bluuebunny/crossref_metadata_2025 huggingface dataset:
SN2′ Reactions between Lithiated Carbon Nucleophiles and Silylated Vinyloxiranes – Effects of Salts and Solvents on the Stereocontrol
Authors: Marié Jean‐Charles , Courillon Christine , Malacria Max
Published: November 2005

(α,β‐Epoxy‐γ,δ‐alkenyl)‐tert‐butyldimethylsilanes 1 display, a priori, three electrophilic centres and two acidic protons. Depending on the configurations of their oxirane rings, the title compounds react towards lithiated bases either through metallation or SN2′ reactions. In this paper we demonstrate that the trans‐2‐(tert‐butyldimethylsilyl)‐3‐vinyloxiran 1a reacts regioselectively with primary, secondary and tertiary butyllithium in SN2′ fashion, which allows the formation of α‐silylated allylic alcohols with diastereomeric ratios of over 7 to 1 in favour of the Z olefins. A study of the effect of temperature, time, addition of salt and polarity of the solvent on the diastereoselectivity of the reaction is described and the results are interpreted in terms of different mechanistic models. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Cover Picture: Synthesis and Structures of Fullerene Bromides and Chlorides (Eur. J. Org. Chem. 23/2005)
Authors: Troyanov Sergey I. , Kemnitz Erhard
Published: November 2005

The cover picture shows a variety of fullerene bromides and chlorides synthesized and structurally investigated in the last few years. A rich “harvest” of fullerene chlorides of C60 and C70 has been “collected” by using inorganic chlorides and oxychlorides for the chlorination of fullerenes. Even a fullerene chloride with a drum‐shaped carbon cage, D3‐C60Cl30, could be obtained. The maximum degree of chlorination of both C60 (left) and C70 (right) is much higher than that of bromination. More about the synthesis and molecular structures of fullerene bromides and chlorides can be found in the Microreview by S. I. Troyanov and E. Kemnitz on p. 4951 ff.
Membrane‐based bimetallic nanoparticles for environmental remediation: Synthesis and reactive properties
Authors: Xu Jian , Bhattacharyya Dibakar
Published: November 2005

Nanoscale bimetallic particles have important applications in the environmentally important catalytic reactions at room temperature because of the novel physical and chemical properties. We report an innovative in situ synthesis method of functionalizing microfiltration membranes with highly reactive bimetallic core/shell Fe/Ni and Fe/Pd nanoparticles. The core/shell structure was confirmed by X‐ray energy dispersive spectroscopy mapping images. Using TCE and PCB as model compounds, the reactivity of membrane‐immobilized bimetallic nanoparticles was quantified in terms of both reaction mechanism shift and product distribution. Complete dechlorination was achieved with both compounds. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Potential and drawbacks of microbiology–membrane interaction in membrane bioreactors
Authors: Drews Anja , Evenblij Herman , Rosenberger Sandra
Published: November 2005

In membrane bioreactors (MBRs), biomass and membranes interact in a number of ways, making it difficult to extrapolate phenomena and models known from conventional activated sludge processes. Originally, MBRs were thought to enable immense process intensifications through very high MLSS (mixed liquor suspended solid) concentrations and resulting low footprint. Economic considerations, however, currently lead to lower concentrations because high biomass content impedes oxygen transfer and increases sludge viscosity. On the other hand, the interactions can lead to a number of new potentials, which as yet were unknown in each unit operation individually such as increased removal efficiencies through a change in the microbial community or sludge age. Here, both potentials and limits of biomass–membrane interactions are reviewed with a focus on recent results from Europe, especially from Germany. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Seismic behaviour of cracked concrete gravity dams
Authors: Pekau O. A. , Zhu Xueye
Published: November 2005

A finite element model of incremental displacement constraint equations (IDCE), based on an existing node‐to‐surface concept, is implemented to deal with dynamic contact surfaces in the seismic behaviour analysis of cracked concrete gravity dams. After verification for sliding, rocking and impact, the IDCE model is applied to study the seismic responses of concrete gravity dams with different profiles and crack locations for a variety of parameters, such as coefficient of friction, water level and type of earthquake, as well as impact damping based on the concept of coefficient of restitution. It is revealed that cracked concrete gravity dams can experience not only sliding and rocking modes, but also the drifting mode in some cases of crack either at the base or at a height. Downstream sliding is normally accompanied by rocking, especially for the cases of crack at a height. Due to rocking and drifting, a cracked dam may still acquire a certain amount of residual sliding even if the effective coefficient of friction is relatively high. Copyright © 2005 John Wiley & Sons, Ltd.
Simplified methods for design of base‐isolated structures in the long‐period high‐damping range
Authors: Weitzmann Ruediger , Ohsaki Makoto , Nakashima Masayoshi
Published: November 2005

A recent trend in the design of base‐isolated structures is the extension of the natural period and the incorporation of high damping. This paper shows that the existing simplified methods perform less accurately in this field of application, mainly due to inappropriate use of spectral data and insufficiently adjusted equivalent models. The paper proposes new period‐dependent concepts to reduce pseudo‐acceleration spectra and to transform these values into total accelerations with respect to the viscous damping ratio. The model of equivalent damping is adjusted to reflect several period‐dependent effects. The estimation of the accelerations in MDOF systems is based on additional period shifts. All modifications are derived for a simplified linear approach based on eigenforms, and a non‐linear approach based on pushover and capacity spectrum analysis. To illustrate observed problems and to demonstrate the capabilities of the proposed concepts, example structures are studied in detail. Furthermore, intensive statistical tests prove the effectiveness of the modifications in a wide parameter range and show considerable improvements over traditional approaches. Copyright © 2005 John Wiley & Sons, Ltd.
Aeolian deposition of dust over hills: the effect of dust grain size on the deposition pattern
Authors: Goossens Dirk
Published: November 2005

Wind tunnel experiments were conducted to investigate the effects of topography on the grain size characteristics of aeolian dust deposits. Experiments were performed on three isolated hills having various size and aspect ratios. The longitudinal profile of the median grain diameter was investigated for each hill. The longitudinal dust deposition profile was also studied for nine grain size classes of between 10 and 104 µm, as were wind and dust concentration profiles in the atmosphere upwind of, over and downwind of a hill. The wind tunnel experiments show that the grain size characteristics of aeolian dust deposits are affected by topography. Most apparent is the occurrence of a zone of reduced grain size on the leeside of hills, which extends from just upwind of the summit to a distance of several times the height of the hill. Slightly coarser than normal dust is deposited on the concave windward hill slope and in a zone downwind of the area of reduced grain size, but the increase in grain size in these zones remains very small. Although the normalized dust deposition profile for a hill does not vary substantially as a function of grain size, systematic trends are observed. The most important tendencies are: (1) a progressive extension, in the downwind direction, of a zone of decreased dust deposition on the leeside of a hill (the coarser the grains, the further downwind the zone of reduced deposition extends); (2) a progressive increase in dust deposition immediately upwind of a hill (the finer the grains, the higher the deposition value upwind of a hill becomes). Both tendencies are explained by the difference in inertia of the grains, which is controlled by grain size. Copyright © 2005 John Wiley & Sons, Ltd.
Structural patterns in river network organization at both infra‐ and supra‐basin levels: the case of a granitic relief
Authors: Cudennec Christophe , Fouad Youssef
Published: November 2005

Within a landform, the channelized water path from any point to the corresponding outlet is split into successive components within the Strahler ordering scheme. The probability density functions (pdf) of the length L of the whole channelized path and of the lengths of the components are studied as multi‐level structural functions. We have considered a granitic area and studied both its main basin and the set of its 48 constituent basins. With respect to the main basin, the pdf of the component lengths exhibit a strong scaling property, except for the highest orders, due to a hierarchical constraint; hence, the pdf of sum L has no particular shape. We have nevertheless identified an underlying structural pattern at particular infra‐ and supra‐basin levels, where the hierarchical constraint is weaker. This identification process entails noting structurally emerging patterns based on multi‐level variables and distributions, which satisfy the general self‐similarity of networks. The fairly good fit of an analytical gamma law with most of these emerging patterns can prove to be a positive step towards both a general modelling approach to the geomorphometric functions and a stronger geomorphological basement of hydrological transfer functions. Copyright © 2005 John Wiley & Sons, Ltd.
Characteristics and dynamics of multiple intertidal bars, north Lincolnshire, England
Authors: van Houwelingen Selma , Masselink Gerhard , Bullard Joanna
Published: November 2005

Multiple intertidal bars and troughs, often referred to as ‘ridges and runnels’, are significant features on many macrotidal sandy beaches. Along the coastline of England and Wales, they are particularly prevalent in the vicinity of estuaries, where the nearshore gradient is gentle and a large surplus of sediment is generally present. This paper examines the dynamics of such bar systems along the north Lincolnshire coast.

A digital elevation model of the intertidal morphology obtained using LIDAR demonstrates that three to five intertidal bars are consistently present with a spacing of approximately 100 m. The largest and most pronounced bars (height = 0·5–0·8 m) are found around mean sea level, whereas the least developed bars (height = 0·2–0·5 m) occur in the lower intertidal zone. Annual aerial photographs of the intertidal bar morphology were inspected to try to track individual bars from year to year to derive bar migration rates; however, there is little resemblance between concurrent photographs, and ‘resetting’ of the intertidal profile occurs on an annual basis. Three‐dimensional beach surveys were conducted monthly at three locations along the north Lincolnshire coast over a one‐year period. The intertidal bar morphology responds strongly to the seasonal variation in the forcing conditions, and bars are least numerous and flattest during the more energetic winter months. Morphological changes over the monthly time scale are strongly affected by longshore sediment transport processes and the intertidal bar morphology can migrate along the beach at rates of up to 30 m per month.

The behaviour of intertidal bars is complex and varies over a range of spatial and temporal scales in response to a combination of forcing factors (e.g. incident wave energy, different types of wave processes, longshore and cross‐shore sediment transport), relaxation time and morphodynamic feedback. Copyright © 2005 John Wiley & Sons, Ltd.
Quantitative V&V of CFD simulations and certification of CFD codes
Authors: Stern Fred , Wilson Robert , Shao Jun
Published: November 2005

Definitions and equations are provided for the quantitative assessment of numerical (verification) and modelling (validation) errors and uncertainties for CFD simulations and of intervals of certification for CFD codes. Verification, validation, and certification methodology and procedures are described. Examples of application of quantitative certification of RANS codes are presented for ship hydrodynamics. Opportunities and challenges for achieving consensus and standard V&V and certification methodology and procedures are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Numerical simulation of incompressible viscous flow past a heaving airfoil
Authors: Sarkar Sunetra , Venkatraman Kartik
Published: November 2005

Numerical simulations of a heaving airfoil undergoing non‐sinusoidal motions in an incompressible viscous flow is presented. In particular, asymmetric sinusoidal motions, constant heave rate oscillations, and sinusoidal motions with a quiescent gap, are considered. The wake patterns, thrust force coefficients, and propulsive efficiency at various values of non‐dimensional heave velocity are computed. These have been compared with those of corresponding sinusoidal heaving motions of the airfoil. It is shown that for a given non‐dimensional heave velocity and reduced frequency of oscillation, asymmetric sinusoidal motions give better thrust and propulsive efficiencies in comparison to pure harmonic motion. On the other hand, constant rate heave motion do not compare favourably with harmonic motion. A train of sinusoidal pulses separated by a quiescent gap compares favourably with a pure sinusoidal motion, but with the notable exception that the quiescent gap induces a discontinuity that induces large impulses to the wake pattern. Copyright © 2005 John Wiley & Sons, Ltd.
Comparisons of CIP, compact and CIP‐CSL2 schemes for reproducing internal solitary waves
Authors: Nakayama K.
Published: November 2005

Six different models were evaluated for reproducing internal solitary waves which occur and propagate in a stratified flow field with a sharp interface. Three stages were used to compute internal solitary waves in a stratified field: (1) first‐phase computation of momentum equations, (2) second‐phase computation of momentum equations, which corresponds to computing the Poisson's equation, and (3) density computation. The six models discussed in this paper consisted of combinations of four different schemes, a three‐point combined compact difference scheme (CCD), a normal central difference scheme (CDS), a cubic‐polynomial interpolation (CIP), and an exactly conservative semi‐Lagrangian scheme (CIP‐CSL2). The residual cutting method was used to solve the Poisson's equation. Three tests were used to confirm the validity of the computations using KdV theory; i.e. the incremental wave speed and amplitude of internal solitary waves, the maximum horizontal velocity and amplitude, and the wave form. In terms of the shape of an internal solitary wave, using CIP for momentum equations was found to provide better performance than CCD. These results suggest one of the most appropriate scheme for reproducing internal solitary waves may be one in which CIP is used for momentum equations and CCD to solve the Poisson's equation. Copyright © 2005 John Wiley & Sons, Ltd.
Droplets on patterned substrates: water off a beetle's back
Authors: Dupuis A. , Yeomans J. M.
Published: November 2005

We present a lattice Boltzmann model to describe the spreading of droplets on chemically and topologically patterned substrates. As an example, we consider the process by which a Namibian beetle captures water on its back which is hydrophobic but covered by peaks with hydrophilic tops. Copyright © 2005 John Wiley & Sons, Ltd.
Pyrometamorphism of 19th‐century kiln artifacts from Caledonia Springs, Ontario, Canada
Authors: Owen J. Victor , Culhane Phil
Published: November 2005

Marked, 19th‐century kiln bricks and rocks from Caledonia Springs (CS) have black glass coatings that can easily be mistaken for glass produced at the elusive CS glassworks (c. 1844–1846). The glass‐on‐brick material, however, is more aluminous (nearly 20% Al2O3) than virtually any analyzed historical glass, and the glass‐on‐rock is compositionally similar to the rock itself, which shows clear signs of having undergone extensive melting. Mineral thermometry (Cpx‐Ol, Pl‐melt) indicates that parts of the kiln‐achieved temperatures of approximately 1200–1300°C. The CS samples show that caution must be exercised when identifying seemingly obvious waste glass near defunct glassworks sites. © 2005 Wiley Periodicals, Inc.
Geoarchaeological studies in Nara, Japan: The integrated findings
Authors: Barnes Gina L. , Nishida Shiro , Okita Masaaki
Published: November 2005

In this article, the authors summarize 20 years of scholarship and two field projects on geoarchaeology in Nara, Japan, carried out by researchers from 12 different institutions in 4 countries. The research goal was to test an aerial photographic reconstruction of surface landforms in the Nara Basin with subsurface data. Project A was conducted at Asawa; it tested, through geological coring, whether a suspected swampy backmarsh in the eastern basin existed and whether it would yield data on the transition to wet rice agriculture in the mid‐1st millennium B.C. Project B was conducted at Miwa; it tested, through geological coring and subsequent excavation, the nature of upland agricultural terrace formation in the southeastern basin and whether the suspected existence of a 4th‐century palace site could be confirmed.

Two layers of carbonaceous clay at Asawa were dated to the Early (˜5000–3500 B.C.) and Final (˜1000‐300 B.C.) phases of the Jomon period. Pollen data revealed the establishment of an evergreen oak forest from 5,000 years ago and anthropogenic changes in forest cover from 2,000 years ago. Phytoliths from rice, millets, reeds, and bamboo were recovered in layers postdating the Final Jomon carbonaceous clay. A fault scarp with anthropogenic modification of the terraces was identified at Miwa. It was discovered that an incised stream valley had been infilled in the Medieval period at the same time surface layers were razed; the front of the terrace was extended in the premodern period. Remains were recovered from the Middle Yayoi (˜100 B.C.–A.D. 100) and the Medieval (˜A.D. 1185–1603) periods. However, as the terracing involved razing the early historic levels, no data were recovered on the alleged 4th‐century palace site.

The significance of these findings lies in the identification of (a) a swampy backmarsh at Asawa, where initial agricultural efforts in growing wet rice in the basin may have occurred, confirming the aerial photographic reconstruction; and (b) hillside terracing activities at Miwa, from the Medieval period onwards, which have radically changed the configuration of the natural topography. © 2005 Wiley Periodicals, Inc.
Generation of a conditional allele of the B‐myb gene
Authors: García Paloma , Berlanga Oscar , Watson Roger , Frampton Jon
Published: November 2005

B‐Myb is an essential transcription factor involved in control of the cell cycle and the regulation of tissue‐specific gene expression in a wide range of cell types. Loss of both alleles results in early embryonic lethality at E4.5–6.5. To address the function of B‐Myb in later stages of embryogenesis and in specific adult tissues, a floxed B‐myb allele (B‐mybF) was generated. Cre‐mediated deletion in vivo was demonstrated by breeding with a transgenic GATA‐Cre mouse line. An intermediate allele produced in the creation of the floxed allele, in which the PGK‐neoR cassette is present in intron 3 (B‐mybloxneo), was deduced to be a weak hypomorph based on the later embryonic death of homozygotes compared to B‐myb−/− embryos. To demonstrate the efficiency and possible consequences of B‐myb inactivation, we performed conditional deletion in cultured MEFs and observed decreased growth that correlated with aberrant nuclear DNA replication. genesis 43:189–195, 2005. © 2005 Wiley‐Liss, Inc.
Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells
Authors: Sasaki Masanori , Hains Bryan C. , Lankford Karen L. , Waxman Stephen G. , Kocsis Jeffery D.
Published: November 2005

Transplantation of olfactory ensheathing cells (OECs) into the damaged rat spinal cord leads to directed elongative axonal regeneration and improved functional outcome. OECs are known to produce a number of neurotrophic molecules. To explore the possibility that OECs are neuroprotective for injured corticospinal tract (CST) neurons, we transplanted OECs into the dorsal transected spinal cord (T9) and examined primary motor cortex (M1) to assess apoptosis and neuronal loss at 1 and 4 weeks post‐transplantation. The number of apoptotic cortical neurons was reduced at 1 week, and the extent of neuronal loss was reduced at 4 weeks. Biochemical analysis indicated an increase in BDNF levels in the spinal cord injury zone after OEC transplantation at 1 week. The transplanted OECs associated longitudinally with axons at 4 weeks. Thus, OEC transplantation into the injured spinal cord has distant neuroprotective effects on descending cortical projection neurons. © 2005 Wiley‐Liss, Inc.
Human attachment security is mediated by the amygdala: Evidence from combined fMRI and psychophysiological measures
Authors: Lemche Erwin , Giampietro Vincent P. , Surguladze Simon A. , Amaro Edson J. , Andrew Christopher M. , Williams Steven C.R. , Brammer Michael J. , Lawrence Natalia , Maier Markus A. , Russell Tamara A. , Simmons Andrew , Ecker Christine , Joraschky Peter , Phillips Mary L.
Published: November 2005

The neural basis of human attachment security remains unexamined. Using event‐related functional magnetic resonance imaging (fMRI) and simultaneous recordings of skin conductance levels, we measured neural and autonomic responses in healthy adult individuals during a semantic conceptual priming task measuring human attachment security “by proxy”. Performance during a stress but not a neutral prime condition was associated with response in bilateral amygdalae. Furthermore, levels of activity within bilateral amygdalae were highly positively correlated with attachment insecurity and autonomic response during the stress prime condition. We thereby demonstrate a key role of the amygdala in mediating autonomic activity associated with human attachment insecurity. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Neural bases of categorization of simple speech and nonspeech sounds
Authors: Husain Fatima T. , Fromm Stephen J. , Pursley Randall H. , Hosey Lara A. , Braun Allen R. , Horwitz Barry
Published: November 2005

Categorization is fundamental to our perception and understanding of the environment. However, little is known about the neural bases underlying the categorization of sounds. Using human functional magnetic resonance imaging (fMRI) we compared the brain responses to a category discrimination task with an auditory discrimination task using identical sets of sounds. Our stimuli differed along two dimensions: a speech–nonspeech dimension and a fast–slow temporal dynamics dimension. All stimuli activated regions in the primary and nonprimary auditory cortices in the temporal cortex and in the parietal and frontal cortices for the two tasks. When comparing the activation patterns for the category discrimination task to those for the auditory discrimination task, the results show that a core group of regions beyond the auditory cortices, including inferior and middle frontal gyri, dorsomedial frontal gyrus, and intraparietal sulcus, were preferentially activated for familiar speech categories and for novel nonspeech categories. These regions have been shown to play a role in working memory tasks by a number of studies. Additionally, the categorization of nonspeech sounds activated left middle frontal gyrus and right parietal cortex to a greater extent than did the categorization of speech sounds. Processing the temporal aspects of the stimuli had a greater impact on the left lateralization of the categorization network than did other factors, particularly in the inferior frontal gyrus, suggesting that there is no inherent left hemisphere advantage in the categorical processing of speech stimuli, or for the categorization task itself. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Protective mechanisms of head and neck squamous cell carcinomas from immune assault
Authors: Young M. Rita I.
Published: November 2005

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that is the sixth most common neoplasm in the world. Despite advances in treatments involving surgery, radiation, and chemotherapy, the 5‐year survival has remained at less than 50% for the past 30 years, primarily because of local recurrences. Thus, the possibility of immunotherapeutic approaches for patients with HNSCC has gained interest. Unfortunately, patients with HNSCC have profound immune defects that are associated with increased recurrence. This review aims to provide an overview of both the defensive and immune subversive mechanisms by which patients with HNSCC can protect themselves from immune antitumor assault. © 2005 Wiley Periodicals, Inc. Head Neck 27: 462–470, 2006
Risk of malignancy in Filipinos with thyroid nodules—A matched pair analysis
Authors: Clark Jonathan R. , Eski Spiro J. , Freeman Jeremy L.
Published: November 2005

Background.

Ethnicity is an infrequently cited risk factor for thyroid cancer. This study aims to determine whether patients of Filipino origin assessed at a tertiary referral center are at increased risk of thyroid cancer and to quantify that risk.

Methods.

This is a retrospective analysis of 72 Filipino patients with thyroid nodules undergoing thyroidectomy individually matched to 72 controls according to demographics, risk factors, and pre‐referral investigations.

Results.

Thyroid cancer was found in 50 (69.4%) Filipino patients compared with 28 (38.9%) controls. Odds ratio for malignancy in Filipinos was 3.57 (95% confidence interval, 1.79–7.12). Pathologic characteristics of thyroid cancer were not significantly different in the two groups. The median follow‐up for Filipino patients was 14.1 months (range, 1.4 months–19.7 years). Recurrence occurred in four Filipino patients, and one patient with anaplastic thyroid cancer died of the disease.

Conclusions.

Filipino patients with thyroid nodules are at significantly increased risk of thyroid cancer compared with matched controls, and hence the index of suspicion for malignancy should be high when evaluating these patients. © 2005 Wiley Periodicals, Inc. Head Neck 27: 427–431, 2006
Does cognitive function influence alaryngeal speech rehabilitation?
Authors: Ho T. P. , Gray J. , Ratcliffe A. A. , Rees S. , Rockey J. , Wight R. G.
Published: November 2005

Background.

We sought to define the cognitive domains that influence valved speech rehabilitation.

Methods.

Sixteen laryngectomees with primary tracheoesophageal punctures were randomly recruited from one head and neck unit. They were assessed by a consultant neuropsychologist and a speech therapist. Speech therapy time was determined from speech therapy notes.

Results.

The Digit Symbol Substitution Test, assessing learning speed and processing speed, correlated significantly with speech therapy time in the first (p = .002) and third (p = .014) postoperative years, respectively. Categorical fluency assessment correlated positively with speech therapy time in the first year (p = .009). Learning speed (p = .007) and categorical fluency (p = .041) correlated positively with the fall in speech therapy input between the first and third year after laryngectomy.

Conclusions.

Learning speed, processing speed, and categorical fluency strongly influence alaryngeal speech rehabilitation. This study highlights the potential for pre‐laryngectomy cognitive assessment to help plan alaryngeal speech rehabilitation. This has significant resource implications. © 2005 Wiley Periodicals, Inc. Head Neck 27: 413–419, 2006
Acute myeloid leukemia with concurrent myeloid sarcoma treated with autologous bone marrow transplantation: two illustrative cases and a literature review
Authors: Finnegan DPJ , Jones FGC , McMullin MF
Published: November 2005

Myeloid sarcoma (MS) is an invasive extramedullary solid tumor composed of immature cells of the myeloid series. It complicates the clinical course of a minority of patients with acute myeloid leukemia (AML). Traditionally its presence has been regarded as an indicator of aggressive disease. Currently, the optimal treatment of AML with concurrent MS remains to be determined. We report two cases of autologous bone marrow transplantation (auto‐BMT) for AML with concurrent MS followed by a review of the literature. Copyright © 2005 John Wiley & Sons, Ltd.
Biallelic deletion within 16p13.13 including SOCS‐1 in Karpas1106P mediastinal B‐cell lymphoma line is associated with delayed degradation of JAK2 protein
Authors: Melzner Ingo , Weniger Marc A. , Bucur Alexandra J. , Brüderlein Silke , Dorsch Karola , Hasel Cornelia , Leithäuser Frank , Ritz Olga , Dyer Martin J.S. , Barth Thomas F.E. , Möller Peter
Published: November 2005

Activity of Janus kinase 2 (JAK2) in the JAK2/STAT5 signaling pathway is critically controlled by suppressor of cytokine signaling‐1 (SOCS‐1). We have previously shown that SOCS‐1 is biallelically mutated in the primary mediastinal B‐cell lymphoma (PMBL) cell line MedB‐1, resulting in impaired JAK2 degradation and sustained phospho‐JAK2 action. SOCS‐1 is frequently mutated in PMBL tumor primaries. Here, we report that the PMBL cell line Karpas1106P has a biallelic deletion of the SOCS‐1 region on chromosome 16p13.13. By fluorescence in situ hybridization and microsatellite analysis, this deletion was narrowed down to a range of 650 kb to 1.48 Mb. Like MedB‐1, Karpas1106P harbors gains of the JAK2 gene on chromosomal region 9p24 and elevated levels of JAK2 mRNA. Nevertheless, JAK2 protein was not increased but constitutively phosphorylated in Karpas1106P cells. In analogy to MedB‐1 cells, Karpas1106P cells exhibited a retarded degradation of de novo synthesized JAK2 protein revealed by pulse/chase experiments. Therefore, we conclude that loss of SOCS‐1 function either by mutation or by the complete deletion of the gene plays an important role in the dysregulation of JAK/STAT signaling in Karpas1106P and PMBL. © 2005 Wiley‐Liss, Inc.
Circulating EM66 is a highly sensitive marker for the diagnosis and follow‐up of pheochromocytoma
Authors: Guillemot Johann , Anouar Youssef , Montero‐Hadjadje Maïté , Grouzmann Eric , Grumolato Luca , Roshmaninho‐Salgado Joana , Turquier Valérie , Duparc Céline , Lefebvre Hervé , Plouin Pierre‐François , Klein Marc , Muresan Mihaela , Chow Billy K.C. , Vaudry Hubert , Yon Laurent
Published: November 2005

We have previously demonstrated that measurement of tissue concentration of the novel secretogranin II‐derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas. The aim of the present study was to characterize EM66 in plasma and urine of healthy volunteers and pheochromocytoma patients, in order to further evaluate the usefulness of this peptide as a circulating marker for the management of the tumors. HPLC analysis of plasma and urine samples demonstrated that the EM66‐immunoreactive material coeluted with the recombinant peptide. In healthy volunteers, plasma and urinary EM66 levels were, respectively, 2.6 (1.9–3.7) ng/ml and 2.9 (1.9–4.6) ng/ml. In patients with pheochromocytoma, plasma EM66 levels were 10‐fold higher than those of healthy volunteers (26.9 (7.3–44) ng/ml), and returned to normal values after removal of the tumor. In contrast, urinary EM66 levels were not significantly different from those of healthy volunteers (3.2 (2.2–3.9) ng/ml). Measurement of total or free plasma metanephrines and 24 hr urinary metanephrines in our series of patients revealed that these tests, taken separately, are less sensitive than the EM66 determination. Pheochromocytes in primary culture secreted high levels of EM66, suggesting that the chromaffin tumor was actually responsible for the increased plasma peptide concentrations in the patients. These data indicate that EM66 is secreted in the general circulation and that elevated plasma EM66 levels are correlated with the occurrence of pheochromocytoma. Thus, EM66 is a sensitive plasma marker that should be considered as a complementary tool in the management of pheochromocytoma. © 2005 Wiley‐Liss, Inc.
Dominant‐negative Rac increases both inherent and ionizing radiation‐induced cell migration in C6 rat glioma cells
Authors: Hwang So‐Young , Jung Jae‐Won , Jeong Jae‐Seob , Kim Yun‐Jung , Oh Eok‐Soo , Kim Tae‐Hyun , Kim Joo‐Young , Cho Kwan‐Ho , Han Inn‐Oc
Published: November 2005

Rho‐like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin cytoskeleton changes required for cell adhesion, migration and invasion. In the present study, we examined the role of Rac signaling in inherent migration, as well as radiation‐induced migration, of rat glioma cells. Stable overexpression of dominant‐negative Rac1N17 in a C6 rat glioma cell line (C6‐RacN17) promoted cell migration, and ionizing radiation further increased this migration. Migration was accompanied by decreased expression of the focal adhesion molecules FAK and paxillin. Focal contacts and actin stress fibers were also reduced in C6‐RacN17 cells. Downstream effectors of Rac include JNK and p38 MAP kinases. Irradiation transiently activated p38, JNK and ERK1/2 MAP kinases in C6‐RacN17 cells, while p38 and JNK were constitutively activated in C6 control cells. Blocking JNK activity with JNK inhibitor SP600125 inhibited migration, suggesting that the JNK pathway may regulate radiation‐induced, as well as inherent, migration of C6‐RacN17 cells. Additionally, the radiation‐induced migration increase was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However, PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This is the first evidence that suppression of Rac signaling may be involved in invasion or metastasis of glioma cells before and/or after radiotherapy. These data further suggest that radiotherapy for malignant glioma needs to be used with caution because of the potential for therapy‐induced cell migration or invasion and that pharmacological inhibition of cell migration and invasion through targeting the Rac signaling pathway may represent a new approach for improving the therapeutic efficacy of radiotherapy for malignant glioma. © 2005 Wiley‐Liss, Inc.
Mantle cell lymphomas acquire increased expression of CCL4, CCL5 and 4‐1BB‐L implicated in cell survival
Authors: Ek Sara , Björck Erik , Högerkorp Carl‐Magnus , Nordenskjöld Magnus , Porwit‐MacDonald Anna , Borrebaeck Carl A.K.
Published: November 2005

We have analyzed mantle cell lymphomas (MCLs), using high‐density DNA microarrays, and confirmed the expression of differentially regulated antigens, using flow cytometry and immunohistochemistry. The results show that MCLs acquire expression of molecules that normally are involved in interaction with other immune cells and, thus, might affect the ability of the tumor to survive. The MCL signature is represented by the overexpression of the chemokine CCL4 (MIP‐1β), implicated in the recruitment of regulatory T cells, as well as CCL5 and 4‐1BB‐L. The latter molecules are normally involved in chemotaxis of T cells and B cell activation, respectively. Signaling through 4‐1BB‐L allows B cells to proliferate and the expression of its ligand, by the intra‐tumoral mesh of follicular dendritic cells (FDC), could thus serve as a paracrine loop facilitating growth and survival of MCL cells. © 2005 Wiley‐Liss, Inc.
Molecular profiling of platinum resistant ovarian cancer
Authors: Helleman Jozien , Jansen Maurice P.H.M. , Span Paul N. , van Staveren Iris L. , Massuger Leon F.A.G. , Meijer‐van Gelder Marion E. , Sweep Fred C.G.J. , Ewing Patricia C. , van der Burg Maria E.L. , Stoter Gerrit , Nooter Kees , Berns Els M.J.J.
Published: November 2005

The aim of this study is to discover a gene set that can predict resistance to platinum‐based chemotherapy in ovarian cancer. The study was performed on 96 primary ovarian adenocarcinoma specimens from 2 hospitals all treated with platinum‐based chemotherapy. In our search for genes, 24 specimens of the discovery set (5 nonresponders and 19 responders) were profiled in duplicate with 18K cDNA microarrays. Confirmation was done using quantitative RT‐PCR on 72 independent specimens (9 nonresponders and 63 responders). Sixty‐nine genes were differentially expressed between the nonresponders (n = 5) and the responders (n = 19) in the discovery phase. An algorithm was constructed to identify predictive genes in this discovery set. This resulted in 9 genes (FN1, TOP2A, LBR, ASS, COL3A1, STK6, SGPP1, ITGAE, PCNA), which were confirmed with qRT‐PCR. This gene set predicted platinum resistance in an independent validation set of 72 tumours with a sensitivity of 89% (95% CI: 0.68–1.09) and a specificity of 59% (95% CI: 0.47–0.71)(OR = 0.09, p = 0.026). Multivariable analysis including patient and tumour characteristics demonstrated that this set of 9 genes is independent for the prediction of resistance (p < 0.01). The findings of this study are the discovery of a gene signature that classifies the tumours, according to their response, and a 9‐gene set that determines resistance in an independent validation set that outperforms patient and tumour characteristics. A larger independent multicentre study should further confirm whether this 9‐gene set can identify the patients who will not respond to platinum‐based chemotherapy and could benefit from other therapies. © 2005 Wiley‐Liss, Inc.
Diabetes mellitus and cancer risk in a population‐based case–controlstudy among men from Montreal, Canada
Authors: Rousseau Marie‐Claude , Parent Marie‐Élise , Pollak Michael N. , Siemiatycki Jack
Published: November 2005

Diabetics may have a higher risk of cancer, notably liver and pancreatic cancers. Evidence about other cancer types remains sparse. The authors examined potential associations between diabetes and several types of cancer in a large multicancer case–control project carried out in Montreal, Canada, in the 1980s. This report, based on 3,107 male cancer cases and 509 population controls, uses information on diabetes and several covariates collected by interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the associations between diabetes and each of 12 cancer types. Risks of pancreatic and liver cancers were increased among diabetics: adjusted ORs were 2.1 (95% CI: 1.0, 4.3) for pancreatic and 3.1 (95% CI: 1.1, 8.8) for liver cancer. The increased risk of pancreatic cancer was completely restricted to those with recent onset of diabetes; this was likely a manifestation of reverse causality. Conversely, the increased risk of liver cancer was independent of the interval between diabetes and cancer diagnoses. No associations were observed with melanoma, non‐Hodgkin's lymphoma, cancers of the esophagus, stomach, colon, rectum, lung, prostate, bladder and kidney. In conclusion, diabetes was associated with an increased risk of liver cancer among men, but with no other cancer type including pancreatic cancer. © 2005 Wiley‐Liss, Inc.
Long‐term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia
Authors: Soutter William Patrick , Sasieni Peter , Panoskaltsis Theo
Published: November 2005

Invasive cancer of the cervix after treatment for cervical intraepithelial neoplasia (CIN) is becoming more important, as screening reduces the incidence of invasive disease. The rate of invasive cervical or vaginal cancer following treatment for CIN in UK remains elevated for at least 8 years. The aim of our study was to determine from international data how long this rate remains elevated and whether the rate of invasive disease reflects the rate of posttreatment CIN. The aim was to determine why the rate of invasive disease does not fall. A search of Medline and a secondary search of cited references identified 1,848 articles referring to the success rate of the treatment of CIN. Only 26 cohorts from 25 articles met all the inclusion criteria. The policy in these was to perform at least annual smears. After the first year following treatment for CIN, the rate of invasive disease remained about 56 per 100,000 woman years until at least 20 years after treatment. This rate is ˜2.8 times greater than expected. In contrast, the risk of posttreatment CIN declined steadily with time to about 190 per 100,000 women in the 10th year. Although the posttreatment rate of CIN falls with time, the rate of invasive disease remains static. It seems likely that this is due to diminishing compliance with follow‐up. Women should be encouraged to persevere with annual smears for at least 10 years after their treatment as this may offer them the best chance of detecting recurrence at a treatable stage. © 2005 Wiley‐Liss, Inc.
Detection of a new mutation in KIT exon 9 in a gastrointestinal stromal tumor
Authors: Hostein Isabelle , Longy Michel , Gastaldello Bernadette , Geneste Gaëlle , Coindre Jean‐Michel
Published: November 2005

Gastrointestinal stromal tumors are mesenchymal tumors arising in the stomach and small bowel and more rarely in the rectum, esophagus, peritoneum and retroperitoneum. These tumors are characterized by KIT or PDGFRA mutations. KIT mutations are all in frame and lead to constitutive tyrosine kinase domain activation without ligand binding. Mutations concern four exons (9, 11, 13 and 17) but mainly exon 11. We report a new mutation in exon 9, since only AY 502–503 duplication/insertion, FAF 506 insertion and P456S substitution have been previously reported. This mutation consists of a large deletion of 43 nucleotides and an insertion of 25 nucleotides. More surprisingly, the sequence inserted corresponds to the complementary sequence of the wild allele but in the opposite sense. To our knowledge, this mutation has never been previously described. © 2005 Wiley‐Liss, Inc.
A report on the current status of European research on the use of human papillomavirus testing for primary cervical cancer screening
Authors: Davies Philip , Arbyn Marc , Dillner Joakim , Kitchener Henry C. , Meijer Chris J.L.M. , Ronco Guglielmo , Hakama Matti
Published: November 2005

Cervical cancer remains a significant public health concern, both at a global and a European level. A number of new technologies such as diagnostic tests for human papillomavirus (HPV) have a potential to assist with the reduction of this disease. However, both the efficacy and the cost‐effectiveness of these new technologies must be established in properly designed trials before they can be implemented within national public health programs. Our study reviews the randomized controlled trials that are currently being conducted in Europe to establish the performance of HPV testing as a primary cervical cancer screening test. © 2005 Wiley‐Liss, Inc.
Sub‐micron texturing for reducing platelet adhesion to polyurethane biomaterials
Authors: Milner Keith R. , Snyder Alan J. , Siedlecki Christopher A.
Published: November 2005

Platelet adhesion is a key event in thrombus development on blood‐contacting medical devices. It has been demonstrated that changes to the chemistry of a material surface can reduce platelet adhesion. In this work, it is hypothesized that sub‐micron surface textures may also reduce adhesion via a decrease in the surface area of material with which platelets can make contact, and hence a decreased probability of interaction with adhesive ligands. A polyether(urethane urea) was textured with two different sizes of sub‐micron pillars using a replication molding technique that did not alter the material surface chemistry. Adhesion of platelets was assessed in a physiologically relevant shear stress range of 0–67 dyn/cm2 using a rotating disk system. Platelets were immunofluorescently labeled and adhesion was compared on smooth and textured samples. Platelet adhesion was greatest at low shear stress ranging from 0 to 5 dyn/cm2, and sub‐micron textures were observed to reduce platelet adhesion in this range. Additionally, non‐adherent platelets did not demonstrate large‐scale activation after exposure to textured samples. We conclude that surface textures with sub‐platelet dimensions may reduce platelet adhesion from plasma to polyether(urethane urea) at low shear stress. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Tissue engineered cartilage using human articular chondrocytes immortalized by HPV‐16 E6 and E7 genes
Authors: Chen Wei‐Hung , Lai Wen‐Fu , Deng Win‐Ping , Yang Wen K. , Lo Wen‐Cheng , Wu Cheng‐Chia , Yang Den‐Mei , Lai Ming‐Tang , Lin Che‐Tong , Lin Tsou‐Wen , Yang Charng‐Bin
Published: November 2005

Chondrocytes are useful as a cell culture system for studying arthritic degeneration in tissue engineered cartilage. However, primary chondrocytes have short in vitro lifespan and rapid shift of collagen phenotype. In this study, we used a high dosage of retroviral vector LXSN16E6E7 to transduce human primary chondrocytes and obtained an actively proliferating cell line, designated hPi, which expresses HPV‐16 E6/E7 mRNA in early passages. Parental primary chondrocytes cease to grow after five passages, whereas hPi could be propagated beyond 100 passages without requiring additional cell elements in defined medium. After 48 passages, hPi can also give many profiles similar to those of parental primary chondrocyte, including type II collagen in mRNA and protein level, aggrecan in mRNA level, lacunae in type I collagen matrices, and morphology with GAG‐specific Alcian blue staining. hPi has shown neoplastic transformation, as examined by NOD‐SCID mice tumorgenicity assays for 3 months. Our results indicated that human primary chondrocytes could be immortalized by transduction with HPV‐16 E6/E7, preserving stable cartilage‐specific differentiation markers. The established chondrocyte cell line could provide a novel model to engineer cartilage in vitro and in vivo for cartilage repair research and clinical application. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Study on blood compatibility with poly(2‐methoxyethylacrylate)—relationship between surface structure, water structure, and platelet compatibility in 2‐methoxyethylacrylate/2‐hydroxyethylmethacrylate diblock copolymer
Authors: Hirota Etsuko , Ute Koichi , Uehara Mitsunari , Kitayama Tatsuki , Tanaka Masaru , Mochizuki Akira
Published: November 2005

Diblock copolymers composed of 2‐methoxyethylacrylate (MEA) and 2‐hydroxyethylmethacrylate (HEMA) were firstly prepared (the composition ratio = 90/10, 79/21, 66/34, and 48/52 mol/mol) by anion living polymerization. ESCA analysis of their surface structures (dry state) revealed that PMEA segment was segregated to the top surface in all of the polymers, whereas the results of contact angle of water (wet state) showed that the surfaces were covered with PHEMA segment. In vitro platelet adhesion test showed that these polymers had the excellent compatibility with platelet compared to PHEMA homopolymer. Water structure in the hydrated copolymers was investigated by DSC and freezing bound water was observed for all the polymers like PMEA homopolymer, whereas it was not found in PHEMA homopolymer. Further investigation of water structure based on the results of DSC and EWCMS (equilibrium water content by moisture sorption) suggested that freezing bound water existed in PHEMA segment in addition to PMEA segment. We have proposed that the water plays a key role in the appearance of good blood compatibility of the copolymer, according to our previous works (Tanaka et al. Biomacromolecules 2002;3:36–41, Tanaka et al. J Biomed Mater Res A 2004;68:684–695). © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006