bluuebunny/crossref_metadata_2025 huggingface dataset:
Currents: Books in Brief
Authors: Lawton LaRoi
Published: November 2004

Unchained Value: The New Logic of Digital Economy

Wharton on Managing Emerging Technologies

Blown to Bits: How the New Economics of Information Transforms Strategy

The Leadership Investment: How the World's Best Organizations Gain Strategic Advantage Through Leadership Development

Value Driven Management

The Value Effect: A Murder Mystery about the Compulsive Pursuit of the Next Big Thing

The Strategy Focused Organization: How Balanced Scorecard Companies Thrive in the New Business Environment

Digital Capital: Harnessing the Power of Business Webs
Identification of a time‐dependent coefficient in a partial differential equation subject to an extra measurement
Authors: Dehghan Mehdi
Published: November 2004

The problem of recovering a time‐dependent coefficient in a parabolic partial differential equation has attracted considerable recent attention. Several finite difference schemes are presented for identifying the function u(x, t) and the unknown coefficient a(t) in a one‐dimensional partial differential equation. These schemes are developed to determine the unknown properties in a region by measuring only data on the boundary. Our goal has been focused on coefficients that presents physical quantities, for example, the conductivity of a medium. For the convenience of discussion, we will present the results of numerical experiment on several test problems. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Superconvergence of a 3D finite element method for stationary Stokes and Navier‐Stokes problems
Authors: Matthies G. , Skrzypacz P. , Tobiska L.
Published: November 2004

For the Poisson equation on rectangular and brick meshes it is well known that the piecewise linear conforming finite element solution approximates the interpolant to a higher order than the solution itself. In this article, this type of supercloseness property is established for a special interpolant of the Q2 − P element applied to the 3D stationary Stokes and Navier‐Stokes problem, respectively. Moreover, applying a Q3 − P postprocessing technique, we can also state a superconvergence property for the discretization error of the postprocessed discrete solution to the solution itself. Finally, we show that inhomogeneous boundary values can be approximated by the Lagrange Q2‐interpolation without influencing the superconvergence property. Numerical experiments verify the predicted convergence rates. Moreover, a cost‐benefit analysis between the two third‐order methods, the post‐processed Q2 − P discretization, and the Q3 − P discretization is carried out. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Rheological properties of injection molded LDPE and mPE foams
Authors: Chen Xue , Heuzey Marie‐Claude , Carreau Pierre J.
Published: November 2004

The rheological properties of molten LDPE and mPE foams have been measured for small‐amplitude oscillatory shear flow. The foam samples were prepared by injection molding, and the effect of injection conditions on the resultant cell structure is discussed. In all cases cellular foams with closed cells were obtained with cell densities in the range of 4 × 105− 7 × 106cells/cm3and cell diameters in the range of 30–110 μm. The viscoelastic behavior of the foams is shown to be well described by the emulsion model proposed by Palierne (1) without using any fitting parameter. The linear viscoelastic properties of LDPE and mPE foams depend only on the properties of the polymer matrix and of the gas volume fraction. The Palierne model is also used to predict the linear properties of microcellular foams. Polym. Eng. Sci. 44:2158–2164, 2004. © 2004 Society of Plastics Engineers.
Metabolomic analysis of saponins in crude extracts of Quillaja saponaria by liquid chromatography/mass spectrometry for product authentication
Authors: Kite Geoffrey C. , Howes Melanie‐Jayne R. , Simmonds Monique S. J.
Published: November 2004

Analysis of 50% aqueous methanolic extracts of bark of Quillaja saponaria Molina (quillaja) by liquid chromatography/mass spectrometry (LC/MS), using negative ion electrospray, revealed over 100 saponins. The majority could be assigned to known structures or generalised variations of these from the product ion spectra obtained by serial mass spectrometry in a quadrupole ion trap mass spectrometer. Ten saponins contained a fatty acid domain terminated with both a pentose and deoxyhexose unit, a feature thus far only reported in QS‐III. Twenty saponins were based on a hydroxylated derivative of quillaic acid, whereas only six 22β‐hydroxyquillaic acid saponins have been described. The occurrence of pairs of saponins differing only by the presence of a rhamnose or xylose unit in the C‐3‐substituted saccharide was readily observed in two‐dimensional mass maps, and these showed the presence of the unreported ‘rhamnose partner’ of QS‐III. However, one sample labelled as Q. saponaria appeared to lack all saponins containing rhamnose in the C‐3 saccharide. Methods to authenticate saponin extracts of quillaja by LC/MS are suggested based on the general metabolomic profile, the occurrence of specific major saponins covering known structural variations, or the presence of saponins containing the unusual fatty acid domain, revealed by neutral loss analysis. Copyright © 2004 John Wiley & Sons, Ltd.
Nitrogen balance and δ15N: why you're not what you eat during pregnancy
Authors: Fuller Benjamin T. , Fuller James L. , Sage Nancy E. , Harris David A. , O'Connell Tamsin C. , Hedges Robert E. M.
Published: November 2004

Carbon (13C/12C) and nitrogen (15N/14N) stable isotope ratios were longitudinally measured in human hair that reflected the period from pre‐conception to delivery in 10 pregnant women. There was no significant change in the δ13C results, but all subjects showed a decrease in δ15N values (−0.3 to −1.1‰) during gestation. The mechanisms causing this decrease in hair δ15N have not been fully elucidated. However, since the δ15N values of dietary nitrogen and urea nitrogen are significantly lower compared to maternal tissues, it is hypothesized that the increased utilization of dietary and urea nitrogen for tissue synthesis during pregnancy resulted in a reduction of the steady state diet to a body trophic level effect by approximately 0.5–1‰. An inverse correlation (R2 = 0.67) between hair δ15N and weight gain was also found, suggesting that positive nitrogen balance results in a reduction of δ15N values independent of diet. These results indicate that δ15N measurements have the ability to monitor not only dietary inputs, but also the nitrogen balance of an organism. A potential application of this technique is the detection of fertility patterns in modern and ancient species that have tissues that linearly record stable isotope ratios through time. Copyright © 2004 John Wiley & Sons, Ltd.
Using design of experiments, sensitivity analysis, and hybrid simulation to evaluate changes to a software development process: a case study
Authors: Wakeland Wayne W. , Martin Robert H. , Raffo David
Published: November 2004

Hybrid simulation models combine the high‐level project issues of System Dynamics models with the process detail of discrete event simulation models. Hybrid models not only capture the best of both of these simulation paradigms, but they also are able to address new issues that are important in managing complex real‐world development projects that neither the System Dynamics nor Discrete Event simulation paradigms are able to address alone.

In order to reap the full benefits from a simulation model, a structured approach for analyzing model results is necessary. This article applies Design of Experiments (DOE) and broad range sensitivity analysis (BRSA) to a hybrid system dynamics and discrete event simulation model of a software development process. DOE is used to analyse the interaction effects, such as the degree to which the impact of the process change depends on worker motivation, schedule pressure and other project environmental variables. The sensitivity of the model to parameter changes over a broad range of plausible values is used to analyse the non‐linear aspects of the model.

The end result is a deeper insight into the conditions under which the process change will succeed, and improved recommendations for process change design and implementation. In this particular study, significant interactions and non‐linearities were revealed, supporting the hypothesis that consideration of these complex effects is essential for insightful interpretation of model results and effective decision‐making. Copyright © 2004 John Wiley & Sons, Ltd.
Allergenic (sensitization, skin and eye irritation) effects of freshwater cyanobacteria—experimental evidence
Authors: Torokne Andrea , Palovics Agnes , Bankine Maria
Published: November 2004

Many studies have been published on the human health effects of cyanobacterial toxicity. As a public health concern, we have to mention that the development of contact dermatitis, asthmalike symptoms, and symptoms resembling hay fever during bathing in cyanobacterial blooms have been also described. Microcystis aeruginosa, Anabaena flos‐aquae, Aphanizomenon flos‐aquae, and Cylindrospermopsis raciborskii are the most common species found in Hungarian freshwaters. A sensitization test on albino guinea pigs, and intradermal reactivity, and occular irritation test on albino rabbits were carried out with freeze‐dried algal suspension in physiological salt solution. The sensitivity of guinea pigs is similar to that of humans. Microcystis, Anabaena, Cylindrospermopsis, and Aphanizomenon bloom and strain samples were examined in sensitization and irritation tests and no correlation was found between the toxin content and the allergenic character. The most toxic one (Microcystis aeruginosa) was not the most allergenic sample, but the nontoxic Aphanizomenon was the most allergenic one. The axenic strains were not allergenic at all. The pure microcystin LR was only slightly allergenic even in high concentration (1.5 mg/ml). Water and lipid soluble fractions were obtained by water and chloroform extraction of lyophilized algal suspensions. The chloroform fraction was bound on C18 cartridges and eluted by methanol in nine fractions. Only one of the lipid soluble fractions was skin irritative whereas the strongest irritative effect was shown by the water soluble fraction. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 512–516, 2001
Concentrations of pesticide residues in tissues of fish from Kolleru Lake in India
Authors: Amaraneni S. R. , Pillala R. R.
Published: November 2004

Kolleru Lake is the largest natural freshwater lake of Andhra Pradesh in India. It is situated between latitudes 16°32′ and 16°47′N and longitudes 81°05′ and 81°27′E. The use of pesticides for agricultural purposes is widespread in the Kolleru Lake region. The biological indicators like fish help in the studies of aquatic pollution by pesticides. Fish species Channa striata and Catla catla and water samples were collected from Kolleru Lake in each of three seasons over a period of three years. Fish samples were analyzed according to a modified method which is proposed for the gas chromatographic determination for the pesticides viz., α‐BHC, γ‐BHC, malathion, chloirpyrifos, isodrin, endosulfan, dieldrin, and p,p‐DDT. Water samples were analyzed for selected physico‐chemical parameters. The extraction efficiency for the selected pesticides is between 82.8% and 91.2%. The maximum concentrations of pesticide residues in Kolleru Lake fish on wet weight basis are 123.8 μg/g for α‐BHC, 98.7 μg/g for γ‐BHC, 2.5 μg/g for malathion, 88.6 μg/g for chlorpyrifos, 0.91 μg/g for isodrin, 76.5 μg/g for endosulfan, 1.98 μg/g for dieldrin, and 157.4 μg/g for p,p′‐DDT. These analyses were used to evaluate the baseline data and the pesticide pollution in the lake's ecosystem. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 550–556, 2001
The acute and chronic toxicity of cadmium and zinc to two hydra species
Authors: Holdway Douglas A. , Lok Katrina , Semaan Michael
Published: November 2004

The potential of two hydra species, Hydra vulgaris (pink) and Hydra viridissima (green), for use as invertebrate models for toxicity testing of waterborne metals was investigated. The acute and subchronic toxicities of cadmium (a nonessential metal) and zinc (an essential metal) were determined. Results showed that both the hydra species were more sensitive to cadmium than to zinc, and that green hydra were more sensitive than pink hydra. The mean (SE) 96 h LC50 values of cadmium and zinc for pink hydra were 83 (8.5) and 2300 (150) μg/L, respectively. For green hydra, the respective 96 h LC50 values for cadmium and zinc were 3.0 (0.0) and 935 (46.5) μg/L. The respective 7‐day no‐observed‐effect‐concentrations (NOEC) and lowest‐observed‐effect‐concentrations (LOEC) for pink hydra were <13 and 13 μg/L for cadmium, and <250 and 250 μg/L for zinc. The respective 7‐day NOEC and LOEC values for green hydra were 0.4 and 0.8, μg/L for cadmium, and 38 and 75 μg/L for zinc. Neither 1, 2, or 3 × 90‐min pulse‐exposures to 0.4, 0.8, or 1.5 μg/L of cadmium had any significant deleterious effect on total green hydra numbers after seven days in clean water. Green hydra appeared to be excellent freshwater invertebrate models for testing dissolved metals based on their sensitivity and the ability to rapidly assess population reproduction in the laboratory. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 557–565, 2001
Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure
Authors: Semaan M. , Holdway D. A. , van Dam R. A.
Published: November 2004

Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no‐observed‐effect‐concentration (NOEC; reproduction) and lowest observed‐effect‐concentration (LOEC; reproduction) for uranium ranged between 8–31 μg L−1 and 20–49 μg L−1, respectively, for all three populations. The 48 h EC50 (immobilization–lethality) for uranium ranged between 160–390 μg L−1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the “wild” populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 365–376, 2001
Increased cardiac atrial‐to‐ventricular length ratio in the fetal four‐chamber view: a new marker for atrioventricular septal defects
Authors: Machlitt A. , Heling K.‐S. , Chaoui R.
Published: November 2004

Objectives

Atrioventricular septal defects (AVSDs) are the most common cardiac abnormality in fetuses with numerical chromosomal aberrations, in particular trisomy 21. The majority of AVSDs are not detected by routine ultrasound examination in pregnancy. We report two simple cardiac measurements that may substantially improve antenatal detection of AVSDs.

Methods

Cross‐sectional ultrasound images through the fetal thorax demonstrating the four‐chamber plane of the heart were obtained in 123 normal fetuses between 10 and 38 weeks of gestation. Heart length was measured at the level of interventricular septum by placing the calipers on the epicardium at the apex of the heart and on the endocardium at the top of the atrium. Ventricular length was measured by shifting the atrial caliper to the crossing point of the ventricular septum and mitral valve. Atrial length was calculated as the difference between the heart length and ventricular length. Based on these measurements, the atrial‐to‐ventricular length (AVL) ratio was calculated. Data were compared to measurements from 29 consecutive fetuses with AVSD between 13 and 39 weeks of gestation.

Results

In normal fetuses, the AVL ratio did not change with gestation and the mean AVL ratio was 0.47 (95% prediction interval 0.35 to 0.63). In the AVSD group, the mean AVL ratio was 0.77 (range, 0.59–0.99). If a cut‐off value for the AVL ratio of 0.6 was chosen, the detection rate of AVSD was 86.2% at a 5.7% false‐positive rate. For a 100% detection rate, the false‐positive rate was 7.3%.

Conclusions

The AVL ratio can accurately discriminate between hearts with AVSDs and normal cardiac anatomy. Incorporation of the AVL ratio measurement into routine antenatal ultrasonography may substantially improve the ability to diagnose AVSDs antenatally. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Three‐dimensional power Doppler imaging of early‐stage cervical cancer
Authors: Hsu K.‐F. , Su J.‐M. , Huang S.‐C. , Cheng Y.‐M. , Kang C.‐Y. , Shen M.‐R. , Chang F.‐M. , Chou C.‐Y.
Published: November 2004

Objectives

To characterize intratumoral vascularization in early‐stage cervical cancer by three‐dimensional (3D) power Doppler ultrasound.

Methods

One hundred and forty‐one patients with carcinoma of the uterine cervix and 30 normal controls were studied by transvaginal 3D power Doppler ultrasound. The tumor volume of the cervical cancer was determined. The blood flow within the tumor or normal cervix was measured and expressed as the vascularization index (VI), flow index (FI) and vascularization flow index (VFI).

Results

Of the 141 patients with cervical cancer, 44 patients had undergone prior cervical conization. Eighty‐seven patients had measurable cervical tumors, of whom five had had prior conization. Abundant intratumoral power Doppler signals could be detected, and the VI, FI and VFI were significantly elevated in cervical cancer patients compared with women with a normal cervix and patients in whom no cervical tumor could be detected (P < 0.05, one‐way ANOVA). We observed four types of intratumoral vascularity patterns, which did not significantly differ in VI, FI and VFI: localized, peripheral, scattered and single‐vessel types. Cervical tumor volume was positively correlated with FI (linear regression, r = 0.373, P = 0.001), but not with VI or VFI.

Conclusions

3D power Doppler ultrasound provides a useful tool to investigate intratumoral vascularization and volume of cervical cancer. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
The role of color and power Doppler ultrasound in the prenatal diagnosis of sirenomelia
Authors: Patel S. , Suchet I.
Published: November 2004

Sirenomelia is a rare congenital abnormality characterized by a variety of anomalies involving the lower limbs, severe oligohydramnios, bilateral renal agenesis, anorectal atresia and aberrant fetal vasculature. The prenatal diagnosis and differentiation from isolated bilateral renal agenesis is severely limited by the accompanying oligohydramnios that hinders visualization of fetal anatomy. We present three prospectively assessed cases of sirenomelia, two of which had bilateral renal agenesis, and all of which had a single umbilical artery derived from the aberrant vasculature that accompanies the syndrome. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the melatonin binding site MT3
Authors: Mailliet François , Ferry Gilles , Vella Fanny , Thiam Kader , Delagrange Philippe , Boutin Jean A.
Published: November 2004

Two melatonin receptors (MT1 and MT2) have been cloned. A third melatonin binding site, MT
3, is known with remarkable and distinct pharmacological properties. We previously reported the purification of MT
3 and identified it as the enzyme dihydronicotinamide riboside:quinone reductase 2 (NQO2). To investigate the relationship between NQO2 and MT
3, we generated a NQO2−/− mouse strain. These mice no longer present MT
3 binding sites as measured with 2‐[125I]‐iodo, 5‐methoxycarbonylamino‐N‐acetyltryptamine, the specific MT
3 radioligand. These data establish NQO2 as part of the MT
3 binding sites in vivo and resolve the matter of the nature of the third melatonin binding site.
Freeze‐fracture and thin section study of the rough ER‐Golgi interface in the pancreatic acinar cell. Resemblance between the intramembranal architecture of the outermost Golgi cisterna and the post‐rough ER vesicular and tubular elements
Authors: Sesso Antonio , Azimovas Sônia Regina Rodrigues Bexiga , Ferreira Marcelo Alves
Published: November 2004

Summary— Post‐ER membranous structures are clearly observed in pancreases fixed with aldehydes and subsequently with reduced osmium. Close to the transitional rough ER, clusters of vesicles of ≈ 56 nm diameter are consistently present. In some cells, tortuous tubules appear enmeshed by the ≈ 56 nm vesicles and by irregular, vesicular formations. In freeze‐fracture replicas, the membranes of the bulges and tubules that protrude from the transitional rough ER differ from those of the donor compartment. These protrusions are herein designated as the budding chamber of the transitional rough ER. Quantitative and qualitative observations performed previously and in the present study show that the P and E freeze‐fracture faces of the outermost Golgi cisternal membrane possess patterns of texture that are unique among membranes. The P‐face exhibits a very high density of intramembranous particles of dimensions among the smallest yet described; E‐faces show rugosities and an unusually high density of intramembranous particles of normal size. The membranes of the budding chamber, the putative transport vesicles of ≈ 56 nm diameter, the sinuous tubules and the vesicles of irregular size and shape exhibit P and E fracture faces with textures indistinguishable from those of the corresponding P and E faces of the outermost Golgi cisterna.
Cellular localization of polyamines: Cytochemical and ultrastructural methods providing new clues to polyamine function in ram spermatozoa
Authors: Rubinstein Sara , Breitbart Haim
Published: November 2004

Summary— Polyamine binding sites have been localized in ram spermatozoa using biochemical and cytochemical tools. Incubating the cells with 14C‐spermine and determining its distribution after sonication and differential centrifugation, revealed that 60% of the radioactive spermine was localized in the head, 21.5% in the tail and about 9% in the plasma membrane. A polyamine specific cytochemical staining by the formaldehyde‐fluorescamine method, revealed that most of the polyamines were localized in the midpiece, where the cell mitochondria are located, and in the acrosome region. Two additional studies used electron microscopy, employing polycationic colloidal gold and spermine‐ferritin as cytochemical markers. The most sensitive and specific method was the staining of the cells with ferritin‐spermine whose synthesis is described in this study. The outer acrosomal membrane was the preferential site for spermine binding which was densely distributed in a highly orderly pattern. There was a sparse distribution of spermine binding sites on the plasma membrane surrounding the acrosome and none on the post acrosomal region. The role of spermine in the acrosome reaction and Ca2+ fluxes in sperm cells is discussed.
Morphometric analysis of Mexican and South American populations of the Anastrepha fraterculus complex (Diptera: Tephritidae) and recognition of a distinct Mexican morphotype
Authors: Hernández-Ortiz V. , Gómez-Anaya J.A. , Sánchez A. , McPheron B.A. , Aluja M.
Published: November 2004

Discriminant function and cluster analyses were performed on 19 morphometric variables of the aculeus, wing and mesonotum to determine whether populations of Anastrepha fraterculus (Wiedemann) from different parts of Mexico could be distinguished from populations from South America., Samples were collected from seven localities across Mexico, two from Brazil, and one each from Colombia and Argentina. Results showed there were statistically significant differences between Mexican and South American populations with respect to the aculeus (tip length, length of serrated section, mean number of teeth) and wing (width of S-band and connection between S- and V-bands). The degree of morphological variation observed among Mexican populations was extremely low, and as a consequence, the Mexican populations were identified as a single morphotype by discriminant analysis. The ‘Andean morphotype’ consisting of the Colombian population, and the ‘Brazilian morphotype’ consisting of the two Brazilian populations plus the single Argentinian population were also distinguished. It was concluded that the macro-geographical morphotypes from Mexico, Colombia, and Brazil plus Argentina correspond to three distinct taxonomic entities. Comparisons of results with those obtained from behavioural, karyotypic, isozyme and DNA studies suggest that sufficient evidence now exists to name a new Mexican species from within the A. fraterculus complex. This will be done in a separate publication. A provisional key to the morphotypes of A. fraterculus studied is provided.
Alphaviral cytotoxicity and its implication in vector development
Authors: Rhême Céline , Ehrengruber Markus U. , Grandgirard Denis
Published: November 2004

A great variety of viruses have been engineered to serve as expression vectors. Among them, the alphaviruses Semliki Forest virus and Sindbis virus represent promising tools for heterologous gene expression in a wide variety of host cells. Several applications have already been described in neurobiological studies, in gene therapy, for vaccine development and in cancer therapy. Both viruses trigger stress pathways in the cells they infect, sometimes culminating in the death of the host. This inherent property is either an advantage or a drawback, depending on the type of application.This review covers the development and applications of alphavirus vectors and, as our work has been mainly with Semliki Forest virus, we have focused on this virus with special emphasis on how the understanding of Semliki Forest virus cytotoxicity enables it to be manipulated and used.
Optimizing regulatable gene expression using adenoviral vectors
Authors: Lee Youn‐Bok , Glover Colin P. J. , Cosgrave A. Siobhan , Bienemann Alison , Uney James B.
Published: November 2004

Inducible gene expression systems have typically encountered limitations, such as pleitropic effects of the inducer, basal leakiness, toxicity of inducing agents and low levels of expression. However, recently non‐toxic, tightly regulated control of transgene expression has been reported for several systems, the most frequently cited being the tetracycline gene control system. We have found that the individual components of the Tet system [the Tet transactivators and tetracycline responsive element (TRE)] function optimally to control gene expression when they are incorporated into separate adenoviral vectors. Furthermore, incorporation of the Woodchuck hepatitis virus post‐transcriptional enhancer (WPRE) allows a dual vector Tet‐regulatable Ad system to be used at very low titres (2 × 104) that elicit a minimal inflammatory response, with no loss of transgene expression or ability to regulate transgene expression. This and similar regulatable systems will benefit studies investigating neuronal gene function and those seeking to develop effective neuronal gene therapy strategies.
Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms
Authors: Al-Saleem Tahseen , Al-Mondhiry Hamid
Published: November 2004

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated α heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (VH) and the constant heavy chain 1 (CH1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of CH1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.
Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice
Authors: Vissers Joost LM , van Esch Betty CAM , Jeurink Prescilla V , Hofman Gerard A , van Oosterhout Antoon JM
Published: November 2004

Background

Previously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. In vitro studies showed that OVA-Mφ start to produce IL-10 upon interaction with allergen-specific T cells, which might mediate their immunosuppressive effects. Herein, we examined whether IL-10 is essential for the immunosuppressive effects of OVA-Mφ in vivo, and whether ex vivo stimulation of the IL-10 production by OVA-Mφ could enhance these effects.

Methods

Peritoneal Mφ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) in vitro. The increase of IL-10 production was examined and, subsequently, ex vivo stimulated OVA-Mφ were used to treat (i.v.) OVA-sensitized mice. To further explore whether Mφ-derived IL-10 mediates the immunosuppressive effects, Mφ isolated from IL-10-/- mice were used for treatment.

Results

We found that stimulation with LPS or ISS-ODN highly increased the IL-10 production by OVA-Mφ (2.5-fold and 4.5-fold increase, respectively). ISS-ODN stimulation of OVA-Mφ significantly potentiated the suppressive effects on allergic airway inflammation. Compared to sham-treatment, ISS-ODN-stimulated OVA-Mφ suppressed the airway eosinophilia by 85% (vs. 30% by unstimulated OVA-Mφ), IL-5 levels in bronchoalveolar lavage fluid by 80% (vs. 50%) and serum OVA-specific IgE levels by 60% (vs. 30%). Importantly, IL-10-/-Mφ that were loaded with OVA and stimulated with ISS-ODN ex vivo, failed to suppress OVA-induced airway inflammation.

Conclusions

These results demonstrate that Mφ-derived IL-10 mediates anti-inflammatory responses in a mouse model of allergic asthma, which both can be potentiated by stimulation with ISS-ODN.
Random allocation software for parallel group randomized trials
Authors: Saghaei Mahmood
Published: November 2004

Background

Typically, randomization software should allow users to exert control over the different aspects of randomization including block design, provision of unique identifiers and control over the format and type of program output. While some of these characteristics have been addressed by available software, none of them have all of these capabilities integrated into one package. The main objective of the Random Allocation Software project was to enhance the user's control over different aspects of randomization in parallel group trials, including output type and format, structure and ordering of generated unique identifiers and enabling users to specify group names for more than two groups.

Results

The program has different settings for: simple and blocked randomizations; length, format and ordering of generated unique identifiers; type and format of program output; and saving sessions for future use. A formatted random list generated by this program can be used directly (without further formatting) by the coordinator of the research team to prepare and encode different drugs or instruments necessary for the parallel group trial.

Conclusions

Random Allocation Software enables users to control different attributes of the random allocation sequence and produce qualified lists for parallel group trials.
Properties and expression of human tartrate-resistant acid phosphatase isoform 5a by monocyte-derived cells
Authors: Janckila Anthony J , Parthasarathy Ranga N , Parthasarathy Latha K , Seelan Ratnam S , Hsueh Yi-Cheung , Rissanen Jukka , Alatalo Sari L , Halleen Jussi M , Yam Lung T
Published: November 2004

Human serum tartrate-resistant acid phosphatase exists as two enzyme isoforms (TRACP 5a and 5b), derived by differential, post-translational processing of a common gene product. Serum TRACP 5b is from bone-resorbing osteoclasts (OC) and becomes elevated in diseases of increased bone resorption. TRACP 5a is secreted by macrophages (MΦ) and dendritic cells (DC) and is increased in many patients with rheumatoid arthritis. Our purpose was to fully characterize the properties of human TRACP isoforms and to produce an antibody specific to TRACP 5a for use as a biomarker in chronic inflammatory diseases. Partially purified, natural serum TRACP isoforms and recombinant TRACP 5a (rTRACP 5a) were compared with respect to specific activity and subunit structure and presence of sialic acid. Mice were immunized with rTRACP 5a, and resulting hybridomas were screened for monoclonal antibody to serum TRACP 5a. One antibody, 220, was tested for its epitope specificity and use in various immunological techniques. rTRACP 5a had properties identical to serum TRACP 5a. Antibody 220 was specific for the trypsin-sensitive epitope in the loop peptide, present only in TRACP 5a. Antibody 220 was effective for specific immunoprecipitation, immunoassay, and immunoblot of TRACP 5a. Intact TRACP was present in MΦ, DC, and OC. TRACP 5a was the predominant isoform secreted by MΦ and DC, whereas TRACP 5b was the predominant isoform secreted by OC. TRACP isoforms 5a and 5b may have different functions inside and outside of monocyte-derived cells. Antibody 220 is an important resource for studies of the biosynthetic relationship among TRACP isoforms and of the significance of serum TRACP 5a as a marker in diseases of bone metabolism and inflammation.
IFN-β treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing -remitting multiple sclerosis
Authors: Espejo C , Brieva L , Ruggiero G , Río J , Montalban X , Martínez-Cáceres E M
Published: November 2004

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-b is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing -remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-b treatment. These data support that one of the immunomodulatory effects of IFN-b treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.
Increased frequencies of serum antibodies to neurofilament light in patients with primary chronic progressive multiple sclerosis
Authors: Ehling R , Lutterotti A , Wanschitz J , Khalil M , Gneiss C , Deisenhammer F , Reindl M , Berger T
Published: November 2004

We investigated whether serum and cerebrospinal fluid (CSF) antibodies to the light subunit of the NF protein (NF-L), a main component of the axonal cytoskeleton, may serve as biological markers for axonal pathology and/or disease progression in multiple sclerosis (MS). IgG to NF-L was measured in sera and CSF of MS patients, patients with inflammatory demyelinating diseases of the PNS, with acute inflammatory neurological diseases (including bacterial and viral meningitis), with neurodegenerative diseases, with acute noninflammatory neurological diseases (including stroke, headache and backache) and healthy controls by enzyme-linked immunosorbent assay. We found that serum anti-NF-L IgG antibodies were significantly elevated in MS patients with primary progressive disease course and we provide evidence for an intrathecal production of these antibodies. Our findings support the use of serum antibodies to NF-L as a marker for axonal destruction.
Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients
Authors: Smith Richard A , Berg James E , Pope Laura E , Callahan Janice D , Wynn Daniel , Thisted Ronald A
Published: November 2004

Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder of affect that occurs in about 10% of multiple sclerosis (MS) patients. The objective of this study was to validate the CNS Emotional Lability Scale (CNS-LS) in MS patients and to correlate the results with the frequency and intensity of episodes of PLC. Physicians at seven private practice referral centers in the United States made a diagnosis concerning PLC based on patient interviews. Clinical coordinators separately administered the CNS-LS, a self-report measure of PLC with seven questions, to MS patients, including patients known to exhibit PLC, patients thought to be free of PLC, and newly diagnosed patients where PLC status was unknown, and the physician was blinded as to the results. A receiver operating characteristic (ROC) curve analysis was performed to define a cut-off best correlating with the physician’s diagnosis. Of 90 MS patients selected to complete the survey, 50 were physician diagnosed with PLC; 40 were without PLC, and 15 of these 90 patients were newly diagnosed with MS (B-6 months). Scores of 17 or higher corresponded to a sensitivity of 0.94 and a specificity of 0.83 (LR -/5.5, LR -/0.07); 89% of patients were correctly diagnosed. The area under the ROC curve was 0.95. Symptoms were greater in patients diagnosed as PLC than in non-PLC patients as evidenced by mean number of episodes/week, number of days/week with episodes, duration of an episode and total time in an episode. Similar results were observed if patients were classified as PLC or non-PLC according to CNS-LS score]-17, suggesting that the CNS-LS is a valid measure for the assessment of PLC in MS patients and could be a useful instrument for clinical and research purposes.
A randomized open label study of pain medications (naproxen, acetaminophen and ibuprofen) for controlling side effects during initiation of IFN β-1a therapy and during its ongoing use for relapsing-remitting multiple sclerosis
Authors: Leuschen M Patricia , Filipi Mary , Healey Kathleen
Published: November 2004

Multiple sclerosis (MS) patients initiating IFN b-1a, Avonex, therapy (Group 1, n-30) or experiencing side effects after 6 months on therapy (Group 2, n-30) were randomized for 5 weeks open label adjunct therapy to naproxen (Aleve®), acetaminophen (Tylenol®)or ibuprofen (Advil®). Our hypothesis was that non-prescription pain medications are effective in decreasing or alleviating the side effects associated with IFN b-1a therapy. Contrary to the hypothesis, most patients in both groups continued to report side effects on all pain medications. After 5 weeks, headache, fever, chills and injection site pain were low in5-50% of patients. Moderate to significant fatigue, muscle or joint pain continued in most patients. As a quality of life measure, the Modified Fatigue Impact Scale (mFIS) improved for Group 1 on naproxen or ibuprofen with greatest improvement in physical subset (P-0.002 for naproxen and PB-0.01 for ibuprofen). Total mFIS for Group 1 on acetaminophen improved (P-0.04) due to improved cognitive subset rather than physical subset. Group 2, with side effects initially, reported less significant fatigue (severity 5-10) but more moderate fatigue (severity 2-4) at study end for all three medications. All medications improved cognitive subset (P=0.05). Physical mFIS subset did not improve for Group 2 on acetaminophen, but did with naproxen (P=0.05) or ibuprofen (P=0.03). Naproxen and ibuprofen were more effective than acetaminophen in minimizing physical side effects of IFN b-1a. None of the three pain medications tested were as effective as hypothesized for minimizing fatigue or muscle and joint pain.
Context‐based generic cross‐lingual retrieval of documents and automated summaries
Authors: Lam Wai , Chan Ki , Radev Dragomir , Saggion Horacio , Teufel Simone
Published: November 2004

We develop a context‐based generic cross‐lingual retrieval model that can deal with different language pairs. Our model considers contexts in the query translation process. Contexts in the query as well as in the documents based on co‐occurrence statistics from different granularity of passages are exploited. We also investigate cross‐lingual retrieval of automatic generic summaries. We have implemented our model for two different cross‐lingual settings, namely, retrieving Chinese documents from English queries as well as retrieving English documents from Chinese queries. Extensive experiments have been conducted on a large‐scale parallel corpus enabling studies on retrieval performance for two different cross‐lingual settings of full‐length documents as well as automated summaries.
The utility of mixed‐effects covariate analysis in rapid selection of doses in pediatric subjects: A case study with fexofenadine hydrochloride
Authors: Krishna Rajesh , Krishnaswami Sriram , Kittner Barbara , Sankoh Abdul J. , Jensen Bradford K.
Published: November 2004

Fexofenadine hydrochloride is a non‐sedating antihistamine that is used in the treatment of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. A pooled analysis of pharmacokinetic data from children 6 months to 12 years of age and adults was conducted to identify the dose(s) in children that produce exposures comparable to those in adults for the treatment of seasonal allergic rhinitis. The pharmacokinetic parameter database included peak and overall exposure data from 269 treatment exposures from 136 adult subjects, and 90 treatment exposures from 77 pediatric allergic rhinitis patients. The data were pooled and analysed using NONMEM software, version 5.0. A covariate model based on body weight and age and a power function model based on body weight were identified as appropriate models to describe the variability in fexofenadine oral clearance and peak concentration, respectively. Individual oral clearance estimates were on average 44%, 36% and 61% lower in children 6 to 12 years (n = 14), 2 to 5 years (n = 21), and 6 months to 2 years (n = 42), respectively, compared with adults. Trial simulations (n = 100) were carried out based on the final pharmacostatistical models and parameter estimates to identify the appropriate dose(s) in children relative to the marketed dose of 60 mg fexofenadine hydrochloride in adults. The trials were designed as crossover studies in 18 subjects comprising various potential dosing regimens with and without weight stratification. Pharmacokinetic parameter variability was assumed to have a log‐normal distribution. Individual weights and ages were simulated using mean (SD) estimates derived from the studies used in this analysis and proportional measurement/model mis‐specification errors derived from the analysis were incorporated into the simulation. The results indicated that a 30 mg dose of fexofenadine hydrochloride administered to children 1 to 12 years of age and weighing >10.5 kg and a 15 mg dose administered to children 6 months and older and weighing ⩽10.5 kg produces exposures similar to those seen with the 60 mg dose in adults. Copyright © 2004 John Wiley & Sons, Ltd.
Clerical child sex abuse: the response of the Roman Catholic Church
Authors: Dunne Elizabeth A.
Published: November 2004

The response of the Roman Catholic Church (RCC) to the clergy child sex abuse crisis is examined in the context of six cases in an Irish archdiocese. The RCC was not proactive in engaging with complainants and did not accept organizational responsibility for its personnel. Its statements on the crisis were abstract and sometimes transcendent in tone and its attempts to account for its inaction used apologia rather than apology. The Church's reliance on apologia is similar to that found in secular bureaucracies that believe themselves to be ‘client‐independent’. It is argued the Church needs to implement a ‘client complaint’ procedure similar to that found in ‘client‐dependent’ commercial enterprises and that it must also reconnect with its own core values. Copyright © 2004 John Wiley & Sons, Ltd.
Action research, emancipation and design thinking
Authors: Romme A. Georges L.
Published: November 2004

This article evaluates the notion and practice of action research, as defined by contributors to the recent special issue ‘Action Research and Emancipation’ in this journal. The author argues that, although action research implicitly has a design orientation, it largely draws on the humanities and sciences as its main role models. As a result, action researchers nowadays do not see themselves as design professionals. Idealized design methods serve to illustrate how design research can help realize the emancipatory intentions of action researchers. Copyright © 2004 John Wiley & Sons, Ltd.
Rendering natural waters taking fluorescence into account
Authors: Cerezo By E. , Seron F. J.
Published: November 2004

The aim of the work presented here is to generalize a system, developed to treat general participating media, to make it capable of considering volumetric inelastic processes such as fluorescence. Our system, based on the discrete ordinates method, is adequate to treat a complex participating medium such as natural waters as it is prepared to deal with not only anisotropic but also highly peaked phase functions, as well as to consider the spectral behaviour of the medium's characteristic parameters. It is also able to generate detailed quantitative illumination information, such as the amount of light that reaches the medium boundaries or the amount of light absorbed in each of the medium voxels. First, we present an extended form of the radiative transfer equation to incorporate inelastic volumetric phenomena. Then, we discuss the necessary changes in the general calculation scheme to include inelastic scattering. We have applied all this to consider the most common inelastic effect in natural waters: fluorescence in chlorophyll‐a. Copyright © 2004 John Wiley & Sons, Ltd.