bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular and molecular tunnels surrounding the forebrain commissures of human fetuses
Authors: Lent Roberto , Uziel Daniela , Baudrimont Marie , Fallet Cathérine
Published: February 2005

Glial cells and extracellular matrix (ECM) molecules surround developing fiber tracts and are implicated in axonal pathfinding. These and other molecules are produced by these strategically located glial cells and have been shown to influence axonal growth across the midline in rodents. We searched for similar cellular and molecular structures surrounding the telencephalic commissures of fetal human brains. Paraffin‐embedded brain sections were immunostained for glial fibrillary acidic protein (GFAP) and vimentin (VN) to identify glial cells; for microtubule‐associated protein‐2 (MAP‐2) and neuronal nuclear protein (NeuN) to document neurons; for neurofilament (NF) to identify axons; and for chondroitin sulfate (CS), tenascin (TN), and fibronectin (FN) to show the ECM. As in rodents, three cellular clusters surrounding the corpus callosum were identified by their expression of GFAP and VN (but not MAP‐2 or NeuN) from 13 to at least 18 weeks postovulation (wpo): the glial wedge, the glia of the indusium griseum, and the midline sling. CS and TN (but not FN) were expressed pericellularly in these cell groups. The anterior commissure was surrounded by a GFAP+/VN+ glial tunnel from 12 wpo, with TN expression seen between the GFAP+ cell bodies. The fimbria showed GFAP+/VN+ cells at its lateral and medial borders from 12 wpo, with pericellular expression of CS. The fornix showed GFAP+ cells somewhat later (16 wpo). Because these structures are similar to those described for rodents, we concluded that the axon guiding mechanisms postulated for commissural formation in nonhuman mammals may also be operant in the developing human brain. J. Comp. Neurol. 483:375–382, 2005. © 2005 Wiley‐Liss, Inc.
Drebrin A is a postsynaptic protein that localizes in vivo to the submembranous surface of dendritic sites forming excitatory synapses
Authors: Aoki Chiye , Sekino Yuko , Hanamura Kenji , Fujisawa Sho , Mahadomrongkul Veeravan , Ren Yong , Shirao Tomoaki
Published: February 2005

Drebrin A is a neuron‐specific, actin binding protein. Evidence to date is from in vitro studies, consistently supporting the involvement of drebrin A in spinogenesis and synaptogenesis. We sought to determine whether drebrin A arrives at the plasma membrane of neurons, in vivo, in time to orchestrate spinogenesis and synaptogenesis. To this end, a new antibody was used to locate drebrin A in relation to electron microscopically imaged synapses during early postnatal days. Western blotting showed that drebrin A emerges at postnatal day (PNd) 6 and becomes progressively more associated with F‐actin in the pellet fraction. Light microscopy showed high concentrations of drebrin A in the synaptic layers of the hippocampus and cortex. Electron microscopy revealed that drebrin A in these regions is located exclusively in dendrites both neonatally and in adulthood. In adulthood, nearly all of the synaptic drebrin A is within spines forming asymmetric excitatory synapses, verified by γ‐aminobutyric acid (GABA) negativity. At PNd7, patches of drebrin A immunoreactivity were discretely localized to the submembranous surfaces of dendrites forming slight protrusions—protospines. The drebrin A sites exhibited only thin postsynaptic densities and lacked axonal associations or were contacted by axons that contained only a few vesicles. Yet, because of their immunoreactivity to the NR2B subunit of N‐methyl‐D‐aspartate receptors and immunonegativity of axon terminals to GABA, these could be presumed to be nascent, excitatory synapses. Thus, drebrin A may be involved in organizing the dendritic pool of actin for the formation of spines and of axospinous excitatory synapses during early postnatal periods. J. Comp. Neurol. 483:383–402, 2005. © 2005 Wiley‐Liss, Inc.
Hodological characterization of the septum in anuran amphibians: I. Afferent connections
Authors: Roden Katja , Endepols Heike , Walkowiak Wolfgang
Published: February 2005

On the basis of Nissl‐stained sections, we subdivided the septum of the gray treefrog Hyla versicolor in the lateral, central, and medial septal complex. The afferent projections of the different septal nuclei were studied by combined retrograde and anterograde tracing with biotin ethylendiamine (Neurobiotin). The central and medial septal complex receives direct input from regions of the olfactory bulb and from all other limbic structures of the telencephalon (e.g., amygdalar regions, nucleus accumbens), whereas projections to the lateral septal complex are absent or less extensive. The medial pallium projects to all septal nuclei. In the diencephalon, the anterior thalamic nucleus provides the main ascending input to all subnuclei of the anuran septum, which can be interpreted as a limbic/associative pathway. The ventromedial thalamic nucleus projects to the medial and lateral septal complex and may thereby transmit multisensory information to the limbic system. Anterior preoptic nucleus, suprachiasmatic nucleus, and hypothalamic nuclei innervate the central and lateral septal complex. Only the nuclei of the central septal complex receive input from the brainstem. Noteworthy is the relatively strong projection from the nucleus raphe to the central septal complex, but not to the other septal nuclei. J. Comp. Neurol. 483:415–436, 2005. © 2005 Wiley‐Liss, Inc.
Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy
Authors: Knopp Andreas , Kivi Anatol , Wozny Christian , Heinemann Uwe , Behr Joachim
Published: February 2005

The subiculum was recently shown to be crucially involved in the generation of interictal activity in human temporal lobe epilepsy. Using the pilocarpine model of epilepsy, this study examines the anatomical substrates for network hyperexcitability recorded in the subiculum. Regular‐ and burst‐spiking subicular pyramidal cells were stained with fluorescence dyes and reconstructed to analyze seizure‐induced alterations of the dendritic and axonal system. In control animals burst‐spiking cells outnumbered regular‐spiking cells by about two to one. Regular‐ and burst‐spiking cells were characterized by extensive axonal branching and autapse‐like contacts, suggesting a high intrinsic connectivity. In addition, subicular axons projecting to CA1 indicate a CA1‐subiculum‐CA1 circuit. In the subiculum of pilocarpine‐treated rats we found an enhanced network excitability characterized by spontaneous rhythmic activity, polysynaptic responses, and all‐or‐none evoked bursts of action potentials. In pilocarpine‐treated rats the subiculum showed cell loss of about 30%. The ratio of regular‐ and burst‐spiking cells was practically inverse as compared to control preparations. A reduced arborization and spine density in the proximal part of the apical dendrites suggests a partial deafferentiation from CA1. In pilocarpine‐treated rats no increased axonal outgrowth of pyramidal cells was observed. Hence, axonal sprouting of subicular pyramidal cells is not mandatory for the development of the pathological events. We suggest that pilocarpine‐induced seizures cause an unmasking or strengthening of synaptic contacts within the recurrent subicular network. J. Comp. Neurol. 483:476–488, 2005. © 2005 Wiley‐Liss, Inc.
Performance‐based middleware for Grid computing
Authors: Nudd G. R. , Jarvis S. A.
Published: February 2005

This paper describes a stateful service‐oriented middleware infrastructure for the management of scientific tasks running on multi‐domain heterogeneous distributed architectures. Allocating scientific workload across multiple administrative boundaries is a key issue in Grid computing and as a result a number of supporting services including match‐making, scheduling and staging have been developed. Each of these services allows the scientist to utilize the available resources, although a sustainable level of service in such shared environments cannot always be guaranteed. A performance‐based middleware infrastructure is described in which prediction data for each scientific task are calculated, stored and published through a Globus‐based performance information service. Distributing these data allows additional performance‐based middleware services to be built, two of which are described in this paper: an intra‐domain predictive co‐scheduler and a multi‐domain workload steering system. These additional facilities significantly improve the ability of the system to meet task deadlines, as well as enhancing inter‐domain load‐balancing and system‐wide resource utilization. Copyright © 2005 John Wiley & Sons, Ltd.
ASKALON: a tool set for cluster and Grid computing
Authors: Fahringer Thomas , Jugravu Alexandru , Pllana Sabri , Prodan Radu , Seragiotto Clovis , Truong Hong‐Linh
Published: February 2005

Performance engineering of parallel and distributed applications is a complex task that iterates through various phases, ranging from modeling and prediction, to performance measurement, experiment management, data collection, and bottleneck analysis. There is no evidence so far that all of these phases should/can be integrated into a single monolithic tool. Moreover, the emergence of computational Grids as a common single wide‐area platform for high‐performance computing raises the idea to provide tools as interacting Grid services that share resources, support interoperability among different users and tools, and, most importantly, provide omnipresent services over the Grid. We have developed the ASKALON tool set to support performance‐oriented development of parallel and distributed (Grid) applications. ASKALON comprises four tools, coherently integrated into a service‐oriented architecture. SCALEA is a performance instrumentation, measurement, and analysis tool of parallel and distributed applications. ZENTURIO is a general purpose experiment management tool with advanced support for multi‐experiment performance analysis and parameter studies. AKSUM provides semi‐automatic high‐level performance bottleneck detection through a special‐purpose performance property specification language. The PerformanceProphet enables the user to model and predict the performance of parallel applications at the early stages of development. In this paper we describe the overall architecture of the ASKALON tool set and outline the basic functionality of the four constituent tools. The structure of each tool is based on the composition and sharing of remote Grid services, thus enabling tool interoperability. In addition, a data repository allows the tools to share the common application performance and output data that have been derived by the individual tools. A service repository is used to store common portable Grid service implementations. A general‐purpose Factory service is employed to create service instances on arbitrary remote Grid sites. Discovering and dynamically binding to existing remote services is achieved through registry services. The ASKALON visualization diagrams support both online and post‐mortem visualization of performance and output data. We demonstrate the usefulness and effectiveness of ASKALON by applying the tools to real‐world applications. Copyright © 2005 John Wiley & Sons, Ltd.
Automatic performance analysis tools for the Grid
Authors: Gerndt M.
Published: February 2005

Applications on Grids require scalable and online performance analysis tools. The execution environment of such applications includes a large number of processors. In addition, some of the resources such as the network will be shared with other applications. This requires applications to adapt dynamically to resource changes. The article presents the requirements of Grid application classes for performance analysis tools. It introduces a new analysis environment currently being developed for teraflop computers within the Peridot project at Technische Universität München. This environment applies a distributed automatic performance analysis approach. It is based on a formal specification of performance properties in the APART specification language. It uses a hierarchy of analysis agents that obtain performance data from a configurable monitoring system. This scalable design allows performance analysis for large Grid applications. Copyright © 2005 John Wiley & Sons, Ltd.
Streamlined analysis of pooled genotype data in SNP‐based association studies
Authors: Moskvina Valentina , Norton Nadine , Williams Nigel , Holmans Peter , Owen Michael , O'Donovan Michael
Published: February 2005

Several groups have developed methods for estimating allele frequencies in DNA pools as a fast and cheap way for detecting allelic association between genetic markers and disease. To obtain accurate estimates of allele frequencies, a correction factor k for the degree to which measurement of allele‐specific products is biased is generally applied. Factor k is usually obtained as the ratio of the two allele‐specific signals in samples from heterozygous individuals, a step that can significantly impair throughput and increase cost. We have systematically investigated the properties of k through the use of empirical and simulated data. We show that for the dye terminator primer extension genotyping method we have applied, the correction factor k is substantially influenced by the dye terminators incorporated, but also by the terminal 3′ base of the extension primer. We also show that the variation in k is large enough to result in unacceptable error rates if association studies are conducted without regard to k. We show that the impact of ignoring k can be neutralized by applying a correction factor kmax that can be easily derived, but this at the potential cost of an increase in type I error. Finally, based upon observed distributions for k we derive a method allowing the estimation of the probability pooled data reflects significant differences in the allele frequencies between the subjects comprising the pools. By controlling the error rates in the absence of knowledge of the appropriate SNP‐specific correction factors, each approach enhances the performance of DNA pooling, while considerably streamlining the method by reducing time and cost. Genet. Epidemiol. © 2005 Wiley‐Liss, Inc.
Impact of young age on prognosis for head and neck cancer: A matched‐pair analysis
Authors: Gilroy Jeffrey S. , Morris Christopher G. , Amdur Robert J. , Mendenhall William M.
Published: February 2005

Background.

The purpose of this study was to review outcomes of young patients (age <40 years) treated with definitive radiotherapy alone for squamous cell carcinoma of the oropharynx, and larynx, and to compare these results with an older matched patient cohort.

Methods.

Since 1983, 30 previously untreated young patients underwent definitive radiotherapy at the University of Florida and were matched with an older group of patients (age >45 years) with respect to primary site, stage of disease, and sex.

Results.

There was no difference in cause‐specific survival, locoregional control, or long‐term complications between the two groups; however, there was a significant difference in overall survival favoring young patients (p = .0174). Older patients had twice as many second malignancies.

Conclusion.

Young age does not confer a worse prognosis in patients treated with definitive radiotherapy for squamous cell carcinoma of the oropharynx and larynx. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Threat perception distortions and psychopathological symptoms in typically developing children
Authors: Muris Peter , Meesters Cor , Smulders Lianne , Mayer Birgit
Published: February 2005

This study examined relationships between symptoms of anxiety, aggression, and depression, on the one hand, and threat perception distortions, on the other hand. A large sample of typically developing children aged 8–12 years (N=157) were interviewed with an instrument for assessing the main types of childhood psychopathology, and were then exposed to a series of ambiguous vignettes in order to measure threat perception. As all measures were obtained twice, some 8 weeks apart, it was also possible to study prospective relationships between threat perception distortions and psychopathological symptoms. Results showed that threat perception was associated with a broad range of psychopathological symptoms, although the connection with anxiety was the most robust. No support was found for the notion that threat perception scores were predictive for the persistence of psychopathological symptoms during the 8‐weeks period. Copyright © 2005 John Wiley & Sons, Ltd.
Exposure to childhood infections and risk of Epstein‐Barr virus–defined Hodgkin's lymphoma in women
Authors: Glaser Sally L. , Keegan Theresa H. M. , Clarke Christina A. , Trinh Muoi , Dorfman Ronald F. , Mann Risa B. , DiGiuseppe Joseph A. , Ambinder Richard F.
Published: February 2005

The role of Epstein‐Barr virus (EBV) in Hodgkin's lymphoma (HL) etiology remains unresolved as EBV is detected in only some HL tumors and few studies have tried to reconcile its presence with factors suggesting viral etiology (e.g., childhood social class, infection history). In a population‐based case‐control study of San Francisco Bay area women, we analyzed interview data by tumor EBV status. Among 211 young adult cases, EBV‐positive HL (11%) was associated with a single vs. shared bedroom at age 11 (OR = 4.0, 95% CI 1.1–14.4); risk was decreased for common childhood infections (OR = 0.3, 95% CI 0.1–1.0), including measles before age 10, but not with prior infectious mononucleosis (IM), which is delayed EBV infection. No study factors affected risk of young adult EBV‐negative HL. Among 57 older adult cases, EBV‐positive HL (23%) was unrelated to study factors; EBV‐negative HL was associated with a single bedroom at age 11 (OR = 3.6, 95% CI 1.5–9.1) and IM in family members (OR = 3.1, 95% CI 1.1–9.0). Thus, delayed exposure to infection may increase risk of EBV‐positive HL in young adults, but risk patterns differ in younger and older women for both EBV‐positive and ‐negative HL. Late EBV infection does not appear relevant to risk, suggesting that other pathogens impact HL etiology in affluent female populations. Inconsistency of findings with prior studies may reflect failure of study risk factors to proxy meaningful exposures, risk differences by gender, or selection or misclassification bias. Null findings for EBV‐negative HL indicate that etiologic models should be reconsidered for this common form. © 2005 Wiley‐Liss, Inc.
Absence of acute apoptotic response to genotoxic carcinogens in p53‐deficient mice is associated with increased susceptibility to azoxymethane‐induced colon tumours
Authors: Hu Ying , Le Leu Richard K. , Young Graeme P.
Published: February 2005

Acute apoptotic response to genotoxic carcinogens (AARGC) might be important for controlling the consequences of mutational load in the colon. It has been shown to occur in parallel with activation of DNA repair mechanisms. Inadequate AARGC might allow development of mutated clones with the potential to progress to cancer. In this study, we tested if p53 levels were important for AARGC in the colon and whether defective AARGC was associated with increased risk for colorectal oncogenesis. Apoptosis was measured in colonic epithelium of mice from each p53 genotype (p53−/−, p53+/−, wild‐type) without and 8 hr following a single injection of azoxymethane (AOM). To determine risk for carcinogen‐induced colorectal cancer (CRC), groups of mice from each p53 genotype received 3 weekly injections of AOM and colons were examined for tumour 20 weeks later. Rates of spontaneous apoptosis in colon were not affected by p53 level. However, AARGC was absent in p53−/− mice and reduced by 50% in p53+/− mice (both p < 0.01) compared to wild‐type mice. AOM induced tumours in 30% of wild‐type mice (average multiplicity 1.0 tumours/mouse) compared to 72% of p53+/− mice (2.0 tumours/mouse, p < 0.01) and 100% of p53−/− mice (2.8 tumours/mouse, p < 0.01). Without AOM, significantly fewer mice in all groups had tumours. Rates of apoptosis in tumours were independent of p53 status. p53 dysfunction puts intestinal epithelia at increased risk of genotoxin‐induced oncogenesis due to impairment of apoptotic response mechanisms. p53 levels do not appear, however, to be important for spontaneous apoptosis in normal epithelium or apoptosis in tumours. Subsequent studies are now warranted to test the converse, namely, that enhanced apoptotic response to carcinogen reduces risk for colorectal oncogenesis. © 2005 Wiley‐Liss, Inc.
Potential attenuation of p38 signaling by DDB2 as a factor in acquired TNF resistance
Authors: Sun Chun‐Ling , Chao Chuck C.‐K.
Published: February 2005

Our previous study demonstrated that DDB2, a DNA repair protein, attenuates cell surface membrane‐associated death signal induced by UV or FasAb; DDB2 is overexpressed in cisplatin‐selected cells. However, the molecular mechanism underlying the protective role of DDB2 along the apoptotic pathway remains unknown. Our study identified the cross‐resistance of the cisplatin‐selected cells to tumor necrosis factor‐α (TNF‐α). Since knock‐down of the DDB2 level rendered cells (HR18) sensitive to the treatment, the cell sensitivity to TNF‐α appears inversely proportional to the cellular level of DDB2. Treatment of HeLa cells with TNF‐α transiently induced activation of p38MAPK signal, but this induction was significantly reduced in the resistant cells. Overexpression of DDB2 attenuated the activation of p38 in cells. TNF‐α‐induced apoptotic signals, represented by caspase‐8 and downstream substrate cleavage, were reduced in resistant cells compared to their sensitive counterparts. Inhibition of p38 signal by SB202190 clearly attenuated TNF‐α‐induced apoptotic signals. Moreover, overexpression of DDB2 in HR18 cells also attenuated TNF‐α induced caspase activation. These results suggest that p38MAPK activation may be a key upstream signal of TNF‐α‐induced apoptosis and that attenuation of p38 signal by DDB2 overexpression may be responsible for acquired TNF‐α resistance. © 2005 Wiley‐Liss, Inc.
Aberrant methylation of Reprimo in human malignancies
Authors: Takahashi Takao , Suzuki Makoto , Shigematsu Hisayuki , Shivapurkar Narayan , Echebiri Chinyere , Nomura Masaharu , Stastny Victor , Augustus Meena , Wu Chew‐Wun , Wistuba Ignacio I. , Meltzer Stephen J. , Gazdar Adi F.
Published: February 2005

Reprimo is a new candidate mediator of p53‐mediated cell cycle arrest at the G2 phase. Loss of Reprimo gene expression accompanied by its promoter methylation was identified in pancreatic and lung cancers. Our aim was to examine the methylation status of Reprimo in a broad range of cancers. We examined Reprimo expression by RT‐PCR and the DNA methylation status of the Reprimo promoter by MSP in 39 tumor cell lines. Loss or downregulation of Reprimo expression was frequent (62%), and we confirmed that transcriptional repression of Reprimo was caused by hypermethylation (overall concordance 92%). Treatment of expression‐negative cells with 5‐aza‐2′‐deoxycytidine restored Reprimo expression. We then examined aberrant methylation of Reprimo in 645 tumors representing 16 tumor types. Promoter methylation of Reprimo was found in 79% of gastric cancers, 62% of gallbladder cancers, 57% of lymphomas, 56% of colorectal cancers, 40% of esophageal adenocarcinomas, 37% of breast cancers and 31% of leukemias. Methylation frequencies in ovarian cancers, bladder cancers, cervical cancers, brain tumors, malignant mesotheliomas and pediatric tumors were lower (0–20%). Reprimo methylation was rarely detected in nonmalignant tissues (0–11%) except for gastric epithelia. While colorectal polyps were also frequently methylated (27%), chronic cholecystitis samples were infrequently methylated (4%). Furthermore, we failed to identify Reprimo mutation in colorectal and gastric cancer cell lines and 50 primary colorectal cancers. Aberrant methylation of Reprimo with loss of expression is a common event and may contribute to the pathogenesis of some types of human malignancy. © 2005 Wiley‐Liss, Inc.
Diethylstilbestrol effects and lymphomagenesis in Mlh1‐deficient mice
Authors: Kabbarah Omar , Sotelo Andrea K. , Mallon Mary Ann , Winkeler Erin L. , Fan Ming‐Yu , Pfeifer John D. , Shibata Darryl , Gutmann David H. , Goodfellow Paul J.
Published: February 2005

Inherited defects in DNA mismatch repair (MMR) predispose to a variety of malignancies in humans and in mouse knockout models. In humans, hemizygosity for one of several DNA MMR genes greatly increases an individual's risk for colon and endometrial carcinoma. Hemizygous mice develop gastrointestinal tumors at a low to moderate frequency. Homozygous nulls have higher rates of gastrointestinal tumors and are particularly susceptible to lymphoma. In an effort to model endometrial carcinoma associated with mutation in MMR, we treated mice carrying knockout alleles for Mlh1 or Msh2 with the synthetic estrogen diethylstilbestrol (DES), a known promoter of uterine endometrial carcinoma. The C57BL/6 mice carrying DNA MMR mutations failed to develop endometrial carcinomas. However, the Mlh1‐deficient mice treated with DES tended to become moribund at an early age and had very early onset of lymphoma. Comparison of DES‐treated and untreated Mlh1−/− animals suggests the combination of Mlh1 deficiency and DES exposure accelerates lymphomagenesis. © 2005 Wiley‐Liss, Inc.
CCR10 is expressed in cutaneous T‐cell lymphoma
Authors: Notohamiprodjo Mike , Segerer Stephan , Huss Ralf , Hildebrandt Bernhard , Soler Dulce , Djafarzadeh Roghieh , Buck Wiebke , Nelson Peter J. , von Luettichau Irene
Published: February 2005

Cutaneous T‐cell lymphoma (CTCL) is characterized by recruitment of malignant T‐cell clones into the skin. The mechanisms involved in tumor homing are still not fully elucidated, though chemokines and chemokine receptors have been suggested to play a role in the pathogenesis. Here, we demonstrate extensive expression of CCR10 in skin biopsies of patients with Sézary syndrome (SS, n = 3), mycosis fungoides (MF, n = 2) and unspecified CTCL (n = 3). In addition, we expand prior findings of CXCR3 expression in MF to other entities of CTCL. Expression of CCR5 was detected in 2 of the examined skin biopsies. The functionality of CCR10 and CXCR3 in SS was demonstrated using the SS T‐cell line HUT78. Our data support a potential role of CXCR3 in CTCL and strongly suggest that CCR10 and its ligand CCL27 may contribute to the skin infiltration of malignant T‐cells in this group of lymphoproliferative disorders. © 2005 Wiley‐Liss, Inc.
Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results
Authors: Chiesa Fausto , Tradati Nicoletta , Grigolato Roberto , Boracchi Patrizia , Biganzoli Elia , Crose Nadia , Cavadini Elena , Formelli Franca , Costa Luigi , Giardini Roberto , Zurrida Stefano , Costa Alberto , De Palo Giuseppe , Veronesi Umberto
Published: February 2005

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5‐year follow‐up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified. © 2005 Wiley‐Liss, Inc.
Mono/oligoclonal pattern of Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV‐8) episomes in primary effusion lymphoma cells
Authors: Boulanger Emmanuelle , Duprez Renan , Delabesse Eric , Gabarre Jean , Macintyre Elizabeth , Gessain Antoine
Published: February 2005

Primary effusion lymphoma (PEL) is a rare lymphoma of B‐cell origin, developed in serous cavities. PEL tumor cells are latently infected with Kaposi sarcoma‐associated herpesvirus (KSHV) and in most cases co‐infected with Epstein‐Barr virus (EBV). In 15 primary PEL tumors including 10 EBV‐positive cases, we analyzed the fused terminal repeat (TR) regions of KSHV episomes using pulsed‐field gel electrophoresis and Southern blot. On the same genomic DNA samples, the cellular clonality was assessed by Southern blot and PCR detection of monoclonal immunoglobulin heavy chain (IGH) VDJ gene rearrangements, associated in the EBV‐infected cases, with Southern blot analysis of the fused termini of EBV episomes. Monoclonal IGH gene rearrangements were detected in 13 tumors using Southern blot, in 11 cases using PCR, and in all cases considering both methods. EBV infection was monoclonal in all EBV‐positive cases. However, only 5 PEL tumors were found to be monoclonally infected with KSHV. In the 10 other cases, we found a biclonal (2 bands; n = 4) or an oligoclonal pattern (3–6 bands; n = 6) of KSHV episomes. We hypothesized that the apparent discrepancy between viral and cellular clonalities in PEL might be due to several phenomena including complex mechanisms of genomic recircularization, insertion of duplicated sequences into the TR region and simultaneous infection of tumor cells with defective KSHV variants. KSHV infection of contaminating nontumoral cells, superinfection from lytically infected cells or viral integration events might also explain the oligoclonal pattern of KSHV infection. Several of these mechanisms, not mutually exclusive, might coexist in a single tumor. © 2005 Wiley‐Liss, Inc.
C‐terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac‐GEF
Authors: Akakura Shin , Kar Bishnupriya , Singh Sukhwinder , Cho Leong , Tibrewal Nitu , Sanokawa‐Akakura Reiko , Reichman Charles , Ravichandran Kodimangalam S. , Birge Raymond B.
Published: February 2005

Genetic studies in Caenorhabiditis elegans identified an evolutionarily conserved CED‐2 (CrkII), CED‐5 (DOCK180), CED‐12 (ELMO), CED‐10 (Rac1) module important for cell migration and phagocytosis of apoptotic cells. Previous studies have shown that DOCK180 and ELMO comprise an unconventional bipartite Dbl homology domain‐independent Rac guanine nucleotide exchange factor (Rac‐GEF); but it is still unclear how CrkII functions in Rac‐GEF activity. In this study, we have characterized a unique function of CrkII in phagocytosis and Rac activation mediated by the C‐terminal SH3 domain, a region of CrkII that has no clear cellular or biochemical function. We found that mutations that disrupt the C‐terminal SH3 domain of CrkII (CrkII‐SH3‐C) abrogate engulfment of apoptotic cells and impair cell spreading on extracellular matrix. Surprisingly, despite the effects on engulfment, W276K CrkII strongly potentiated Rac‐GTP loading when ectopically expressed in HEK 293T cells. Contrary to the effects of the true dominant negative SH2 domain mutants (R38K CrkII) and SH3‐N domain mutants (W170K CrkII) that prevent macromolecular assembly of signaling proteins, W276K CrkII increases association between DOCK180 and CrkII as well as constitutive tethering of the Crk/DOCK180/ELMO protein complex that interacted with RhoG. Our results indicate that while N‐terminal SH3 of CrkII promotes assembly between CrkII and DOCK180, the C‐terminal SH3 of CrkII regulates the stability and turnover of the DOCK180/ELMO complex. Studies with W276K CrkII may offer a unique opportunity to study the structure and function of the DOCK180/ELMO Rac‐GEF. © 2005 Wiley‐Liss, Inc.
Insulin‐like growth factor binding protein‐5 (IGFBP‐5) interacts with thrombospondin‐1 to induce negative regulatory effects on IGF‐I actions
Authors: Moralez Anna M. , Maile Laura A. , Clarke Jane , Busby Walker H. , Clemmons David R.
Published: February 2005

Insulin‐like growth factor binding protein‐5 (IGFBP‐5) and thrombospondin‐1 (TS‐1) are both present in extracellular matrix (ECM). Both proteins have been shown to bind to one another with high affinity. The purpose of these studies was to determine how the interaction between IGFBP‐5 and TS‐1 modulates IGF‐I actions in porcine aortic smooth muscle cells (pSMC) in culture. The addition of increasing concentrations of TS‐1 to pSMC cultures enhanced the protein synthesis and cell migration responses to IGF‐I; whereas the addition of IGFBP‐5 alone resulted in minimal changes. In contrast, the addition of IGFBP‐5 to cultures that were also exposed to IGF‐I and TS‐1 resulted in inhibition of protein synthesis. When the cell migration response was assessed, the response to IGF‐I plus TS‐1 was also significantly inhibited by the addition of IGFBP‐5, whereas 1.0 μg/ml of IGFBP‐5 alone had no effect on the response to IGF‐I.To determine the molecular mechanism by which this inhibition occurred, a mutant form of IGFBP‐5 that does not bind to IGF‐I was tested. This mutant was equipotent compared to native IGFBP‐5 in its ability to inhibit both protein synthesis and cell migration responses to IGF‐I plus TS‐1 thus excluding the possibility that IGFBP‐5 was inhibiting the response to TS‐1 and IGF‐I by inhibiting IGF‐I binding to the IGF‐I receptor. To determine if an interaction between TS‐1 and IGFBP‐5 was the primary determinant of the inhibitory effect of IGFBP‐5, an IGFBP‐5 mutant that bound poorly to TS‐1 was utilized. The addition of 1.0 μg/ml of this mutant did not inhibit the protein synthesis or cell migration responses to IGF‐I plus TS‐1. To determine the mechanism by which IGFBP‐5 binding to TS‐1 inhibited cellular responses to TS‐1 plus IGF‐I, TS‐1 binding to integrin associated protein (IAP) was assessed. The addition of IGFBP‐5 (1.0 μg/ml) inhibited TS‐1–IAP association. In contrast, a mutant form of IGFBP‐5 that bound poorly to TS‐1 had a minimal effect on TS‐1 binding to IAP. Further analysis showed that IGFBP‐5 addition altered the ability of TS‐1 to modulate the SHPS‐1/IAP interaction. When the IGFBP‐5 mutant that did not bind to IGF‐I was incubated with TS‐1 and IGF‐I, it inhibited the capacity of TS‐1 to enhance the IGF‐I receptor phosphorylation and MAP kinase activation in response to IGF‐I. In contrast, the IGFBP‐5 mutant that did not bind to TS‐1 had no effect on IGF‐I stimulated IGF‐I receptor phosphorylation or MAP kinase activation. These results indicate that IGFBP‐5 inhibits the binding of TS‐1 to IAP, and this results in an alteration of the ability of TS‐1 to modulate the disruption of the IAP/SHPS‐1 interaction which leads to attenuation of the ability of TS‐1 to enhance cellular responsiveness to IGF‐I. © 2005 Wiley‐Liss, Inc.
A Low Curing Temperature Silver Ink for Use in Ink‐Jet Printing and Subsequent Production of Conductive Tracks
Authors: Dearden Angela L. , Smith Patrick J. , Shin Dong‐Youn , Reis Nuno , Derby Brian , O'Brien Paul
Published: February 2005

Summary: A drop‐on‐demand ink‐jet printer has been used to print a silver‐organic solution onto glass substrates. Conductive silver tracks were obtained by heat treatment of the ink‐jet printed deposits at temperatures ranging from 125 °C–200 °C in air. Resistivity values were found to have dropped to two to three times the theoretical resisitivity of bulk silver after temperatures of 150 °C and above were used.

Resistivity values of a silver‐based ink.

magnified image

Resistivity values of a silver‐based ink.
Diffuse Interface Modeling of Droplet Impact on a Pre‐Patterned Solid Surface
Authors: Khatavkar Vinayak V. , Anderson Patrick D. , Duineveld Paul C. , Meijer Han H. E.
Published: February 2005

Summary: The impact of a droplet on a solid surface, pre‐patterned with a barrier, was studied using a diffuse interface model. The effect of the wettability of the barrier material and the width of the barrier on droplet spreading was investigated. The results show that depending on the barrier wettability and width, the flow of the spreading droplet can be controlled and that the droplet may or may not overflow the barrier.

Droplet shapes with the corresponding velocity field for different barrier contact angles at ± = 1.5.

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Droplet shapes with the corresponding velocity field for different barrier contact angles at ± = 1.5.
Polymer‐Based Rectifying Diodes on a Glass Substrate Fabricated by Ink‐Jet Printing
Authors: Liu Yi , Cui Tianhong
Published: February 2005

Summary: The fabrication of polymer diodes on a glass substrate by an ink‐jet printing technique is reported. Both an n‐type semiconductive polymer, poly[2‐methoxy‐5‐(2‐ethylhexyloxy)‐1,4‐(1‐cyanovinylene)phenylene] (CN‐PPV), and a p‐type semiconductive polymer, polypyrrole (PPy) or poly(3,4‐ethylenedioxythiophene) (PEDOT), were printed through a piezoelectric ink‐jet printer. The printed CN‐PPV/PPy and CN‐PPV/PEDOT diodes showed good rectifying characteristics. These results indicate the potential of the low‐cost ink‐jet printing technique to produce polymer microelectronic devices and circuits.

Schematic diagram of the printed polymer diode

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Schematic diagram of the printed polymer diode
Ink‐Jet Printing of Functional Polymers and Materials: First International Workshop in Eindhoven
Authors: de Gans B.‐J. , Schubert U. S.
Published: February 2005

This section contains reports on topical conferences. Reports are usually written at the request of the editorial office, but unsolicited contributions are also welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de.
Ink‐Jet Printing of Linear and Star Polymers
Authors: de Gans Berend‐Jan , Xue Lijing , Agarwal Uday S. , Schubert Ulrich S.
Published: February 2005

Summary: The influence of architecture on ink‐jet printability of polymer solutions is investigated by comparing linear and 6‐arm star PMMA. At comparable concentration and molecular weight, filament formation is much more pronounced for linear PMMA than for star PMMA. Visual examination of filament stretching allows estimation of the involved elongation rates, which are at high voltages sufficiently large for coil‐stretch transition of the chains, suggesting its role in filament formation.

The results obtained in this study suggest a possible role of the coil‐stretch transition of the polymer chains in filament formation.

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The results obtained in this study suggest a possible role of the coil‐stretch transition of the polymer chains in filament formation.
Polymerization of Aniline by Auric Acid: Formation of Gold Decorated Polyaniline Nanoballs
Authors: Mallick Kaushik , Witcomb Mike J. , Dinsmore Andy , Scurrell Mike S.
Published: February 2005

Summary: We report a new method for the preparation of polyaniline nanoballs by using HAuCl4 as an oxidizing agent. During the reaction, aniline is oxidized and forms polyaniline whilst the hydrogen tetrachloroaurate is reduced and forms gold nanoparticles. These gold nanoparticles are found to decorate the nanoballs.

The resultant precipitate and corresponding TEM image of the gold‐nanoparticle covered polyaniline nanoball.

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The resultant precipitate and corresponding TEM image of the gold‐nanoparticle covered polyaniline nanoball.
Functionalization of the active chain ends of poly(vinyl chloride) obtained by single‐electron‐transfer/degenerative‐chain‐transfer mediated living radical polymerization: Synthesis of telechelic α,ω‐di(hydroxy)poly(vinyl chloride)
Authors: Percec Virgil , Popov Anatoliy V.
Published: February 2005

The chloroiodomethyl chain ends of poly(vinyl chloride) (PVC) obtained by the single‐electron‐transfer/degenerative‐chain‐transfer mediated living radical polymerization of vinyl chloride initiated with iodoform were quantitatively functionalized by the reaction with 2‐allyloxyethanol (CH2CHCH2OCH2CH2OH). This reaction was performed in dimethyl sulfoxide at 70 °C and was catalyzed by sodium dithionite/sodium bicarbonate. The resulting product is the first example of telechelic PVC [α,ω‐di(hydroxy)PVC]. A possible mechanism for this reaction was suggested. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1255–1260, 2005
Room‐temperature 1.53 µm emission in Er3+‐doped PbWO4 single crystals
Authors: Huang Yanlin , Seo Hyo Jin , Zhu Wenliang , Yang Yu
Published: February 2005

In this work, room temperature 1.53 µm emissions were investigated for the first time in Er3+‐doped PbWO4 crystals. J–O calculations demonstrated that the high rates of nonradiative relaxation from the excited states to the level 4I13/2 ensure its effective population. Consequently there is a possibility of generation of stimulated emission based on the 4I13/2 → 4I15/2 transition. Fluorescence intensity and lifetime of 1.53 µm emission (4I13/2 → 4I15/2) with a wider full wave at half maximum show a dependence on crystal orientation, which become stronger with increasing Er3+ doping. Annealing exerts a distinct influence on the 1.53 µm emission and its fluorescence lifetime in PbWO4:Er3+ crystals, which might be caused by a reduction of defects in the lattice and to make Er3+ ions optically active. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Withdrawal: Dependence of giant magnetoresistance on the thicknesses of magnetic and nonmagnetic layers in dual spin valves [phys. stat. sol. (a) 201, 2995 (2004)]
Authors: Wang Yong , Xu Ming , Mai Zhenhong
Published: February 2005

The authors withdraw their article published in phys. stat. sol. (a) 201, 2995 (2004). (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Investigation of copper doped InP single crystals grown by Czochralski technique for use in X‐ray detection
Authors: Zdansky K. , Zavadil J. , Pekarek L. , Gorodynskyy V. , Kozak H.
Published: February 2005

Copper doped InP crystals were synthesized by Bridgman method and further grown by Czochralski technique. Samples of as grown crystals were of n‐type conductivity with the estimated concentration of copper smaller than 5 × 1015 cm–3. The electron mobility in these samples is largely reduced at low temperatures, which is attributed to a strong scattering of electrons on copper impurities similar to other atomic impurities with partly occupied 3d shells. The samples were converted to p‐type semi‐insulating state after annealing at 500 °C and quenched to room temperature. The energy of copper acceptor causing the semi‐insulating state was determined by temperature dependent Hall measurements as 0.29 eV in agreement with the low temperature photoluminescence spectroscopy. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High spatial resolution micro‐Raman temperature measurements of nitride devices (FETs and light emitters)
Authors: Kuball M. , Pomeroy J. W. , Rajasingam S. , Sarua A. , Uren M. J. , Martin T. , Lell A. , Härle V.
Published: February 2005

Knowledge of the temperature in the active area of III‐nitride semiconductor devices such as AlGaN/GaN HFETs is essential for optimizing device design, performance and reliability, however, direct measurement of this temperature is not readily achieved. Infrared techniques often employed to measure the temperature of an active device are not well suited for AlGaN/GaN HFETs due to their limited spatial resolution when compared with the only micron‐size source‐drain device openings. The novel use of micro‐Raman spectroscopy for in‐situ measurements of device temperature, i.e., self‐heating effects, in single‐ and multi‐finger AlGaN/GaN HFETs with micrometer‐size resolution is discussed. Effects of device design on device temperature are illustrated. Variations in device temperature over a full wafer are studied considering that device reliability is strongly affected by device temperature. Applications of the technique to opto‐electronic devices in particular to InGaN/GaN laser diodes are also presented. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Resonant Raman spectroscopy on InN
Authors: Kuball M. , Pomeroy J. W. , Wintrebert‐Fouquet M. , Butcher K. S. A. , Lu Hai , Schaff W. J. , Shubina T. V. , Ivanov S. V. , Vasson A. , Leymarie J.
Published: February 2005

The novel use of resonant Raman spectroscopy to elucidate the band gap of InN is illustrated in a study of MBE‐grown films. This technique can distinguish between electronic transitions related to the InN from transitions related to defects and impurities that are so typical for current InN material. Using excitation energies from 1.49 eV (830 nm) to 2.54 eV (488 nm), we identify a critical point in the InN band structure within ≈200–300 meV below 1.5 eV. The origin of this critical point, whether band gap or higher critical point, is discussed. Furthermore, Raman results are presented on the temperature dependence of the InN phonons. Analysis of the data provides information on phonon lifetimes and decay mechanisms, important to assess whether hot phonon effects need to be considered in future InN devices. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical characterisation of Bi‐doped GaN films grown by molecular beam epitaxy
Authors: Ibáñez J. , Pastor D. , Cuscó R. , Artús L. , Avella M. , Jiménez J. , Novikov S. V. , Foxon C. T.
Published: February 2005

We use cathodoluminescence and Raman spectroscopy to investigate GaN layers grown by plasma‐assisted molecular beam epitaxy with different Bi fluxes. We find that the growth of GaN with an additional Bi flux favours the formation of submicron cubic domains, which results in layers with reduced crystalline quality and lower luminescence emission. We detect a Bi‐related Raman feature at low frequencies that we tentatively assign to local Bi modes in GaN, which indicates that a fraction of Bi atoms incorporates into the GaN lattice. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Molecular structural conformations and hydration of internally hydrogen‐bonded salicylic acid: Ab initio and DFT studies
Authors: Anandan K. , Kolandaivel P. , Kumaresan R.
Published: February 2005

We studied molecular structural conformations and hydration of internally hydrogen‐bonded salicylic acid using ab initio and density functional theory methods. Molecular geometries and energetical parameters were obtained in gaseous phase using MP2 and B3LYP levels of theory, implementing the 6‐311G(2d,2p) atomic basis set. Chemical hardness and chemical potential were calculated at HF/6‐311G(2d,2p) level of theory for all the optimized structures, and the principle of maximum hardness was tested. The condensed Fukui functions were calculated using the atomic charges obtained through a natural population analysis scheme for all optimized structures at B3LYP/6‐311G(2d,2p) level of theory, and the most reactive sites of the molecules were identified. NMR studies were carried out for all the conformers in gaseous phase on the basis of Cheeseman et al.'s method at B3LYP/6‐311G(2d,2p) level of theory; the calculated chemical shift values are discussed. The self‐consistent reaction field theory (SCRF) was used to optimize all the conformers in aqueous phase (ε = 78.39) at B3LYP/6‐311G(2d,2p) level of theory and the solvent effect was studied. The geometrical and energetical parameters of all the conformers are compared and analyzed. The dimeric structure of the most stable conformer in the gaseous phase was optimized at B3LYP/6‐311G(2d,2p) level of theory and the interaction energy studied. Selected conformers were allowed to interact with water molecule; optimized parameters are discussed. Vibrational frequency analyses were performed at MP2/6‐311G(2d,2p) level of theory and the stationary point corresponding to local minima without imaginary frequencies are obtained for all the optimized structures. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005