bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissipative mechanism in Godunov‐type schemes
Authors: Xu Kun , Li Zuowu
Published: January 2005

This paper concerns the dissipative mechanism in the shock capturing schemes, where exact or approximate Riemann solvers are used in the flux evaluation. More specifically, we are going to analyze the dissipation in the flux vector splitting (FVS) scheme and the Godunov method, from which some pathological phenomena from the FVS scheme and the Godunov method will be explained, such as the artificial dissipation and the shock instability. Copyright © 2001 John Wiley & Sons, Ltd.
An adaptive mesh adjoint data assimilation method applied to free surface flows
Authors: Fang F. , Pain C. C. , Piggott M. D. , Gorman G. J. , Goddard A. J. H.
Published: January 2005

In this paper, we describe the construction of a three‐dimensional adaptive mesh data assimilation method for oceanographic/coastal applications, including a free surface. This is the first attempt at introducing a moving computational domain into an adjoint model with mesh adaptivity. We also provide insight into the feasibility and reliability of the adaptive mesh adjoint model. The use of differing adapting meshes for forward and adjoint problems is considered here, where each mesh is optimized with respect to the individual properties of each solution. The free surface test case considered is that of flow in a two‐dimensional vertical fluid slice. In this test case the sea surface elevation boundary conditions is optimized by assimilating sea surface height observations. The feasibility of an assimilation approach on adapting moving domains is demonstrated by comparison with a fixed mesh result. Copyright © 2005 John Wiley & Sons, Ltd.
Numerical modelling of flow with heat transfer in petroleum reservoirs
Authors: Amara M. , Capatina D. , Denel B. , Terpolilli P.
Published: January 2005

We model and analyse the single‐phase flow in a petroleum reservoir by taking into account a nonstandard energy equation. The numerical approximation is based on Raviart–Thomas mixed finite elements and a code is developed and validated. Copyright © 2005 John Wiley & Sons, Ltd.
High order interpolation methods for semi‐Lagrangian models of mobile‐bed hydrodynamics on Cartesian grids with cut cells
Authors: Rosatti Giorgio , Chemotti Roberto , Bonaventura Luca
Published: January 2005

High order approximation methods based on radial basis functions are applied to the extension of semi‐Lagrangian shallow water models to staggered Cartesian meshes with cut boundary cells. The accuracy and efficiency of the resulting semi‐Lagrangian method is demonstrated by test cases simulating open channel flow. The derivative reconstruction provided by radial basis function interpolators is also employed successfully in the discretization of sediment transport models for mobile bed river flow. Copyright © 2005 John Wiley & Sons, Ltd.
Assessing trilobite biodiversity change in the Ordovician of the British Isles
Authors: McCormick Tim , Owen Alan W.
Published: January 2005

The Ordovician Period saw the most sustained, steep rise in marine biodiversity in the history of life on Earth and set the ecological pattern for the rest of the Palaeozoic Era. The long history of research, wide variety of depositional settings and juxtaposition of terranes with very different palaeobiogeographical histories makes the Ordovician of the British Isles an excellent laboratory in which to study this change. A database approach to analysis of trilobite biodiversity change is described using a simple compilation of stratigraphical ranges of 663 species of Avalonian trilobites, and a much more sophisticated information‐rich relational database based on the fundamental information of the fossil record–species at localities. The latter includes 2001 occurrence records of 617 trilobite species at 508 localities in the Welsh Basin. The first ever species‐level diversity curves for the whole Ordovician of an entire region are presented. Both databases reveal an overall increase in species‐ and genus‐level diversity through the Ordovician. Random resampling tests and environmental information are used to remove sampling effects from the Welsh Basin diversity curves. The main features of trilobite biodiversity change in Avalonia are the following: a late Arenig–early Llanvirn increase, during which time the highest species‐to‐genus ratios occur, is contemporaneous with a rise in global diversity and rifting of Avalonia from Gondwana; a late Abereiddian dip is followed by recovery during the Llandeilian–early Caradoc; decline during the late Caradoc–early Ashgill is at least partly attributable to lack of preserved rock and restriction of most of the preserved faunas to deep‐water environments. The greatest diversity occurs in the palaeoenvironmentally differentiated Rawtheyan and is followed by the diversity crash seen in the Hirnantian throughout the world. Copyright © 2001 John Wiley & Sons, Ltd.
How good is the fossil record of arthropods? An assessment using the stratigraphic congruence of cladograms
Authors: Wills Matthew A.
Published: January 2005

A total of 179 published cladograms of arthropods was tested for their congruence with the palaeontological record. Congruence for data sets including 510 tetrapod and 157 fish trees was also calculated for comparison. Results provide support for the hypothesis that the fossil record of arthropods is less complete (at levels of stratigraphic and taxonomic resolution pertinent to most macroevolutionary studies) than the records of several other taxa. Differences in tree size, shape, balance and the distribution of first stratigraphic appearances (potential sources of bias) were controlled for by various randomization procedures. Most measures of congruence for arthropods were statistically poorer than those for other groups, even when the sample was divided into broad temporal bins. Many of the most robust and widely reproduced sister groupings of arthropods are attended by ghost ranges of many tens or hundreds of millions of years. Fossils of a number of presently very diverse and abundant arthropod groups are conspicuously absent from the record, despite many spectacular examples of the detailed preservation of others. There is probably no single reason for the apparently poor record of arthropods. Low preservation potential, small size of individuals, small numbers of individuals, and restricted palaeobiogeography almost certainly play a role in particular cases. Copyright © 2001 John Wiley & Sons, Ltd.
History of marine biodiversity
Authors: Sheehan Peter M.
Published: January 2005

During the Phanerozoic, three steps of increasing diversity each had a unique Evolutionary Fauna (EF). During each EF, there were geologically long intervals of community stasis referred to as Ecological Evolutionary Units (EEUs). These intervals were characterized by communities composed of incumbent faunas that dominated particular habitats. Niches that were already occupied by incumbents were seldom invaded by new taxa, and the resilience of the incumbents to new competitors resulted in the long interval stasis.

Most EEUs were terminated by extinction events that were caused by severe disruptions of the physical environment such as glaciations and extraterrestrial impacts. During mass extinctions many niches were vacated when incumbents were eliminated. Mass extinctions were followed by recovery intervals lasting on the order of 5 million years during which many surviving clades evolved adaptations which allowed them to move into vacated niches. New incumbents were established during these recovery intervals, and the next EEU began. In many ways, the recovery intervals resemble times when organisms invaded previously unoccupied ecospace, such as the emergence of life on land or the progressive filling of previously unoccupied habitats such as deep‐burrowing and high epifaunal tiers that were colonized during the Palaeozoic.

The recognition of long intervals of ecological stasis and the importance of physical disruptions in clearing incumbents is forcing revision of the traditional evolutionary viewpoint. The idea that most evolutionary change was accomplished very gradually by competition between organisms and by becoming better adapted to a relatively stable environment is being replaced by a recognition that major morphological and synecological changes tend to occur very rapidly and at times when there are few established competitors. Copyright © 2001 John Wiley & Sons, Ltd.
Laser debulking in malignant upper airway obstruction
Authors: Paleri Vinidh , Stafford Frank William , Sammut Mario S.
Published: January 2005

Background.

The conventional treatment for patients with upper airway obstruction secondary to malignancy is a tracheostomy. Although this effectively resolves the problem, a tracheostomy can be associated with complications and is irreversible in most patients. An alternative is to debulk part of the tumor causing airway obstruction to maintain the airway until the definitive procedure.

Methods.

The clinical course of 43 patients who underwent laser debulking for airway obstruction caused by laryngeal or hypopharyngeal malignancies was retrospectively studied. We present our technique of laser debulking and the efficacy of the procedure in avoiding a tracheostomy.

Results.

Fourteen patients who underwent this procedure received palliative treatment only. The number of debulking procedures per patient ranged from one to six, with a mean of 1.9 episodes. Although these patients had a higher comorbid burden, none were thought unsuitable for the procedure. A tracheostomy was avoided in 91% of patients. No laser‐related complications were encountered.

Conclusions.

Laser debulking is a viable alternative to tracheostomy in patients with malignant upper airway obstruction. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Time‐dependent involvement of the dorsal hippocampus in trace fear conditioning in mice
Authors: Misane Ilga , Tovote Philip , Meyer Michael , Spiess Joachim , Ögren Sven Ove , Stiedl Oliver
Published: January 2005

Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time‐dependent involvement of N‐methyl‐D‐aspartate (NMDA) receptors in the dorsal hippocampus in one‐trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS‐US (trace) intervals of 1–45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context‐dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45‐s trace interval prevented the formation of conditioned tone‐dependent fear. Context‐dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15–30‐s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time‐dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS‐US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley‐Liss, Inc.
Synthesis of Fusion‐Isomeric Imidazopyridines and Their Evaluation as Inhibitors of syn‐ and anti‐Protonating Glycosidases
Authors: Mohal Narinder , Vasella Andrea
Published: January 2005

The galacto‐ and gluco‐configured imidazopyridines 4 and 5 were synthesised as potential inhibitors of syn‐protonating β‐glycosidases. Methyl α‐D‐lyxopyranoside (9) was transformed into the 3,4‐anhydro‐β‐L‐riboside 16, which, upon treatment with Et2AlCN, gave the nitrile 17 (76–85%). Reaction of 17 with the dimethyl aluminate of aminoacetaldehyde dimethyl acetal led directly to the branched chain lyxo‐configured imidazole 27 (53%) that was hydrolysed to an equilibrating mixture of 4 and 28–30. Oxido reduction of 27 provided the arabino‐configured imidazole 42 (ca. 48% from 27). Hydrolysis of 42 led to the mixture 5/45 (63–90%). anti‐Protonating β‐galactosidases and β‐glucosidases (families 1 and 2) were only weakly inhibited by 4/28–30 and 5/45, respectively. Also the syn‐protonating cellulase (Cel7A) was weakly inhibited by the monosaccharide mimics 5/45, suggesting either that monosaccharide mimics are too small to inhibit Cel7A, or that fusion isomeric tetrahydroimidazo[1,2‐a]pyridines are not a suitable scaffold for the inhibition of syn‐protonating glycosidases.
A New and Simply Available Class of Hydrosoluble Bioconjugates by Coupling Paclitaxel to Hyaluronic Acid through a 4‐Hydroxybutanoic Acid Derived Linker
Authors: Leonelli Francesca , La Bella Angela , Francescangeli Andrea , Joudioux Roberta , Capodilupo Agostina‐Lina , Quagliariello Marina , Migneco Luisa M. , Bettolo Rinaldo Marini , Crescenzi Vittorio , De Luca Gilda , Renier Davide
Published: January 2005

A simple preparation of a new hydrosoluble paclitaxel bioconjugate 8, representing a new class of paclitaxel derivatives, is described. Bioconjugate 8 was obtained by coupling hyaluronic acid (2) to paclitaxel (1) by means of a 4‐hydroxybutanoic acid derived linker (Scheme 2).
Novel Sesquiterpenoids from Siegesbeckia orientalis
Authors: Xiang Ying , Fan Cheng‐Qi , Yue Jian‐Min
Published: January 2005

Five new sesquiterpenoids, namely, 8β‐(angeloyloxy)‐4β,6α,15‐trihydroxy‐14‐oxoguaia‐9,11(13)‐dien‐12‐oic acid 12,6‐lactone (1), 4β,6α,15‐trihydroxy‐8β‐(isobutyryloxy)‐14‐oxoguaia‐9,11(13)‐dien‐12‐oic acid 12,6‐lactone (2), 11,12,13‐trinorguai‐6‐ene‐4β,10β‐diol (3), (1(10)E,4E,8Z)‐8‐(angeloyloxy)‐6α,15‐dihydroxy‐14‐oxogermacra‐(1(10),4,8,11(13)‐tetraen‐12‐oic acid 12,6‐lactone (9), and (1(10)E,4β)‐8β‐(angeloyloxy)‐6α,14,15‐trihydroxygermacra‐1(10),11(13)‐dien‐12‐oic acid 12,6‐lactone (11), and three new artifacts, (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α‐ethoxy‐6α,15‐dihydroxy‐14‐oxogermacra‐1(10),4,11(13)‐trien‐12‐oic acid 12,6‐lactone (6), (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α,13‐diethoxy‐6α,15‐dihydroxy‐14‐oxogermacra‐1(10),4‐dien‐12‐oic acid 12,6‐lactone (7), and (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α‐ethoxy‐6α,15‐dihydroxy‐13‐methoxy‐14‐oxogermacra‐1(10),4‐dien‐12‐oic acid 12,6‐lactone (8), together with the three known sesquiterpenoids 4, 5, and 10, were isolated from the aerial parts of Siegesbeckia orientalis L. Their structures were established by spectral methods, especially 1D‐ and 2D‐NMR spectral methods.
Noncovalent Attachment of Nucleotides by FluorousFluorous Interactions: Application to a Simple Purification Principle for Synthetic DNA Fragments
Authors: Beller Christian , Bannwarth Willi
Published: January 2005

We report a highly efficient noncovalent immobilization of DNA fragments on surfaces by fluorous fluorous interactions. The principle was applied to a simple and straightforward purification protocol for synthetic DNA. The method is completely compatible with standard solid‐phase synthesis of DNA.
Photochemistry of N‐(2‐Acylphenyl)‐2‐methylprop‐2‐enamides: Competition between Photocyclization and Long‐Range Hydrogen Abstraction
Authors: Nishio Takehiko , Tabata Megumi , Koyama Hiroyuki , Sakamoto Masami
Published: January 2005

The photochemical reactions of various ‘N‐methacryloyl acylanilides’ (=N‐(acylphenyl)‐2‐methylprop‐2‐enamides) have been investigated. Under irradiation, the acyl‐substituted anilides 1a–1c and 1o afforded exclusively the corresponding quinoline‐based cyclization products of type 2 (Table 1). In contrast, irradiation of the benzoyl (Bz)‐substituted anilides 1e–1h afforded a mixture of the open‐chain amides 4e–4h and the cyclization products 2e–2h. Irradiation of the para‐acyl‐substituted anilides 6a–6e and 6h afforded the corresponding quinoline‐based cyclization products of type 5 as the sole products (Table 2). The formation of the cyclization products 2a–2c and 2o can be rationalized in terms of 6π‐electron cyclization, followed by thermal [1,5] acyl migration, and that of compounds 3p, 5a–5e, and 5h can be explained by a 6π‐electron cyclization only. The formation of the open‐chain amides 4e–4h probably follows a mechanism involving a 1,7‐diradical, C and a spirolactam of type D (Scheme). Long‐range ζ‐H abstraction by the excited carbonyl O‐atom of the benzoyl group on the aniline ring is expected to proceed via a nine‐membered cyclic transition state, as proposed on the basis of X‐ray crystallographic analyses (Fig. 2).
Modular Microreaction Systems for Homogeneously and Heterogeneously Catalyzed Chemical Synthesis
Authors: Snyder Daniel A. , Noti Christian , Seeberger Peter H. , Schael Frank , Bieber Thomas , Rimmel Guido , Ehrfeld Wolfgang
Published: January 2005

Until now, microreaction devices designed for a specific type of reaction were used mainly for highly exothermic, very fast reactions. Described is a modular microreaction system and its application to representative homogeneous and heterogeneous reactions important in organic synthesis. The modular microreaction system allows continuous flow processes to be optimized and employed effectively in the chemical laboratory. The modular microreaction systems proved also versatile for syntheses requiring moderate reaction times, thus extending their application to a large fraction of organic reactions. The use of the modular and cleanable microreaction systems to rapidly develop optimized reaction conditions provides an excellent basis for the development of many chemical transformations scalable from milligram to ton production quantities.
The Reed–Sternberg cell in classical Hodgkin's disease
Authors: Chan Wing C.
Published: January 2005

There has been substantial advances in our understanding of the nature of the Hodgkin/Reed–Sternberg (H/RS) cell in recent years. There is now compelling evidence that the H/RS cells in the vast majority of cases of classical Hodgkin's disease (CHD) are derived from the B‐cell lineage and a major clonal population is present. The immunoglobulin heavy chain variable region gene generally has a high load of somatic mutations suggesting that the H/RS cells are derived from germinal center (GC) (GC) or post‐GC cells. The cellular milieu in the tumour is largely determined by the cytokines and chemokines secreted by the H/RS cells and the surrounding reactive elements. The pattern of secretion is partially determined by signals transduced through direct surface interactions between H/RS cells and infiltrating T‐cells. Immunosuppressive cytokines and cytokines that preferentially induce a TH2 type of immune response may be partially responsible for the escape of the H/RS cells from immune surveillance. Multiple genes that have been shown to be involved in neoplastic transformation have been studied in HD. The significance of the data generated has been difficult to interpret. Efforts have been made to study the global gene expression pattern of the H/RS cells. There are many difficulties inherent in this approach, but new insight into the pathogenesis and evolution of HD would be expected from the studies. Copyright © 2001 John Wiley & Sons, Ltd.
A comparison of normal and leukemic stem cell biology in Chronic Myeloid Leukemia
Authors: JØrgensen Heather G. , Holyoake Tessa L.
Published: January 2005

Chronic Myeloid Leukemia (CML), a myeloproliferative disease of stem cell origin, is characterized by the presence of the Philadelphia (Ph) chromosome and the bcr‐abl oncogene. The BCR‐ABL fusion gene product, thought to be causative in CML, has multiple effects on diverse cell functions such as growth, differentiation and turnover as well as adhesion and apoptosis. Persistent Ph‐negative progenitors co‐exist with leukemic cells, both in the marrow and blood of patients, in the early chronic phase of the disease. Despite accumulating knowledge of hemopoiesis and the disease process, CML remains incurable with conventional chemotherapy. Nonetheless, with the efficacy of the ABL tyrosine kinase inhibitor STI‐571 (signal transduction inhibitor 571) as a novel therapy in CML recently being realized in clinical trials, it is therefore timely to review our current understanding of the cell biology of this fascinating disease. Copyright © 2001 John Wiley & Sons, Ltd.
Evidence based primary care? A multi‐tier, multiple stakeholder perspective from Chile
Authors: Bedregal Paula , Ferlie Ewan
Published: January 2005

A new challenge in health policy is the implementation of evidence‐based practice. It is useful to look at international experiences which go beyond the conventional USA and UK examples. Health sector restructuring in Chile has as its goals: using evidence‐based decision‐making to reduce variations of practice, contain costs and increase the effectiveness of clinical practice. A key area of change is within primary health care. But how does the implementation of evidence‐based health care proceed in reality? In order to understand this, it was decided to assess the policy environment using stakeholder analysis.

Methods

Fifteen stakeholders from the public health sector were interviewed in depth using a snowball strategy for sampling. Material relating to perceptions, thoughts and aspirations about evidence‐based innovations in primary health care was collected. Content analysis of the material produced a matrix of criteria and indicators of operational power.

Results

Concepts of evidence and effectiveness are different according to the role of each stakeholder in the health system. Most innovations proposed by government are related to management and stakeholders considered them as not being evidence‐based. Informal mechanisms of decision‐making predominated over the formal. Political issues are more important than formal evidence. All stakeholders felt they had power to define policy criteria but not to implement them. Implementation difficulties are related to how the system is organized and the culture within each organization. Most stakeholders indicated the need for human resources with appropriate knowledge and personal skills in order to implement these changes. These findings reveal again the importance of human factors within organizations. Policy‐making should consider such processual aspects in order to implement changes in practices in Chilean health care system more effectively. Copyright © 2001 John Wiley & Sons, Ltd.
Crossing the public–private sector divide with reproductive health in Cambodia: out‐patient services in a local NGO and the national MCH clinic
Authors: Huff‐Rousselle Maggie , Pickering Helen
Published: January 2005

Set within the context of recent literature on the private–public divide in the health sector of developing countries generally and Asia specifically, this study considers the major government and the major indigenous non‐government clinics offering out‐patient reproductive health services in Phnom Penh, Cambodia. Reproductive health is of critical importance in Cambodia, which has one of the highest levels of unmet need for family planning in the developing world and suffers from what is arguably the most severe STD and HIV/AIDS problem in Asia. The study is unusual in that it examines and compares aspects of service delivery and pricing along with the socio‐economic profile and health‐seeking behaviour of clients self‐selecting services in the two settings. The socio‐economic status of clients was much higher than the norm in Cambodia but did not differ significantly between the two clinics. A few service indicators suggested that the quality of care was better in the NGO clinic. Underlying variables—such as the broader mandate of the public sector institution and the significant discrepancy between public and private sector salaries—offer an obvious explanation for these differences. The Ministry of Health in Cambodia has been developing policies related to the NGO sector, which has expanded rapidly in Cambodia during the 1990s, and it is struggling to increase staff remuneration within the public sector. Copyright © 2001 John Wiley & Sons, Ltd.
Decentralization and human resource management in the health sector: a case study (1996–1998) from Nampula province, Mozambique
Authors: Saide Mouzinho A. O. , Stewart Donald E.
Published: January 2005

Despite political, cultural and geographical diversity, health care reforms implemented in many developing countries share a number of common features regarding management and structural issues. Decentralization of decision‐making from the central authority to local and provincial levels is generally regarded in the literature to be an important way of achieving a more equitable distribution of health care and better management practices, aligned with local priorities and needs. However, in the absence of clear guidelines, continuous monitoring and an adequate supply of financial and human resources, decentralization processes are more likely to have a low impact on the process of health care reform and can, to a certain extent, provoke inequalities between regions in the same country. This qualitative study in Nampula province, Mozambique, was conducted to assess the impact of decentralization, through an analysis of the viewpoints of provincial health managers regarding their perceptions of the process, particularly with regard to the management of basic and elementary nurses. Secondary data from Nampula provincial reports and documents from the Mozambican Health Ministry were also reviewed and comparisons made with the experiences of other developing countries. Copyright © 2001 John Wiley & Sons, Ltd.
Quantifying and explaining changes in geographical inequality of infant mortality in England and Wales since the 1890s
Authors: Congdon P. , Campos R. M. , Curtis S. E. , Southall H. R. , Gregory I. N. , Jones I. R.
Published: January 2005

This paper considers the changing spatial pattern of infant mortality in England and Wales over the last century for a constant area definition. The analysis proceeds at the level of registration districts as defined in the 1890s, generated using the British Isles Historical Geographical Information System. Infant mortality at this spatial definition is followed over four points in time, the most recent being the early 1990s. Using a variety of inequality measures, the analysis demonstrates a decline in relative small‐area differentials in the chances of infant deaths up to 1958, but some resurgence since then. Regression methods are then used to evaluate the effect of available social variables, such as population density and housing conditions. The analysis incorporates adjustments for the sampling variability in what are often small counts of infant deaths by adopting ‘pooling strength’ techniques. Urban–rural differentiation has followed the same evolution: it was most marked in the 1890s and reappears by the 1990s, after being reduced somewhat in the earliest years of the UK National Health Service. Differentials in infant mortality according to the housing quality and economic status of different registration districts also gain in importance in the twentieth century compared with the 1890s. Copyright © 2001 John Wiley & Sons, Ltd.
Chemistry and toxicology of building timbers pressure‐treated with chromated copper arsenate: a review
Authors: Katz Sidney A. , Salem Harry
Published: January 2005

A recent agreement between the United States Environmental Protection Agency (USEPA) and the wood‐treating industry will result in a phase‐out of building timbers preserved with chromated copper arsenate (CCA). This agreement was motivated by a desire to reduce exposure to arsenic in the production, utilization and disposal of such material. The leaching of chromium, copper and arsenic from CCA‐treated building timbers into water and soil and the subsequent environmental effects have been reviewed, as have the laboratory and epidemiological studies on the toxicology of CCA‐treated building timbers. The beneﬁts of the phase‐out agreement are questionable because much arsenic will remain in the environment, and the alternatives to wood preservation with CCA are not without environmental consequences. Copyright © 2005 John Wiley & Sons, Ltd.
Developmental toxicity assessment of the new ﬂuoroquinolone antibacterial DW‐116 in rabbits
Authors: Kim J. C. , Kim S. H. , Shin D. H. , Bae C. S. , Oh K. S. , Kim J. H. , Yun H. I. , Lim J. H. , Chung M. K.
Published: January 2005

DW‐116 is a newly developed ﬂuoroquinolone antibacterial with a broad spectrum against both Gram‐positive and Gram‐negative bacteria. We have reported recently that DW‐116 is embryotoxic and teratogenic in rats. The present study was conducted to investigate the teratogenicity of DW‐116, together with maternal toxicity and developmental toxicity using New Zealand White rabbits. The test chemical was administered by gavage to pregnant rabbits from gestational day (GD) 6 through to GD 18 at dose levels of 0, 5, 19.5 and 76.1 mg kg−1 day−1. All does were subjected to caesarean section on day 28 of gestation and their foetuses were examined for external, visceral and skeletal abnormalities. In the 76.1 mg kg−1 group, a minimal maternal toxicity, as evidenced by decreased body weight gain during treatment period, was observed in pregnant rabbits. Signiﬁcant embryo‐foetal toxicity, including increased number of foetal deaths and delayed foetal ossiﬁcation, was seen. However, no treatment‐related morphological changes were detected in foetal external, visceral and skeletal examinations. There were no adverse effects on either pregnant dams or embryo‐foetal development at 19.5 and 5 mg kg−1. It was concluded that administration of DW‐116 during the major organogenetic period in rabbits produced decreased maternal body weight gain, increased number of foetal deaths and foetal developmental delay but no evidence of teratogenicity. The no‐observed‐adverse‐effect levels (NOAELs) of DW‐116 are considered to be 19.5 mg kg−1 day−1 for does and embryo‐foetuses, respectively. Copyright © 2005 John Wiley & Sons, Ltd.
Bis(4,7‐dimethyl and 5‐dinitro‐1,10‐phenanthroline) sulfato‐oxovanadium(IV)‐mediated in vivo male germ cell apoptosis
Authors: D'Cruz Osmond J. , Uckun Fatih M.
Published: January 2005

Oxovanadium(IV) [VO] complexes of 1,10‐phenanthroline are a new class of potent apoptosis‐inducing cytotoxic agents against human testicular cancer cells in vitro. The present study investigated the in vivo ability of four(bis)‐chelated 1,10‐phenanthroline [phen] complexes of sulfato‐oxovanadium(IV)—VO(phen)2, VO(Cl−phen)2, VO(Me2−phen)2 and VO(NO2−phen)2—with and without substitutions, to induce testicular germ cell apoptosis. Male germ cell loss in mice was measured by determining the epididymal sperm count, testicular weight and histological evaluation of the testes. Repetitive intratesticular injection (7.5 mg kg−1 testis−1) of bis‐chelated 1,10‐phenanthroline complexes of oxovanadium(IV) with 4,7‐dimethyl [VO(Me2−phen)2] and 5‐dinitro [VO(NO2−phen)2] substitution led to decreased sperm counts and reduced testicular weights. Histopathological examination of testicular sections from VO(Me2−phen)2‐ and VO(NO2−phen)2‐treated mice revealed a marked inhibition of spermatogenesis and preferential loss of maturing, as well as elongated spermatids. In situ evaluation of seminiferous tubule cross‐sections by terminal deoxynucleotidyl transferase‐mediated FITC‐deoxyuridine triphosphate nick end‐labeling (TUNEL) and laser scanning confocal microscopy showed characteristic apoptotic germ cells delineating the periphery of the seminiferous tubules. The ability of bis‐chelated 4,7‐dimethyl‐ and 5‐dinitro‐substituted 1,10‐phenanthroline complexes of oxovanadium(IV) to induce germ cell apoptosis in vivo may have potential utility in the treatment of human testicular germ cell tumors. Copyright © 2001 John Wiley & Sons, Ltd.
Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice
Authors: Jagannathan R. , Husain K. , Somani S. M.
Published: January 2005

Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg−1 p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn‐SOD + Mn‐SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn‐SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice. Copyright © 2001 John Wiley & Sons, Ltd.
Biomarkers as biological indicators of xenobiotic exposure
Authors: Gil Fernando , Pla Antonio
Published: January 2005

The presence of a xenobiotic in the environment always represents a risk for living organisms. However, to talk about impregnation there is a need to detect toxicity in the organism, and the concept of intoxication is related to specific organ alterations and clinical symptoms. Moreover, the relationship between the toxic levels within the organism and the toxic response is rather complex and has a difficult forecast because it depends on several factors, namely toxicokinetic and genetic factors. One of the methods to quantify the interaction with xenobiotics and its potential impact on living organisms, including the human being, is monitoring by the use of the so‐called biomarkers. They can provide measures of the exposure, toxic effect and individual susceptibility to environmental chemical compounds and may be very useful to assess and control the risk of long‐term outcomes associated with exposure to xenobiotic (i.e. heavy metals, halogenated hydrocarbons, pesticides). Copyright © 2001 John Wiley & Sons, Ltd.
Teeth and blood lead levels in egyptian schoolchildren: relationship to health effects
Authors: Omar Magdy , Ibrahim Mohamed , Hala Assem , Yehia Moustafa , Battah Fathi
Published: January 2005

The objective of this work was to study teeth and blood lead levels in Egyptian schoolchildren and to relate lead levels to sociodemographic and environmental factors, the degree of urbanization and suspected manifestations of possible lead exposure.

The study was conducted on 60 children aged 6–12 years: 30 children living in an urban area at Alexandria City and 30 children living in a rural area at Kafr El‐Sheikh Province. Both groups are matched for age and gender. Every child was subjected to history taking, clinical examination and IQ measurements. Laboratory investigations included measuring teeth and blood lead levels, haemoglobin, serum iron and total iron binding capacity. The results showed that the mean blood lead level of children in Alexandria was significantly higher than that of the children in Kafr El‐Sheikh; also 56.7% and 6.7% of children from Alexandria and Kafr El‐Sheikh had a blood lead level of >20 µg dl−1, with the most frequent symptoms of headache, arthralgia and lack of school interest. The children in Alexandria had significantly lower mean teeth lead and haemoglobin levels than those of the Kafr El‐Sheikh group. A history of wrapping sandwiches in newspapers, age and distance between the home and school were significant predictors of lead exposure.

These findings support the concept that teeth lead concentration may be a valid addition to the indicators used for assessment of the body burden of environmental lead. In addition, children living in urban areas such as Alexandria need special consideration regarding protection from lead exposure, as well as teeth and blood lead evaluation. Copyright © 2001 John Wiley & Sons, Ltd.
Chromatin modification of the human imprinted NDN (necdin) gene detected by in vivo footprinting
Authors: Hanel Meredith L. , Lau Jason C.Y. , Paradis Isabelle , Drouin Régen , Wevrick Rachel
Published: January 2005

Allele‐specific transcription is a characteristic feature of imprinted genes. Many imprinted genes are also transcribed in a tissue‐ or cell type‐specific manner. Overlapping epigenetic signals must, therefore, modulate allele‐specific and tissue‐specific expression at imprinted loci. In addition, long‐range interactions with an Imprinting Center (IC) may influence transcription, in an allele‐specific or cell‐type specific manner. The IC on human chromosome 15q11 controls parent‐of‐origin specific allelic identity of a set of genes located in cis configuration within 2 Mb. We have now examined the chromatin accessibility of the promoter region of one of the Imprinting Centre‐controlled genes, NDN encoding necdin, using in vivo DNA footprinting to identify sites of DNA–protein interaction and altered chromatin configuration. We identified sites of modified chromatin that mark the parental alleles in NDN‐expressing cells, and in cells in which NDN is not expressed. Our results suggest that long‐lasting allele‐specific marks and more labile tissue‐specific marks layer epigenetic information that can be discriminated using DNA footprinting methodologies. Sites of modified chromatin mark the parental alleles in NDN‐expressing cells, and in cells in which NDN is not expressed. Our results suggest that a layering of epigenetic information controls allele‐ and tissue‐specific gene expression of this imprinted gene. J. Cell. Biochem. 94: 1046–1057, 2005. © 2005 Wiley‐Liss, Inc.
Does endogenous fatty acid metabolism allow cancer cells to sense hypoxia and mediate hypoxic vasodilatation? Characterization of a novel molecular connection between fatty acid synthase (FAS) and hypoxia‐inducible factor‐1α (HIF‐1α)‐related expression of vascular endothelial growth factor (VEGF) in cancer cells overexpressing her‐2/neu oncogene
Authors: Menendez Javier A. , Vellon Luciano , Oza Bharvi P. , Lupu Ruth
Published: January 2005

Her‐2/neu (erbB‐2) oncogene overexpression is associated with increased tumor progression and metastasis. Fatty acid synthase (FAS), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, has been shown to be one of the genes regulated by Her‐2/neu at the level of transcription, translation, and biosynthetic activity. Interestingly, we recently established that both pharmacological inhibition of FAS activity and silencing of FAS gene expression specifically suppress Her‐2/neu oncoprotein expression and tyrosine‐kinase activity in breast and ovarian Her‐2/neu overexpressors. Unraveling the functional organization of this novel bi‐directional molecular connection between Her‐2/neu and FAS‐dependent neoplastic lipogenesis is a major challenge that the field is only beginning to take on. Considering that Her‐2/neu overexpression correlates with increased expression of the hypoxia inducible factor‐1α (HIF‐1α), which, in a mitogen‐activated protein kinase (MAPK)‐dependent manner, plays a key role in the expression of several genes including cytokines such as vascular endothelial growth factor (VEGF), we hypothesized that FAS blockade should result in a concomitant down‐regulation of VEGF. Unexpectedly, the specific inhibition of the de novo fatty acid synthesis with the small‐molecule inhibitor of FAS activity C75 resulted in a dramatic dose‐dependent enhancement (up to 500% increase) of VEGF secretion in Her‐2/neu‐overexpressing SK‐Br3, BT‐474, and SKOV3 cancer cells. Concurrently, FAS blockade drastically activated MAPK and promoted further a prominent accumulation of HIF‐1α in Her‐2/neu overexpressors. Moreover, U0126‐induced inhibition of MAPK activity completely abolished C75‐induced up‐regulation of HIF‐1α expression and VEGF secretion, whereas it did not modulate C75‐induced down‐regulation of Her‐2/neu oncogene. Importantly, RNA interference (RNAi)‐mediated silencing of the FAS gene recapitulated C75's effects by up‐regulating VEGF secretion, MAPK activation and HIF‐1α expression. Therefore, it appears that perturbation of cancer‐associated endogenous fatty metabolism triggers a “hypoxia‐like” (oxygen‐independent) condition that actively rescues Her‐2/neu‐dependent MAPK → HIP‐1α → VEGF cascade. It is tempting to suggest that an intact FAS‐catalyzed endogenous fatty acid metabolism is a necessary metabolic adaptation to support the enhanced ability of Her‐2/neu‐overexpressing cancer cells to survive cellular hypoxia in a HIF‐α‐dependent manner. J. Cell. Biochem. 94: 857–863, 2005. © 2005 Wiley‐Liss, Inc.
Leukemia fusion proteins and co‐repressor complexes: Changing paradigms
Authors: Redner Robert L. , Liu Johnson M.
Published: January 2005

Many cases of acute myelogenous leukemia (AML) are characterized by non‐random chromosomal translocations that fuse a DNA‐binding protein with a transcriptional regulator, which in turn may aberrantly recruit a co‐repressor complex. The similarities in this pattern between different AML chimeric fusions have led to a paradigm that stresses the importance of the co‐repressor complex in altering the pattern of expression of genes targeted by the DNA‐binding moiety of the fusion. Such findings beg the question of whether the fusion proteins merely serve as anchors to recruit the co‐repressor complex or whether they play other significant roles in leukemogenesis. The answers to this question may have therapeutic importance since we now have the ability to target various components of the co‐repressor complex, such as the histone deacetylase (HDAC) enzymes. In this Prospect, we wish to highlight some of the complexities and difficulties with the existing molecular paradigm of this challenging group of disorders. J. Cell. Biochem. 94: 864–869, 2005. © 2005 Wiley‐Liss, Inc.
Role of the retinoblastoma tumor suppressor protein in cellular differentiation
Authors: Nguyen Don X. , McCance Dennis J.
Published: January 2005

The retinoblastoma protein (pRb105) is a true tumor suppressor as deregulation of the Rb pathway by either mutation of pRb105 itself or other proteins in the pathway, such as p16INK4a, occur in most cancers. This prototypical family member, along with the related p107 and p130, are involved in the control of cell cycle regulation, but pRb105 has also been shown to be involved in tissue development and differentiation. This prospective will discuss the increasing evidence for a role of pRb105 in cellular differentiation and the fact that various cancers, which contain mutant pRb105, or mutations in proteins in the pRb105 pathway, are perhaps a result of deregulation of differentiation. J. Cell. Biochem. 94: 870–879, 2005. © 2005 Wiley‐Liss, Inc.
Association of cottontail rabbit papillomavirus E6 oncoproteins with the hDlg/SAP97 tumor suppressor
Authors: Du Minjie , Fan Xueli , Hanada Toshihiko , Gao Hua , Lutchman Mohini , Brandsma Janet L. , Chishti Athar H. , Chen Jason J.
Published: January 2005

Papillomaviruses are small DNA viruses that infect epithelial tissues and cause warts. Human papillomavirus (HPV) infection is the primary risk factor for the development of cervical cancer. The E6 and E7 oncogenes are the only genes consistently expressed in HPV‐positive cervical cancer cells. Cottontail rabbit papillomavirus (CRPV) induces papillomas and carcinomas on cottontail and domestic rabbits and provides an excellent animal model of HPV infection and vaccine development. CRPV encodes three transforming proteins; LE6, SE6, and E7. Each of these proteins is required for papilloma formation. Like HPV E7, the CRPV E7 protein binds to the tumor suppressor pRB. In contrast, unlike HPV E6, the CRPV E6 proteins do not bind the tumor suppressor p53. Although more than a dozen cellular proteins have been identified as HPV E6 interacting proteins, nothing is known about the cellular interacting proteins of CRPV E6s. Here we describe the association of CRPV E6s with hDlg/SAP97, the mammalian homolog of the Drosophila discs large tumor suppressor protein. HPV E6 has previously shown to bind and target hDlg/SAP97 for degradation. Our results demonstrate that both LE6 and SE6 interact with hDlg/SAP97, although their association does not lead to the degradation of hDlg/SAP97. The PDZ domains of hDlg were shown to be sufficient for interaction with CRPV E6 proteins while the C‐terminus of CRPV E6 is essential for the interaction with hDlg. The association of hDlg with SE6 may be important but not sufficient for the transformation of NIH 3T3 cells by SE6. Importantly, a CRPV SE6 mutant defective for papilloma formation did not interact with hDlg. These results suggest that interaction with hDlg/SAP97 plays a role in the biological function of CRPV E6s. J. Cell. Biochem. 94: 1038–1045, 2005. © 2005 Wiley‐Liss, Inc.
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion
Authors: Peyton Shelly R. , Putnam Andrew J.
Published: January 2005

Increasing evidence suggests that mechanical cues inherent to the extracellular matrix (ECM) may be equally as critical as its chemical identity in regulating cell behavior. We hypothesized that the mechanical properties of the ECM directly regulate the motility of vascular smooth muscle cells (SMCs) and tested this hypothesis using polyacrylamide substrates with tunable mechanical properties. Quantification of the migration speed on uniformly compliant hydrogels spanning a range of stiffnesses (Young's moduli values from 1.0 to 308 kPa for acrylamide/bisacrylamide ratios between 5/0.1% and 15/1.2%, respectively) revealed a biphasic dependence on substrate compliance, suggesting the existence of an optimal substrate stiffness capable of supporting maximal migration. The value of this optimal stiffness shifted depending on the concentration of ECM protein covalently attached to the substrate. Specifically, on substrates presenting a theoretical density of 0.8 μg/cm2 fibronectin, the maximum speed of 0.74 ± 0.09 μm/min was achieved on a 51.9 kPa gel; on substrates presenting a theoretical density of 8.0 μg/cm2 fibronectin, the maximum speed of 0.72 ± 0.06 μm/min occurred on a softer 21.6 kPa gel. Pre‐treatment of cells with Y27632, an inhibitor of the Rho/Rho‐kinase (ROCK) pathway, reduced these observed maxima to values comparable to those on non‐optimal stiffnesses. In parallel, quantification of TritonX‐insoluble vinculin via Western blotting, coupled with qualitative fluorescent microscopy, revealed that the formation of focal adhesions and actin stress fibers also depends on ECM stiffness. Combined, these data suggest that the mechanical properties of the underlying ECM regulate Rho‐mediated contractility in SMCs by disrupting a presumptive cell‐ECM force balance, which in turn regulates cytoskeletal assembly and ultimately, cell migration. © 2005 Wiley‐Liss, Inc.