bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Life Testing
Authors: Bagdonavicius V. , Nikulin M.
Published: October 2006

In industry the failure time data are used for product reliability estimation. Failures of highly reliable units are rare and other information should be used than traditional censored failure time data. One way of obtaining this complementary reliability information is to apply the methods of the so‐called accelerated life‐testing (ALT). The purpose of the ALT is to give estimators of the main reliability characteristics under usual (design) stress using data of accelerated experiments when units are tested at higher than usual stress conditions, i.e. in ALT is supposed to use higher levels of experimental time varying factors or covariates (such as temperature, voltage or pressure) to increase the number of failures and, hence, to obtain reliability information more quickly. In biomedical studies the data are often obtained under different time‐varying conditions and there is a problem to compare the distributions of failure time variables among several different treatment or intervention groups. To treat these data in ALT are used the so‐called accelerated life models with time depending explanatory variables (stresses). The considered models are well known in reliability theory and survival analysis. They are well adapted to obtain the statistical inference in accelerated experiments with dynamic environment, when data are censored. All famous models such as Cox (proportional hazards) model, linear transformation (Dabrowska‐Doksum) model, frailty model, generalized proportional model, additive hazards model, proportional hazards model, accelerated failure time model, etc…, are in the class of accelerated life models. The most famous model in ALT is the accelerated failure time (AFT) model. Here we develop a general approach for construction of the accelerated life models in accelerated experiments (in ALT) with dynamic environment, which reveals some interesting connections among many well known and new models.
Charlier (Series) Distributions, Discrete
Authors: Nadarajah Saraless , Kotz Samuel
Published: October 2006

The Charlier series distribution (both univariate and bivariate) and some its properties are discussed.
Dependence, Kent–O'Quigley Measure
Authors: Nadarajah Saraless , Kotz Samuel
Published: October 2006

A dependence measure attributable to Kent and O'Quigley and some of its properties are discussed.
Engineering Statistics
Authors: Vardeman Stephen B.
Published: October 2006

Some classes of statistical methods have traditionally been associated with engineering problems and applications, and some of these methods have become very important to this field. In this entry, we will identify these classes of statistical methods and indicate how they contribute to modern engineering practice
Geographic Information Systems
Authors: Griffith Daniel A.
Published: October 2006

A geographic information system (GIS) is a computer hardware and software information system designed to capture, edit, manage, house, manipulate, analyze, and display georeferenced data. It comprises high‐resolution scientific visualization capabilities, large‐capacity electronic storage devices, efficient and effective structures for data storage and retrieval, high‐volume communication channels, specialized algorithms for data integration and reliability analysis, and specialized query languages. Its reference point is a digital map. The first GIS was developed by the Canadian government and implemented in 1964. A differentiating feature among GISs is whether the underlying map involves a raster or vector surface partitioning. Spatial statistics requires attribute data, a map, and the tagging of each data observation to a location on a map, items furnished by a GIS. A GIS also supplies a practical and useful way to reveal spatial and temporal relationships among data. The UCGIS is an organization whose mission is to serve as an effective unified voice for the community of GIS users.
Koksma–Hlawka Inequality
Authors: Hickernell Fred J.
Published: October 2006

The Koksma–Hlawka inequality is a tight error bound on the approximation of an integral by the sample average of integrand values. The integration error is bounded by a product of two terms, the discrepancy of the sample points,

\documentclass{article}\usepackage{amsmath}\pagestyle{empty}\begin{document}$D(\{\vec{x}_{i}\})$ \end{document}

, and the variation of the integrand,
V
(
g
). These two quantities measure the quality of the sample points and the roughness of the integrand, respectively. The Koksma–Hlawka inequality plays a key role in the development of quasi–Monte Carlo methods. Such methods replace simple random sample points by low discrepancy points. The Koksma–Hlawka inequality has also influenced the study of experimental design and led to the creation of UNIFORM DESIGNS.
Multivariate Symmetry and Asymmetry
Authors: Serfling Robert J.
Published: October 2006

Univariate symmetry has interesting and diverse forms of generalization to the multivariate case. Here several leading concepts of multivariate symmetry—spherical, elliptical, central, and angular—are examined and various closely related notions discussed. Methods for testing the hypothesis of symmetry and approaches for measuring the direction and magnitude of skewness are reviewed.
Multivariate Uniformity, Liang–Fang–Hickernell–Li Test of
Authors: Kotz Samuel , Nadarajah Saraless
Published: October 2006

A test of multivariate uniformity attributable to Liang, Fang, Hickernell, and Li is discussed.
Psychology, Statistics in
Authors: Everitt Brian
Published: October 2006

Statistics is of central importance in psychology but the realtionship between staisticians and psychologists has not always been an easy one. For example, the latter's obsession with significance tests and p‐values has often not met with the approval of the former. But research in psychology offers a rich source or problems for the statistician, and developments in statistics offer the opportunity for psychologists to raise their statistical horizons beyond ANOVA and hypothesis tests.
Self‐Selected Samples
Authors: Rutherford Andrew
Published: October 2006

The term “Self‐Selected Samples" is explained. The nature of selection with respect to such samples is described, its relation to other sampling techniques is considered briefly and a distinction between strong and weak selection is made. Strong self‐selected samples are not representative of the population of interest and may very likely differ on pertinent factors. Hence, there are serious problems in generalizing inferences from self‐selected samples to their populations. A very brief outline is provided for three statistical approaches to problems with self‐selected samples: the use of covariates, mixture modeling, and selection modeling.
Continuous Multivariate Distributions
Authors: Balakrishnan N.
Published: October 2006

In this article, we present a concise review of developments on various continuous multivariate distributions. We first present some basic definitions and notations. Then, we present several important continuous multivariate distributions and list their significant properties and characteristics.
Forensic Science, Statistics in
Authors: Aitken Colin G. G.
Published: October 2006

Forensic statistics requires careful consideration and weighing of scientific evidence under two opposing propositions, that of the defence and the other of the prosecution. In this entry, some of the important concepts and ideas that are practiced in forensic statistics are described and some considerations for future direction are also outlined.
Cancer Stochastic Models
Authors: Tan Wai Y. , Chen Chao W.
Published: October 2006

In this article, we present an overview of cancer stochastic models. These models include single pathway models and multiple pathways models as well as state space models. To analyze these models, different mathematical approaches are reviewed and discussed. The results are illustrated by using a multievent model as an example.
Forestry, Statistics in
Authors: Gregoire Timothy , Lappi Juha
Published: October 2006

Statistical methods are used in surveys of forest resources, and in the development of predictive models of individual‐tree size and growth, as well as the growth and yield of aggregations of trees in forest stands. Statistically designed experiments are conducted in order to understand better the responses to(i)management interventions, such as fertilization, genetic improvement, site preparation, harvesting; and to(ii)natural events like insect infestations, ice storms, hurricanes, temperature change.
Correspondence Analysis
Authors: Kroonenberg Pieter M. , Greenacre Michael J.
Published: October 2006

Correspondence analysis is a multivariate technique to investigate the association in a two‐way table of nonnegative quantities, usually counts. In particular, graphical representations of the row and column variables are derived that highlight the salient aspects of their relationship. We give an exposition of the technique as well as some equivalent definitions, a selection of extensions of the basic method and a collection of applications from various disciplines to illustrate its use in practice.
Sequential Order Statistics
Authors: Cramer Erhard
Published: October 2006

Sequential order statistics have been introduced in order to model effects of component failures on the reliability ofk‐out‐of‐nsystems. Aside from this interpretation, they are related to several other models of ordered random variables such as Pfeifer's record values and generalized order statistics.
Statistical Signal Processing
Authors: Kannan Nandini , Kundu Debasis
Published: October 2006

Statistical signal processing is an important area of research with extensive applications in the fields of communication theory, array processing, seismology, and medical diagnosis. The goal of signal processing is to recover characteristics of the underlying process from observed data. The random nature of the signals underscores the need for statistical techniques in model formulation, estimation, and data analysis. A brief discussion of two models that have been widely studied in the signal processing literature is provided. In addition, different methods of estimation are presented, and some unique characteristics of these models are highlighted.
Bayesian Networks
Authors: Castillo Enrique , Hadi Ali S.
Published: October 2006

Many practical applications require the specification of the joint probability density (JPD) of a large set of random variables. This task can be very difficult in practice. Bayesian and Markov networks are two graphically based models that make the specification of the JPD and the propagation of uncertainty simple and efficient because they exploit the conditional independence structure of the JPD. This entry deals with Bayesian networks, also known as Belief networks. Markov networks are discussed in another entry. Bayesian networks are defined and their usefulness is illustrated by examples of the two most commonly used Bayesian networks, namely, the multinomial and Gaussian networks. The questions about how Bayesian networks can be constructed, how Bayesian networks can be learnt from data, and how uncertainty can be propagated when new evidence becomes available are also discussed.
Vaccine Studies, Statistics in
Authors: Datta Susmita
Published: October 2006

Statistical methodologies have been used in estimating the efficacy of a vaccine from field trials and observational studies. Dynamics of disease transmission interferes with the efficacy of a vaccine. This is a very brief summary of some statistical work related to vaccine studies, especially, in the context of HIV/AIDS vaccine.
Actuarial Science
Authors: Klugman Stuart
Published: October 2006

Actuaries use results from probability, statistics, economics, and finance to price, value, and manage contingent events that have monetary consequences. Two techniques developed by actuaries, construction and graduation of mortality tables, and credibility are discussed here.
Assessment Bias
Authors: Gøtzsche Peter C.
Published: October 2006

Assessment bias in a clinical trial arises if there is bias in the assessment of the outcome. It is also called
ascertainment bias, diagnostic bias
, or
detection bias

. A major cause of assessment bias is lack of blinding. Other problems relate to differential identification of harmless or false positive cases of disease, bias in assessment of disease‐specific mortality, the use of composite outcomes, competing risks, timing of the assessments, and bias in assessment of harms.
Group‐Randomized Trials, Planning and Analysis of
Authors: Murray David M.
Published: October 2006

Planning a group‐randomized trial is a complex process. Care must be taken to delineate the research question, to create the research team, to plan the research design, to avoid potential design and analytic problems, to select variables of interest and their measures, to plan the intervention, and to ensure adequate power. Failure in any of these areas may lead to a dissappointing result; attention to each will increase the likelihood of success
Hazard Change Point Estimation
Authors: Gürler Ülkü
Published: October 2006

In survival and reliability studies, hazard‐rate function plays an important role. Sudden changes in the hazard function may occur due to treatment effects or maintenance activities. A problem of statistical interest is the estimation of the times of the changes, as well as their sizes. In this note, we review the basic estimation methods for hazard change‐point models for complete data. Some related literature is also provided for estimation with incomplete data and hypothesis testing.
Statistical Software
Authors: Wegman Edward J. , Solka Jeffrey L.
Published: October 2006

This article is a short exposition on the state of the art with regard to statistical software, along with some prognostications as to the future trends in the area. The article is somewhat biased in its discussions, with a focus on those packages that seem most promising in their current and future role in the academic research communities.
Paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed chronic myelogenous leukemia
Authors: Bryant Barbara J. , Alperin Jack B. , Elghetany M. Tarek
Published: October 2006

Extramedullary tumors, also known as granulocytic sarcomas (GS), occur most frequently in acute myelogenous leukemia (AML). They may signal the onset of the accelerated phase of chronic myelogenous leukemia (CML) or the blastic transformation of a myeloproliferative disorder. Occasionally, a GS may be the presenting sign of undiagnosed AML, and rarely the presenting sign of undiagnosed CML or aleukemic leukemia. Paraplegia due to a spinal cord GS is an extremely rare presentation of undiagnosed leukemia. This is the first case report of paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed CML. A 53‐year‐old woman reported back pain for 6 days, rapidly progressing to paraplegia. Physical examination noted a large abdominal mass and flaccid paralysis in both lower extremities. Spinal MRI revealed a T4–T6 vertebral mass causing spinal stenosis and cord compression. Tumor debulking and laminectomy were performed emergently. The tumor consisted of noncohesive blast cells. The CBC revealed a leukocyte count of 238,300/μl and a differential consistent with CML. Reexamination of the patient found that the abdominal mass was a giant spleen. Further immunohistochemical studies of the tumor were consistent with extramedullary acute megakaryoblastic blast transformation of CML. Although extramedullary blast crises herald the accelerated phases in ∼10% of CML cases, megakaryoblastic blast transformation of CML accounts for less than 3% of these cases. The combination of acute paraplegia and megakaryoblastic transformation in a previously undiagnosed patient with CML is extremely rare and may pose a diagnostic dilemma. Am. J. Hematol. 2006. © Wiley‐Liss, Inc.
Tandem high‐dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: A monocenter prospective study
Authors: Castagna Luca , Magagnoli Massimo , Balzarotti Monica , Sarina Barbara , Siracusano Licia , Nozza Andrea , Todisco Elisabetta , Bramanti Stefania , Mazza Rita , Russo Filippo , Timofeeva Inna , Santoro Armando
Published: October 2006

We designed a prospective study to evaluate the feasibility and efficacy of tandem high‐dose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty‐two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo‐sensitive patients received a first HDCT course with melphalan 200 mg/m2 (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34+ cells was 4.7 x 106/kg after MEL200 and 5.8 x 106/kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention‐to‐treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL. Am. J. Hematol. 2006. © 2006 Wiley‐Liss, Inc.
Synthesis of novel derivatives of closo‐dodecaborate anion with azido group at the terminal position of the spacer
Authors: Orlova Anna V. , Kondakov Nikolay N. , Kimel Boris G. , Kononov Leonid O. , Kononova Elena G. , Sivaev Igor B. , Bregadze Vladimir I.
Published: October 2006

Two novel azido‐derivatives of closo‐dodecaborate anion with hydrophobic and hydrophilic spacers were prepared by reaction of tetrabutylammonium azide with cyclic oxonium derivatives of the closo‐dodecaborate anion. The compounds prepared can be regarded as precursors of derivatives of closo‐dodecaborate anion with amino group at the terminal position of a spacer or as building blocks for ‘click chemistry’, which are useful for preparation of various conjugates with targeting molecules. A concentration dependence of the 11B NMR spectra of functionalized derivatives of closo‐dodecaborate anion was discovered, which is of great importance for analytical purposes. Copyright © 2006 John Wiley & Sons, Ltd.
A preliminary study of oscillating electromagnetic field effects on human spermatozoon motility
Authors: Iorio R. , Scrimaglio R. , Rantucci E. , Monache S. Delle , Di Gaetano A. , Finetti N. , Francavilla F. , Santucci R. , Tettamanti E. , Colonna R.
Published: October 2006

Some effects of extremely low frequency electromagnetic fields (ELF‐EMFs) on human spermatozoa are reported. Significant increases in the values of the motility and of the other kinematic parameters have been observed when spermatozoa were exposed to an ELF‐EMF with a square waveform of 5 mT amplitude and frequency of 50 Hz. By contrast, a 5 mT sine wave (50 Hz) and a 2.5 mT square wave (50 Hz) exposure did not produce any significant effect on sperm motility. The effects induced by ELF‐EMF (50 Hz; 5 mT) during the first 3 h of exposure persisted for 21 h after the end of the treatment. These results indicate that ELF‐EMF exposure can improve spermatozoa motility and that this effect depends on the field characteristics. Bioelectromagnetics. © 2006 Wiley‐Liss, Inc.
Cover Picture: 2‐Anilinobenzamides as SIRT Inhibitors (ChemMedChem 10/2006)
Authors: Suzuki Takayoshi , Imai Keiko , Nakagawa Hidehiko , Miyata Naoki
Published: October 2006

The cover picture shows the model of a SIRT inhibitor, 2‐anilinobenzamide, bound to the catalytic core of a SIRT homologue. SIRTs catalyze the deacetylation of several proteins such as histones, p53, and γ‐tubulin, and are involved in certain disease states including cancer. SIRT inhibitors can be considered as potential therapeutic agents. This simple compound, which was discovered from a nicotinamide‐ and benzamide‐focused chemical library, shows potent SIRT1 inhibition competitive with the acetylated lysine substrate and causes p53 acetylation in human colon cancer HCT116 cells. For more details, see the Communication by T. Suzuki, N. Miyata et al. on p. 1059 ff.
Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high‐risk for hepatocellular carcinoma
Authors: Lu Sheng‐Nan , Wang Jing‐Houng , Liu Shiann‐Long , Hung Chao‐Hung , Chen Chien‐Hung , Tung Hung‐Da , Chen Tsung‐Ming , Huang Wu‐Shiung , Lee Chuan‐Mo , Chen Chia‐Cheng , Changchien Chi‐Sin
Published: October 2006

BACKGROUND.

The objective of this study was to examine the usefulness of platelet counts in the diagnosis of cirrhosis and for identifying high‐risk individuals in a community‐based hepatocellular carcinoma (HCC) screening program.

METHODS.

Pilot Study 1 determined the correlation between platelet counts and pathologic hepatic fibrosis scores among individuals with chronic hepatitis B virus (HBV) infection (n = 122 patients) and hepatitis C virus (HCV) infection (n = 244 patients). Pilot Study 2 investigated proportions of individuals with thrombocytopenia (<150 × 103/mm3) among patients with HCC (n = 4042 patients). Pilot Study 3 demonstrated the correlation between platelet counts and ultrasonographic (US) parenchyma scores among anti‐HCV‐positive individuals (n = 75 patients). The core study was a 2‐stage, community‐based screening for HCC among residents age 40 years or older in townships with a high prevalence of anti‐HCV (n = 4616 individuals) and in townships with a low prevalence of anti‐HCV (n = 1694 individuals). Patients with thrombocytopenia were identified for US and α‐fetoprotein screening.

RESULTS.

Among the individuals who were positive for anti‐HCV, platelet counts decreased according to increased pathologic fibrosis scores or US scores for liver parenchyma disease: The best cutoff platelet count was 150 × 103/mm3 for a diagnosis of cirrhosis. The sensitivity and specificity were 68.2% and 76.4%, respectively, for pathologic cirrhosis and 76.2% and 87.8%, respectively, for US cirrhosis. Forty‐eight percent of patients with HCC were thrombocytopenic. The proportion of thrombocytopenia was significantly greater in patients with HCV‐related HCC (63%) than in patients with HBV‐related HCC (42%). In the townships with high and low anti‐HCV prevalence, the prevalence of thrombocytopenia was 17.9% and 6.1%, respectively, (P < .001), respectively. Twenty‐five patients were diagnosed with HCC, and all of those patients resided in the high‐prevalence township.

CONCLUSIONS.

Thrombocytopenia was a valid surrogate of cirrhosis and a valid marker for the identification of individuals at high‐risk for HCC, especially in areas that had a high prevalence of HCV. Cancer 2006. © 2006 American Cancer Society.
Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease
Authors: Nakamura Kazuo , Yamagishi Sho‐ichi , Adachi Hisashi , Kurita‐Nakamura Yayoi , Matsui Takanori , Yoshida Takafumi , Sato Akira , Imaizumi Tsutomu
Published: October 2006

Background

Advanced glycation end products (AGEs)‐receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non‐diabetic healthy subjects.

Methods

Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 ± 11 years) and 75 age‐ and sex‐matched non‐diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients.

Results

Serum sRAGE levels were significantly higher in diabetic patients than in non‐diabetic subjects (965.3 ± 544.2 vs 415 ± 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A1c, and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 ± 891.1 vs 855.2 ± 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD.

Conclusions

The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non‐diabetic subjects and positively associated with the presence of CAD. Copyright © 2006 John Wiley & Sons, Ltd.
Embryo dune development on a large, actively accreting macrotidal beach: Calais, North Sea coast of France
Authors: Anthony Edward J. , Vanhée Stéphane , Ruz Marie‐Hélène
Published: October 2006

Sediment budget data from an 18‐month topographic survey were analysed with data from brief experiments on wind parameters, beach moisture contents, bedforms and sand mobilization in order to monitor conditions and patterns of embryo dune development over a flat 150–1000 m wide accreting upper beach. The surface conditions over the upper beach locally affect aeolian transport, but net dune development over time depends on sustained strong winds and their orientation. Incoming marine sand supplied by storms and onshore winds is reorganized by the dominant offshore to longshore winds into elongated embryo dunes over this upper beach, imprinting a regional morphology of long‐term longshore dune ridge development. Copyright © 2006 John Wiley & Sons, Ltd.
Contribution of NR2A and NR2B NMDA subunits to bidirectional synaptic plasticity in the hippocampus in vivo
Authors: Fox Christopher J. , Russell Kyle I. , Wang Yu Tian , Christie Brian R.
Published: October 2006

It has recently been proposed that activation of the NR2A subunit results in Long‐term potentiation (LTP) induction, whereas activation of the NR2B subunit results in long‐term depression (LTD) induction. The present study undertakes to replicate these findings in vivo to determine if a role for specific subunits in synaptic plasticity can be shown in the intact brain. Field recordings were made from the CA1 subfield of the hippocampus using Schaffer collateral stimulation in anesthetized male Sprague‐Dawley rats. Antagonists of the N‐methyl‐D‐aspartate receptors NR2A and NR2B subunits were administered by either intraperitoneal (i.p.) or intrahippocampal (i.h.) injections to assess their involvement in LTP (100 Hz stimuli) and LTD (200 Paired‐burst stimuli). i.h. injection of Ro25–6981 (100 μM) significantly attenuated hippocampal LTP expression and completely blocked LTD expression. When administered i.p., Ro25–6981 (6 mg/kg) again blocked LTD, but did not significantly diminish the expression of LTP. When NVP‐AAM077 was administered i.h. (80 μM) both LTP and LTD were completely abolished. The administration of this compound i.p. (1.2 mg/kg) also significantly attenuated LTP, but did not affect LTD. These data suggest that both NR2A and NR2B subunits can play roles in LTP and LTD in the hippocampus in vivo. © 2006 Wiley‐Liss, Inc.
Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity
Authors: Cantor Joshua P. , Iliopoulos Dimitrios , Rao Atul S. , Druck Teresa , Semba Shuho , Han Shuang‐Yin , McCorkell Kelly A. , Lakshman Thiru V. , Collins Joshua E. , Wachsberger Phyllis , Friedberg Joseph S. , Huebner Kay
Published: October 2006

Epigenetic changes involved in cancer development, unlike genetic changes, are reversible. DNA methyltransferase and histone deacetylase inhibitors show antiproliferative effects in vitro, through tumor suppressor reactivation and induction of apoptosis. Such inhibitors have shown activity in the treatment of hematologic disorders but there is little data concerning their effectiveness in treatment of solid tumors. FHIT, WWOX and other tumor suppressor genes are frequently epigenetically inactivated in lung cancers. Lung cancer cell clones carrying conditional FHIT or WWOX transgenes showed significant suppression of xenograft tumor growth after induction of expression of the FHIT or WWOX transgene, suggesting that treatments to restore endogenous Fhit and Wwox expression in lung cancers would result in decreased tumorigenicity. H1299 lung cancer cells, lacking Fhit, Wwox, p16INK4a and Rassf1a expression due to epigenetic modifications, were used to assess efficacy of epigenetically targeted protocols in suppressing growth of lung tumors, by injection of 5‐aza‐2‐deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299 tumors. High doses of intraperitoneal AZA/TSA suppressed growth of small tumors but did not affect large tumors (200 mm3); lower AZA doses, administered intraperitoneally or intratumorally, suppressed growth of small tumors without apparent toxicity. Responding tumors showed restoration of Fhit, Wwox, p16INKa, Rassf1a expression, low mitotic activity, high apoptotic fraction and activation of caspase 3. These preclinical studies show the therapeutic potential of restoration of tumor suppressor expression through epigenetic modulation and the promise of re‐expressed tumor suppressors as markers and effectors of the responses. © 2006 Wiley‐Liss, Inc.
Spatial clustering of endemic Burkitt's lymphoma in high‐risk regions of Kenya
Authors: Rainey Jeanette J. , Omenah Dorine , Sumba Peter O. , Moormann Ann M. , Rochford Rosemary , Wilson Mark L.
Published: October 2006

Endemic Burkitt's lymphoma (eBL), the most common childhood cancer in sub‐Saharan Africa, occurs at a high incidence in western Kenya, a region that also experiences holoendemic malaria. Holoendemic malaria has been identified as a co‐factor in the etiology of this cancer. We hypothesized that eBL may cluster spatially within this region. Medical records for all eBL cases diagnosed from 1999 through 2004 at Nyanza Provincial General Hospital were reviewed for case residential information to examine this hypothesis. Two cluster detection methods, Anselin's Local Moran test for spatial autocorrelation and a spatial scan test statistic, were applied to this residential data to determine whether statistically significant high‐ and low‐risk areas were present in the Province. During the 6‐year study period, 272 children were diagnosed with eBL, with an average annual incidence of 2.15 cases per 100,000 children. Using Empirical Bayes smoothed rates, the Local Moran test identified 1 large multi‐centered area of low eBL risk (p‐values < 0.01) and 2 significant multi‐centered clusters of high eBL risk (p‐values < 0.001). The spatial scan detected 3 small independent low‐risk areas (p‐values < 0.02) and 2 high‐risk clusters (p‐values = 0.001), both similar in location to those identified from the Local Moran analysis. Significant spatial clustering of elevated eBL risk in high‐malaria transmission regions and of reduced incidence where malaria is infrequent suggests that malaria plays a role in the complex eBL etiology, but that additional factors are also likely involved. © 2006 Wiley‐Liss, Inc.
Recreational physical activity and risk of prostate cancer: A prospective population‐based study in Norway (the HUNT study)
Authors: Nilsen Tom I.L. , Romundstad Pål R. , Vatten Lars J.
Published: October 2006

Physical activity has been studied in relation to prostate cancer risk, but the findings have been inconclusive. We prospectively examined the association between self‐reported recreational physical activity and overall risk of prostate cancer, risk of advanced disease and risk of prostate cancer death in a cohort of 29,110 Norwegian men. Incident prostate cancers were obtained from the Norwegian Cancer Registry, and prostate cancer deaths were obtained from the national Cause of Death Registry. During 17 years of follow‐up, 957 incident cases were identified, 266 of them were advanced (i.e. metastases at diagnosis) and 354 of the incident cases died from prostate cancer. In multivariable analysis, frequency and duration of exercise were inversely associated with the risk of advanced prostate cancer (p for trend = 0.04 and 0.02). We computed a summary score that combined frequency, duration and intensity of exercise, and this score showed inverse associations with advanced prostate cancer risk and mortality (p for trend = 0.02 and 0.07). Compared to men who reported no activity, the relative risks (95% confidence intervals) among men in the highest category of physical exercise was 0.64 (0.43–0.95) for advanced prostate cancer and 0.67 (0.48–0.94) for prostate cancer death. We found no association between physical activity and overall risk of prostate cancer. We conclude that recreational physical exercise is associated with reduced risk of advanced prostate cancer and prostate cancer death. © 2006 Wiley‐Liss, Inc.
Selective Chk1 inhibitors differentially sensitize p53‐deficient cancer cells to cancer therapeutics
Authors: Chen Zehan , Xiao Zhan , Gu Wen‐zhen , Xue John , Bui Mai H. , Kovar Peter , Li Gaoquan , Wang Gary , Tao Zhi‐Fu , Tong Yunsong , Lin Nan‐Horng , Sham Hing L. , Wang Jean Y. J. , Sowin Thomas J. , Rosenberg Saul H. , Zhang Haiying
Published: October 2006

The majority of cancer therapeutics induces DNA damage to kill cells. Normal proliferating cells undergo cell cycle arrest in response to DNA damage, thus allowing DNA repair to protect the genome. DNA damage induced cell cycle arrest depends on an evolutionarily conserved signal transduction network in which the Chk1 kinase plays a critical role. In mammalian cells, the p53 and RB pathways further augment the cell cycle arrest response to prevent catastrophic cell death. Given the fact that most tumor cells suffer defects in the p53 and RB pathways, it is likely that tumor cells would depend more on the Chk1 kinase to maintain cell cycle arrest than would normal cells. Therefore Chk1 inhibition could be used to specifically sensitize tumor cells to DNA‐damaging agents. We have previously shown that siRNA‐mediated Chk1 knockdown abrogates DNA damage‐induced checkpoints and potentiates the cytotoxicity of several DNA‐damaging agents in p53‐deficient cell lines. In this study, we have developed 2 potent and selective Chk1 inhibitors, A‐690002 and A‐641397, and shown that these compounds abrogate cell cycle checkpoints and potentiate the cytotoxicity of topoisomerase inhibitors and γ‐radiation in p53‐deficient but not in p53‐proficient cells of different tissue origins. These results indicate that it is feasible to achieve a therapeutic window with 1 or more Chk1 inhibitors in potentiation of cancer therapy based on the status of the p53 pathway in a wide spectrum of tumor types. © 2006 Wiley‐Liss, Inc.
Calculus attainment and grades received in intermediate economic theory
Authors: Li Mingliang , Tobias Justin L.
Published: October 2006

We revisit the work of Butler et al. (1998) who examine the effect of mathematical preparation on grades received in intermediate economic theory courses. Using a Bayesian approach under reasonably ‘diffuse’ priors, we are able to replicate their two‐step point estimates almost exactly. We also introduce a new model specification that accounts for the censoring and discrete nature of the outcome variable (grade received). The results from this specification echo the conclusions of the original paper—the level of calculus attained plays an important role in explaining grades received in intermediate micro theory. Copyright © 2006 John Wiley & Sons, Ltd.
Amine‐containing core‐shell nanoparticles as potential drug carriers for intracellular delivery
Authors: Feng Min , Li Pei
Published: October 2006

The present study aimed at exploring the use of amine‐containing core‐shell nanoparticles as potential drug carriers for intracellular delivery. Stable nanoparticles (100–200 nm in diameter) that consisted of poly(methyl methacrylate) (PMMA) cores with hydrophilic poly(ethyleneimine) (PEI) shells were synthesized and used to study their complexation with model drug, ibuprofen (IB), and release it under various electrolyte concentrations. The complexed IB/PEI–PMMA nanoparticles were characterized with FTIR, photon correlation spectroscopy, ζ‐potential, and transmission electron microscopy (TEM). Results suggested that the PEI–PMMA nanoparticles could effectively complex with the IB via electrostatic interaction. The thick PEI shells (∼30 nm) significantly enhanced the drug loading capacity up to 23% (w/w) of the complexed nanopartricle.In vitrorelease of the drug from the complexed nanoparticles was sensitive to the ionic strength of the media. Study of cellular entry of fluorescently labeled IB/nanoparticle complexes using a confocal laser scanning microscopy demonstrated that the entry of the complexed nanoparticles strongly depended on the complexing ratio between IB and PEI–PMMA nanoparticles. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Dissolution kinetics of a Si‐rich nanocomposite and its effect on osteoblast gene expression
Authors: Gupta Gautam , Kirakodu Sreenatha , El‐Ghannam Ahmed
Published: October 2006

Silica–calcium phosphate nanocomposite (SCPC) has recently been proposed as a novel resorbable, bioactive, and mechanically compatible template for bone reconstruction. The effect of the physicochemical properties on the surface reactivity and dissolution kinetics of SCPC immersed in simulated body fluid (SBF) was investigated and compared to that of bioactive glass (BG). Moreover, the stimulatory effect on osteoblast gene expression of SCPC was determined using quantitative real‐time polymerase chain reaction (qRT‐PCR), and compared to that of hydroxyapatite (HA‐200). Mercury porosimetry revealed that surface areas of SCPC particles containing 10 (SCPC10), 30 (SCPC30), and 50 (SCPC50) wt % Si‐content were 14‐, 18‐, and 32‐times higher than that of BG. Inductively coupled plasma analysis showed that after 192 h of immersion, Si‐rich SCPC50 exhibited controlled bulk‐dissolution and released 43.1 ppm Si, which was sixfold higher than that released from BG (7.7 ppm). Moreover, SCPC50 showed a rapid Ca‐uptake from SBF and developed a surface apatite layer after only 2 h, whereas a similar layer was detected on BG after 8 days of immersion under the same experimental conditions. qRT‐PCR revealed that osteopontin and osteocalcin mRNA expression by osteoblast‐like cells attached to Si‐rich SCPC50 was significantly higher than that on HA‐200 or polystyrene after 2 days in culture. This suggested a role of dissolved Si in stimulating the differentiation and mineralization of osteoblast precursor cells. The favorable physiochemical and bioactivity properties of Si‐rich SCPC nanocomposite indicate that SCPC can have wide applications as a synthetic bone graft for cell delivery applications in tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Water exchange dynamics of manganese(II), cobalt(II), and nickel(II) ions in aqueous solution
Authors: Loffler Hannes H. , Mohammed Ahmed M. , Inada Yasuhiro , Funahashi Shigenobu
Published: October 2006

The first row transition metal ions Mn2+, Co2+, and Ni2+ have been studied by classical umbrella sampling molecular dynamics simulations. The water exchange mechanisms, estimates of reaction rates, as well as structural changes during the activation process are discussed. Mn2+ was found to react via an IA mechanism, whereas Co2+ and Ni2+ both proceed via ID. Reaction rate constants are generally higher than those obtained by experiment but the simply constructed metal(II) ion–water potential reproduces the relative order quite well. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
The use of a generalized born model for the analysis of protein conformational transitions: A comparative study with explicit solvent simulations for chemotaxis Y protein (CheY)
Authors: Formaneck Mark S. , Cui Qiang
Published: October 2006

To investigate whether implicit solvent models are appropriate for mechanistic studies of conformational transition in proteins, a recently developed generalized Born model (GBSW) was applied to a small signaling protein, chemotaxis protein Y (CheY), with different combinations of the phosphorylation state and conformation of the system; the results were compared to explicit solvent simulations using a stochastic boundary condition. The subtle but distinct conformational transitions involved in CheY activation makes the system ideally suited for comparing implicit and explicit solvent models because these conformational transitions are potentially accessible in both types of simulations. The structural and dynamical properties analyzed include not only those localized to the active site region but also throughout the protein, such as sidechain methyl group order parameters, backbone hydrogen bonding lifetime and occupancy as well as principal components of the trajectories. Overall, many properties were well reproduced by the GBSW simulations when compared with the explicit solvent calculations, although a number of observations consistently point to the suggestion that the current parameterization of the GBSW model tends to overestimate hydrogen‐bonding interactions involving both charged groups and (charge‐neutral) backbone atoms. This deficiency led to overstabilization of certain secondary structural motifs and more importantly, qualitatively different behaviors for the active site groups (Thr 87, Ala 88, the β4–α4 loop) in response to phosphorylation, when compared with explicit solvent simulations. The current study highlights the value of carrying out both explicit and implicit solvent simulations for complementary mechanistic insights in the analysis of conformational transition in biomolecules. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Antennal structure of male and female Aphidius rhopalosiphi DeStefani‐Peres (Hymenoptera:Braconidae): Description and morphological alterations after cold storage or heat exposure
Authors: Bourdais Delphine , Vernon Philippe , Krespi Liliane , Le Lannic Jo , Van Baaren Joan
Published: October 2006

Several species of the genus Aphidius are used in biological control programs against aphid pests throughout the world and their behavior and physiology are well studied. But despite knowing the importance of sensory organs in their behavior, their antennal structure has never been described. We describe here the types and distribution of antennal sensilla in Aphidius rhopalosiphi, a larval parasitoid of several aphid species and observe how this antennal structure is modified after cold storage or heat exposure. Six types of sensilla were found on both male and female antennae. Male and female antennae differed in the total number of antennomeres (16 in males, 14 in females) and in the number and distribution of three of the six types of sensilla. After cold storage or heat exposure, we observed the appearance of a small number of abnormal sensilla. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Tandem mass spectra of divalent metal ion adducts of glycosyl sulfides, sulfoxides and sulfones; distinction among stereoisomers
Authors: Madhusudanan K. P. , Kumar Brijesh , Kanojiya Sanjeev , Agnihotri Geetanjali , Misra Anup Kumar
Published: October 2006

The tandem mass spectra of the divalent metal ion (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Ni2+, Co2+ and Zn2+) adducts of acetylated 1,2‐trans‐glycosyl sulfides, sulfoxides and sulfones were examined using low energy collision‐induced dissociation on a Quattro II quadrupole tandem mass spectrometer. Abundant doubly charged ions, such as [3M + Met]2+ and [2M + Met]2+, were observed with alkaline earth metal chlorides. The other ions observed were [M + MetCl]+, [M + MetOAc]+, [M + MetO2SPh]+ and [2M + MetCl]+. The deprotonated metal adducts [M + Met‐H]+ were seen only in the sulfones. The divalent metal ion adducts showed characteristic fragmentation pathways for the glycosyl sulfides, sulfoxides and sulfones, depending on the site of metal attachment. The doubly charged metal ion adducts dissociate to two singly charged ions, [M + MetOAc]+ and [M − OAc]+, in the sulfides and sulfoxides. In the sulfones, the adducts dissociate to [M + MetO2SPh]+ and [M − O2SPh]+. In contrast to the alkaline earth metals, which attach to the acetoxy functions, the transition metals attach to the sulfide and sulfoxide functions. The metal chloride adducts display characteristic fragmentation for the sulfides, sulfoxides and sulfones. The glucosyl, mannosyl and galactosyl sulfides, sulfoxides and sulfones could be differentiated on the basis of the stereochemically controlled MS/MS fragmentations of the metal chloride adducts. Copyright © 2006 John Wiley & Sons, Ltd.
A generic stepwise optimization strategy for liquid chromatography electrospray ionization tandem mass spectrometry methods
Authors: Moberg My , Bergquist Jonas , Bylund Dan
Published: October 2006

The feasibility and advantages of using sophisticated chemometric tools in combination with the execution of thoroughly planned experiments to determine experimental conditions for optimal performance of an LC‐ESI‐MS/MS analysis is demonstrated. A stepwise strategy is proposed, which provides a controlled optimization procedure of the chromatographic quality (in terms of separation among the sample constituents) and maximizes the mass spectrometric signal of the selected product ions. Design of experiments (DOE) and response surface methodology are applied throughout the procedure. The stepwise approach has the advantage of dealing with the different optimization criteria separately, i.e. first ensuring sufficient chromatographic separation, then maximizing the amount of precursor ion entering the mass spectrometer, and finally generating high amounts of selected product ions. The experiments are performed on a linear ion trap mass spectrometer. Retention mapping using the band‐tracking model is applied during LC development, which facilitates the optimization of segmented gradients. A set of different siderophores, strong iron chelates, is used as the model substances. Copyright © 2006 John Wiley & Sons, Ltd.
Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples
Authors: DiMarco Theresa , Giulivi Cecilia
Published: October 2006

Dityrosine is a fluorescent molecule formed as a result of normal posttranslational processing. In many structural proteins, dityrosine confers resistance to proteolysis and physicochemical trauma as a stabilizing crosslink. Dityrosine has also been found in oxidative/nitrative stress under a variety of conditions and biological systems. In this regard, it has been used as an important biomarker for oxidatively modified proteins during UV and γ‐irradiation, aging, and exposure to oxygen free radicals, nitrogen dioxide, peroxynitrite, and lipid hydroperoxides. Renewed interest in dityrosine and other tyrosine oxidation products as clinical indicators of oxidative modification has driven the development of important techniques for the specific analysis and quantification of these molecules. The presence of elevated levels of dityrosine in mammalian tissue and urine samples has been measured by chromatographic separation followed by mass spectrometry GC‐MS and HPLC‐MS/MS. Increases in dityrosine levels have been associated with pathologies such as eye cataracts, atherosclerosis, acute inflammation, and Alzheimer's disease. The continued development of, and increased accessibility to, improved mass spectrometric instrumentation will expand the capability, feasibility, and sensitivity with which specific biomarkers like dityrosine can be measured. © 2006 Wiley Periodicals, Inc., Mass Spec Rev 26:108–120, 2007