bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Electrostatics and Size Effect within a Crowded Bioenvironment
Authors: Li Zhidong , Wu Jianzhong 
Published: January 2005

AbstractBiological fluids typically contain a large number of macromolecules occupying up to 40% of the total volume. Current understanding of the effect of high concentration, or ‘macromolecular crowding’, on cellular processes is primarily based on the excluded‐volume considerations in which all intermolecular interactions beyond the short‐ranged repulsion are neglected. In this work, a density functional theory (DFT) accompanied by Monte Carlo simulations is employed to investigate the structural and thermodynamic properties of a crowded cellular environment within the primitive model where biomacromolecules are represented by neutral and charged hard spheres and the solvent by a continuous dielectric medium. The performance of the DFT has been tested with extensive results from Monte Carlo (MC) simulations for the pair correlation functions (PCFs), excess internal energies, and osmotic coefficients under a variety of solution conditions.
Domain Size and Fluctuations at Domain Interfaces in Lipid Mixtures
Authors: Seeger Heiko M. , Fidorra Matthias , Heimburg Thomas 
Published: January 2005

AbstractBiomembranes consist of a complex mixture of a large number of lipids and proteins. In such mixtures, microscopic domains and macroscopically separated phases may exist. Here, we discuss phase behavior and domains formation of binary lipid mixtures. We show that the domain formation is accompanied by large fluctuations at the domain boundaries, resulting in altered physical properties at the boundaries, for instance in a pronounced increase of the elastic constants. Therefore, we argue that the physics of the membrane depends on the overall length scale of its domains interfaces. We present here confocal microscopy images, calorimetric melting profiles and Monte‐Carlo simulations to understand the factors that determine domain formation, their sizes and the role of the domain interfaces.
Spontaneously Forming Unilamellar Phospholipid Vesicles
Authors: Yue Baohua , Huang Chien‐Yueh , Nieh Mu‐Ping , Glinka Charles J. , Katsaras John 
Published: January 2005

AbstractUnilamellar vesicles (ULV) consisting of a single lipid bilayer are of special interest as drug delivery vehicles. Here, we report on a spontaneously forming ULV system composed of the short‐ and long‐chain phospholipids, dihexanoyl (DHPC) and dimyristoyl (DMPC) phosphorylcholine, respectively, doped with the negatively charged lipid, dimyristoyl phosphorylglycerol (DMPG). Small‐angle neutron scattering (SANS) and dynamic light scattering (DLS) were employed to systematically investigate the effects of lipid concentration, salinity, and time on vesicle stability. It is found that ULV size is practically constant over a range of lipid concentration and temperature. The spontaneously formed ULV are stable for periods of four months, or greater, without the use of stabilizers.
Structural Phase Behavior of High‐Concentration, Alignable Biomimetic Bicelle Mixtures
Authors: Nieh Mu‐Ping , Raghunathan V.A. , Glinka Charles J. , Harroun Thad , Katsaras John 
Published: January 2005

AbstractThe structures of bicelle mixtures composed of dimyristoyl and dihexanoyl phosphatidylcholines (DMPC and DHPC) with DMPC/DHPC molar ratios of 3.2 and 5 are characterized using polarized optical microscopy (POM) and small angle neutron scattering (SANS). Three phases, isotropic (I), chiral nematic (N*) and smectic (S) are observed as temperature (T) varies from 10 to 70 °C. The structure of the magnetically alignable N* phase, which was previously considered to be made up of discoidal micelles, is found to be composed of “ribbons”. Doping with the charged lipid, dimyristoyl phosphatidylglycerol (DMPG), which has the same 14:0 hydrocarbon chains as DMPC, results in a structural change of the aggregates where only the isotropic and smectic phases are observed. The smectic phase for the mixtures doped with DMPG is shear‐alignable and follows one‐dimensional swelling. However, at high‐T zwitterionic DMPC/DHPC mixtures form multi‐lamellar vesicles (MLV) with a relatively constant lamellar spacing of 66 Å, independent of water content.
Cover Picture: Macromol. Theory Simul. 1/2005
Authors: Vergara Alessandro 
Published: January 2005

Cover: Distinct diffusion coefficients (${\rm D}^d_{ii}$, ${\rm D}^d_{i0}$ and ${\rm D}^d_{00}$) in the number fixed reference frame, DDCs, for the binary mixture PEG 200‐water as a function of the PEG weight fraction (Xg) are drawn. Values are evaluated according to the equation reported, where xi is a positional coordinate of a particle of species i, pointed brackets represent a canonical ensemble average, V is the total volume, N is the total number of particles in the system, t is the time. Real DDCs, in blue, are compared with a novel hard‐sphere (HS) based standard reference, in red.Further details can be found in the Full paper by A. Vergara on page 21.
An efficient indirect RBFN‐based method for numerical solution of PDEs
Authors: Mai‐Duy Nam , Tran‐Cong Thanh 
Published: January 2005

AbstractThis article presents an efficient indirect radial basis function network (RBFN) method for numerical solution of partial differential equations (PDEs). Previous findings showed that the RBFN method based on an integration process (IRBFN) is superior to the one based on a differentiation process (DRBFN) in terms of solution accuracy and convergence rate (Mai‐Duy and Tran‐Cong, Neural Networks 14(2) 2001, 185). However, when the problem dimensionalityNis greater than 1, the size of the system of equations obtained in the former is aboutNtimes as big as that in the latter. In this article, prior conversions of the multiple spaces of network weights into the single space of function values are introduced in the IRBFN approach, thereby keeping the system matrix size small and comparable to that associated with the DRBFN approach. Furthermore, the nonlinear systems of equations obtained are solved with the use of trust region methods. The present approach yields very good results using relatively low numbers of data points. For example, in the simulation of driven cavity viscous flows, a high Reynolds number of 3200 is achieved using only 51 × 51 data points. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Molecular evolution of breast cancer
Authors: Simpson Peter T , Reis‐Filho Jorge S , Gale Theodora , Lakhani Sunil R 
Published: January 2005

AbstractMolecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi‐step pathways of breast cancer progression have been delineated through genotypic–phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low‐ and high‐grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR‐negative and show Her‐2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well‐differentiated/low‐grade ductal and lobular carcinomas have been blurred, with changes in E‐cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non‐obligate precursors of atypical ductal hyperplasia (ADH) and well‐differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting‐edge molecular tools can this knowledge be translated into clinical practice and patient management. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Molecular and cellular themes in cancer research: II
Authors: Hall Peter A , Lowe Scot W 
Published: January 2005

AbstractContemporary cancer research encompasses a broad range of activities spanning basic molecular and cell biology, in vitro and in vivo models and clinical studies. Much current activity in cancer research endeavours to translate the former through model systems into clinical practice. The purpose of the reviews in this issue is to exemplify the strategies and approaches used in such endeavours. The first group of reviews focus on specific key molecules of interest in cancer biology including elements of the cell cycle machinery, the WNT pathway and HOX genes, as well as the epigenetic regulation of cancer critical genes. The second cohort of reviews consider novel transgenic model systems and how such models can be non‐invasively imaged. The final reviews in this group consider the huge advances in our understanding of the p53 pathway and stress responses that have come from in vivo systems. Finally, the clinical relevance of these approaches is highlighted in essays on the use of gene profiling modern technologies to assess tumours of unknown origin, the molecular basis of breast cancer and gastrointestinal lymphoma, and the key area of drug resistance in cancer. These reviews highlight the multidisciplinary nature of current cancer research, which is increasingly having impact on patient care. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Advances in imaging mouse tumour models in vivo
Authors: Lyons Scott K 
Published: January 2005

AbstractSignificant progress has been made recently in the variety of ways that cancer can be non‐invasively imaged in murine tumour models. The development and continued refinement of specialized hardware for an array of small animal imaging methodologies are only partly responsible. So too has been the development of new imaging techniques and materials that enable specific, highly sensitive and quantitative measurement of a wide range of tumour‐related parameters. Included amongst these new materials are imaging probes that selectively accumulate in tumours, or that become activated by tumour‐specific molecules in vivo. Other tumour imaging strategies have been developed that rely upon the detection of reporter transgene expression in vivo, and these too have made a significant impact on both the versatility and the specificity of tumour imaging in living mice. The biological implications resulting from these latest advances are presented here, with particular emphasis on those associated with MRI, PET, SPECT, BLI, and fluorescence‐based imaging modalities. Taken together, these advances in tumour imaging are set to have a profound impact on our basic understanding of in vivo tumour biology and will radically alter the application of mouse tumour models in the laboratory. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cell and tissue responses to genotoxic stress
Authors: Coates Philip J , Lorimore Sally A , Wright Eric G 
Published: January 2005

AbstractCancers arise as a consequence of the accumulation of multiple genetic mutations in a susceptible cell, resulting in perturbation of regulatory networks that control proliferation, survival, and cellular function. Here, the sources of cellular stress that can cause oncogenic mutations and the responses of cells to DNA damage are reviewed. The role of different repair pathways and the potential for cell‐ and tissue‐specific reliance on individual repair mechanisms are discussed. Evidence for cell‐ and tissue‐specific activation of p53‐mediated growth arrest and apoptosis after exposure to an individual genotoxin is assessed and some of the potential mediators of these different responses are provided. These cell‐ and tissue‐specific responses to particular forms of DNA damage are likely to be key determinants of tissue‐specific tumour susceptibility, and there is good evidence for genetic variations in these responses. The role that genotoxic agents play in altering the microenvironment to produce indirect effects on tumourigenesis through altered production of free radicals and cytokines that are characteristic of inflammatory‐type processes is also evaluated. Changes to the microenvironment as direct or indirect effects of genotoxic stress can be involved in both tumour initiation and progression and may even be a prerequisite for tumourigenesis. Therefore, tumour susceptibility after endogenous or exogenous genotoxic stress represents a balance between cell‐intrinsic responses of target cells and changes to the microenvironment. A fuller understanding of cell‐ and tissue‐specific responses, alterations to the microenvironment, and genetic modifiers of these responses could lead to novel prevention and therapeutic strategies for common forms of human malignancy. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Hunting the primary: novel strategies for defining the origin of tumours
Authors: Dennis Jayne L , Oien Karin A 
Published: January 2005

AbstractIn 1995, two methods of genome‐wide expression profiling were first described: expression microarrays and serial analysis of gene expression (SAGE). In the subsequent 10 years, many hundreds of papers have been published describing the application of these technologies to a wide spectrum of biological and clinical questions. Common to all of this research is a basic process of data gathering and analysis. The techniques and statistical and bio‐informatic tools involved in this process are reviewed. The processes of class discovery (using clustering and self‐organizing maps), class prediction (weighted voting, k nearest neighbour, support vector machines, and artificial neural networks), target identification (fold change, discriminant analysis, and principal component analysis), and target validation (RT‐PCR and tissue microarrays) are described. Finally, the diagnostic problem of adenocarcinomas that present as metastases of unknown origin is reviewed, and it is demonstrated how integration of expression profiling techniques promises to throw new light on this important clinical challenge. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Gastrointestinal lymphoma: where morphology meets molecular biology
Authors: Isaacson Peter G , Du Ming‐Qing 
Published: January 2005

AbstractPrimary gastrointestinal lymphomas are best exemplified by mucosa‐associated lymphoid tissue (MALT) lymphoma of the stomach and enteropathy‐type T‐cell lymphoma (ETL). Both lymphomas were initially recognized on morphological grounds and their identification as distinct clinicopathological entities has subsequently been vindicated following integrated immunophenotypic, molecular, and cellular biological investigations. Delineation of the phenotypic, molecular, and biological properties of these lymphomas at various clinicopathological stages of their development has also provided critical information for the clinical management of patients with these diseases. Here, the histopathology and recent advances in phenotypic and molecular characterization of gastric MALT lymphoma and ETL and their applications in diagnosis and clinical management are reviewed. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
What have animal models taught us about the p53 pathway?
Authors: Lozano Guillermina , Zambetti Gerard P 
Published: January 2005

AbstractMouse models have provided important insight into the in vivo significance of upstream and downstream signals that regulate the p53 tumour suppressor. One important lesson learned from these models is that negative regulators of p53 are critical in vivo modulators of p53 activity. Additionally, upstream regulators of p53 activity, such as p19Arf and Atm, are themselves critical tumour modifiers/suppressors. The presence of multiple positive regulators of p53 and numerous downstream targets indicates a redundancy that ensures activation of the p53 pathway. Importantly, p53 plays a prominent role as a tumour suppressor in vivo by virtue of its ability both to block cell cycle progression and to induce cell death. Finally, different p53 mutants have different properties in vivo. Three missense mutations have been generated at the p53 locus and all three exhibit unique differences in their ability to contribute to the tumour phenotype. Clearly, determining the levels of p53 inhibitors, and the typing of p53 mutations in human tumours should be performed to determine the best avenue for treatment. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dormant hypermethylated tumour suppressor genes: questions and answers
Authors: Esteller Manel 
Published: January 2005

AbstractThe epigenetic inactivation of tumour suppressor genes by promoter CpG island methylation is nowadays one of the hottest topics in cancer research. However, there are still several important open questions: Can we use CpG island hypermethylation to classify tumours according to their clinical behaviour and chemosensitivity? How do we prove that our hypermethylated gene is important for cancer development and/or progression? Which enzymes are directly responsible for the CpG island hypermethylation of tumour suppressor genes? How is the chromatin structure and molecular environment in and around the hypermethylated CpG islands? Can we wake up these dormant hypermethylated tumour suppressor genes in an epigenetic therapy of cancer? Some answers are provided in this review, but other questions remain unsolved, awaiting the eager epigenetic researcher. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cell‐cycle‐dependent regulation of DNA replication and its relevance to cancer pathology
Authors: Tachibana Kiku‐e K , Gonzalez Michael A , Coleman Nicholas 
Published: January 2005

AbstractThe highly orchestrated process of DNA replication ensures the accurate inheritance of genetic information from one cell generation to the next. The exact execution of DNA replication depends on a large number of proteins that are being studied extensively in the cell cycle field. Some of these proteins, such as the minichromosome maintenance proteins (MCMs), are essential for the process of DNA replication itself. Others such as geminin are specifically required to limit DNA replication to once per cell cycle. Together, these proteins protect the stability of the human genome in cycling cells. Their expression has been compared with routinely used proliferation markers, such as Ki‐67 (MIB‐1) and proliferating cell nuclear antigen (PCNA), which fulfil the requirements of molecular tumour markers to varying extents. However, it is with regard to the depth of our understanding of antigen biology that the MCM proteins and geminin qualify exceptionally well as novel cell‐cycle biomarkers for routine use in clinical practice, particularly in cancer detection and estimation of prognosis. Expression microarray analysis has also independently identified MCMs and their interacting proteins as determinants of the inherent aggressiveness of a wide range of epithelial malignancies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The pathophysiology of HOX genes and their role in cancer
Authors: Grier DG , Thompson A , Kwasniewska A , McGonigle GJ , Halliday HL , Lappin TR 
Published: January 2005

AbstractThe HOM‐C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho‐physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co‐ordinated during development, so that the 3′ genes are expressed more anteriorly and earlier than the 5′ genes. Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand–foot–genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly. Haematopoietic progenitors express HOX genes in a pattern characteristic of the lineage and stage of differentiation of the cells. In leukaemia, dysregulated HOX gene expression can occur due to chromosomal translocations involving upstream regulators such as the MLL gene, or the fusion of a HOX gene to another gene such as the nucleoporin, NUP98. Recent investigations of HOX gene expression in leukaemia are providing important insights into disease classification and prediction of clinical outcome. Whereas the oncogenic potential of certain HOX genes in leukaemia has already been defined, their role in other neoplasms is currently being studied. Progress has been hampered by the experimental approach used in many studies in which the expression of small subsets of HOX genes was analysed, and complicated by the functional redundancy implicit in the HOX gene system. Attempts to elucidate the function of HOX genes in malignant transformation will be enhanced by a better understanding of their upstream regulators and downstream target genes. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mechanical properties of polymer‐ceramic nanocomposite coatings by depth‐sensing indentation
Authors: Sun Jiakuan , Francis Lorraine F. , Gerberich William W. 
Published: January 2005

AbstractThe mechanical properties of antimony‐doped tin oxide (ATO) nanoparticle/poly (vinyl acetate‐co‐acrylic) (PVAc‐co‐acrylic) coatings with various ATO contents were investigated using depth‐sensing indentation. These coatings were prepared from aqueous dispersions of ATO and PVAc‐co‐acrylic latex. Three types of methods, including a prolonged load holding time, analysis of the pull‐off portion of the unloading curve, and dynamic indentation, were used to characterize the mechanical properties of these composite coatings. As compared to dynamic indentation, quasistatic conventional indentation even with a prolonged load holding time and analysis of the pull‐off portion of unloading curves generate more scattered coating modulus data. This is due to the effect of creep deformation and inconsistency of the pull‐off portion dimension, respectively. The results obtained using dynamic indentation are more reliable because the technique minimizes the effect of creep deformation using a combination load including static and dynamic components. The dynamic indentation results indicate that the addition of the ATO nanoparticles made the composite coatings stiffer and more elastic solid–like. For example, the storage indentation modulus of the PVAc‐co‐acrylic coating is ∼1 GPa and tan δ is ∼1.6; the addition of 0.50 volume fraction of ATO increased the modulus to ∼5 GPa and reduced the tan δ to ∼0.01. POLYM. ENG. Sci. 45:207–216, 2005. © 2005 Society of Plastics Engineers.