bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire loads in commercial premises
Authors: Zalok E. , Hadjisophocleous G. V. , Mehaffey J. R.
Published: September 2008

This paper presents the results of a survey conducted in the Canadian cities of Ottawa and Gatineau to characterize fire loads in commercial premises. The survey included various commercial establishments such as restaurants, travel agencies, and pharmacies, as well as, retail stores selling clothing, shoes, food, alcohol, computers, and computer supplies. Five different types of combustible material groups were selected as the base of analyses: textiles, plastics, wood/paper, food, and miscellaneous. The data collected were analyzed to determine the total fire load in each establishment, the fire load density, and the contribution of different combustible materials to the total fire load. A total of 168 commercial premises were surveyed with a total floor area of 17127 m2. The area of the surveyed stores ranged from 3.25 to 1707 m2. The fire load densities of the 168 surveyed stores had a lognormal distribution with a mean value of 747 MJ/m2, a maximum value of 5305 MJ/m2, a minimum value of 56 MJ/m2, and a standard deviation of 833 MJ/m2. In most stores, the 95th percentile and the mean fire load density showed a tendency to decrease with an increase of floor area, which is consistent with those of earlier surveys. Copyright © 2008 John Wiley & Sons, Ltd.
Prenatal and perinatal risk factors for neuroblastoma
Authors: Bluhm Elizabeth , McNeil Dawn Elizabeth , Cnattingius Sven , Gridley Gloria , El Ghormli Laure , Fraumeni Joseph F.
Published: September 2008

Neuroblastoma is a rare embryonal tumor of childhood for which risk factors are not well known. Using a nested case–control design, we investigated prenatal, perinatal and neonatal risk factors in detail by linking 245 pediatric neuroblastoma cases identified in the Swedish Cancer Register diagnosed in the year 1973–1995 with the Swedish Medical Birth Register. Five living controls per case were randomly selected from the birth registry, matched by gender and age. Increased risks were associated with maternal anemia during pregnancy (odds ratio (OR) = 2.95, 95% confidence interval (CI): 1.53, 5.69), neonatal respiratory distress (OR = 3.61, 95% CI: 1.41, 9.24) and low (below or equal to 7) 1‐min Apgar score (OR = 2.23, 95% CI: 1.41, 3.52). Increased risks were limited to cases diagnosed before 1 year of age. Markers of prenatal, perinatal and neonatal distress may be associated with neuroblastoma in infancy, but not with diagnoses at 1 year or above. Published 2008 Wiley‐Liss, Inc.
Selective expression of inhibitory Fcγ receptor by metastatic melanoma impairs tumor susceptibility to IgG‐dependent cellular response
Authors: Cassard Lydie , Cohen‐Solal Joel F.G. , Fournier Emilie M. , Camilleri‐Broët Sophie , Spatz Alain , Chouaïb Salem , Badoual Cécile , Varin Audrey , Fisson Sylvain , Duvillard Pierre , Boix Charlotte , Loncar Shannon M. , Sastre‐Garau Xavier , Houghton Alan N. , Avril Marie‐Françoise , Gresser Ion , Fridman Wolf H. , Sautès‐Fridman Catherine
Published: September 2008

During melanoma progression, patients develop anti‐tumor immunity including the production of anti‐tumor antibodies. Although the strategies developed by malignant cells to escape anti‐tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (FcγR) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the FcγRIIB1, an inhibitory isoform of FcγR. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of FcγRIIB is restricted to melanoma and is acquired during tumor progression. We show that FcγRIIB expression prevents the lysis of human metastatic melanoma cells by NK cell‐mediated antibody‐dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of FcγRIIB. Using experimental mouse models, we demonstrate that expression of FcγRIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti‐tumor IgG in vivo. Thus, our results identify FcγRIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to FcγR‐dependent innate effector responses. © 2008 Wiley‐Liss, Inc.
Lysophosphatidic acid activates telomerase in ovarian cancer cells through hypoxia‐inducible factor‐1α and the PI3K pathway
Authors: Yang Kun , Zheng Danhua , Deng Xiaoli , Bai Lin , Xu Yan , Cong Yu‐Sheng
Published: September 2008

Telomerase is reactivated in over 90% of tumors and plays critical roles in tumor progression. The mechanisms by which telomerase is up‐regulated in cancer cells are poorly understood. Here we showed that a bioactive lipid, lysophophatidic acid (LPA), up‐regulated the expression of human telomerase reverse transcriptase (hTERT) and telomerase activity in serous ovarian adenocarcinoma cell lines SKOV3, A2780, and HEY, but not in OCC1, a clear cell ovarian cancer cell line. This cell type specific effect of LPA on telomerase regulation may reflect distinctive genetic backgrounds in different histological subtype of ovarian cancer cells. Our data further suggest that the phosphatidylinositol 3‐phosphate kinase (PI3K) pathway and hypoxia‐inducible factor‐1α (HIF‐1α) are likely to be involved in LPA‐induced hTERT expression. Targeting human telomerase by LPA is potentially involved in its role of promoting tumor progression. J. Cell. Biochem. 105: 1194–1201, 2008. © 2008 Wiley‐Liss, Inc.
Multicultural competence and evidence‐based practice in group therapy
Authors: Chen Eric C. , Kakkad Dhruvi , Balzano Julie
Published: September 2008

The multicultural competence (MC) and evidence‐based practice (EBP) initiatives have each generated healthy debates in the mental health field, with ample implications for clinical training and practice. Using two case illustrations, we highlight practical challenges and prospects in the intersection of MC and EBP. To facilitate complementary practice of MC and EBP, we offer strategies for the group therapist as a “local clinical scientist” to deliver culturally responsive treatments. We stress the importance of cultural adaptation of EBP models, namely, modifying evidence‐based interventions that involve changes in service delivery, in the nature of the therapeutic relationship, or in components of the treatment itself to accommodate the cultural beliefs and behaviors of racial‐cultural minority clients. Cultural adaptation of EBP in group therapy needs to be grounded in developmental contextualism and social justice. We discuss the two cases with an eye toward advancing multicultural competence in group therapy. © 2008 Wiley Periodicals, Inc. J Clin Psychol: In Session 64:1–18, 2008.
Intrinsic disorder explains diverse nuclear roles of chromatin remodeling proteins
Authors: Sandhu Kuljeet Singh
Published: September 2008

Chromatin remodelers, a group of proteins involved in nucleosome re‐positioning and modification, have extensive range of interacting partners. They form multimeric complexes and interact with modified histones, transcription, splicing, and replication factors, DNA, RNA, and the factors related to the maintenance of chromosome structure. Such diverse range of interactions is hard to explain with the presumed highly structured form of the protein. In the current analysis, the conformations of chromatin remodelers were explored using protein disorder prediction algorithms. The study revealed that a significant proportion (p < 2.2e‐16) of these proteins harbor at least one long region of intrinsic disorder (>70 aa). These unstructured regions do not exhibit any preference to the N/C terminal or middle of the protein. They do not show any significant representation in the Protein Data Bank (PDB) structure repository. Limited examples from PDB indicate direct involvement of disordered regions in binding of chromatin remodeling proteins to naked or modified DNA, histones, and other chromatin‐related factors. Furthermore, intrinsic disorder seen in these proteins correlates to the presence of low sequence complexity regions (p = 1.851e‐10) particularly the tandem repeats of hydrophilic and charged amino acids. This probably hints at their evolutionary origin via repeat expansion. The disordered regions may enable these proteins to reversibly bind to various interacting partners and eventually contribute to functional diversity and specialization of chromatin remodeling complexes. These could also endow combinatorial action of multiple domains within a protein. We further discuss the prominent association of intrinsic disorder with other chromatin‐related proteins and its functional relevance therein. Copyright © 2008 John Wiley & Sons, Ltd.
Gallbladder cancer (GBC): 10‐year experience at Memorial Sloan‐Kettering Cancer Centre (MSKCC)
Authors: Duffy A. , Capanu M. , Abou‐Alfa G.K. , Huitzil D. , Jarnagin W. , Fong Y. , D'Angelica M. , DeMatteo R.P. , Blumgart L.H. , O'Reilly E.M.
Published: September 2008

Background

The incidence of gallbladder cancer (GBC) in the US is 1.2/100,000. This report examines the patterns of presentation, adjuvant treatment and survival of a large cohort of patients with GBC evaluated at MSKCC over a 10‐year period.

Methods

A retrospective analysis of patients referred to MSKCC with a diagnosis of GBC between January 1995 and December 2005 was performed. Patients were identified from the MSKCC cancer registry. Information extracted included, demographics, clinical and pathological stage, surgical management, pathology, adjuvant and palliative therapy, date of relapse, death or last follow‐up. Date of diagnosis was defined as date of surgery or biopsy. Survival curves were estimated using the Kaplan–Meier method and compared using the log‐rank test.

Results

Four hundred thirty‐five GBC cases were identified: 285 (65.5%) females,150 (34.5%) males. Median age 67 years (range 28–100). Pathology: 88% adenocarcinoma, 4% squamous, 3% neuroendocrine, 2% sarcoma. 36.6% presented as AJCC Stage IV. 47% were discovered incidentally at laparoscopic cholecystectomy. One hundred thirty‐six of these were re‐explored, of whom 100 (73.5%) had residual disease. Of those who underwent curative resections (N = 123), 8 (6.5%) received adjuvant chemotherapy, 8 (6.5%) chemoradiation alone and 8 (6.5%) both chemoradiation and systemic chemotherapy. Median overall survival for the cohort was 10.3 months (95% CI 8.8–11.8) with a median follow up of 26.6 months. The median survival for those presenting with stage Ia–III disease was 12.9 months (95% CI 11.7–15.8 months) and 5.8 months (95% CI 4.5–6.7) for those presenting with stage IV disease. Median survival was 15.7 months (95% CI 12.4–18.4) for those discovered incidentally at laparoscopic cholecystectomy. For those who underwent re‐exploration, median survival was 14.6 months (95% CI 12.6–18.3) if residual disease was present, and 72 months (95% CI 34 to infinity) if no evidence of disease. The median survival for those who received adjuvant therapy was 23.4 months (95% CI 15.7–47).

Conclusions

GBC is commonly diagnosed incidentally (47%). Re‐exploration reveals a high incidence of residual disease (74%). Median survival is better for patients who have no evidence of disease on re‐exploration (72 months) compared to those with residual disease detected (P < 0.0001). Overall prognosis is poor. Although we did not observe a survival benefit for those who received adjuvant therapy, the study did not have sufficient power to address this question. In addition, the number of patients who received adjuvant therapy was small with marked heterogeneity in clinical and therapeutic details, precluding any definitive conclusions being drawn. Prospective randomized trials of adjuvant therapy are needed in this disease. J. Surg. Oncol. 2008;98:485–489. © 2008 Wiley‐Liss, Inc.
A network management tool for resource‐partition based layer 1 virtual private networks
Authors: Wu Jing , Savoie Michel , Campbell Scott , Zhang Hanxi
Published: September 2008

A Layer 1 Virtual Private Network (L1‐VPN) has two models for service management: the resource‐partition based model and the domain‐service based model. In this paper, we present a network management tool for resource‐partition based L1‐VPNs. A Transaction Language One (TL1) proxy is designed to achieve resource partitioning at the network element level. Building on top of a TL1 proxy, we implemented a User‐Controlled LightPath (UCLP) system to support physical network brokers to assign and allocate virtually dedicated resources to customers, and to enable customers to directly manage their resources. With such a capability, customers are able to create wide area networks based on their traffic pattern, and to adjust their traffic pattern based on available resources. Copyright © 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Testing the psychometric properties of a Chinese version of the Level of Expressed Emotion scale
Authors: Chien Wai‐Tong , Chan Sally W.C.
Published: September 2008

Expressed emotion of families of people with schizophrenia is useful and important to evaluate the effects of family interventions. This study tested the reliability and validity of a Chinese version of the Level of Expressed Emotion scale. This psychometric analysis included tests of content validity and reliability, and an exploratory factor analysis. Results indicated that the Chinese version had a high level of equivalence with the original English version and demonstrated good internal consistency and test–retest reliability. The refined 52‐item Chinese version consisted of four factors, indicating satisfactory correlation with two theoretically relevant scales. The Chinese version appears psychometrically sound as a measure of schizophrenic patients' perceptions of their family members' expressed emotion. © 2008 Wiley Periodicals, Inc. Res Nurs Health 32:59–70, 2009
Locally divergence‐preserving schemes of higher order
Authors: Artebrant Robert
Published: September 2008

Violation of the divergence constraint on the magnetic flux density in magnetohydrodynamical (MHD) simulations leads to stability problems. It is therefore of great importance to numerically respect this intrinsic constraint. Since the divergence preservation is a local phenomenon inherent in the MHD‐system it is appealing to mimic this property numerically by a locally divergence‐preserving scheme.

A common numerical technique for simulation of the MHD‐system of conservation laws is the finite volume (FV) method. In [SISC 26 2005 pp. 1166] a local procedure to redistribute the numerical fluxes in a FV‐scheme so that a discrete divergence operator vanishes was presented. This procedure stabilizes the base scheme and respects the accuracy to the second order level.

The present note describes a development of the above procedure that complies with the finite volume framework, preserves a fourth order discrete divergence operator locally and retains the accuracy of a generic semi‐discrete finite volume scheme up to fourth order. The redistribution of the numerical magnetic field fluxes is formulated in a standard conservative setting, making it trivial to implement the divergence‐preserving modification in an existing FV‐scheme; see [JCP 227 2008 pp.3405] for the details. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Jamming, plasticity and diffusion in dense granular materials
Authors: Behringer R.P.
Published: September 2008

In this paper, we present experimental results based on photoelastic techniques that allow us to obtain complete details of processes in dense granular materials. This work focuses in particular on the jamming transition and on the nature of affine and non‐affine deformations in the shear band occuring in granular Couette flow. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Applications on variational inequalities involving multivalued maps
Authors: Benedetti Irene , Zecca Pietro
Published: September 2008

We present a connection between variational inequalities of Stampacchia's type involving multivalued maps and partial differential inclusions. We solve the variational inequalities considered and, as a consequence, the differential inclusion associated, using the topological degree theory. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The balance of material momentum at a shock wave propagating in a thermo‐elastic material
Authors: Braun Manfred
Published: September 2008

At a surface of discontinuity, the mechanical balance laws are represented by jump conditions. It is shown how the balance of material momentum at an adiabatic shock propagating in a thermo‐elastic material is obtained from the discontinuous balances of physical momentum and energy. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Some software aspects of DAE simulation & optimization software
Authors: Campbel S. L. , Betts J. T. , Engelsone A. , Nikoukhah R. , Najafi M.
Published: September 2008

Considerable numerical software has been written for simulation and optimization of dynamical systems. From the beginning of their development, differential algebraic equations (DAEs) have often been proposed as a way to make modeling easier. The modeler need only write down equations relating the variables in the model. However, much DAE software requires at least as much user numerical and mathematical expertise as explicit methods. An important aspect of our research has been working toward helping the idea of DAEs achieve its promise in modeling and simulation by both pushing the software to handle more general problems and to also allow for less user expertise. Some recent examples are presented where this research impacts on software and their underlying algorithms. Space necessitates we assume the reader has a rough idea of what a DAE is. The examples are implicit Scicos, and optimization of DAE models. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Blind source separation and automatic transcription of music using tensor decompositions
Authors: FitzGerald Derry
Published: September 2008

Recent advances in the use of tensor decompositions for the analysis of music are described. In particular, the use of such decompositions for sound source separation and the automatic transcription of music are explored. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Global instability computations of separated flows
Authors: Logue R.P. , Gajjar J. , Ruban A.
Published: September 2008

The primary motivation for the current work is to develop suitable techniques for studying the global instability in many different flows such as that occuring in the subsonic flow past a corner. In this paper we will discuss the methodology and some of the results obtained. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The cosymmetric bifurcations in the planar filtrational convection problem: numerical results
Authors: Govorukhin V.N. , Shevchenko I.V.
Published: September 2008

Here we present survey of our numerical results concerning possible bifurcation in cosymmetric filtrational convection problem. We study bifurcations connected with existence of cycles of equilibria and scenarios for onset of unsteady regimes. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Interaction of point defects in ferroelectrics ‐parameter identification and simulation
Authors: Goy Oliver , Mueller Ralf , Gross Dietmar
Published: September 2008

Ferroelectric materials are used in a wide field of applications, where they are exposed to a high number of mechanical and electrical load cycles. This involves degradation of the material and a decrease of the electromechanical coupling capability, which is usually called electric fatigue. The causes are assumed to be ionic and electronic charge carriers, which interact with each other, with microstructural elements in the bulk and with interfaces. Accumulation of defects can lead to degradation, mechanical damage and dissociation reactions, for more details see e.g. [3].

In order to get a better understanding of the defect accumulation processes, a model based on material forces is used in [6] to simulate the interaction of defects in periodic and in infinite cells. Applying thermodynamically reasonable kinetic laws, defect migration is simulated in a deterministic way in order to understand the general tendency of defect formations. The transversally isotropic material is modelled with linear electromechanical coupling. Here, the defect parameters used in the continuum model are obtained by fitting the results of molecular dynamics (MD) simulations to the continuous spatial fields. Transferring data from the atomic to the continuum level is a field of active research and no unique solution can be presented. On the atomic level, Coulomb–interaction causes a displacement field incompatible to an elastic solution. To address this difficulty, the volume change of a domain around the defect is used to determine defect parameters. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
One‐shot multigrid method for aerodynamic shape optimization
Authors: Hazra Subhendu Bikash
Published: September 2008

This paper presents a numerical method for aerodynamic shape optimization problems. It is based on simultaneous pseudotime‐stepping in which the optimality is reached simultaneously with the state and costate feasibility. An optimization‐based multigrid strategy results in efficient convergence of the method. The total effort of optimization is less than two forward simulation runs. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Amplitude‐dependent phenomena of filler‐reinforced rubber: Experiments, modelling and simulation
Authors: Höfer Philipp , Lion Alexander
Published: September 2008

It's a matter of common knowledge, that carbon black‐or silica‐loaded elastomers show a pronounced nonlinearity when excited with dynamic deformation amplitudes, namely the Payne‐effect. Furthermore, several experiments prove a very complex history‐dependence and significant recovery‐behaviour of this effect. In the present paper, a few experimental results of dynamical measurements on filler‐loaded rubber are shown with importance attached to the complicated history dependence. In order to describe the depicted phenomena, a model, based on intrinsic time scales is presented with corresponding simulation results. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Energy functionals for microstructured multi‐phase materials
Authors: Langhoff T.‐A. , Böhlke T. , Schnack E.
Published: September 2008

For describing the influence of multi‐phase materials with microstructure on different length scales as well as the evolution of phase changes under thermomechanical loading, an energetic model is developed. Relying on the incremental formulation of the energetic model, a new solution procedure for the coupled thermomechanical problem is proposed. This model can be applied to describe e.g. the macroscopic response of carbon fibre reinforced carbon. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Jamming in attractive granular media
Authors: Lois Gregg , Blawzdziewicz Jerzy , O'Hern Corey S.
Published: September 2008

The jamming transition is studied numerically in systems of particles with attraction. Unlike the purely repulsive case where a single transition separates the jammed from unjammed phase, the presence of even an infinitesimal amount of attraction yields two distinct transitions: connectivity and rigidity percolation. We measure critical exponents of these two percolation transitions and find that they are different than the corresponding lattice values. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Blow‐up and regularity problems of hypoviscous fluid equations
Authors: Ohkitani Koji
Published: September 2008

We consider 1D Burgers equation with hypoviscosity at a critical exponent under periodic boundary conditions. Assuming global (in time) regularity, we derive an asymptotic equation by a simple transformation. It turned out that it has exactly the same form as the one obtained by applying Moore's asymptotic analysis, originally developed for the Birkhoff‐Rott equation, to the inviscid Burgers equation. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
δ ‐ and δ ′‐shocks and the transportation and concentration processes
Authors: Shelkovich V.M.
Published: September 2008

Using the definitions of δ ‐ and δ ′‐shocks for some systems of conservation laws, the corresponding Rankine–Hugoniot conditions are derived. We also derive the balance laws describing area, volume, mass and momentum transportation between the area outside the wave front and the wave front. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An improved scheme for accelerating the convergence of the simulated annealing algorithm applied to real world problems
Authors: Verdiell Adriana Beatriz , Maciel María Cristina , Vidal Marta Cecilia
Published: September 2008

When formulated in mathematical terms, the problem of zoning a protected natural area subject to both box and spatial constraints results in a large combinatorial optimization problem belonging to the NP‐hard class. These facts suggest the need to apply a heuristic approach. In this contribution a new proposal to decrease the control parameter, known as temperature, in the simulated annealing algorithm is presented. The strategy is based on that proposed by Lundy and Mees [4], and developed in order to decrease the running time of the algorithm applied to large scale problems. When applied to solving small‐size simulated problems, results were indistinguishable from those obtained via an exact, enumerative method.

A coarse‐scale zoning of Talampaya National Park (Argentina) rendered maps remarkably similar to those produced by subject area experts using a non‐quantitative consensus‐seeking approach. Results are encouraging and show particular potential for the periodical update of zoning of protected natural areas. Such a capability is crucial for application in developing countries where both human and financial resources are usually scarce but still critical for updating zoning and management plans. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optimal design of frames under stochastic uncertainties
Authors: Zier Simone
Published: September 2008

In the following the design of frames is treated where the load is supposed to be stochastic. The recourse problem will be formulated in the standard form of stochastic linear programming (SLP). After this formulation the recourse problem with discretization and the expected value problem are introduced as representatives of substitute problems. Subsequently, optimization results using these methods for the robust optimal design of a two‐storey frame are presented. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Transdermal buprenorphine in children with cancer‐related pain
Authors: Attinà Giorgio , Ruggiero Antonio , Maurizi Palma , Arlotta Annalisa , Chiaretti Antonio , Riccardi Riccardo
Published: September 2008

We present three cases of children (aged 3–5 years) in which cancer‐related pain was adequately controlled by Transdermal Buprenorphine. The endpoints for evaluating analgesic efficacy consisted of the assessment of pain using a visual scale and the possibility of reducing other pain treatment. Improvement of pain level was demonstrated by the decrease in pain scores, by reduction of the overall amount of medications, especially opioids, and by improvement of uninterrupted sleep. Only limited data is available on the use of Transdermal Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed good analgesia without significant side effects in these three children with cancer‐related pain. Pediatr Blood Cancer 2009;52:125–127. © 2008 Wiley‐Liss, Inc.
The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors
Authors: Kim AeRang , Ji Lingyun , Balmaceda Casilda , Diez Blanca , Kellie Stewart J. , Dunkel Ira J. , Gardner Sharon L. , Sposto Richard , Finlay Jonathan L.
Published: September 2008

Background

To determine the impact of diagnostic serum and/or cerebrospinal fluid (CSF) alpha‐fetoprotein (AFP) and beta‐human chorionic gonadotropin (b‐HCG) elevations on survival in newly diagnosed patients with central nervous system germ cell tumors (CNS GCT) treated with chemotherapy with the intent to avoid irradiation.

Procedure

Seventy‐five patients with newly diagnosed CNS GCT enrolled in two sequential internationally conducted clinical trials with serum and CSF AFP and b‐HCG levels available from initial diagnosis were retrospectively analyzed. Subjects received platinum based chemotherapy and were followed with serial imaging and tumor marker evaluations.

Results

The 5‐year overall survival (OS) and event free survival (EFS) for patients with normal tumor markers compared with those with elevated markers at diagnosis was 78% (95% CI 51–91%) versus 60% (95% CI 46–72%) (P = 0.08) and 22% (95% CI 7–43%) versus 28% (95% CI 16–40%) (P = 0.68). The hazard ratio of death for patients with elevated markers was 1.9 times as high as that for those with normal markers (95% CI 0.58–6.5) after adjusting for other baseline characteristics. There was no observed difference in survival among patients with histologically confirmed germinomas, irrespective of level of b‐HCG.

Conclusions

Patients with elevated tumor markers appear to have poorer OS independent of tumor histology, although these differences do not reach statistical significance (P ≤ 0.05). No differences were observed in EFS between groups likely due to the poor response of chemotherapy only approach to patients with normal markers. b‐HCG elevations in biopsy proven germinomas do not seem to alter a patient's prognosis. Pediatr Blood Cancer 2008;51:768–773. © 2008 Wiley‐Liss, Inc.
Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda according to HIV infection
Authors: Orem Jackson , Maganda Albert , Mbidde Edward Katongole , Weiderpass Elisabete
Published: September 2008

Background

Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before.

Procedure

We reviewed records at Uganda Cancer Institute (UCI) for years 1994–2004, to compare clinical features and outcome of BL in children who are HIV positive and negative (HIV+, HIV−). As statistical methods we used Student's t‐test, Chi‐square and Kaplan–Meier's to compare both groups.

Results

Of 1,462 records of children retrieved, 228 met the eligibility criteria and were reviewed (158 HIV−, 70 HIV+). There were 139 (61%) males and 89 (39%) females. The mean age was 6.9 years (HIV+ 6.7, HIV− 7.1). One hundred seventy‐one cases (75%) had facial tumor (HIV+ 71.4%, HIV− 76.6%). HIV positive children presented significantly with extrafacial disease (lymphadenopathy 67%, hepatic masses 51%, and thoracic masses 10%). Presentation with advanced stage disease occurred more frequently in HIV positive patients compared to HIV negative patients. Treatment response rates to chemotherapy were similar irrespective of HIV status. However, overall survival was poorer in HIV positive patients with a median survival of 11.79 months (P‐value < 0.000, 95% CI 8.65–14.92).

Conclusions

BL in Uganda presents frequently with facial disease irrespective of HIV status. However HIV+ BL also presents commonly with extra facial sites, mainly lymphadenopathy. There is no difference in response to treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is need for further characterization of BL in Uganda to understand the role of HIV in disease process and outcome. Pediatr. Blood Cancer © 2008 Wiley‐Liss, Inc.
Prevalence of and risk factors for prostatitis in African American men: The Flint Men's Health Study
Authors: Wallner Lauren P. , Clemens J. Quentin , Sarma Aruna V.
Published: September 2008

INTRODUCTION

Prostatitis is a common, yet ill‐defined condition without clear diagnostic criteria and treatment strategies. Previous studies examining the prevalence and correlates of prostatitis are limited in their inclusion of primarily white populations. The objective of the current study was to identify prevalence of and risk factors for prostatitis in a population‐based sample of African‐American men.

METHODS

In 1996, a probability sample of 703 African‐American men, aged 40–79, residing in Genesee County, Michigan without a prior history of prostate cancer/surgery provided responses to a structured interview‐administered questionnaire which elicited information regarding sociodemographics, current stress and health ratings, and past medical history, including history of physician diagnosed prostatitis, BPH and sexually transmitted diseases. Logistic regression was used to identify predictors of prostatitis after adjustment for age.

RESULTS

Forty‐seven (6.7%) of the 703 men reported a history of prostatitis. Increased frequency of sexual activity and physical activity were significantly associated with decreased odds of disease. Moderate to severe lower urinary tract symptoms (LUTS) and a history of BPH were significantly associated with prostatitis after adjustment for age.

CONCLUSION

After adjustment for age, LUTS severity and history of BPH were associated with increased odds of prostatitis. BMI, physical activity and sexual frequency were associated with decreased odds of prostatitis. Finally, poor emotional and physical health, high perceived stress and low social support were associated with an increased risk of prostatitis history. Importantly, these findings suggest that the primary risk factors for this condition are largely modifiable and highlight potential targets for future prevention. Prostate 69: 24–32, 2009. © 2008 Wiley–Liss, Inc.
Selected‐fit versus induced‐fit protein binding: Kinetic differences and mutational analysis
Authors: Weikl Thomas R. , von Deuster Carola
Published: September 2008

The binding of a ligand molecule to a protein is often accompanied by conformational changes of the protein. A central question is whether the ligand induces the conformational change (induced‐fit), or rather selects and stabilizes a complementary conformation from a pre‐existing equilibrium of ground and excited states of the protein (selected‐fit). We consider here the binding kinetics in a simple four‐state model of ligand–protein binding. In this model, the protein has two conformations, which can both bind the ligand. The first conformation is the ground state of the protein when the ligand is off, and the second conformation is the ground state when the ligand is bound. The induced‐fit mechanism corresponds to ligand binding in the unbound ground state, and the selected‐fit mechanism to ligand binding in the excited state. We find a simple, characteristic difference between the on‐ and off‐rates in the two mechanisms if the conformational relaxation into the ground states is fast. In the case of selected‐fit binding, the on‐rate depends on the conformational equilibrium constant, whereas the off‐rate is independent. In the case of induced‐fit binding, in contrast, the off‐rate depends on the conformational equilibrium, while the on‐rate is independent. Whether a protein binds a ligand via selected‐fit or induced‐fit thus may be revealed by mutations far from the protein's binding pocket, or other “perturbations” that only affect the conformational equilibrium. In the case of selected‐fit, such mutations will only change the on‐rate, and in the case of induced‐fit, only the off‐rate. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Molecular basis for dimer formation of TRβ variant D355R
Authors: Jouravel Natalia , Sablin Elena , Togashi Marie , Baxter John D. , Webb Paul , Fletterick Robert J.
Published: September 2008

Protein quality and stability are critical during protein purification for X‐ray crystallography. A target protein that is easy to manipulate and crystallize becomes a valuable product useful for high‐throughput crystallography for drug design and discovery. In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. The structure of D335R TR LBD mutant was solved using X‐ray crystallography and refined to 2.2 Å resolution with Rfree/R values of 24.5/21.7. The crystal asymmetric unit reveals the TR dimer with two molecules of the hormone‐bound LBD related by twofold symmetry. The ionic interface between the two LBDs comprises residues within loop H10‐H11 and loop H6‐H7 as well as the C‐terminal halves of helices 8 of both protomers. Direct intermolecular contacts formed between the introduced residue Arg 355 of one TR molecule and Glu 324 of the second molecule become a part of the extended dimerization interface of 1330 Å2 characteristic for a strong complex assembly that is additionally strengthened by buffer solutes. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Structural characterization of the α‐hemolysin monomer from Staphylococcus aureus
Authors: Meesters Christian , Brack Antje , Hellmann Nadja , Decker Heinz
Published: September 2008

α‐Hemolysin from Staphylococcus aureus is secreted as a water‐soluble monomer and assembles on membranes to oligomerize into a homo‐heptameric, water‐filled pore. These pores lead to lysis and cell death. Although the structure of the heptameric pore is solved by means of X‐ray crystallography, structures of intermediate states—from the soluble monomer to all potential “pre‐pore” structures—are yet unknown. Here, we propose a model of the monomeric α‐hemolysin in solution based on molecular modeling, verified by small angle X‐ray scattering data. This structure reveals details of the monomeric conformation of the α‐hemolysin, for example inherent flexibility, along with definite differences in comparison to the structures used as templates. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Substrate induced structural and dynamics changes in human phosphomevalonate kinase and implications for mechanism
Authors: Olson Andrew L. , Yao Huili , Herdendorf Timothy J. , Miziorko Henry M. , Hannongbua Supa , Saparpakorn Patchareenart , Cai Sheng , Sem Daniel S.
Published: September 2008

Phosphomevalonate kinase (PMK) catalyzes an essential step in the mevalonate pathway, which is the only pathway for synthesis of isoprenoids and steroids in humans. PMK catalyzes transfer of the γ‐phosphate of ATP to mevalonate 5‐phosphate (M5P) to form mevalonate 5‐diphosphate. Bringing these phosphate groups in proximity to react is especially challenging, given the high negative charge density on the four phosphate groups in the active site. As such, conformational and dynamics changes needed to form the Michaelis complex are of mechanistic interest. Herein, we report the characterization of substrate induced changes (Mg‐ADP, M5P, and the ternary complex) in PMK using NMR‐based dynamics and chemical shift perturbation measurements. Mg‐ADP and M5P Kd's were 6–60 μM in all complexes, consistent with there being little binding synergy. Binding of M5P causes the PMK structure to compress (τc = 13.5 nsec), whereas subsequent binding of Mg‐ADP opens the structure up (τc = 15.6 nsec). The overall complex seems to stay very rigid on the psec‐nsec timescale with an average NMR order parameter of S2 ∼0.88. Data are consistent with addition of M5P causing movement around a hinge region to permit domain closure, which would bring the M5P domain close to ATP to permit catalysis. Dynamics data identify potential hinge residues as H55 and R93, based on their low order parameters and their location in extended regions that connect the M5P and ATP domains in the PMK homology model. Likewise, D163 may be a hinge residue for the lid region that is homologous to the adenylate kinase lid, covering the “Walker‐A” catalytic loop. Binding of ATP or ADP appears to cause similar conformational changes; however, these observations do not indicate an obvious role for γ‐phosphate binding interactions. Indeed, the role of γ‐phosphate interactions may be more subtle than suggested by ATP/ADP comparisons, because the conservative O to NH substitution in the β‐γ bridge of ATP causes a dramatic decrease in affinity and induces few chemical shift perturbations. In terms of positioning of catalytic residues, binding of M5P induces a rigidification of Gly21 (adjacent to the catalytically important Lys22), although exchange broadening in the ternary complex suggests some motion on a slower timescale does still occur. Finally, the first nine residues of the N‐terminus are highly disordered, suggesting that they may be part of a cleavable signal or regulatory peptide sequence. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the VL–VH interface
Authors: Kuroda Daisuke , Shirai Hiroki , Kobori Masato , Nakamura Haruki
Published: September 2008

Antibody modeling is widely used for the analysis of antibody–antigen interactions and for the design of potent antibody drugs. The antibody combining site is composed of six complementarity determining regions (CDRs). The CDRs, except for CDR‐H3, which is the most diverse CDR, form limited numbers of canonical structures, which can be identified from the amino acid sequences. A method to classify the CDR‐H3 structure from its amino acid sequence was previously proposed. However, since those CDR structures were classified, many more antibody crystal structures have been determined. We performed systematic analyses of the CDR‐L3 structures and found novel canonical structures, and we also classified a previously identified canonical structure into two subtypes. In addition, two differently defined canonical structures in the κ and λ subtypes were classified into the same canonical structure. We also identified a key residue in CDR‐L3, which determines the conformation of CDR‐H3. Several analyses of CDR‐L3 loops longer than nine residues were performed. These new findings should be useful for structural modeling and are eventually expected to accelerate the design of antibody drugs. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Modelling MOSFET gate length variability for future technology nodes
Authors: Patsis G. P.
Published: September 2008

Gate length variability due to intra or inter die variations can lead to considerable mismatch between devices even inside the same chip. This variability has to be considered in detail and new device models should be developed, aiming in modelling its effects on the electrical characteristics devices. In this work the Philips MM11 MOSFET model is extended to incorporate gate length variability. This is introduced by dividing the device width into sub‐units following a Gaussian gate length distribution, with appropriate line‐width roughness. The combined model is used to quantify the drain‐source current in terms of gate line‐width roughness. The model is coded in VHDL‐AMS in order to be used for simulation of circuit behaviour inside the framework of appropriate system simulation software such as Ansfoft's Simplorer. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
TEM investigations of (In,Ga)N/GaN quantum structures
Authors: Manolaki P. , Häusler I. , Kirmse H. , Neumann W. , Smałc‐Koziorowska J. , Skierbiszewski C.
Published: September 2008

The paper reports on the influence of the growth temperature on the structural and chemical properties of (In,Ga)N quantum wells (QWs) on GaN. Two different samples A and B were fabricated. The QWs of the sample A were grown at a constant temperature of 600 °C. For the QWs of the sample B the temperature was 530 °C, while for the GaN barrier it was raised to 600 °C. The chemical and structural properties were studied by electron diffraction contrast imaging using the 0001 and 0002 reflection, respectively. Sample A exhibits homogeneous (In,Ga)N QWs. For sample B some undulated strain contrast of the QWs is visible hinting to the formation of quantum dots (QDs). The self‐organisation of (In,Ga)N QDs in sample B is also evidenced by composition sensitive STEM‐HAADF imaging, where the individual (In,Ga)N layers exhibit inhomogeneous intensity as well as varied thickness. Moreover, energy dispersive X‐ray spectroscopy yielded enrichment of indium at QD sites. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth of III‐nitride quantum dots and their applications to blue‐green LEDs
Authors: Moustakas T. D. , Xu Tao , Thomidis C. , Nikiforov A. Yu , Zhou Lin , Smith David J.
Published: September 2008

In this paper we discuss the growth of InN, GaN and InGaN QDs by MBE on either GaN or AlN templates. InN QDs on GaN templates were found to occur without an InN wetting layer, a result consistent with the large lattice mismatch of 11% between InN and GaN. Self‐assembled GaN QDs were grown on AlN templates, using the modified Stranski‐Krastanov mode of growth. The microstructure and the size distribution of such QDs in a single layer or a superlattice structure were investigated by electron microscopy and atomic force microscopy. Finally, the self assembly of InGaN QDs on GaN templates using the Stranski‐Krastanov mode and the applications of such QDs to blue‐green LEDs are addressed. The results indicate that InGaN / GaN multiple quantum dots (MQDs) are highly strained and their emission at low injection is red shifted with respect to that of a single layer of QDs due to quantum confined Stark effect. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Connection between a few Jeziorski‐Monkhorst ansatz‐based methods
Authors: Kong Liguo
Published: September 2008

Different Jeziorski‐Monkhorst ansatz‐based methods are unified according to how to group terms to eliminate the redundancy problem. It is found that some seemingly different methods used to do MRCC are equivalent. It is argued that the various defining equations are not entirely proper, in the sense that the proper residual condition is not satisfied. This may partially rationalize the unsatisfactory performance of the various methods for single reference systems. In contrast, the MRexpT method satisfies the proper residual condition and it is expected that it will outperform other JM ansatz‐based methods in single‐reference cases. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Complexity analysis of ionization processes and isoelectronic series
Authors: Antolín J. , Angulo J. C.
Published: September 2008

Information‐theoretic magnitudes measuring randomness (Shannon entropy, exponential entropy, power entropy), spread (variance), localization (disequilibrium or self‐similarity) and intrinsic accuracy (Fisher information) are used to compute several measures of complexity consisting, each one, of two localization–delocalization factors. These proposals have been tested on known, simple, but strongly organized and hierarchical systems (atoms) and processes (ionization). A complete numerical analysis at the Hartree–Fock level is done in position, momentum, and product spaces, where similar trends are followed by all studied complexities. It is also found that the complexity planes clearly reveal shell‐filling patterns across the periodic table. Characteristic features accompanying the ionization process are identified, and the physical reasons for the observed patterns are described. We conclude that (i) the studied complexity measures detect not only randomness or localization, but also pattern and organization, and (ii) their study is not only sufficient in the usual position space, but also in the complementary momentum space, to have a complete description of the information–theoretic behavior of these systems. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009