ideas and Knowledge
Epiphenomenalism
Authors: Robinson William S.
Published: February 2010

Epiphenomenalists hold that mental properties are not reducible to neural properties and are not efficacious. The view and its motivations are explained for two kinds of mental properties. Objections, and replies on behalf of epiphenomenalism, are considered. While strict epiphenomenalism is a philosophical view, there are related views that have some empirical support. Examples of this work are discussed, and their relation to the strictly philosophical view is explained. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Philosophy > Consciousness
Hormonal effects on the plasticity of cognitive brain functions
Authors: Hausmann Markus
Published: February 2010

Sex hormones have powerful neuronal actions in the brain and affect the interaction between functionally linked cortical areas within and across cerebral hemispheres, probably via their neuromodulatory properties on gamma‐aminobutyric acid and glutamate receptors. Menstrual cycle‐related dynamic fluctuations in functional cerebral asymmetries and interhemispheric crosstalk have been shown to be a useful experimental model to investigate the activating effects of sex hormones on cognitive brain functions, particularly those of estradiol and progesterone. Besides a better understanding of sex hormonal effects on cognitive brain functions, this research may significantly contribute to addressing the question of whether sex differences in cognitive brain functioning truly exist and where they originate from. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Brain Function and Dysfunction

Neuroscience > Cognition
The self: as a construct in psychology and neuropsychological evidence for its multiplicity
Authors: Klein Stanley B.
Published: February 2010

Whatisthe self? Philosophers and psychologists pursuing an answer to this question immediately find themselves immersed in a host of questions about mind and body, subject and object, object and process, the homunculus, free will, self‐awareness, and a variety of other puzzling matters that largely have eluded satisfying theoretical explication. In this paper I argue that some of this difficulty is attributable to our implicit, phenomenologically‐based belief that the self is unitary entity—i.e., a singular “I” that remembers, chooses, thinks, plans, and feels. In this article I address the question of what the self is by reviewing research, conducted primarily with neuropsychological participants, that converges on the idea that the self may be more complex and differentiated than many previous treatments of the topic have assumed. Although some aspects of self‐knowledge such as episodic recollection may be compromised by cognitive and neurological disorders, other aspects—for instance, semantic trait summaries—appear largely intact. Taken together, these findings support the idea that there is no single, unified “I” to be found. Rather, I argue “the” self may best be construed as a set of interrelated, functionally independent systems. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Memory
Simulation theory
Authors: Shanton Karen , Goldman Alvin
Published: February 2010

Simulation plays a significant role in human cognition. This article reviews evidence for a simulational account of mind reading. Drawing on findings in developmental psychology and cognitive neuroscience, it shows that mind reading involves the imitation, copying, or reexperience of the mind reading target's mental processes. The article also introduces evidence for simulational accounts of episodic memory and prospection. It identifies relevant similarities between mind reading, memory, and prospection as well as independent evidence for a role for simulation in memory. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Reasoning and Decision Making

Philosophy > Action
Inductive reasoning
Authors: Hayes Brett K. , Heit Evan , Swendsen Haruka
Published: February 2010

Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category‐based induction as well as theoretical models of these results, including similarity‐based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity‐based phenomena but not knowledge‐based phenomena. Recent models that aim to account for both similarity‐based and knowledge‐based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well‐established and emerging lines of induction research is the need to develop well‐articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Reasoning and Decision Making
Systems analysis of alternative splicing and its regulation
Authors: Xiao Xinshu , Lee Jae‐Hyung
Published: February 2010

Alternative splicing (AS) has emerged as a key mechanism that accounts for gene expression diversity in metazoan organisms. Splicing is tightly regulated by a repertoire of RNA and protein factors and RNA sequence elements that function in a cooperative manner. Systems‐level experimental and computational approaches have been instrumental in establishing comprehensive profiles of transcript variants generated by AS. In addition, systems biology approaches are starting to define how combinatorial splicing regulation shapes the complex splicing phenotypes observed in different tissue types and developmental stages and under different conditions. Here, we review recent progress in these areas. Copyright © 2010 John Wiley & Sons, Inc.

This article is categorized under:

Biological Mechanisms > Regulatory Biology