bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple procedure to approximate slip displacement of freestanding rigid body subjected to earthquake motions
Authors: Taniguchi Tomoyo , Miwa Takuya
Published: October 2006

A simple calculation procedure for estimating absolute maximum slip displacement of a freestanding rigid body placed on the ground or floor of linear/nonlinear multi‐storey building during an earthquake is developed. The proposed procedure uses the displacement induced by the horizontal sinusoidal acceleration to approximate the absolute maximum slip displacement, i.e. the basic slip displacement. The amplitude of this horizontal sinusoidal acceleration is identical to either the peak horizontal ground acceleration or peak horizontal floor response acceleration. Its period meets the predominant period of the horizontal acceleration employed. The effects of vertical acceleration are considered to reduce the friction force monotonously. The root mean square value of the vertical acceleration at the peak horizontal acceleration is used. A mathematical solution of the basic slip displacement is presented. Employing over one hundred accelerograms, the absolute maximum slip displacements are computed and compared with the corresponding basic slip displacements. Their discrepancies are modelled by the logarithmic normal distribution regardless of the analytical conditions. The modification factor to the basic slip displacement is quantified based on the probability of the non‐exceedence of a certain threshold. Therefore, the product of the modification factor and the basic slip displacement gives the design slip displacement of the body as the maximum expected value. Since the place of the body and linear/nonlinear state of building make the modification factor slightly vary, ensuring it to suit the problem is essential to secure prediction accuracy. Copyright © 2006 John Wiley & Sons, Ltd.
Shape reconstruction from medical images and quality mesh generation via implicit surfaces
Authors: Peiró J. , Formaggia L. , Gazzola M. , Radaelli A. , Rigamonti V.
Published: October 2006

The ability of automatically reconstructing physiological shapes, of generating computational meshes, and of calculating flow solutions from medical images is enabling the introduction of computational fluid dynamics (CFD) techniques as an additional tool to aid clinical practice.

This article presents a set of procedures for the shape reconstruction and triangulation of geometries derived from a set of medical images representing planar cross sections of the object. The reconstruction of the shape of the boundary is based on the interpolation of an implicit function through a set of points obtained from the segmentation of the images. This approach is favoured for its ability of smoothly interpolating between sections of different topology. The boundary of the object is an iso‐surface of the implicit function that is approximated by a triangulation extracted by the method of marching cubes. The quality of this triangulation is often neither suitable for mesh generation nor for flow solution. We discuss the use of mesh enhancement techniques to maximize the quality of the triangulation together with curvature adaption to optimize mesh resolution.

The proposed methodology is applied to the reconstruction and discretization of two physiological geometries: a femoral by‐pass graft and a nasal cavity. Copyright © 2006 John Wiley & Sons, Ltd.
Health systems in East Asia: what can developing countries learn from Japan and the Asian Tigers?
Authors: Wagstaff Adam
Published: October 2006

The health systems of Japan and the Asian Tigers (Hong Kong, Korea, Singapore and Taiwan), and the recent reforms to them, provide many potentially valuable lessons to East Asia's developing countries. All five systems have managed to keep a check on health spending despite their different approaches to financing and delivery. These differences are reflected in the progressivity of health finance, but the precise degree of progressivity of individual sources and the extent to which households are vulnerable to catastrophic health payments depend on the design features of the system – the height of any ceilings on social insurance contributions, the fraction of health spending covered by the benefit package, the extent to which the poor face reduced copayments, whether there are caps on copayments, and so on. On the delivery side, too, Japan and the Tigers offer some interesting lessons. Singapore's experience with corporatizing public hospitals – rapid cost and price inflation, a race for the best technology, and so on – illustrates the difficulties of corporatization. Korea's experience with a narrow benefit package illustrates the danger of providers shifting demand from insured services with regulated prices to uninsured services with unregulated prices. Japan, in its approach to rate setting for insured services, has managed to combine careful cost control with fine‐tuning of profit margins on different types of care. Experiences with DRGs in Korea and Taiwan point to cost‐savings but also to possible knock‐on effects on service volume and total health spending. Korea and Taiwan both offer important lessons for the separation of prescribing and dispensing, including the risks of compensation costs outweighing the cost savings caused by more ‘rational’ prescribing, and cost‐savings never being realized because of other concessions to providers, such as allowing them to have onsite pharmacists. Copyright © 2006 John Wiley & Sons, Ltd.
Reactions of Alkyl Radicals with Substituted Toluenes and the Effect of Substituents on Dissociation Energies of Benzyl CH Bonds
Authors: Arafat Abdelfattah M. , Mathew Samuel K. , Akintobi Solademi O. , Zavitsas Andreas A.
Published: October 2006

Reactions of isopropyl and of undecyl radicals with meta‐ and para‐substituted toluenes are reported. The results demonstrate that the reactivities of toluenes are due to both benzyl‐H abstraction and addition of the alkyl radicals to the aromatic ring. Relative reactivities yield curved Hammett plots, consistent with kinetic data reported by Dütsch and Fischer. Abstractions and ring additions occur with comparable rates, but opposite Hammett slopes. Addition is favored by electron‐withdrawing and abstraction by electron‐donating substituents. The effects of substituents on the dissociation energies of benzyl CH bonds are shown to be the major factor influencing reaction rates for benzyl‐H abstraction by alkyl radicals.
2,5‐Dihydro‐1H‐imidazole‐Based Nitroxides as Prospective Mediators in Living Radical Polymerization
Authors: Zubenko Dmitry , Kirilyuk Igor , Roshchupkina Galina , Zhurko Irina , Reznikov Vladimir , Marque Sylvain R. A. , Bagryanskaya Elena
Published: October 2006

A number of spectroscopic methods were applied to obtain kinetic parameters of reactions modelling the 2,5‐dihydro‐1H‐imidazole 1‐oxide mediated living polymerization of acrylates. The homolysis rate constants of alkoxyamines based on five nitroxides were measured by EPR spectroscopy at different temperatures. The recombination rate constants kc between the corresponding alkyl radicals and the nitroxides were measured by means of laser flash photolysis. The time‐resolved chemically induced dynamic nuclear polarization (TR‐CIDNP) experiments revealed the negligible contribution of disproportionation in the recombination reaction. In addition, the thermodecomposition of alkoxyamines in the NMR probe showed the absence of intramolecular elimination of hydroxylamines from the corresponding alkoxyamines. Analysis of the kinetic parameters showed that the 2,5‐dihydro‐1H‐imidazole 1‐oxide type radicals are promising mediators for the living polymerization of acrylates and methacrylates.
Modification of Guanine with Photolabile N‐Hydroxypyridine‐2(1H)‐thione: Monomer Synthesis, Oligonucleotide Elaboration, and Photochemical Studies
Authors: Vrantza Despoina , Kaloudis Panagiotis , Leondiadis Leondios , Gimisis Thanasis , Vougioukalakis Georgios C. , Orfanopoulos Michael , Gasparutto Didier , Cadet Jean , Encinas Susana , Paris Cecilia , Miranda Miguel A.
Published: October 2006

The photochemistry of N‐hydroxypyridine‐2(1H)‐thione (NHPT), inserted as a photolabile modifier at the 6‐position of 2′‐deoxyguanosine or guanosine, has been evaluated. In particular, 6‐[(1‐oxidopyridin‐2‐yl)sulfanyl]‐ (1a) and 6‐[(pyridin‐2‐yl)sulfanyl]‐2′,6‐dideoxyguanosine (2a), novel photolabile derivatives of the natural nucleosides, were synthesized and characterized. The observed photolysis products of 1a in organic solvents could only be rationalized by assuming a rapid equilibrium with the corresponding 6‐[(2‐thioxopyridin‐1(2H)‐yl)oxy] analogue 3a (Scheme 5). Transient spectroscopy of 1a indicated a strong triplet‐excited state suitable for triplet → triplet energy transfer or singlet‐oxygen generation. The NHPT function was stable enough for (slightly modified) automated solid‐phase oligonucleotide synthesis. The utility of the above compounds is discussed, as well as their potential use in photosensitization of reactive oxygen species in DNA.
The Reaction of Peroxynitrite with Morpholine (Secondary Amines) Revisited: The Overlooked Hydroxylamine Formation
Authors: Kirsch Michael , Korth Hans‐Gert , Wensing Angela , Lehnig Manfred , Sustmann Reiner , de Groot Herbert
Published: October 2006

The reaction of peroxynitrite/peroxynitrous acid with morpholine as a model compound for secondary amines is reinvestigated in the absence and presence of carbon dioxide. The concentration‐ and pH‐dependent formation of N‐nitrosomorpholine and N‐nitromorpholine as reported in three previous papers ([25] [26] [14]) is basically confirmed. However, 13C‐NMR spectroscopic product analysis shows that, in the absence of CO2, N‐hydroxymorpholine is, at pH ≥ 7, the major product of this reaction, even under anaerobic conditions. The formation of N‐hydroxymorpholine has been overlooked in the three cited papers. Additional (ring‐opened) oxidation products of morpholine are also detected. The data account for radical pathways for the formation of these products via intermediate morpholine‐derived aminyl and α‐aminoalkyl radicals. This is further supported by EPR‐spectrometric detection of morpholine‐derived nitroxide radicals, i.e., morpholin‐4‐yloxy radicals. N‐Nitrosomorpholine, however, is very likely formed by electrophilic attack of peroxynitrite‐derived N2O4. 15N‐CIDNP Experiments establish that, in the presence of CO2, N‐nitro‐ and C‐nitromorpholine are generated by radical recombination. The present results are in full accord with a fractional (28 ± 2%) homolytic decay of peroxynitrite/peroxynitrous acid with release of free hydroxyl and nitrogen dioxide radicals.
Proton‐Coupled Electron Transfer of Unsaturated Fatty Acids and Mechanistic Insight into Lipoxygenase
Authors: Fukuzumi Shunichi
Published: October 2006

A proton‐coupled electron transfer (PCET) process plays an important role in the initial step of lipoxygenases to produce lipid radicals which can be oxygenated by reaction with O2 to yield the hydroperoxides stereoselectively. The EPR spectroscopic detection of free lipid radicals and the oxygenated radicals (peroxyl radicals) together with the analysis of the EPR spectra has revealed the origin of the stereo‐ and regiochemistry of the reaction between O2 and linoleyl (= (2Z)‐10‐carboxy‐1‐[(1Z)‐hept‐1‐enyl]dec‐2‐enyl) radical in lipoxygenases. The direct determination of the absolute rates of H‐atom‐transfer reactions from a series of unsaturated fatty acids to the cumylperoxyl (= (1‐methyl‐1‐phenylethyl)dioxy) radical by use of time‐resolved EPR at low temperatures together with detailed kinetic investigations on both photoinduced and thermal electron‐transfer oxidation of unsaturated fatty acids provides the solid energetic basis for the postulated PCET process in lipoxygenases. A strong interaction between linoleic acid (= (9Z,12Z)‐octadeca‐9,12‐dienoic acid) and the reactive center of the lipoxygenases (FeIIIOH) is suggested to be involved to make a PCET process to occur efficiently, when an inner‐sphere electron transfer from linoleic acid to the FeIII state is strongly coupled with the proton transfer to the OH group.
Interaction between Molecular Oxygen and Nitroxide Radicals: A Search for a Reversible Complex
Authors: Moscatelli Alberto , Ottaviani M. Francesca , Adam Waldemar , Buchachenko Anatoly , Jockusch Steffen , Turro Nicholas J.
Published: October 2006

At high concentrations of oxygen, the EPR spectrum of the nitroxide radical 4‐oxo‐TEMPO (= 4‐oxo‐2,2,6,6‐tetramethylpiperidin‐1‐yloxy) is found to broaden significantly. In addition to the expected broadening, double integration of the EPR signals indicates that a significant fraction of the nitroxide spins has ‘disappeared’. In perfluoro(2‐butyltetrahydrofuran) at 273 K, the extent of diminution of the EPR signal intensity is ca. 20%. The results are analyzed in terms of collision and supramolecular complexes between oxygen and 4‐oxo‐TEMPO. It is concluded that a supramolecular complex is responsible for the observed phenomenon.
The Persistent Radical Effect: From Mechanistic Curiosity to Synthetic Tool
Authors: Focsaneanu Kathy‐Sarah , Scaiano Juan C.
Published: October 2006

The Fischer–Ingold persistent radical effect (PRE) provides a simple conceptual framework to rationalize reactivities in systems involving two radicals with very different self‐reaction rate constants; in a limiting, but rather common case, one of these radicals is persistent at room temperature. In these cases, the cross‐coupling product is strongly favored. This contribution summarizes some of the work carried out at the University of Ottawa, where the PRE plays a key role in determining product distributions. Much of this work was inspired by the seminal contributions of Hanns Fischer.
Photo‐CIDNP Studies of Hydroxy Ketones and Higher‐Molecular‐Weight Systems
Authors: Bargon Joachim , Kuhn Lars T.
Published: October 2006

In situ NMR spectroscopy can be applied to investigate chemical reactions during which free radicals occur as intermediates. In chemical systems of low molecular weight, nuclear‐spin polarization results from the spin selectivity of free‐radical reactions, because a pair of radicals has to obey the exclusion principle according to Pauli; therefore, this system reacts in a spin‐selective manner when forming a chemical single bond. As a consequence, strong transient absorption and emission lines occur in the NMR spectra acquired during free‐radical reactions. This phenomenon is known as ‘chemically induced dynamic nuclear polarization’ (CIDNP). However, long correlation times associated with short proton spin–lattice relaxation times T1 render it difficult to observe CIDNP in macromolecules. Therefore, in these and in many other cases, it can be attractive to utilize the simultaneously occurring heteronuclear polarization or to selectively transfer the 1H polarization to heteronuclei, since their T1 times can be substantially shorter than those of protons.

In this paper, we present examples of how CIDNP can be observed both in low‐molecular‐weight systems as well as in systems exhibiting a rather macromolecular character. Also, CIDNP can assist in obtaining useful information about macromolecular systems that normally is very difficult to obtain otherwise. Since CIDNP is primarily a qualitative method by which free‐radical intermediates may be identified, we have developed a procedure allowing the quantitative determination of the magnetic properties of the intermediate free radicals. This process is especially useful for very short‐lived radicals, which are frequently elusive to ESR spectroscopy conducted in solution. In particular, g values of a variety of radical ions have been determined in this fashion by CIDNP‐NMR spectroscopy. The data thus obtained provide an alternative to ESR and, hence, complement this traditional method (manuscript in preparation).
Selective antibody‐mediated targeting of class I MHC to EGFR‐expressing tumor cells induces potent antitumor CTL activity in vitro and in vivo
Authors: Novak Hila , Noy Roy , Oved Kfir , Segal Dina , Wels Winfried S. , Reiter Yoram
Published: October 2006

Epidermal growth factor receptor (EGFR) is highly overexpressed in many tumor types. We present a new fusion molecule that can target solid tumors that express EGFR. The fusion molecule combines the advantage(s) of the well‐established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes. A recombinant chimeric molecule was created by the genetic fusion of the scFv antibody fragment derived from the anti‐EGFR monoclonal antibody C225, to monomeric single‐chain HLA‐A2 complexes containing immunodominant tumor or viral‐specific peptides. The fusion protein can induce very efficiently CTL‐dependent lysis of EGFR‐expressing tumor cells regardless of the expression of self peptide‐MHC complexes. Moreover, the molecule exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results indicate that recombinant scFv‐MHC‐peptide fusion molecules might represent a novel and powerful approach to immunotherapy of solid tumors, bridging antibody and T lymphocyte attack on cancer cells. © 2006 Wiley‐Liss, Inc.
Risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain: A population‐based study
Authors: Taylor Aliki J. , Winter David L. , Stiller Charles A. , Murphy Mike , Hawkins Mike M.
Published: October 2006

There is now widespread evidence that female survivors of Hodgkin's disease who have been treated with supradiaphragmatic radiotherapy are at an increased risk of breast cancer. Mantle irradiation, which includes irradiation of the mediastinum, conveys a particularly high risk. Previously published studies have found a wide variation in risk. To provide British estimates of risk to inform surveillance programmes, we carried out the first British population‐based cohort study of breast cancer in female survivors of childhood Hodgkin's disease. From the underlying cohort of the British Childhood Cancer Survivor Study, a cohort of 18,123 British 5‐year survivors of childhood cancer diagnosed between 1940 and 1991, there were in total 383 female 5‐year survivors of childhood Hodgkin's disease. Sixteen of these 383 survivors went on to develop invasive breast cancer subsequent to 5‐year survival (standardised incidence ratio, 11.5; 95% confidence interval (95% CI), 6.6–18.6) and all of these 16 survivors had been treated with supradiaphragmatic irradiation as treatment for childhood Hodgkin's disease. The cumulative risk of breast cancer by 25 years of follow up was 9.9% (95% CI, 3.3–16.6) for all patients and 12.2% (95% CI, 4.3–20.1) for those treated with supradiaphragmatic radiotherapy. The cumulative risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain is at the lower end of previous estimates. We hope that our data may provide a basis for future surveillance and for counselling survivors as to their likely risk of breast cancer. © 2006 Wiley‐Liss, Inc.
Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias
Authors: Suspitsin Evgeny N. , Sokolenko Anna P. , Togo Alexandr V. , Lazareva Yulia R. , Turkevich Elena A. , Matsko Dmitry E. , Henrich Kai‐Oliver , Borresen‐Dale Anne‐Lise , Schwab Manfred , Cornelisse Cees J. , Imyanitov Evgeny N.
Published: October 2006

Amplification of HER2, C‐MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real‐time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3‐fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C‐MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification‐positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C‐MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification‐negative first BC have sufficient chances to survive until the development of the contralateral carcinoma. © 2006 Wiley‐Liss, Inc.
Detection of novel quantitative trait loci for cutaneous melanoma by genome‐wide scan in the MeLiM swine model
Authors: Zhi‐Qiang Du , Silvia Vincent‐Naulleau , Hélène Gilbert , Florence Vignoles , Françoise Créchet , Takeshi Shimogiri , Hiroshi Yasue , Jean‐Jacques Leplat , Stephan Bouet , Joseph Gruand , Vratislav Horak , Denis Milan , Roy Pascale Le , Claudine Geffrotin
Published: October 2006

Human cutaneous melanoma is a complex trait inherited in about 10% of cases. Although 2 high‐risk genes, CDKN2A and CDK4, and 1 low risk gene, MC1R, have been identified, susceptibility genes remain to be discovered. Here, we attempted to determine new genomic regions linked to melanoma using the pig MeLiM strain, which develops hereditary cutaneous melanomas. We applied quantitative trait loci (QTL) mapping method to a significant genome‐wide scan performed on 331 backcross pigs derived from this strain. QTLs were detected at chromosome‐wide level for a melanoma synthetic trait corresponding to the development of melanoma. The peak positions on Sus scrofa chromosomes (SSC) were at 49.4 and 88.0 cM (SSC1), 56.0 cM (SSC13), 86.5 cM (SSC15) and 39.8 cM (SSC17), and, on SSC2, at 16.9 cM, in families derived from F1 males only (p < 0.05, except for SSC13, p < 0.01). Analysis of 7 precise specific traits revealed highly significant QTLs on SSC10 (ulceration), on SSC12 (presence of melanoma at birth), on SSC13 (lesion type), and on SSC16 and SSC17 (number of aggressive melanomas) at the respective positions 42.0, 95.6, 81.0, 45.3 and 44.8 cM (p < 0.001 and p < 0.05 respectively at the chromosome‐ and genome‐wide levels). We also showed that MeLiM MC1R*2 allele, which determines black coat colour in pigs, predisposes significantly to melanoma. Interactions were observed between MC1R and markers located on SSC1 (p < 0.05). Taken together, these results indicate that MeLiM swine is a model for human multigenic diseases. Comparative mapping revealed human regions of interest to search for new melanoma susceptibility candidates. © 2006 Wiley‐Liss, Inc.
Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis
Authors: Maurin Nicole , Forgue‐Lafitte Marie‐Elisabeth , Levy Pierre , Zimber Amazia , Bara Jacques
Published: October 2006

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment. In the treated rats, the MUC5AC mucin was mainly expressed in ACF compared with the histologically normal mucosae, which showed few isolated MUC5AC‐positive normal crypts. During carcinogenesis, the percentage of large ACF [≥≥10 aberrant crypts] increased and the number of MUC5AC‐positive (NCs) decreased. At Week 30, small tumors were observed arising from large ACF, both types of lesions expressing MUC5AC. At Week 66, large tumors showed remnants of MUC5AC‐positive ACF in their adjacent mucosae. This observation suggests that the expression of MUC5AC is associated with the ACF/adenoma sequence and supports the notion of large ACF as precursors of adenomas/adenocarcinomas. Moreover, the expression of MUC5AC in the transitional mucosa adjacent to both rat and human colon tumors suggests that some human tumors could arise from large ACF, and reinforces the concept of the premalignant potential of these lesions. © 2006 Wiley‐Liss, Inc.
The interaction of adenovirus E1A with p300 family members modulates cellular gene expression to reduce tumorigenicity
Authors: Miura Tanya A. , Cook James L. , Potter Terence A. , Ryan Sharon , Routes John M.
Published: October 2006

The use of adenovirus serotype 2 or 5 (Ad2/5) E1A as therapy for human malignancy requires an understanding of the mechanisms involved in E1A‐induced tumor suppression. The prevailing use of E1A in the treatment of human malignancy stresses the non‐immunologically mediated, anti‐tumorigenic activities of E1A. However, the capacity of E1A to elicit a NK‐cell and T‐cell anti‐tumor immune response and to sensitize tumor cells to lysis by immune effector molecules utilized by NK cells and T cells is also an important component of the anti‐tumorigenic activity of E1A. This immune‐mediated anti‐tumorigenic activity of E1A is not shared by functionally similar viral oncoproteins such as the human papillomavirus type 16 (HPV16) E7 oncoprotein and is dependent on the capacity of E1A to interact with transcriptional coadapter, p300. To further define the molecular mechanisms whereby E1A reduces tumorigenicity, we compared total cellular gene expression in H4 cells, a human fibrosarcoma cell line, to gene expression in H4 cells stably expressing E1A, E7, or mutant forms of E1A that do not bind p300. The expression of E1A, but not E7, in H4 cells modulated the expression of cellular genes that may promote apoptosis, enhance immunogenicity and reduce tumor cell metastasis. The difference in the ability of E1A and E7 to modulate the expression of cellular genes that may influence tumorigenicity was largely attributable to distinct interactions of E1A and E7 with p300. Results of this study will be useful in designing novel strategies to augment the anti‐tumorigenic activities of E1A. J. Cell. Biochem. 100: 929–940, 2007. © 2006 Wiley‐Liss, Inc.
Radiation‐induced bystander effect: Activation of signaling molecules in K562 erythroleukemia cells
Authors: Mitra Anirban Kumar , Krishna Malini
Published: October 2006

Gap junction independent signaling mechanism was investigated using K562 human erythroleukemia cells. They were exposed to 2, 5, or 10 Gy of 60Co γ irradiation, the medium isolated 20 min post‐irradiation and added to fresh cells. Evidence of radiation‐induced bystander effect was observed wherein there was activation of p21, nuclear factor‐κB (NF‐κB), Bax, Bcl‐2 and cleavage of poly(ADP‐ribose) polymerase in bystander cells. The study implicates the involvement of signaling molecules released into the medium and factors like stable free radicals that are generated in the surrounding medium. The response elicited appears to be primarily via NF‐κB and p21 activation. J. Cell. Biochem. 100: 991–997, 2007. © 2006 Wiley‐Liss, Inc.
The kinetics of p53‐binding and histone acetylation at target promoters do not strictly correlate with gene expression after UV damage
Authors: Magrini Roberta , Russo Debora , Fronza Gilberto , Inga Alberto , Menichini Paola
Published: October 2006

We have addressed the correlation between sequence‐specific DNA binding by the tumor suppressor p53 and transactivation of various target genes, in the context of UV irradiation responses. In A549 cells (p53WT), p53 occupancy at the p21, mdm2, and puma promoters increased significantly after UV irradiation. In contrast, p21 mRNA levels did not change, mdm2 mRNA decreased and both p21 and mdm2 proteins were downregulated shortly after UV. At later times, higher p53 occupancy correlated with enhanced expression of these two genes both at mRNA and protein levels. In the p53 mutant cell lines LX1 (R273H) and SKMes1 (R280K), no significant p53‐binding was detected at the gene targets analyzed. Accordingly, p21 and mdm2 proteins were not upregulated after UV irradiation. The kinetics of histone acetylation did not strictly correlate with gene expression. In fact, high levels of acetylated H3 (AcH3) and, particularly, acetylated H4 (AcH4) histones were found shortly after UV irradiation on p21 and mdm2 promoters. At the later time point, when transactivation was detected, acetylation levels decreased significantly although remaining higher than basal levels. Our results indicate that p53 transcription‐dependent and ‐independent responses are activated with different kinetics after UV, possibly relating to the repair of UV‐induced DNA damage. Based on the histone acetylation pattern we hypothesize that the DNA repair function of p53, associated to global genome repair and foci of DNA damage, may be relevant for all p53‐binding sites, including those where occupancy by p53 is also associated to transcriptional modulation. J. Cell. Biochem. 100: 1276–1287, 2007. © 2006 Wiley‐Liss, Inc.
Observation and characterisation of rainfall over Hawaii and surrounding region from the Tropical Rainfall Measuring Mission
Authors: Kidd Chris , McGregor Glenn
Published: October 2006

Satellite observations of clouds and precipitation have a history stretching back over 40 years. The observations of clouds initially led to the inference of precipitation from cloud top features and subsequently more direct methods derived from passive microwave observations. More recently, the Tropical Rainfall Measuring Mission (TRMM) has provided unprecedented information from the first active microwave instrument specifically designed to measure rainfall, the precipitation radar (PR). This paper utilises data from the TRMM PR for the period December 1997 to November 2005 to investigate rainfall over Hawaii and the surrounding ocean. The PR instrument not only provides spatial information on rainfall, but also vertical profiles of precipitation. Data from the PR instrument is used to map rainfall at a spatial resolution of 5 km and, utilising the information from the vertical profiles, map the distribution of trade‐wind and non‐trade‐wind precipitation. This paper provides quantitative estimates of rainfall over Hawaii and the surrounding ocean that generally match those of surface observations and models. It is found that the islands exert a significant influence on the distribution of the amount and occurrence of precipitation over this region. Copyright © 2006 Royal Meteorological Society
Predictions of future climate change in the caribbean region using global general circulation models
Authors: Angeles Moises E. , Gonzalez Jorge E. , Erickson David J. , Hernández José L.
Published: October 2006

Since the 1800s the global average CO2 mixing ratio has increased and has been related to increases in surface air temperature (0.6 ± 0.2 °C) and variations in precipitation patterns among other weather and climatic variables. The Small Island Developing States (SIDS), according to the 2001 report of the Intergovernmental Panel on Climate Change (IPCC), are likely to be among the most seriously impacted regions on Earth by global climate changes. In this work, three climate change scenarios are investigated using the Parallel Climate Model (PCM) to study the impact of the global anthropogenic CO2 concentration increases on the Caribbean climate. A climatological analysis of the Caribbean seasonal climate variation was conducted employing the National Center for Environmental Prediction (NCEP) reanalysis data, the Xie–Arkin precipitation and the Reynolds–Smith Sea Surface Temperature (SST) observed data. The PCM is first evaluated to determine its ability to predict the present time Caribbean climatology. The PCM tends to under predict the SSTs, which along with the cold advection controls the rainfall variability. This seems to be a main source of bias considering the low model performance to predict rainfall activity over the Central and southern Caribbean. Future predictions indicate that feedback processes involving evolution of SST, cloud formation, and solar radiative interactions affect the rainfall annual variability simulated by PCM from 1996 to 2098. At the same time two large‐scale indices, the Southern Oscillation Index (SOI) and the North Atlantic Oscillation (NAO) are strongly related with this rainfall annual variability. A future climatology from 2041 to 2058 is selected to observe the future Caribbean condition simulated by the PCM. It shows, during this climatology range, a future warming of approximately 1 °C (SSTs) along with an increase in the rain production during the Caribbean wet seasons (early and late rainfall seasons). Although the vertical wind shear is strengthened, it typically remains lower than 8 m/s, which along with SST > 26.5 °C provides favorable conditions for possible future increases in tropical storm frequency. Copyright © 2006 Royal Meteorological Society
Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma
Authors: Kwak Cheol , Park Yong Hyun , Jeong Chang Wook , Jeong Hyeon , Lee Sang Eun , Moon Kyung Chul , Ku Ja Hyeon
Published: October 2006

Background

The objective of the current study was to determine the significance of sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma (RCC).

Methods

Patients with metastatic RCC were included in this study and were categorized according to sarcomatoid differentiation.

Results

Patients with sarcomatoid differentiation had more aggressive tumor characteristics than those without sarcomatoid differentiation. After immunotherapy, the median progression‐free survival was 9.0 months (95% confidence interval [CI] 1.4–52.7) for patient without sarcomatoid differentiation and 3.2 months (95% CI 0.4–42.9) for patients with sarcomatoid differentiation, respectively (P = 0.0001). The median overall survival was 22.2 months (95% CI 3.2–75.4) and 10.0 months (95% CI 0.7–60.1) in both groups. When comparing patients with sarcomatoid differentiation, there was no significant difference of overall survival in the immunotherapy group and the no immunotherapy group. Multivariate Cox proportional hazards model analysis showed that T stage (Hazard ratio [HR] 1.71; 95% CI 1.07–2.74; P = 0.024), sarcomatoid differentiation (HR 2.18; 95% CI 1.30–3.66; P = 0.003), and the number of metastasis sites (HR 1.81; 95% CI 1.14–2.88; P = 0.012) were independent predictors of progression‐free survival. Sarcomatoid differentiation and the number of metastasis sites were independent prognostic predictors of overall survival. The estimated relative risks of sarcomatoid differentiation and the number of metastasis sites were 2.83 (95% CI 1.49–5.40; P = 0.002) and 2.31 (95% CI 1.29–4.16; P = 0.005), respectively.

Conclusions

Our findings suggest that sarcomatoid differentiation is an important prognostic factor for immunotherapy in metastatic RCC. J. Surg. Oncol. © 2006 Wiley‐Liss, Inc.
Tissue factor expression is a clinical indicator of lymphatic metastasis and poor prognosis in gastric cancer with intestinal phenotype
Authors: Yamashita Hiroharu , Kitayama Joji , Ishikawa Makoto , Nagawa Hirokazu
Published: October 2006

Background and Objectives

Tissue factor (TF), which normally safeguards vascular integrity by inducing hemostasis upon injury, has received widespread attention in the pathogenesis of cancer progression and metastasis. Aberrantly expressed TF in cancer cells has been reported to be associated with advanced stages of malignancy in various cancers.

Methods

The expression of TF and microvessel density (MVD) were immunohistochemically evaluated in 207 gastric cancers, and their relationship with clinicopathological features was examined.

Results

TF was preferentially expressed (41.8%) in intestinal‐type cancer at a significantly higher rate than that in diffuse‐type cancer (12.1%, P < 0.0001). The expression of TF was associated with advanced stage of disease and showed a positive correlation with a higher rate of lymphatic and venous invasion and lymphatic metastasis in intestinal‐type, but not in diffuse‐type carcinoma. Moreover, TF expression was associated with high MVD in the tumor and a worse outcome only in intestinal‐type carcinoma.

Conclusions

TF may be critically involved in tumor progression in intestinal‐type, but not in diffuse‐type, gastric carcinoma. The difference in clinical features between these two histological types might be partially dependent on TF expression profile. J. Surg. Oncol. © 2006 Wiley‐Liss, Inc.
Preparation and application of poly(dimethylsiloxane)/β‐cyclodextrin solid‐phase microextraction fibers
Authors: Fu Yue‐li , Hu Yu‐ling , Zheng Yan‐jie , Li Gong‐Ke
Published: October 2006

A novel poly(dimethylsiloxane)/β‐cyclodextrin (PDMS/β‐CD) coating was prepared for solid‐phase microextraction (SPME). The PDMS/β‐CD coating proved to have a porous structure, providing high surface areas and allowing for high extraction efficiency. The coating had a high thermal stability (340°C) and a long lifetime due to its chemical binding to the fiber surface. Polar phenols and amines were used to evaluate the character of the coating fiber by headspace (HS) extraction and thermal desorption, followed by GC–FID analysis. Parameters that affected the extraction process were investigated; these include extraction time and temperature, desorption time, pH, and ionic strength of the solution. For phenols, the range of linearity of the method was 4–500 μg/L and the LOD was 1.3–2.1 μg/L. For amines, the range of linearity was 1–1000 μg/L and the LOD was 1.2–2.8 μg/L. The presence of β‐CD not only increases the thermal stability of the fiber coating, but also enhances its selectivity. Compared with commercially available SPME fibers, the new phases show better selectivity and sensitivity towards polar compounds.
Multiple‐region gradient arrays for extended field of view, increased performance, and reduced nerve stimulation in magnetic resonance imaging
Authors: Parker Dennis L. , Hadley J. Rock
Published: October 2006

This article presents a novel design for magnetic resonance imaging (MRI) gradient systems. This design may allow the development of MRI scanners that are capable of imaging large regions with high performance while minimizing the potential for nerve stimulation. The general concept of the gradient system is that spatial oscillation is incorporated such that each gradient coil creates multiple, approximately linear gradient regions that oscillate in gradient polarity. Separate radiofrequency (RF) coil arrays are designed to be sensitive to the signals within each linear region and thus allow signal measurements to be obtained separately from each region. Enabling image acquisition in the transition region that separates each pair of adjacent linear regions requires a second gradient system with imaging regions that overlap and coincide with the transition regions of the first gradient system. Imaging the extended field of view (FOV) is accomplished by interleaved operation of the two gradient systems. Simulated annealing is used to create designs for both longitudinal and transverse gradient systems with two imaging regions. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Demographic correlates of body size changes in children undergoing treatment for acute lymphoblastic leukemia
Authors: Baillargeon Jacques , Langevin Anne‐Marie , Lewis Margaret , Estrada Jaime , Grady James J. , Mullins Judith , Pitney Aaron , Pollock Brad H.
Published: October 2006

Introduction

While it is known that leukemia therapy is associated with obesity in survivorship, limited information is available on its time‐related pattern of development and its variation across patient subgroups. The goal of the present study was to examine demographic correlates of body mass index (BMI) changes over time from diagnosis through chemotherapy for children with B‐precursor acute lymphoblastic leukemia (ALL).

Methods

The study cohort consisted of 307 pediatric patients diagnosed with ALL who were treated at four South Texas pediatric oncology centers between 1990 and 2002. To minimize treatment‐related variability, we excluded patients who received cranial irradiation as part of their treatment. Variation in age‐ and gender‐standardized BMI z‐scores according to age at diagnosis, gender, and ethnicity were assessed.

Results

The overall study cohort exhibited an increase in age‐ and gender‐adjusted BMI z‐scores for the first 24 months of chemotherapy followed by a slight decrease in BMI at 30 months (end of therapy). A repeated measures analysis indicated a statistically significant difference in the time‐related pattern of BMI changes for age at diagnosis (P = 0.001) but no significant effect for gender (P = 0.32) or Hispanic versus non‐Hispanic ethnicity (P = 0.89).

Discussion

In our cohort of ALL patients, BMI was elevated at diagnosis (mean standardized BMI z‐score = 0.22, standard deviation = 1.4) then increased and remained elevated for the entire duration of chemotherapy. Children who were 2–9 years of age at diagnosis began therapy with a substantially lower BMI and remained lower over the course of chemotherapy than patients aged 10–18 years at diagnosis. It will be important for future investigations to explore the biological and behavioral factors that may underlie such differential patterns of BMI change over time. Pediatr Blood Cancer 2007;49:793–796. © 2006 Wiley‐Liss, Inc.
A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor
Authors: Stecher Chalotte W. , Grønbæk Kirsten , Hasle Henrik
Published: October 2006

A 20‐month‐old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain‐tumor (PNET). A novel splice site mutation of the TP53‐gene, likely to be associated with a nonfunctional protein, was found in the proband, his father and younger sister, but only the proband has so far developed malignancy. The clinical phenotype in the boy is suggestive of Li–Fraumeni syndrome, but the family does not strictly conform to the canonical definition. Pediatr Blood Cancer 2008;50:701–703. © 2006 Wiley‐Liss, Inc.
Myelodysplastic syndrome with trisomy 8 associated with Behçet syndrome: An immunologic link to a karyotypic abnormality
Authors: Thachil Jecko V. , Salim Rahuman , Field Anne , Moots Robert , Bolton‐Maggs Paula
Published: October 2006

Myelodysplastic syndrome (MDS) in children is often associated with chromosomal anomalies and trisomy 8 is a characteristic karyotypic feature in up to 20% of the cases. Behçet disease is a rare multisystem inflammatory disorder characterized by recurrent mouth and genital ulcers. MDS with trisomy 8 has been observed in adult patients with Behçet syndrome with some cases developing prior to the clinical manifestations of the latter. We present a female with a similar association and explain the importance of identifying the coexisting conditions. The immunological abnormalities, which may be observed in MDS and their possible mechanisms, are also discussed. Pediatr Blood Cancer 2008;50:649–651. © 2006 Wiley‐Liss, Inc.
Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research
Authors: Lewis James D. , Schinnar Rita , Bilker Warren B. , Wang Xingmei , Strom Brian L.
Published: October 2006

Background

The Health Improvement Network (THIN) is a new medical records database that contains records from general practices some of which have or continue to participate in the General Practice Research Database (GPRD) and others that never participated in GPRD. We sought to replicate in THIN well‐established associations from the medical literature and to compare results from the GPRD practices to the non‐GPRD practices within THIN.

Methods

Using THIN data from 1986–2003, we conducted case‐control studies of associations between diseases (e.g., hypertension and stroke) and between diseases and drugs (e.g., aspirin and colon cancer). Conditional logistic regression was used to calculate odds ratios adjusted for potential confounders. Differences between GPRD and non‐GPRD practices were assessed by testing for a statistical interaction by practice type in each outcome‐exposure association.

Results

We observed the expected positive associations (p < 0.05) of stroke with hypertension and diabetes mellitus; of myocardial infarction with hypertension, hypercholesterolemia, obesity, and smoking; and of peptic ulcer disease with aspirin, NSAIDs, and potassium. We observed the expected negative associations (p < 0.05) of colorectal cancer with aspirin, NSAIDs, and cox‐2 inhibitors. The expected protective effect of aspirin use for myocardial infarction was not observed. In all cases, the results obtained from the GPRD practices were similar to the results obtained from the non‐GPRD practices, only being statistically different for the associations of myocardial infarction with diabetes and aspirin use.

Conclusions

THIN data that are collected outside of the GPRD appear as valid as the data collected as part of the GPRD. Copyright © 2006 John Wiley & Sons, Ltd.