bluuebunny/crossref_metadata_2025 huggingface dataset:
CD73 is expressed on invading T lymphocytes in the inflamed peripheral nerve
Authors: Meyer Zu Hörste Gerd , Reiners Jens , Lehmann Helmar C. , Airas Laura , Kieseier Bernd C.
Published: July 2009

CD73 is a cell surface enzyme that modulates immune and inflammatory responses by affecting adenosine‐receptor‐mediated signaling. We examined its expression and cellular distribution in the inflamed human peripheral nerve. CD4+ and CD8+ T lymphocytes stained positive for CD73, with no differences in numbers between acute and chronic inflammatory polyneuropathies. Endothelial cells in the peripheral nerve did not express CD73. Our findings support the concept that CD73 is involved in lymphocyte entry into the inflamed nervous system. Muscle Nerve 40: 287–289, 2009
Effects of prednisolone on skeletal muscle contractility in mdx mice
Authors: Baltgalvis Kristen A. , Call Jarrod A. , Nikas Jason B. , Lowe Dawn A.
Published: July 2009

Current treatment for Duchenne muscular dystrophy (DMD) is chronic administration of the glucocorticoid prednisolone. Prednisolone improves muscle strength in boys with DMD, but the mechanism is unknown. The purpose of this study was to determine how prednisolone improves muscle strength by examining muscle contractility in dystrophic mice over time and in conjunction with eccentric injury. Mdx mice began receiving prednisolone (n = 23) or placebo (n = 16) at 5 weeks of age. Eight weeks of prednisolone increased specific force of the extensor digitorum longus muscle 26%, but other parameters of contractility were not affected. Prednisolone also improved the histological appearance of muscle by decreasing the number of centrally nucleated fibers. Prednisolone treatment did not affect force loss during eccentric contractions or recovery of force following injury. These data are of clinical relevance, because the increase in muscle strength in boys with DMD taking prednisolone does not appear to occur via the same mechanism in dystrophic mice. Muscle Nerve, 2009
Quantitative sensation and autonomic test abnormalities in transthyretin amyloidosis polyneuropathy
Authors: Kim Dong Hwee , Zeldenrust Steven R. , Low Phillip A. , Dyck Peter J.
Published: July 2009

This study assesses the value of standard quantitative autonomic (QAT) and sensation (QST) tests in detecting, characterizing, and quantitating the severity of transthyretin amyloid polyneuropathy (TTR‐A‐PN). This information is needed for prospective therapeutic trials, epidemiologic surveys, and medical practice. We reviewed 36 patients with TTR‐A‐PN who were evaluated between 1997 and 2007. They had neurologic, genetic, electrodiagnostic, and autonomic reflex screen evaluations and allowed their medical records and test results to be evaluated for research purposes. Of these, 22 patients had also been tested by quantitative sensation tests (QSTs). The median symptom duration was 4 years (range 1–30 years). Among quantitative nerve tests evaluated, composite scores of nerve conduction (Σ5 NC nds), a composite score of QSTs (Σ3 QST nds), and quantitative autonomic tests (QSART, HRdb, and CASS) gave high frequencies of abnormality. The results show that peripheral autonomic and small‐fiber sensory dysfunction was prominent and characteristic of most of the patients we studied. However, this involvement was not selective for small‐diameter sensory and autonomic nerve fibers; large motor and sensory fibers were also shown to be dysfunctional. Dysfunction of large fibers was approximately as frequent as that of small fibers. This study provides a rationale for the use of QAT, QST, and Σ5 NC nds as standard, objective, and quantitative measures for assessing the severity of TTR‐A‐PN in epidemiologic surveys, therapeutic trials, and medical practice. Muscle Nerve, 2009
Clinical utility of electrodiagnostic studies in the inpatient setting
Authors: Perry Daryl I. , Tarulli Andrew W. , Nardin Rachel A. , Rutkove Seward B. , Gautam Shiva , Narayanaswami Pushpa
Published: July 2009

Although nerve conduction studies/electromyograms are often requested to evaluate hospitalized patients (inpatients) with suspected neuromuscular diseases, their clinical utility has not been studied. They can be technically challenging, especially in intensive care units. We studied the contribution of inpatient electromyograms (IP‐EMGs) to the management of patients with suspected neuromuscular disorders. A total of 103 IP‐EMGs in 98 patients were analyzed. IP‐EMGs confirmed the clinical diagnosis in 53.3% and provided a new, clinically relevant diagnosis in 12.6%. IP‐EMGs revealed only an incidental diagnosis in 14.5%, were inconclusive in 16.5%, and were normal in 3%. In over a quarter of patients, IP‐EMGs assisted in planning further diagnostic evaluation or treatment. Although IP‐EMGs most often only confirm already suspected diagnoses, in a substantial minority of patients they lead to the identification of clinically unsuspected, significant diagnoses that alter subsequent clinical care. Muscle Nerve 40: 195–199, 2009
Acetylcholine receptor‐α subunit expression in myasthenia gravis: A role for the autoantigen in pathogenesis?
Authors: Sheng Jian Rong , Li Liang Cheng , Prabhakar Bellur S. , Meriggioli Matthew N.
Published: July 2009

Previous studies have shown increased expression of acetylcholine receptor‐alpha (AChR‐α) subunit transcripts in myasthenia gravis (MG) and experimental MG (EAMG), but none examined the functional properties of this overexpression. In this study we examined the mRNA and protein expression of AChR‐α as well as the pattern of α‐bungarotoxin labeling in muscle tissue from EAMG mice with varying disease severity. AChR‐α expression was increased considerably in endplates from mice with severe EAMG, but it was distinct and greatly in excess of α‐bungarotoxin labeling. This “aberrant expression” occurred in mice with morphologic endplate damage, and the pattern of complement and immunoglobulin deposition in muscle from these mice appeared to mirror the pattern of AChR‐α expression. The loss of functional AChR in severe MG increases transcription of AChR‐α mRNA, but the expressed protein is “functionally inert,” failing to compensate for loss of AChR. This enhanced expression of AChR may play a role in driving the ongoing autoimmune response. Muscle Nerve 40: 279–286, 2009
Clinical and experimental aspects of Adreno‐muscarinic synergy in the bladder base and prostate
Authors: Roosen Alexander , Blake‐James Ben T. , Wood Daniel , Fry Christopher H.
Published: July 2009

Recent clinical trials have shown that combination therapy using an alpha‐receptor antagonist and an antimuscarinic is more effective than either agent alone in improving quality of life and objective urodynamic variables in men with bladder outflow obstruction. There appear to be no negative effects on bladder function. The mode of action of this combination is unknown but presumed to be an antimuscarinic reduction in detrusor overactivity and the alpha‐receptor antagonist reduced outflow tract resistance. We have shown with in vitro experiments that in smooth muscles influencing outflow tract resistance (prostate, trigone) there is a profound contractile synergy between adrenergic and muscarinic pathways. We propose the hypothesis that both arms of the combination therapy reduce contractile tone of the outflow tract and that their simultaneous attenuation has a disproportionately large effect on outflow tract resistance. Our data from trigone muscle suggest that adrenergic and muscarinic receptor activation increase the intracellular [Ca2+] but the adrenergic pathway also operates through Ca2+‐sensitisation of the contractile apparatus, primarily through a PKC‐dependent pathway. Neurourol. Urodynam. 28:938–943, 2009. © 2009 Wiley‐Liss, Inc.
Intravaginal pressure generated during voluntary pelvic floor muscle contractions and during coughing: The effect of age and continence status
Authors: Madill Stéphanie J. , McLean Linda
Published: July 2009

Aims

The purpose of this study was to determine if, compared to continent women, women with stress urinary incontinence (SUI) generate lower intravaginal pressure (IVP) during maximum voluntary pelvic floor muscle contractions (PFM MVCs) or coughing, slower contraction times or less ability to sustain IVP, and if there are reductions in the ability to generate IVP during these tasks associated with increasing age.

Methods

Eighty‐seven (35 continent, 35 with mild SUI and 17 with severe SUI) women participated. IVP data were acquired while participants performed PFM MVCs, maximum effort coughs and a sustained PFM contraction. The maximum IVP amplitudes measured during the MVCs and coughs, the time for IVP to reach a peak during coughing and the time for the IVP to drop by 50% during the sustained contraction were compared among the groups using separate analyses of covariance, with age included as a covariate.

Results

There were no differences in maximum PFM MVC IVP or in endurance time among the groups. Women with SUI produced higher cough IVP amplitudes than continent women. Age was associated with a reduction in IVP and with longer contraction times during coughing.

Conclusions

The data suggest that PFM weakness may not be an important factor in the pathophysiology of SUI. Women with SUI may intuitively use their PFMs to compensate for urethral sphincter or fascial deficits. The IVP generated during coughing and the speed at which peak IVP is attained are, however, substantially reduced with increasing age, which might affect continence in older women. Neurourol. Urodynam. 29:437–442, 2010. © 2009 Wiley‐Liss, Inc.
Is pegfilgrastim safe and effective in congenital neutropenia? An analysis of the French Severe Chronic Neutropenia registry
Authors: Beaupain Blandine , Leblanc Thierry , Reman Oumédaly , Hermine Olivier , Vannier Jean‐Pierre , Suarez Felipe , Lutz Patrick , Bordigoni Pierre , Jourdain Anne , Schoenvald Michele , Ouachee Marie , François Sylvie , Kohser Fréderic , Jardin Fabrice , Devouassoux Gilles , Bertrand Yves , Nove‐Josserand Raphaele , Donadieu Jean
Published: July 2009

Aims

To examine the efficacy and safety of pegfilgrastim in patients with congenital neutropenia (CN).

Methods

Seventeen patients enrolled in the French Severe CN Register received pegfilgrastim.

Results

Median age at pegfilgrastim introduction was 19.1 years (range 3.9–52.3 years). In 14 cases pegfilgrastim replaced GCSF (filgrastim or lenograstim), after a median of 6.9 years of GCSF therapy. The dose of pegfilgrastim was usually one full vial per injection (except in five children, who received 1/6 to 1/2 a vial), resulting in a dose of between 50 and 286 µg/kg. The pegfilgrastim schedule ranged from two injections every 7 days to one injection every 30 days, with treatment‐free periods. The median interval between the first and last dose of pegfilgrastim was 0.8 years (0.01–4.1 years). The absolute neutrophil count tended to increase more strongly on pegfilgrastim than on GCSF, but the difference was not statistically significant. During pegfilgrastim therapy, a severe infection occurred in two patients and recurrent ENT infections in two other patients. Bone pain was reported by nine patients, anemia and thrombocytopenia occurred in one patient (WHO grade III), chronic urticaria occurred in one patient (WHO grade III), and a single pegfilgrastim injection was followed by respiratory distress and death 15 days later in a patient with GDSIb. At the last update, 10 patients had stopped receiving pegfilgrastim and seven patients were still receiving pegfilgrastim.

Conclusion

Compared to conventional GCSF, pegfilgrastim is more difficult to use in congenital neutropenia, with more frequent adverse events and sometimes poor efficacy. Pediatr Blood Cancer 2009;53:1068–1073. © 2009 Wiley‐Liss, Inc.
Family, demographic and illness‐related determinants of HRQL in children with brain tumours in the first year after diagnosis
Authors: Penn Anthony , Lowis Stephen P. , Stevens Michael C.G. , Hunt Linda P. , Shortman Robert I. , McCarter Renee J. , Pauldhas Darwin , Curran Andrew L. , Sharples Peta M.
Published: July 2009

Aims

To evaluate the relationship between parent‐ and child‐report Health‐Related Quality of Life (HRQL) and demographic, tumour and family variables in children with a brain tumour in the first year after diagnosis and to identify determinants of HRQL at 12 months.

Procedure

Longitudinal prospective study: Semi‐structured interviews took place approximately 1, 6 and 12 months after diagnosis. HRQL was measured using the self‐ and parent‐report PedsQL 4.0 Total Scale Score. Tumour and treatment variables considered included tumour site and grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family variables included measures of family function, family support and family stress, the primary carer's coping strategies and symptoms of depression and anxiety. Univariate analyses were used at all three time points, and to identify potential early predictors of HRQL at 1 year. Regression analysis was then used to identify the most important determinants of HRQL at 1 year.

Results

Thirty‐five patients completed the 12‐month interviews. There were consistent significant negative correlations between concurrent family impact of illness and parent and self‐report HRQL, and positive correlations between concurrent family support and parent‐report HRQL. Treatment with radio‐ or chemotherapy correlated with child‐report HRQL only at some time points. Multivariate analysis showed infratentorial tumour site, and poor HRQL at 1 month best predicted poor self‐ and parent‐report HRQL at 12 months.

Conclusion

Children with infratentorial tumours and poor HRQL early after diagnosis tend to have poor HRQL at 1 year. While family factors are important modulators of concurrent HRQL, they do not appear important in predicting HRQL. Pediatr Blood Cancer 2009;53:1092–1099. © 2009 Wiley‐Liss, Inc.
Epidemiology of bone tumours in children and young adults
Authors: Eyre Rachel , Feltbower Richard G. , Mubwandarikwa Emmanuel , Eden Tim O.B. , McNally Richard J.Q.
Published: July 2009

Although the epidemiology of malignant bone tumours in children and young adults has been explored, no definitive causation of any specific tumour has yet been identified. We performed a literature review (1970–2008) to find all papers covering possible aetiological factors involved in the development of bone tumours in children and young adults. Several associations have been reported with some consistency: the presence of hernias and Ewing sarcoma; high fluoride exposure and osteosarcoma; and parental farming and residence on a farm, younger age at puberty and family history of cancer for all bone tumours, especially osteosarcoma. Clearly further research is needed to confirm or refute these putative risk factors. It is likely that studies of gene–environment interactions may prove to be the most fruitful of future research. Pediatr Blood Cancer 2009;53:941–952. © 2009 Wiley‐Liss, Inc.
Conscientiousness and achievement motivation predict performance
Authors: Richardson Michelle , Abraham Charles
Published: July 2009

A prospective survey was conducted to identify predictors of university students' grade point average (GPA) using separate samples of female (N = 472) and male (N = 142) students over 9 months. Big five personality traits and achievement motivation were measured. Correlations show that conscientiousness (C) and achievement motivation explained variation in GPA. Latent variable structural equation modelling showed that the effect of C on GPA is fully mediated by achievement motivation for both female and male students. Invariant factor and structural mediation models across the female and male groups are also reported. Finally, the mediation model is shown to remain significant after scholastic achievement is controlled. The findings are interpreted within the framework of Neo‐Socioanalytic theory. Copyright © 2009 John Wiley & Sons, Ltd.
Novel functional profiling approach combining reverse phase protein microarrays and human 3‐D ex vivo tissue cultures: Expression of apoptosis‐related proteins in human colon cancer
Authors: Pirnia Farzaneh , Pawlak Michael , Thallinger Gerhard G. , Gierke Berthold , Templin Markus F. , Kappeler Andi , Betticher Daniel C. , Gloor Beat , Borner Markus M.
Published: July 2009

Cancer is caused by a complex pattern of molecular perturbations. To understand the biology of cancer, it is thus important to look at the activation state of key proteins and signaling networks. The limited amount of available sample material from patients and the complexity of protein expression patterns make the use of traditional protein analysis methods particularly difficult. In addition, the only approach that is currently available for performing functional studies is the use of serial biopsies, which is limited by ethical constraints and patient acceptance. The goal of this work was to establish a 3‐D ex vivo culture technique in combination with reverse‐phase protein microarrays (RPPM) as a novel experimental tool for use in cancer research. The RPPM platform allows the parallel profiling of large numbers of protein analytes to determine their relative abundance and activation level. Cancer tissue and the respective corresponding normal tissue controls from patients with colorectal cancer were cultured ex vivo. At various time points, the cultured samples were processed into lysates and analyzed on RPPM to assess the expression of carcinoembryonic antigen (CEA) and 24 proteins involved in the regulation of apoptosis. The methodology displayed good robustness and low system noise. As a proof of concept, CEA expression was significantly higher in tumor compared with normal tissue (p<0.0001). The caspase 9 expression signal was lower in tumor tissue than in normal tissue (p<0.001). Cleaved Caspase 8 (p=0.014), Bad (p=0.007), Bim (p=0.007), p73 (p=0.005), PARP (p<0.001), and cleaved PARP (p=0.007) were differentially expressed in normal liver and normal colon tissue. We demonstrate here the feasibility of using RPPM technology with 3‐D ex vivo cultured samples. This approach is useful for investigating complex patterns of protein expression and modification over time. It should allow functional proteomics in patient samples with various applications such as pharmacodynamic analyses in drug development.
Use of narrow‐range peptide IEF to improve detection of lung adenocarcinoma markers in plasma and pleural effusion
Authors: Pernemalm Maria , De Petris Luigi , Eriksson Hanna , Brandén Eva , Koyi Hirsh , Kanter Lena , Lewensohn Rolf , Lehtiö Janne
Published: July 2009

In this study we applied narrow‐range peptide IEF to plasma or pleural effusion prior to LC/MS/MS. Two methods for narrow‐range IEF were run; IPG strips and free‐flow electrophoresis. Data from this study was compared with cell line data to evaluate the method performance in body fluids. To test the methods potential in quantitative biomarker discovery studies, plasma and pleural effusion from patients with lung adenocarcinoma (n=3) were compared with inflammatory pleuritis (n=3) using iTRAQ quantification. Using narrow‐range IEF on the peptide level we were able to identify and quantify 282 proteins in plasma and 300 proteins in pleural effusion. These body fluid proteomes demonstrated high degree of overlap; however, more proteins significantly differently altered levels related to adenenocarcinoma were found in pleural effusion compared with plasma, suggesting enrichment of lung tissue‐related proteins in pleural effusion. Nine proteins were chosen for initial validation with Western blot, and one protein (NPC2) was chosen for further validation using imunohistochemistry. Overall, the quantitative results from IEF/LC/MS/MS showed good correlation with the results from Western blot and imunohistochemistry, showing the potential of this methodology in quantitative biomarker discovery studies.
Identification of blood group A/A‐Leb/y and B/B‐Leb/y active glycotopes co‐expressed on the O‐glycans isolated from two distinct human ovarian cyst fluids
Authors: Yu Shin‐Yi , Yang Zhangung , Khoo Kay‐Hooi , Wu Albert M.
Published: July 2009

Although the individual human blood group A and B determinants are well defined, their co‐expression pattern on a particular glycan carrier in individuals of blood group AB status has not been delineated. To address this issue, complex O‐glycans were isolated from two distinct sources of human ovarian cyst glycoproteins (HOC 89 and Cyst 19) and profiled by advanced MS analyses, in conjunction with defining their binding characteristics against a panel of lectins and monoclonal antibodies. The major O‐glycans of HOC 89 were found to correspond to sialyl Tn, mono‐ and di‐sialyl T structures, whereas those of Cyst 19 were apparently more heterogeneous and extended to larger sizes. A minimal structure that carries both A and B determinants on the same molecule was identified, in which the A epitope is attached directly to the core GalNAc, whereas the B epitope is preferentially located on the six arms of a core 2 structure. Both arms can be further extended with internal fucosylation that appears to be restricted to those non‐sialylated chains already carrying the terminal ABH determinants, thus giving rise to rather prominent A/B‐Leb/y glycotopes on larger O‐glycans.
Chronic ethanol feeding affects proteasome‐interacting proteins
Authors: Bousquet‐Dubouch Marie‐Pierre , Nguen Sheila , Bouyssié David , Burlet‐Schiltz Odile , French Samuel W. , Monsarrat Bernard , Bardag‐Gorce Fawzia
Published: July 2009

Studies on alcoholic liver injury mechanisms show a significant inhibition of the proteasome activity. To investigate this phenomenon, we isolated proteasome complexes from the liver of rats fed ethanol chronically, and from the liver of their pair‐fed controls, using a non‐denaturing multiple centrifugations procedure to preserve proteasome‐interacting proteins (PIPs). ICAT and MS/MS spectral counting, further confirmed by Western blot, showed that the levels of several PIPs were significantly decreased in the isolated ethanol proteasome fractions. This was the case of PA28α/β proteasome activator subunits, and of three proteasome‐associated deubiquitinases, Rpn11, ubiquitin C‐terminal hydrolase 14, and ubiquitin carboxyl‐terminal hydrolase L5. Interestingly, Rpn13 C‐terminal end was missing in the ethanol proteasome fraction, which probably altered the linking of ubiquitin carboxyl‐terminal hydrolase L5 to the proteasome. 20S proteasome and most 19S subunits were however not changed but Ecm29, a protein known to stabilize the interactions between the 20S and its activators, was decreased in the isolated ethanol proteasome fractions. It is proposed that ethanol metabolism causes proteasome inhibition by several mechanisms, including by altering PIPs and proteasome regulatory complexes binding to the proteasome.
Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways
Authors: Matsumoto Masaki , Oyamada Koji , Takahashi Hidehisa , Sato Takamichi , Hatakeyama Shigetsugu , Nakayama Keiichi I.
Published: July 2009

Activation of the T‐cell receptor (TCR) and that of the B‐cell receptor (BCR) elicits tyrosine‐phosphorylation of proteins that belongs to similar functional categories, but result in distinct cellular responses. Large‐scale analyses providing an overview of the signaling pathways downstream of TCR or BCR have not been described, so it has been unclear what components of these pathways are shared and which are specific. We have now performed a systematic analysis and provide a comprehensive list of tyrosine‐phosphorylated proteins (PY proteome) with quantitative data on their abundance in T cell, B cell, and nonlymphoid cell lines. Our results led to the identification of novel tyrosine‐phosphorylated proteins and signaling pathways not previously implicated in immunoreceptor signal transduction, such as clathrin, zonula occludens 2, eukaryotic translation initiation factor 3, and RhoH, suggesting that TCR or BCR signaling may be linked to downstream processes such as endocytosis, cell adhesion, and translation. Thus comparative and quantitative studies of tyrosine‐phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level.
Proteomic profiling of Cronobacter turicensis 3032, a food‐borne opportunistic pathogen
Authors: Carranza Paula , Hartmann Isabel , Lehner Angelika , Stephan Roger , Gehrig Peter , Grossmann Jonas , Barkow‐Oesterreicher Simon , Roschitzki Bernd , Eberl Leo , Riedel Kathrin
Published: July 2009

Members of the genus Cronobacter are opportunistic pathogens for neonates and are often associated with contaminated milk powder formulas. At present little is known about the virulence mechanisms or the natural reservoir of these organisms. The proteome of Cronobacter turicensis 3032, which has recently caused two deaths, was mapped aiming at a better understanding of physiology and putative pathogenic traits of this clinical isolate. Our analyses of extracellular, surface‐associated and whole‐cell proteins by two complementary proteomics approaches, 1D‐SDS‐PAGE combined with LC‐ESI‐MS/MS and 2D‐LC‐MALDI‐TOF/TOF MS, lead to the identification of 832 proteins corresponding to a remarkable 19% of the theoretically expressed protein complement of C. turicensis. The majority of the identified proteins are involved in central metabolic pathways, translation, protein folding and stability. Several putative virulence factors, whose expressions were confirmed by phenotypic assays, could be identified: a macrophage infectivity potentiator involved in C. turicensis persistence in host cells, a superoxide dismutase protecting the pathogen against reactive oxygen species and an enterobactin‐receptor protein for the uptake of siderophore‐bound iron. Most interestingly, a chitinase and a metalloprotease that might act against insects and fungi but no casein hydrolysing enzymes were found, suggesting that there is an environmental natural habitat of C. turicensis 3032.
Shikonin inhibits fat accumulation in 3T3‐L1 adipocytes
Authors: Lee Haeyong , Kang Ryunhwa , Yoon Yoosik
Published: July 2009

Shikonin, 5,6‐dihydroxyflavone‐7‐glucuronic acid, is the main ingredient of Lithospermum erythrorhizon Sieb. et Zucc, and was reported to have various biological activities including antiinflammatory, anticancer, antimicrobial and others. This study aimed to elucidate, for the first time, the antiobesity activity of shikonin and its mechanism of action. Shikonin was found to inhibit fat droplet formation and triglyceride accumulation in 3T3‐L1 adipocytes. The half inhibitory concentration, IC50, for the inhibition of triglyceride accumulation was found to be 1.1 μM. The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARγ and C/EBPα, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARγ and C/EBPa were significantly down‐regulated following shikonin treatment. Among the upstream regulators of adipogenesis, only SREBP1C was found to be down‐regulated by shikonin. The results of this study suggest that shikonin down‐regulates the expression of SREBP1C and subsequently the expression of PPARγ and C/EBPα. Together, these changes result in the down‐regulation of lipid metabolizing enzymes and reduced fat accumulation. Copyright © 2009 John Wiley & Sons, Ltd.
The protective effects of hydroxytyrosol against UVB‐induced DNA damage in HaCaT cells
Authors: Guo Wei , An Yu , Jiang Liping , Geng Chengyan , Zhong Laifu
Published: July 2009

The chemoprotective effect of hydroxytyrosol (HT) against UVB‐induced DNA damage was investigated in a human skin keratinocyte cell line, HaCaT. The comet assay was used to monitor DNA strand breaks. Intracellular reactive oxygen species (ROS) formation was measured by flow cytometry using 2,7‐dichlorofluorescein diacetate (DCFH‐DA). The levels of oxidatively generated damage to DNA were estimated by immunocytochemistry analysis of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). The protein expression of p53 and NF‐κB was estimated by western blotting. The results showed that HT significantly reduced the DNA strand breaks caused by UVB. It was also found that HT reduced intracellular ROS formation and 8‐OHdG level caused by UVB. Furthermore, HT attenuated the expression of p53 and NF‐κB in a concentration‐dependent manner. These results strongly suggest that HT has a significant protective ability against UVB‐induced DNA damage and that oxidative stress plays an important part in it. Copyright © 2009 John Wiley & Sons, Ltd.
Empirically based modelling of radar‐rainfall uncertainties for a C‐band radar at different time‐scales
Authors: Villarini Gabriele , Krajewski Witold F.
Published: July 2009

Radar‐based estimates of rainfall are affected by several sources of systematic and random errors. The propagation of these uncertainties is required for improving the understanding and interpretation of the results obtained when radar‐rainfall estimates are used as input or initial conditions. Despite the relevance of the problem, modelling of radar‐rainfall uncertainties is still at an early stage. The authors apply an empirically based model in which the relation between true rainfall and radar‐rainfall can be described as the product of a systematic distortion function (accounting for systematic biases) and random component (describing the remaining random errors). The proposed results are based on a large sample (more than six years) of data from a C‐band radar (Wardon Hill) located in southwest England. The true ground rainfall is approximated by rain gauge measurements from a highly dense network deployed in the Brue catchment, located about 40 km from the radar site.

The authors present results from their modelling of the radar‐rainfall errors at four time‐scales of hydrologic interest (5‐ and 15‐minute, hourly and three‐hourly) and 2 km spatial resolution, discussing the impact of spatial sampling errors on the proposed results. Copyright © 2009 Royal Meteorological Society
Wavelet transform‐based analysis of periodicities and trends of Sakarya basin (Turkey) streamflow data
Authors: Partal Turgay
Published: July 2009

In this study, the wavelet transform and the Mann–Kendall test are used to determine possible trends in annual streamflow series. The wavelet analysis provides detailed information about the time‐frequency contents of the data. Using wavelet components of the original data, it was aimed to find which periodicities are mainly responsible for a trend in the original data. Also, the global wavelet spectra and the continuous wavelet transform (CWT) were used for the analysis of the streamflow data, in order to explain its time‐frequency characteristics. Annual streamflow series across Turkey were used for the detection of trends for the original data and the periodic wavelet components (obtained by discrete wavelet transform). It was found that some periodic events clearly affect the trend in the streamflow series. The DW4 component (16‐yearly periodic component) at the stations of the Sakarya basin is the effective periodic component and is responsible for producing a real trend in the data. The effects of regional differences on the wavelet‐trend analysis are studied using records of the stations located in different climate areas. DW2 (4‐yearly component) and DW3 (8‐yearly component) are the dominant periodic components of this data. This study aims to explain the trend structure in the data. Copyright © 2009 John Wiley & Sons, Ltd.
The relations between ‘standard’ fluvial habitat variables and turbulent flow at multiple scales in morphological units of a gravel‐bed river
Authors: Roy M. L. , Roy A. G. , Legendre P.
Published: July 2009

Fluvial fish habitat is often characterized by highly turbulent flow conditions. Several laboratory experiments suggest that unpredictable turbulent fluctuations can increase the swimming energy costs of fish. At the scale of fish habitat models, it can be hypothesized that turbulence can be captured by the combined effects of the standard habitat variables: depth, velocity and substrate. However, recent studies conducted at the reach scale suggest that turbulent properties are more controlled by the large‐scale bed morphology than by individual roughness elements. In this study, we investigate the spatial structure of turbulent flow and the potential relationships between ‘standard’ habitat variables and turbulent flow properties in pools and riffles of a shallow gravel‐bed river. The study explores these relations at multiple spatial scales. Mean turbulent properties and turbulent flow structures statistics were computed from 1932 near bed velocity time series sampled with acoustic Doppler velocimeters on a regular grid in four morphological units (two pools and two riffles) presenting a gradient of complexity. We used a novel multivariate variation partitioning analysis involving principal coordinates of neighbour matrices (PCNM) to partition turbulent flow properties into six significant spatial scales (VF: 0.35, F: 0.75, M: 1.25, L: 2, XL: 2.5 and XXL: 3 m). Between 45 and 70% of the variance of the turbulent flow properties were explained by the spatial PCNM. In the four units, turbulent properties exhibited a spatial dependence across the entire range of scales. However, the proportion of variation explained by the larger‐scaled PCNMs was higher in the most homogeneous units. In general, the spatial dependence of turbulent flow was lower in the riffles than in the pools, where the mean flow velocity was slower. The capacity of ‘standard’ fish habitat variables to explain turbulent properties was relatively low, especially in the smaller scales, but varied greatly between the units. From a practical point of view, this level of complexity suggests that turbulence should be considered as a ‘distinct’ ecological variable within the range of spatial scales included in this study. Further research should attempt to link the spatial scales of turbulent flow variability to benthic organism patchiness and fish habitat use. Copyright © 2009 John Wiley & Sons, Ltd.
Research in social entrepreneurship: past contributions and future opportunities
Authors: Short Jeremy C. , Moss Todd W. , Lumpkin G. T.
Published: July 2009

Social entrepreneurship has been a topic of academic inquiry for nearly 20 years, yet relatively little scholarly output has appeared in mainstream management and entrepreneurship journals. Our review of this literature reveals that conceptual articles outnumber empirical studies, and empirical efforts often lack formal hypotheses and rigorous methods. These findings suggest that social entrepreneurship research remains in an embryonic state. Future research would benefit from the incorporation of multivariate methods to complement the case study techniques that have dominated previous efforts. Our review also suggests that social entrepreneurship is informed by common areas of interest to management scholars like entrepreneurship, public/nonprofit management, and social issues, all of which represent fruitful venues for future research efforts. Therefore, we recommend that scholars embrace key themes in strategic entrepreneurship and frame their research using established theories, such as contingency theory, creation theory, discovery theory, innovation diffusion theory, resource dependence theory, and other theoretical bases relevant to strategic entrepreneurship research. Copyright © 2009 Strategic Management Society.
A comparison of PCA and MAF for ToF‐SIMS image interpretation
Authors: Henderson Alex , Fletcher John S. , Vickerman John C.
Published: July 2009

While time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) image generation has been useful in the determination of the spatial distribution of chemistry in a broad application area, the amount of secondary ion signal available in each pixel remains small, hampering the use of multivariate analysis (MVA) approaches. The pre‐treatment of data commonly comprises two approaches to increase pixel signal intensity prior to MVA: mass channel summation and pixel summation. Recent advances in instrumentation have lead to much greater signal per image pixel such that a true spectrum can be discerned at each point across the sample. In this study, we determine the outcomes of these two pre‐treatments prior to principal components analysis (PCA) and maximum autocorrelation factor (MAF) analysis in comparison with high signal intensity data.

Both PCA and MAF analyses of the high signal intensity data are presented with MAF being identified as the most effective approach. Image data was reduced in intensity to determine the effectiveness of MVA with lower spectral intensity. MAF was found to outperform PCA on such data, although both techniques were useful in the identification of the chemistry present. The data were then mass summed, using a number of different approaches, to reduce mass resolution, leading to a detrimental effect on PCA analysis, but little discernable change to MAF output. Reducing the spatial resolution by summing spectra from adjacent pixels, however, lead to a severe blurring of the MAF image structure, with PCA performing well.

Conclusions and recommendation for pre‐treatment and MVA technique selection are presented. Copyright © 2009 John Wiley & Sons, Ltd.
Correlating MALDI and SIMS imaging mass spectrometric datasets of biological tissue surfaces
Authors: Eijkel G. B. , Kükrer Kaletaş B. , van der Wiel I. M. , Kros J. M. , Luider T. M. , Heeren R. M. A.
Published: July 2009

Imaging mass spectrometry (IMS) is a rapidly evolving tool for combined chemical and spatial analysis of biological tissues. The complexity of the biological data requires various analytical methods to process the raw datasets. In this article, we report on the ‘semi‐automated’ correlation of two imaging MS datasets obtained with secondary ion mass spectrometry (SIMS) and matrix‐assisted laser desorption/ionization (MALDI) on the same, single brain tissue sample. Prior to statistical analysis, the raw datasets are preprocessed with novel algorithms for baseline correction and peak picking. Principal component analysis (PCA) and canonical correlation analysis (CCA) are used in concert to extract the maximum amount of information about the location of different biochemical molecules on the tissue surface. More importantly, the results show that combining the information from MALDI and SIMS, by using CCA, enables us to correlate and improve the individual results of these two imaging MS experiments. Copyright © 2009 John Wiley & Sons, Ltd.
On the use of propensity scores in principal causal effect estimation
Authors: Jo Booil , Stuart Elizabeth A.
Published: July 2009

We examine the practicality of propensity score methods for estimating causal treatment effects conditional on intermediate posttreatment outcomes (principal effects) in the context of randomized experiments. In particular, we focus on the sensitivity of principal causal effect estimates to violation of principal ignorability, which is the primary assumption that underlies the use of propensity score methods to estimate principal effects. Under principal ignorability (PI), principal strata membership is conditionally independent of the potential outcome under control given the pre‐treatment covariates; i.e. there are no differences in the potential outcomes under control across principal strata given the observed pretreatment covariates. Under this assumption, principal scores modeling principal strata membership can be estimated based solely on the observed covariates and used to predict strata membership and estimate principal effects. While this assumption underlies the use of propensity scores in this setting, sensitivity to violations of it has not been studied rigorously. In this paper, we explicitly define PI using the outcome model (although we do not actually use this outcome model in estimating principal scores) and systematically examine how deviations from the assumption affect estimates, including how the strength of association between principal stratum membership and covariates modifies the performance. We find that when PI is violated, very strong covariate predictors of stratum membership are needed to yield accurate estimates of principal effects. Copyright © 2009 John Wiley & Sons, Ltd.
Causation, counterfactuals, and competitive advantage
Authors: Durand Rodolphe , Vaara Eero
Published: July 2009

Causation is still poorly understood in strategy research, and confusion prevails around key concepts such as competitive advantage. In this paper, we define epistemological conditions that help dispel some of this confusion and provide a basis for more developed approaches. In particular, we argue that a counterfactual approach—one that builds on a systematic analysis of ‘what‐if’ questions—can advance our understanding of key causal mechanisms in strategy research. We offer two concrete methodologies—counterfactual history and causal modeling—as useful solutions. We also show that these methodologies open up new avenues in research on competitive advantage. Counterfactual history can add to our understanding of the context‐specific construction of resource‐based competitive advantage and path dependence, and causal modeling can help to reconceptualize the relationships between resources and performance. In particular, resource properties can be regarded as mediating mechanisms in these causal relationships. Copyright © 2009 John Wiley & Sons, Ltd.
De novoventure strategy: arch incumbency at inaugural entry
Authors: Fan Terence Ping Ching
Published: July 2009

By definition,de novoindustry ventures do not share many market‐contact points with incumbents—itself an important source of competitive ‘stability’ through mutual forbearance. As such, these ventures are often subject to aggressive retaliation at the outset, which could threaten their very survival. In this study, the notion of an arch incumbent is developed, hypothesizing that, in general, a large market overlap with an incumbent lowers the survival odds of ade novoentrant. However, a large market overlap with the arch incumbent combined with an aggressive inaugural market entry or a different market positioning reduces the probability of retaliation by the arch incumbent (and subsequently other incumbents as well), and hence increases the probability of survival for ade novoentrant. The empirical experience ofde novoventures in the intra‐European passenger airline industry supports these hypotheses. Copyright © 2009 John Wiley & Sons, Ltd.
Recognizing authors: an examination of the consistent programmer hypothesis
Authors: Hayes Jane Huffman , Offutt Jeff
Published: July 2009

Software developers have individual styles of programming. This paper empirically examines the validity of theconsistent programmer hypothesis: that a facet or set of facets exist that can be used to recognize the author of a given program based on programming style. The paper further postulates that the programming style means that different test strategies work better for some programmers (or programming styles) than for others. For example, all‐edges adequate tests may detect faults for programs written by Programmer A better than for those written by Programmer B. This has several useful applications: to help detect plagiarism/copyright violation of source code, to help improve the practical application of software testing, and to help pursue specific rogue programmers of malicious code and source code viruses. This paper investigates this concept by experimentally examining whether particular facets of the program can be used to identify programmers and whether testing strategies can be reasonably associated with specific programmers. Copyright © 2009 John Wiley & Sons, Ltd.
Occurrence of microcystin‐producing cyanobacteria in Ugandan freshwater habitats
Authors: Okello William , Portmann Cyril , Erhard Marcel , Gademann Karl , Kurmayer Rainer
Published: July 2009

Microcystins (MCs) are cyclic heptapeptides, which are the most abundant toxins produced by cyanobacteria in freshwater. The phytoplankton of many freshwater lakes in Eastern Africa is dominated by cyanobacteria. Less is known, however, on the occurrence of MC producers and the production of MCs. Twelve Ugandan freshwater habitats ranging from mesotrophic to hypertrophic conditions were sampled in May and June of 2004 and April of 2008 and were analyzed for their physicochemical parameters, phytoplankton composition, and MC concentrations. Among the group of the potential MC‐producing cyanobacteria, Anabaena (0–107 cells ml−1) and Microcystis (103–107 cells ml−1) occurred most frequently and dominated in eutrophic systems. A significant linear relationship (n = 31, r2 = 0.38, P < 0.001) between the Microcystis cell numbers and MC concentration (1.3–93 fg of MC cell−1) was observed. Besides [MeAsp3, Mdha7]‐MC‐RR, two new MCs, [Asp3]‐MC‐RY and [MeAsp3]‐MC‐RY, were isolated and their constitution was assigned by LC‐MS2. To identify the MC‐producing organism in the water samples, (i) the conserved aminotransferase domain part of the mcyE gene that is indicative of MC production was amplified by general primers and cloned and sequenced, and (ii) genus‐specific primers were used to amplify the mcyE gene of the genera Microcystis, Anabaena, and Planktothrix. Only mcyE genotypes that are indicative of Microcystis sp. were obtained via the environmental cloning approach (337 bp, 96.1–96.7% similarity to the Microcystis aeruginosa strain PCC7806). Accordingly, only the mcyE primers, which are specific for Microcystis, revealed PCR products. We concluded that Microcystis is the major MC‐producer in Ugandan freshwater. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 367–380, 2010.
Vagal Nerve Function in Obesity: Therapeutic Implications
Authors: Kral John G. , Paez Wencesley , Wolfe Bruce M.
Published: July 2009

The primal need for nutrients is satisfied by mechanisms for sensing internal stores and detecting food; ATP is the most primitive signal. With increasing density of sensory neurons and glia (the primordial brain) and the emergence of autonomic neural activity throughout the endoderm, transmitters and other signaling molecules enable alimentation before the appearance of innate storage functions. Memory and, ultimately, cognition are prerequisites for processing and producing food to facilitate assimilation and safeguard the supply of nutrients. The gut–brain–gut axis via the vagus nerve is the autonomic neurohumoral pathway integrating these elements of energy homeostasis. Humans uniquely override obligate nutrient needs, eating in the absence of deprivation, resulting in pathological chronic overnutrition arising from dysautonomia. Obesity surgery circumvents powerful redundant mechanisms of alimentation and reduces excess stores of body fat from chronic overnutrition while preventing re‐accumulation of fat. All bariatric operations, whether purely restrictive, maldigestive and malabsorptive, or combinations, rely on regulatory mechanisms related to autonomic nervous system function and the brain–gut axis. We review the functional anatomy and the importance of the vagus nerve for maintaining maladaptive chronic overnutrition and describe interventions to abrogate its effects. In aggregate, the preponderance of evidence supported by laboratory and clinical mechanistic studies interrupting abdominal bi‐directional vagal transmission demonstrates that the majority of patients report less “hunger” and lose weight.