bluuebunny/crossref_metadata_2025 huggingface dataset:
The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma
Authors: Franchina M , Woo AJ , Dods J , Karimi M , Ho D , Watanabe T , Spagnolo DV , Abraham LJ
Published: October 2007

CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over‐expression provides a diagnostic marker for a subset of non‐Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti‐CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one‐hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over‐expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Macrophage involvement in the kidney repair phase after ischaemia/reperfusion injury
Authors: Vinuesa E , Hotter G , Jung M , Herrero‐Fresneda I , Torras J , Sola A
Published: October 2007

Macrophage infiltration is a common feature of the early phase of renal ischaemia/reperfusion injury. Indeed, it is generally regarded as the cause of tissue injury in this phase, although it is also clear that it can lead to tissue repair in other phases. In order to ascertain whether macrophages are directly involved in the repair/late phase, which follows the pro‐inflammatory and injury process of renal ischaemia/reperfusion, we used two different approaches based on macrophage depletion. Firstly, we produced renal ischaemia in mice that were previously treated with clodronate liposome. Secondly, during reperfusion we re‐injected RAW 264.7 to macrophage‐depleted mice 24 h prior to sacrifice. The results showed that regeneration, as evaluated by stathmin and PCNA markers, was macrophage‐dependent: it was blocked when macrophage depletion was provoked and recovered with macrophage re‐injection. The cytokine profile revealed the influence of the inflammatory environment on kidney repair: pro‐inflammatory cytokines (MCP‐1, MIP‐1α) increased during the early stages of reperfusion, coinciding with low regeneration, and the anti‐inflammatory cytokine IL‐10 increased during the longer periods of reperfusion when regeneration was more evident. We conclude that macrophages induce renal regeneration after ischaemia/reperfusion, depending on the inflammatory milieu. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Haematopoietic antigen‐presenting cells in the human thymic cortex: evidence for a role in selection and removal of apoptotic thymocytes
Authors: Paessens LC , Fluitsma DM , van Kooyk Y
Published: October 2007

Only a small proportion of thymocytes survive T cell selection in the thymus and leave the thymus as mature T cells. The vast majority of thymocytes undergo cell death during selection, either due to failure to undergo positive selection on self peptide‐MHC presented by thymic antigen presenting cells (APC) or due to negative selection. In the murine thymus it has been shown that most thymocytes that fail selection undergo apoptosis in the thymic cortex and are removed by cortical macrophages. However, it is unknown how apoptotic thymocytes are cleared from the cortex of the human thymus. Here we report the identification of antigen‐presenting cells of haematopoietic origin (hAPCs) by expression of dendritic cell (DC) specific C‐type lectin DC‐SIGN (CD209) in the cortex of the human thymus, and show that these cells exhibit features of both immature DCs and macrophages. The analysis of cellular markers, in particular the expression of the molecular chaperone HLA‐DM, on cortical hAPCs further suggests that these hAPCs may participate in selection of thymocytes in the cortex. Using in situ terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), we demonstrated that these cortical hAPCs are surrounded by apoptotic, TUNEL+ thymocytes in situ. Futhermore, in situ immuno‐cryo‐electron microscopy suggests that cortical hAPCs take up and remove apoptotic thymocytes. Thus, DC‐SIGN+ hAPCs in the human thymic cortex appear to function in thymocyte selection and removal of apoptotic thymocytes from the thymic cortex. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sickle cell disease complicated by post‐streptococcal glomerulonephritis, cerebral hemorrhage and reversible posterior leucoencephalopathy syndrome
Authors: Pashankar Farzana D. , Ment Laura R. , Pearson Howard A.
Published: October 2007

A patient with homozygous hemoglobin SS disease presented with an intracerebral hemorrhage complicating reversible posterior leucoencephalopathy syndrome (RPLS), secondary to hypertension associated with acute post‐streptococcal glomerulonephritis (APSGN). Distinguishing potentially reversible causes of central nervous system events from primary cerebral infarction or hemorrhage in patients with sickle cell disease is important because the management and prognosis of these complications is very different. Similarly, because of the difference in prognosis between APSGN and other forms of sickle cell nephropathy, it is also important to differentiate these conditions. Pediatr Blood Cancer 2008;50:864–866. © 2007 Wiley‐Liss, Inc.
Skeletal Langerhans cell histiocytosis in children: Permanent consequences and health‐related quality of life in long‐term survivors
Authors: Lau Loretta MS , Stuurman Kyra , Weitzman Sheila
Published: October 2007

Background

The skeleton is the most frequently involved organ in Langerhans cell histiocytosis (LCH) in children, and bone LCH generally has an excellent long‐term survival. Although permanent consequences (PC) are described in half of the survivors thus raising concerns for quality of life (QOL), the impact on quality of life has not been formally studied.

Methods

A retrospective review was performed on 124 LCH patients with skeletal involvement, followed by prospective evaluation of PC and health‐related QOL using age‐appropriate validated study tools (PedsQL or SF‐36).

Results

Of the 116 survivors, PC were found in 34 (29%) patients, of whom 8 had more than 1 PC. PC were significantly more frequent in multi‐system (M‐S) than in single system (S‐S) LCH (73% vs. 17%; P < 0.0001). While diabetes insipidus (65%) was the most common PC in M‐S LCH, cosmetic and orthopedic problems made up the majority of PC in S‐S LCH. The median follow‐up time was 8.5 years. 27 patients completed the PedsQL survey and 22 the SF‐36 survey. The QOL scores for LCH patients were not significantly different from healthy children in the PedsQL survey and from young adults in the SF‐36 survey. In addition, the QOL scores were very similar between patients with and without PC and between patients with M‐S and S‐S LCH.

Conclusions

Children with M‐S LCH had a significantly higher risk of developing PC. Skeletal LCH did not adversely affect the quality of life of survivors, including those with PC who appeared to adapt to their disabilities and medical problems. Pediatr Blood Cancer 2008;50:607–612. © 2007 Wiley‐Liss, Inc.
Radiation and chemotherapy combination for nasopharyngeal carcinoma in children: Radiotherapy dose adaptation after chemotherapy response to minimize late effects
Authors: Orbach Daniel , Brisse Hervé , Helfre Sylvie , Klijanienko Jerzy , Bours Danielle , Mosseri Véronique , Rodriguez José
Published: October 2007

Objectives

To retrospectively report the clinical and therapeutic features of children with nasopharyngeal carcinoma (NPC) treated by chemotherapy and doses adapted of radiotherapy.

Patients and Methods

From 1978 to 2005, 34 children were treated for NPC. All histologic and/or cytologic samples and CT scans were reviewed. Cervical nodal irradiation was reduced (<50 Gy) in the case of a good response to chemotherapy (≥90% of initial tumor volume).

Results

Thirty‐two children had metastatic cervical nodes and one child had systemic metastases at diagnosis. All children had AJJC‐TNM Stage IV. Thirty‐one children received neoadjuvant chemotherapy with various regimens. The overall chemotherapy response rate was 78%. Fifteen patients had cervical nodal irradiation dose reduced: Median 47 Gy (range: 45–50). Nasopharyngeal radiotherapy was delivered at a dose of 59.4 Gy (range: 45–66). Local and distant failure rates were 10% and 18%, respectively. The 5‐year overall survival was 73 ± 8% and the event‐free survival (EFS) was 75 ± 8%.

Conclusions

The overall prognosis was not influenced by TNM status, dose of local radiotherapy delivered or response to initial chemotherapy, but EFS was better in patients with a good response to chemotherapy. The cervical local failure rate was low despite radiotherapy dose reduction in the case of a good response to neoadjuvant chemotherapy. We also propose a reduction of nasopharyngeal radiation (≤50 Gy) in the case of good response to initial chemotherapy. Pediatr Blood Cancer 2008;50:849–853. © 2007 Wiley‐Liss, Inc.
Neurochemical markers of brain damage in cerebrospinal fluid during induction treatment of acute lymphoblastic leukemia in children
Authors: Österlundh Gustaf , Kjellmer Ingemar , Lannering Birgitta , Rosengren Lars , Nilsson Ulf A. , Márky Ildikó
Published: October 2007

Background

Central nervous system (CNS) irradiation has been replaced by systemic high‐dose methotrexate (MTX) and intrathecal MTX in acute lymphoblastic leukemia treatment due to the risk of late effects. However, treatment without CNS irradiation might also cause brain damage.

Procedure

Cerebrospinal fluid (CSF) was analyzed in 121 patients in an attempt to detect CNS injury. Seventy‐three samples were analyzed for neuron‐specific enolase (NSE), 108 for glial fibrillary acidic protein (GFAp), 110 for neurofilament protein light chain (NFp), and 70 for ascorbyl radical (AsR). Samples were taken at day 0, 8, 15, and 29 during induction treatment, including intrathecal MTX. Levels at days 8, 15, and 29 were compared with the levels before treatment.

Results

NSE levels were 9.0 (±3.5) µg/L (mean (±SD)) at day 0, 15.0 (±5.3) at day 8 (P < 0.001), 13.6 (±4.7) at day 15 (P < 0.001) and 11.1 (±4.3) at day 29 (P < 0.001). GFAp were 177 (±98) ng/L at day 0, 206 (±101) at day 8 (P < 0.001), 200 (±106) at day 15 (n.s.) and 228 (±137) at day 29 (P < 0.001). NFp were below the detection limit 125 ng/L at day 0 in all 110 CSF samples analyzed, and increased significantly above the detection limit in 6/77 samples at day 8, in 11/84 at day 15 and in 22/91 at day 29. The AsR content did not change significantly.

Conclusions

Levels of NSE, GFAp, and NFp increased in CSF, which can be interpreted as early signs of brain damage. AsR levels do not show any convincing signs of oxidative stress. Pediatr Blood Cancer 2008;50:793–798. © 2007 Wiley‐Liss, Inc.
Brain‐sparing radiotherapy for neuroblastoma skull metastases
Authors: Wolden Suzanne L. , Barker Christopher A. , Kushner Brian H. , Bodduluri Haritha , Della‐Biancia Cesar , Kramer Kim , Modak Shakeel , Cheung Nai‐Kong V.
Published: October 2007

Background

Neuroblastoma (NB) frequently metastasizes to the skull, often diffusely involving the calvarium and skull base. Radiotherapy may enhance local control; however, irradiating the brain is undesirable in young patients. The purpose of this study was to describe the technique, outcome and toxicities in patients with high risk NB metastatic to the skull treated with brain‐sparing skull radiotherapy (BSRT).

Procedure

Between 1999 and 2007, 31 patients with INSS stage four high risk NB, aged 2–32 years (median 6 years), underwent multimodality therapy, including radiotherapy to the whole skull using a brain‐sparing technique never previously described in this population. Dosimetric analyses were performed to compare the BSRT technique to a whole brain radiotherapy (WBRT) technique. Patients were either treated to consolidate upfront induction therapy (n = 22) or to palliate relapsed disease (n = 9).

Results

Thirty of 31 patients (97%) completed the full course of BSRT. Median follow‐up was 19 months (range 1–83 months). Radiographic response to therapy was noted in 89% of patients. The actuarial rate of disease control in the skull was 89% and 60% 1 year after starting BSRT in patients treated in consolidation and for palliation, respectively. BSRT delivered half of the mean radiation dose to the brain when dosimetrically compared to whole brain radiotherapy. Few patients experienced significant toxicity.

Conclusions

BSRT in NB patients with diffuse skull metastases offers dosimetric advantages over WBRT and results in good local control when used in the consolidative setting. The technique is well tolerated and while toxicity appears acceptable, longer follow‐up is necessary. Pediatr Blood Cancer 2008;50:1163–1168. © 2007 Wiley‐Liss, Inc.
UICC‐2002 TNM classification is not suitable for differentiated thyroid cancer in children and adolescents
Authors: Oommen Prasad T. , Romahn Annika , Linden Tobias , Frühwald Michael C. , Bucsky Peter
Published: October 2007

Background

Recently the UICC‐TNM classification for differentiated thyroid cancer (DTC) was changed neglecting the special circumstances for children affected by the disease. While the 1997 TNM classification grouped tumours ≤1 cm as T1, the 2002 system changed this to a margin of ≤2 cm. The consequences of this change were evaluated by analysing patients enrolled in the multicentre interdisciplinary therapy study of the German Society of Paediatric Oncology and Haematology (GPOH) on malignant endocrine tumours in children and adolescents, GPOH‐MET 97.

Procedure

Between 1998 and 2005, 82 patients with histologically proven DTC entered the study. Patients classified according to UICC‐TNM classification 1997 were reclassified according to the new classification (2002/2003) and vice versa by cross checking with original pathologist's reports.

Results

Twenty males and 62 females at a mean age of 12.5 years were evaluated. We observed a definite shift from patients formerly classified as T2 (1–4 cm) to category T1 (≤2 cm) according to the 2002 TNM classification. Among these patients a threefold increase of lymph node involvement and/or distant metastases could be demonstrated.

Conclusions

The 2002 UICC‐classification may have a disadvantage for children with tumours measuring between 1 and 2 cm, as those are now classified as T1. A high rate of lymph node involvement in this group reflects the risk of under‐diagnosis and ‐treatment of this group. The current TNM classification for DTC in children should be changed taking the physiological and anatomical differences between children and adults into consideration. Pediatr Blood Cancer 2008;50:1159–1162. © 2007 Wiley‐Liss, Inc.
Early relapse after rituximab chemoimmunotherapy
Authors: Kiss Flora , Buslig Julia , Szegedi Istvan , Scholtz Beata , Kappelmayer Janos , Kiss Csongor
Published: October 2007

In relapsed/refractory childhood acute lymphoblastic leukemia (ALL) of the B‐cell lineage rituximab, a monoclonal anti‐CD20 antibody was used successfully in some cases. We report on a 15‐year‐old female with relapsed CD20‐positive B‐cell progenitor ALL treated with rituximab because of positive minimal residual disease signals after chemotherapy, as checked by flow cytometry and real time quantitative‐PCR. Rituximab eliminated the CD20‐positive subpopulation, but not the more immature leukemic cells. The patient died with fulminant aspergillosis before hematopoietic stem cell transplantation could be performed. Pediatr Blood Cancer 2008;50:372–375. © 2007 Wiley‐Liss, Inc.
Transient sialoadenitis: A complication of 131I‐metaiodobenzylguanidine therapy
Authors: Modak Shakeel , Pandit‐Taskar Neeta , Kushner Brian H. , Kramer Kim , Smith‐Jones Peter , Larson Steven , Cheung Nai‐Kong V.
Published: October 2007

Radioiodinated metaiodobenzylguanidine [131I‐MIBG] is commonly used to treat resistant neuroblastoma or metastatic pheochromocytoma [MP] with little non‐hematopoietic toxicity. We describe here transient sialoadenitis, a previously unreported complication. Ten patients [9 neuroblastoma and 1 MP] received 12–18 mCi/kg of 131I‐MIBG. Five patients had bilateral parotid swelling, two with associated buccal discomfort within 24 hr of injection which subsided within 48 hr. Grade 3 or 4 serum amylase elevation was documented in 8/8 patients tested [median 1,336; range: 576–8,830 U/L] which normalized [25–125 U/L] within 4–14 [median 5.5] days. Serum lipase remained normal. Patients did not develop subsequent dry mouth or dysphagia. Pediatr Blood Cancer 2008;50:1271–1273. © 2007 Wiley‐Liss, Inc.
Cultural adaptation, translation and validation of a functional outcome questionnaire (TESS) to Portuguese with application to patients with lower extremity osteosarcoma
Authors: Saraiva Daniela , de Camargo Beatriz , Davis Aileen M.
Published: October 2007

Background

Evaluation of physical functioning is an important tool for planning rehabilitation. Instruments need to be culturally adapted for use in non‐English speaking countries. The aim of this study was to culturally adapt, including translation and preliminary validation, the Toronto extremity salvage score (TESS) for Brazil, in a sample of adolescents and young adults treated for lower extremity osteosarcoma.

Procedure

The process included two independent forward translations of TESS questionnaire, consensus between translators on a forward translation, back‐translation by two independent translators, and a review of the back‐translations. Internal consistency of the TESS and known groups validity were also evaluated.

Results

Internal consistency for the 30 item TESS was high (coefficient alpha = 0.87). TESS score ranges from 0 to 100. Forty‐eight patients completed the questionnaire and scores ranged from 56 to 100 (mean score: 89.6). Patients receiving no pain medications scored higher on the TESS than those who were receiving pain medication (P = 0.014), and patients using walking aids had slightly higher but not statistically different scores. Those who were treated with amputation had higher scores than those who were treated with limb salvage procedures (P = 0.003).

Conclusion

Preliminary evidence suggests that Brazilian‐Portuguese translation is acceptable, understandable, reliable, and valid for evaluating the function in adolescents and young adults with osteosarcoma in lower extremity in Brazil. Pediatr Blood Cancer 2008;50:1039–1042. © 2007 Wiley‐Liss, Inc.
Paired intervention model for identified alcohol misuse in secondary care
Authors: Sims John , Kristian Marc R , Pritchard Karen , Jones Linda
Published: October 2007

High numbers of individuals with identified alcohol misuse are being admitted to the secondary care setting. Once individuals are stabilized, from a physical treatment point of view, there is a ‘window of opportunity’ that presents itself from a psychological perspective. Once individuals are stabilized, they often do not require any acute care input but they stay in hospital in order to complete a cross‐tolerance prescribing regimen. Listening to the voice of the service user and considering their experience of care, this article discusses the merits of a ‘paired intervention’ response during this period. This refers to the concept of initiating psychological interventions to run in ‘tandem’ with chemically based treatments. Giving equal importance to psychological interventions delivered in conjunction with physical treatments is a way of optimizing this window of opportunity. Initiating a group‐based psychological response utilizing a motivational model of intervention can be an extremely facilitative experience within the in‐patient environment. The importance of a collaborative delivery of the message regarding the benefits to a paired intervention is discussed. Recognition from medical colleagues of the benefits to a paired intervention is acknowledged. A coordinated response is important if individuals are to be facilitated towards maintenance of positive behavioural change following hospital discharge. Copyright © 2007 John Wiley & Sons, Ltd.
Two‐dimensional separation of human plasma proteins using iterative free‐flow electrophoresis
Authors: Nissum Mikkel , Kuhfuss Sabine , Hauptmann Monika , Obermaier Christian , Sukop Ute , Wildgruber Robert , Weber Gerhard , Eckerskorn Christoph , Malmström Johan
Published: October 2007

Blood plasma is the most complex human‐derived proteome, containing other tissue proteomes as subsets. This proteome has only been partially characterized due to the extremely wide dynamic range of the plasma proteins of more than ten orders of magnitude. Thus, the reduction in sample complexity prior to mass spectrometric analysis is particularly important and alternative separation methodologies are required to more effectively mine the lower abundant plasma proteins. Here, we demonstrated a novel separation approach using 2‐D free‐flow electrophoresis (FFE) separating proteins and peptides in solution according to their pI prior to LC‐MS/MS. We used the combination of sequential protein and peptide separation by first separating the plasma proteins into specific FFE fractions. Tryptic digests of the separated proteins were generated and subsequently separated using FFE. The protein separation medium was optimized to segregate albumin into specific fractions containing only few other proteins. An optimization of throughput for the protein separation reduced the separation time of 1 mL of plasma to approximately 3 h providing sufficient material for digestion and the subsequent peptide separation. Our approach revealed low‐abundant proteins (e.g., L‐selectin at 17 ng/mL and vascular endothelial‐cadherin precursor at 30 ng/mL) and several tissue leakage products, thus providing a powerful orthogonal separation step in the proteomics workflow.
Proteomics in free‐living Mus spretus to monitor terrestrial ecosystems
Authors: Montes‐Nieto Rafael , Fuentes‐Almagro Carlos A. , Bonilla‐Valverde Daniel , Prieto‐Álamo María‐José , Jurado Juan , Carrascal Montserrat , Gómez‐Ariza José Luis , López‐Barea Juan , Pueyo Carmen
Published: October 2007

We evaluated the suitability of high‐throughput proteomic methods to monitor terrestrial ecosystems. Free‐living Mus spretus from three sites along the “Domingo Rubio” (DR) stream were compared with mice from Doñana Biological Reserve (“Santa Olalla” lagoon (SOL) negative control), using specimens from an industrial settlement (phosphogypsum stacks (PS)) and rice fields (“Matochal” rice fields (ARZ)) as positive controls. Our 2‐DE analysis showed 36 spots with significantly altered expression. Sixteen were identified by MALDI‐TOF‐PMF and peptide matching with Mus musculus databases. Identified proteins play different roles: cytoskeletal dynamics, proteolysis, biotransformation, oxidative‐stress adaptation, and metabolism. Animals from different polluted environments showed contrasting differences in their proteomes, with specific increases and decreases in selected groups of proteins that seem to be co‐ordinately regulated. Proteomic data were consistent with metal biomonitoring and conventional biomarker responses, indicating that DR (and PS/ARZ) animals sustained a heavier pollutant burden than SOL specimens and suffered a chronic oxidative stress. Whereas some protein expression differences may protect mice from pollutant toxicity, others should make them more susceptible. Transcript expression signatures agree with the documented lack of correlation between mRNA and protein levels. Nonetheless, a positive significant correlation was found between the gpx1 mRNA molecules and the intensity of one of the two identified GPX1 isospots.
The cytoplasmic phosphoproteome of the Gram‐negative bacterium Campylobacter jejuni: Evidence for modification by unidentified protein kinases
Authors: Voisin Sébastien , Watson David C. , Tessier Luc , Ding Wen , Foote Simon , Bhatia Smita , Kelly John F. , Young N. Martin
Published: October 2007

We have undertaken a comprehensive analysis of cytoplasmic protein phosphorylation in Campylobacter jejuni by mass spectrometric identification of phosphoproteins and localization of the sites of modification by phosphopeptide analyses. Cell extracts, enriched for phosphoproteins using Fe(III) IMAC or commercial phosphoprotein purification kits, were analyzed by 1‐D and 2‐D SDS‐PAGE and subjected to mass fingerprinting by in‐gel tryptic digestion and MALDI‐TOF MS. Fifty‐eight phosphopeptides were identified from 1‐D gel bands by nano‐LC‐MS/MS and automated searching in a C. jejuni ORF database resulting in the unequivocal identification of 36 phosphoproteins of diverse function. In addition to elongation factors and chaperonins, which have been reported to be phosphorylated in other bacteria, the major phosphoproteins included bacterioferritin and superoxide dismutase. The sequences around the phosphorylated Ser and Thr residues are indicative of specific kinases being responsible for some of the modifications. However, many of the other identified proteins are enzymes that have phosphorylated substrates, including ATP, hence other modifications may arise from autophosphorylation. Comparative analyses of IMAC extracts from the Escherichia coli strain AD202 and Helicobacter pylori resulted in the identification of homologs of six of the C. jejuni phosphoproteins, though their overall phosphoproteome maps were distinctly different.
Evaluation of protein N‐glycosylation in 2‐DE: Erythropoietin as a study case
Authors: Llop Esther , Gallego Ricardo Gutiérrez , Belalcazar Viviana , Gerwig Gerrit J. , Kamerling Johannis P. , Segura Jordi , Pascual José A.
Published: October 2007

The structure, function, and physico‐chemical properties of many proteins are determined by PTM, being glycosylation the most complex. This study describes how a combination of typical proteomics methods (2‐DE) combines with glycomics strategies (HPLC, MALDI‐TOF‐MS, exoglycosidases sequencing) to yield comprehensive data about single spot‐microheterogeneity, providing meaningful information for the detection of disease markers, pharmaceutical industry, antidoping control, etc. Recombinant erythropoietin and its hyperglycosylated analogue darbepoetin‐α were chosen as showcases because of their relevance in these fields and the analytical challenge they represent. The combined approach yielded good results in terms of sample complexity (mixture glycoforms), reproducibility, sensitivity (∼25 pmoles of glycoprotein/spot), and identification of the underlying protein. Heterogeneity was present in all spots but with a clear tendency; spots proximal to the anode contained the highest amount of tetra‐antennary tetra‐sialylated glycans, whereas the opposite occurred for spots proximal to the cathode with the majority of the structures being undersialylated. Spot microheterogeneity proved a consequence of the multiple glycosylation sites as they contributed directly to the number of possibilities to account for a discrete charge in a single spot. The interest of this combined glycoproteomics method resides in the efficiency for detecting and quantifying subtle dissimilarities originated from altered ratios of identical glycans including N‐acetyl‐lactosamine repeats, acetylation, or antigenic epitopes, that do not significantly contribute to the electrophoretic mobility, but affect the glycan microheterogeneity and the potential underlying related functionality.
Induction of growth arrest and polycomb gene expression by reversine allows C2C12 cells to be reprogrammed to various differentiated cell types
Authors: Shan Sze Wan , Tang Mei Kuen , Chow Pak Ham , Maroto Miguel , Cai Dong Qing , Lee Kenneth K. H.
Published: October 2007

Reversine is a small, cell permeable synthetic chemical that has the ability to reprogram C2C12 myogenic cells to become various differentiated cell types. However, we still do not know how reversine works or the genes and proteins involved. Hence, we have used comparative proteomic techniques to address this issue. We have identified several proteins that were associated with cell cycle progression which were downregulated by reversine. Simultaneously, there were proteins associated with the induction of growth arrest that were upregulated. Consequently, we investigated the effects of reversine on C2C12 cell growth and established that it inhibited cell growth. Reversine had little affects on cell survival. We also investigated whether expressions of the polycomb genes, polycomb repressive complex 1 (PHC1) and Ezh2, were affected by reversine. Polycomb group genes are normally involved in chromatin based gene silencing. We found that PHC1 and Ezh2 expressions were enhanced by reversine and that it correlated with the inhibition of muscle specific transcriptional factor genes, myogenin, MyoD, and Myf5. Therefore, we believe that reversine is able to reprogram C2C12 cells to various differentiated cell types by inducing cell growth arrest, and promoting PHC1 and Ezh2 expressions.
Screening for distress in patients with brain cancer using the NCCN's rapid screening measure
Authors: Keir Stephen T. , Calhoun‐Eagan Roberta D. , Swartz Jonas J. , Saleh Oussama A. , Friedman Henry S.
Published: October 2007

Goals of work: Patients with brain cancer are at a risk of experiencing elevated levels of distress due to the severe functional, neurocognitive, and neuropsychological sequelae of the disease. Using the National Comprehensive Cancer Network's Distress Thermometer, we evaluated the extent and sources of distress within a population of patients with brain cancer.

Patients and methods: Participants were asked to complete the Distress Thermometer, a single‐item rapid screening tool for distress. The Distress Thermometer is a visual analog scale on which participants rate their level of distress from ‘0’ (none) to ‘10’ (extreme). Participants were also asked to designate which items from a 34‐item list constitute sources of distress.

Main results: Fifty‐two percent of participants met the ⩾4 cut‐off score for distress. The scores were positively correlated with patient‐reported emotional sources of distress (r=0.444, p<0.001), physical sources of stress (r=0.231, p<0.05), and total number of concerns (r=0.368, p<0.001). On average, brain tumor patients reported 5.8 cancer‐related items of concern.

Conclusion: Brain cancer patients are likely to experience distress at some point during their disease trajectory. Patient‐reported emotional sources of distress should be targeted and interventions should be designed to address sources of distress such as worry, sadness, and depression. Copyright © 2007 John Wiley & Sons, Ltd.
Effects of socioeconomic factors and cancer survivors' worries on their quality of life (QOL) in Japan
Authors: Kobayashi K. , Morita S. , Shimonagayoshi M. , Kobayashi M. , Fujiki Y. , Uchida Y. , Yamaguchi K.
Published: October 2007

Effects of socioeconomic factors and cancer survivors' worries on their quality of life (QOL) were investigated. In 2002, Japanese national survey was performed to assess distress among cancer patients using a semi‐structured questionnaire (http://www.scchr.jp/yorozu/pdf/taiken_koe_eng.pdf). We investigated relationships between patients' distress and their QOL measured by European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ‐C30) and Functional Assessment of Chronic Illness Therapy ‐ 12‐item Spiritual Well‐Being Scale (FACIT‐Sp), using a covariance structure analysis and multivariate regression analysis. A total of 130 outpatients (male: 42%; average age: 59 years; performance status rating 0–2:89%; breast/lung/gastrointestinal cancer: 38/22/21%) answered the questionnaires. A covariance structure analysis extracted latent variables, which were named socioeconomic distress and cancer worries, using a model that sufficiently represented the observed data (Goodness of fit index=0.833). Regression analysis demonstrated that higher family income significantly correlated with better Global health status/QOL (p=0.003) but that losing a job negatively correlated with all of the scales on functioning in the QLQ‐C30 (p<0.05) and spiritual well‐being (p<0.05). Patients' QOL was also affected by physical worries and spiritual issues in terms of emotional, cognitive, and social functioning. In conclusion, cancer survivors' QOL was doubly affected by socioeconomic distress and cancer worries. In the former, lower family income and losing employment by experiencing cancer had a negative impact on patients' QOL. As to the latter, physical worries and spiritual issues also affected patients' QOL. Copyright © 2007 John Wiley & Sons, Ltd.
Spontaneous radiative decay rates in Ga‐like ions
Authors: Charro E. , Curiel Z. , Martín I.
Published: October 2007

The analysis of forbidden lines, such as E2 and M1, in the atomic spectra emitted by certain ions is important for the study of the plasma in astrophysical objects and fusion devices. Atomic data, such as wavelengths and transition rates for 4p3/2 → 4p1/2 emission lines in the gallium sequence have been calculated with the Relativistic Quantum Defect Orbital (RQDO) method. The present results are tested by comparison with other theoretical values available in the literature. The regularity of the transition intensities along the isoelectronic sequence for both (E2 and M1) lines, as well as their relative magnitude, are also analyzed. M1 transitions were found to dominate by at least a factor of ten times, being in many cases bigger that this. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008
Biomarkers of alcohol abuse in racehorses by liquid chromatography/tandem mass spectrometry
Authors: You Youwen , Uboh Cornelius E. , Soma Lawrence R. , Guan Fuyu , Li Xiaoqing , Rudy Jeffrey A. , Chen Jinwen
Published: October 2007

A rapid and sensitive method was developed for the screening, quantification and confirmation of ethyl glucuronide (EG) and ethyl sulfate (ES) as biomarkers for alcohol administration to racehorses using liquid chromatography coupled on‐line with triple quadrupole tandem mass spectrometry. Urine sample aliquots (0.1 mL) were pre‐treated by protein precipitation. Separation of EG and ES was achieved on an Ultra PFP column. Isocratic elution with a flush step was performed using 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). Analysis was performed by negative electrospray ionization in multiple reaction monitoring mode. The retention times for EG and ES were 1.7 ± 0.30 and 3.4 ± 0.30 min, respectively. The internal standard used was d5‐ethyl glucuronide with a retention time of 1.7 ± 0.30 min. The entire separation was completed in <5 min. The limit of detection (LOD) and of quantification (LOQ) for both analytes were 100 ng/mL (S/N ≥3) and 500 ng/mL, respectively. The limit of confirmations (LOC) for EG and ES were 500 ng/mL and 1.0 µg/mL, respectively. The assay was linear over a concentration range of 0.5–100 µg/mL (r2 > 0.995). Intra‐ and inter‐day accuracy and precision were less than 15%. The analytes were stable in urine for 24 h at room temperature, 10 days at 4°C and 21 days at −20°C and −70°C. Ion suppression or enhancement due to matrix effect was negligible. The measurement uncertainty was <14% for EG and <25% for ES. This method was successfully used for the quantification of EG and ES in urine samples following alcohol administration to research horses and for screening and confirmation of EG and ES in urine samples obtained from racehorses post‐competition. The method is simple, rapid, inexpensive, and reliably reproducible. Copyright © 2007 John Wiley & Sons, Ltd.
Probing the non‐covalent binding interaction of the Na+channel inactivation gate peptide in a linker between domain III and IV with 5,5‐diphenyhydantoin in electrospray ion trap tandem mass spectrometry
Authors: Lou Bih‐Show , Chen Yuan‐Chin , Wu Hui‐Fen
Published: October 2007

The Na+channel‐subunit containing an Ile1488, Phe1489 and Met1490 (IFM) motif is critical for a fast inactivation process. BL‐1, a model IFM‐containing peptide with a sequence of acetyl‐GGQDIFMTEEK‐OH, was observed as a doubly charged potassium‐adduct ion by electrospray ionization mass spectrometry (ESI‐MS) and a singly charged ion by atmospheric‐pressure matrix‐assisted laser desorption/ionization mass spectrometry (AP‐MALDI‐MS). Two crown ethers were applied to demonstrate their desalting ability and then to confirm the potassium‐adduct assignments. In order to probe the best binding condition for BL‐1 with a local anesthetic drug, 5,5‐diphenyhydantoin (DPH), a series of experiments were performed and the parameters affecting complexation were carefully investigated including molar ratios, reaction time and reaction temperature. The most effective conditions for the observation of the complex by ESI‐MS were molar ratio of BL‐1 and DPH of 1:28 after 18 h of incubation at 40°C. In addition, collision‐activated dissociation (CAD) was successfully applied to confirm the formation of the complex between BL‐1 with DPH that is via a weak non‐covalent bonding with a 1:1 stoichiometry. Copyright © 2007 John Wiley & Sons, Ltd.
Distributed control over structured and packet‐dropping networks
Authors: Jiang Shengxiang , Voulgaris Petros G. , Neogi Natasha
Published: October 2007

In this paper we consider distributed control ofndynamic agents to optimize an overall system performance metric. Due to limited communication resources, there exist structured interconnections among the agents and the interest is placed on synthesizing a suitably distributed control law to provide a given performance level. Based on a Youla–Kucera (Y–K) parameterization approach, the problem of designing a distributed controller to deliver given performance levels for different network topologies is shown to be convex in the Y–K parameterQ. Furthermore, if in addition to structured interconnections, packet drops exist in information transmission among the agents, we provide convex conditions to guarantee mean square (MS) stability and to optimize ℋ︁2system performance. The proposed method is also extended to deal with systems of triangular structure. Copyright © 2007 John Wiley & Sons, Ltd.
Bridging the gaps between theory and practice: a service niche approach to urban sustainability indicators
Authors: Keirstead James , Leach Matt
Published: October 2007

Urban sustainability indicators play an important role in helping policy‐makers ensure the continued success of their cities. However, a review of current practice suggests that priority is often given to the measurability and policy relevance of these metrics. Their analytical validity – i.e. their ability to act as meaningful representations of the urban system and thus inform appropriate policy responses – is less certain. An examination of London's USIs confirms this gap between theory and practice and identifies vague definitions of urban sustainability as part of the problem. A ‘service niche’ approach to indicator selection is therefore outlined, using pervasive goal‐oriented urban services such as energy or water systems to guide the selection of policy‐relevant interconnected metrics. Strategies for expanding such niches to wider assessments of urban sustainability are also discussed. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment.
CoPlot: A tool for visualizing multivariate data in medicine
Authors: Bravata Dena M. , Shojania Kaveh G. , Olkin Ingram , Raveh Adi
Published: October 2007

Many critical questions in medicine require the analysis of complex multivariate data, often from large data sets describing numerous variables for numerous subjects. In this paper, we describe CoPlot, a tool for visualizing multivariate data in medicine. CoPlot is an adaptation of multidimensional scaling (MDS) that addresses several key limitations of MDS, namely that MDS maps do not allow for visualization of both observations and variables simultaneously and that the axes on an MDS map have no inherent meaning. By addressing these issues, CoPlot facilitates rich interpretation of multivariate data. We present an example using CoPlot on a recently published data set from a systematic review describing clinical features and disease progression of children with anthrax and provide recommendations for the use of CoPlot for evaluating and interpreting other healthcare data sets. Copyright © 2007 John Wiley & Sons, Ltd.
Do bridging ties complement strong ties? An empirical examination of alliance ambidexterity
Authors: Tiwana Amrit
Published: October 2007

This study examines the underexplored tensions and complementarities between bridging ties and strong ties in innovation‐seeking alliances. Bridging ties span structural holes to provide innovation potential but lack integration capacity, and strong ties provide integration capacity but lack innovation potential. We theoretically develop the idea that—notwithstanding their tensions—strong ties complement bridging ties in enhancing alliance ambidexterity at the project level. While bridging ties provide access to diverse, structural hole‐spanning perspectives and capabilities, strong ties help integrate them to realize an innovation. We also propose that their effects and complementarities influence alliance ambidexterity because they facilitate knowledge integration at the project level. Tests using data on 42 innovation‐seeking project alliances involving a major American services conglomerate and its alliance partners support the majority of the proposed ideas. Implications for interfirm network configuration, strategic alliances, and the broader strategy literature are also discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Enzymatic Interesterification of Palm Stearin and Coconut Oil by a Dual Lipase System
Authors: Ibrahim Nuzul A. , Guo Zheng , Xu Xuebing
Published: October 2007

Enzymatic interesterification of palm stearin with coconut oil was conducted by applying a dual lipase system in comparison with individual lipase‐catalyzed reactions. The results indicated that a synergistic effect occurred for many lipase combinations, but largely depending on the lipase species mixed and their ratios. The combination of Lipozyme TL IM and RM IM was found to generate a positive synergistic action at all test mixing ratios. Only equivalent amount mixtures of Lipozyme TL IM with Novozym 435 or Lipozyme RM IM with Novozym 435 produced a significant synergistic effect as well as the enhanced degree of interesterification. The interesterification catalyzed by Lipozyme TL IM mixed with thermally inactivated immobilized lipase preparations indicated that the carrier property may play an important role in affecting the interaction of two mixed lipases and the subsequent reactions. A dual enzyme system, consisting of immobilized lipases and a non‐immobilized one (Lipase AK), in most cases apparently endows the free lipase with a considerably enhanced activity. 70% Lipase AK mixed with 30% immobilized lipase (Lipozyme TL IM, RM IM and Novozym 435) can achieve an increase in activity greater than 100% over the theoretical value when the reaction proceeds for 2 h. The co‐immobilization action of the carrier of the immobilized lipases towards the free lipase was proposed as being one of the reasons leading to the synergistic effect and this has been experimentally verified by a reaction catalyzed by a Lipase AK‐inactivated preparation. No apparently synergistic effect of the combinations of Lipozyme TL IM and RM IM was observed when the dual enzyme systems applied to the continuous reaction performed in a packed bed reactor. In brief, this work demonstrated the possibility of increasing the reaction rate or enhancing the degree of conversion by employing a dual lipase system as a biocatalyst.
Diffusion et réception de la dynamique la correspondance entre leibniz et wolff
Authors: Rey Anne-Lise
Published: October 2007

À travers l'analyse de la correspondance entre Leibniz et Wolff, l'article cherche à restituer les modalités démonstratives utilisées par Leibniz pour transmettre sa dynamique ainsi que le dispositif métaphysique qui lui est inhérent. Il est question ici de l'ambivalence du vocable d'action, à la fois objet du principe de conservation et essence de la substance. C'est en étudiant sa réception par Wolff qu'il est possible de mettre en évidence, dès 1705, la singularité d'un cadre métaphysique wolffien qui accueille la dynamique leibnizienne de l'action, puis la publicise, tout en proposant une acception irréductiblement différente de la substance.
Comment les monades conduisent au scepticisme
Authors: Rohrbasser Jean-Marc
Published: October 2007

La métaphysique de Leibniz revue par Wolff est débattue dans la correspondance qu'entretiennent Voltaire et Frédéric, futur Frédéric II. Ce dernier tente d'initier et de convertir Voltaire au wolffisme. Même s'il la prétend remarquable, Voltaire estime peu la méthode wolffienne. Refusant le fidéisme à la Bayle, Frédéric ne se résout pas à renoncer volontairement aux connaissances que l'on peut acquérir par le raisonnement. Selon Voltaire, les vérités métaphysiques demeurent inaccessibles. La seule position défendable s'avère donc être le scepticisme métaphysique. Frédéric l'admet: après avoir étudié les sciences et observé l'esprit des hommes, l'inclination au scepticisme est naturelle. Ainsi, le débat sur les monades a conduit Frédéric à dénier son wolffisme antérieur: il est prêt à devenir le parfait despote pragmatique et réaliste, disciple des Lumières françaises.
Leibniz, wolff et la métaphysique traitée selon la méthode scientifique
Authors: Paccioni Jean-Paul
Published: October 2007

La philosophie de Wolff est souvent définie par les commentateurs comme un « leibnizianisme dogmatisé ». Si on tente de lire positivement cette expression, on découvre ce qui distingue la métaphysique wolffienne de celle de Leibniz, et son apport dans l'histoire de la pensée. C'est d'abord la notion de «dogme» dans la philosophie wolffienne qui est analysée. Elle renvoie au modèle démonstratif fournit par les mathématiques et particulièrement les Éléments d'Euclide. C'est sur le modèle des axiomes que l'ontologie est pensée comme philosophie première. Cet aspect est indissociable du rôle de la connaissance a posteriori dans la pensée de Wolff. Cela permet de comprendre la fonction de l'ontologie, ce qu'est la cosmologie wolffienne et l'invention de la notion de« téléologie».
La modernité de la raison d'état et le masque du temps
Authors: Caiteeuw Laurie
Published: October 2007

Au cours des XVIe et XVIIe siècles, les théoriciens de la raison d'État définissent la nouvelle notion par comparaison des temps anciens et modernes: ils affirment, dans une quasi-unanimité, que les Anciens connaissaient la raison d'État - la privant volontiers de sa modernité. Pourtant, il n'en demeure pas moins qu'historiquement la raison d'État accompagne l'avènement de l'État moderne et participe à l'élaboration de sa rationalité politique. Dans cet article, on entend rappeler ces multiples figures antiques de la raison d'État, mises au jour et exploitées par ses propres théoriciens, afin de saisir leurs enjeux pour l'histoire de la notion, leurs rapports à la modernité politique et leurs effets sur l'art de gouverner propre à l'État moderne. À partir de la description de sa polymorphie constitutive, par laquelle elle semble s'adapter à toutes les époques, il s'agit de saisir en quoi consiste la modernité de la raison d'État.