bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hp mortar domain decomposition method for problems in fluid mechanics
Authors: Chilton Lawrence K. , Seshaiyer Padmanabhan 
Published: December 2002

AbstractWe consider the incompressible Stokes equations in primal velocity–pressure variables and present the mortar finite element formulation for this problem. The local approximation within each subdomain is designed using divergence stable hp‐mixed finite elements. The velocity is computed in a mortared space while the pressure is not subjected to any constraints across the interfaces. Our computational results show that the mortar finite element method for the Stokes problem satisfies similar rates of convergence as the conforming finite element method, in the presence of various h, p and hp discretizations (including the case of exponential hp convergence over geometric meshes). We also present the numerical results for the Lagrange multiplier when the method is implemented as a mixed method. Copyright © 2002 John Wiley & Sons, Ltd.
Parallel implementation of an optimal two level additive Schwarz preconditioner for the 3‐D finite element solution of elliptic partial differential equations
Authors: Nadeem S. A. , Jimack P. K. 
Published: December 2002

AbstractThis paper presents a description of the extension and parallel implementation of a new two level additive Schwarz (AS) preconditioner for the solution of 3‐D elliptic partial differential equations (PDEs). This preconditioner, introduced in Bank et al. (SIAM J. Sci. Comput. 2002; 23: 1818), is based upon the use of a novel form of overlap between the subdomains which makes use of a hierarchy of meshes: with just a single layer of overlapping elements at each level of the hierarchy. The generalization considered here is based upon the restricted AS approach reported in (SIAM J. Sci. Comput. 1999; 21: 792) and the parallel implementation is an extension of work in two dimensions (Concurrency Comput. Practice Experience 2001; 13: 327). Copyright © 2002 John Wiley & Sons, Ltd.
Differential response of primary and metastatic melanomas to neutrophils attracted by IL‐8
Authors: Schaider Helmut , Oka Masahiro , Bogenrieder Thomas , Nesbit Mark , Satyamoorthy Kapaettu , Berking Carola , Matsushima Kouji , Herlyn Meenhard 
Published: December 2002

AbstractIL‐8 is a strong chemoattractant for neutrophils, and it is constitutively produced by many tumors, including human melanomas. To determine the biologic importance of IL‐8 for melanoma cells from primary and metastatic lesions, we transduced selected cell lines constitutively producing low levels of IL‐8 with IL‐8 cDNA using a replication‐deficient adenoviral vector. Nontumorigenic SBcl2 primary melanoma cells formed tumors when transduced with increasing plaque‐forming units of IL‐8 per cell. However, at high IL‐8 transduction levels (100 ng/ml/105 cells in 48 hr), tumor growth was impaired due to massive neutrophil infiltration. A similar biphasic response was observed in WM115 primary melanomas, which are tumorigenic but not metastatic. Depletion of neutrophils with an antibody that blocks the accumulation of granulocytes at the site of inflammation enabled transduced primary melanomas secreting high levels of IL‐8 to survive and grow. In contrast, highly tumorigenic and metastatic 451Lu cells showed marked increases in tumor growth and number of metastatic foci in the lungs depending on the expression levels of IL‐8. Cytotoxicity assays with isolated neutrophils confirmed the preferential killing of primary over metastatic melanoma cells. SBcl2 cells stimulated by IL‐8 to form tumors in immunodeficient mice were induced to produce VEGF, suggesting that the angiogenic response is enhanced due to increased growth factor production. Our results demonstrate that nontumorigenic primary melanomas depend on IL‐8 stimulation in vivo for growth and that tumor growth depends on the level of neutrophil infiltration. Metastatic melanomas proliferate in vivo independently of infiltrating neutrophils. © 2002 Wiley‐Liss, Inc.
The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER‐2/neu transgenic mice
Authors: Anisimov Vladimir N. , Alimova Irina N. , Baturin Dmitri A. , Popovich Irina G. , Zabezhinski Mark A. , Manton Kenneth G. , Semenchenko Anna V. , Yashin Anatoly I. 
Published: December 2002

AbstractThe effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER‐2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age‐related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER‐2/neu transgenic mice. The data demonstrate the regimen‐dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER‐2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer. © 2002 Wiley‐Liss, Inc.
β2‐microglobulin induces caspase‐dependent apoptosis in the CCRF‐HSB‐2 human leukemia cell line independently of the caspase‐3, ‐8 and ‐9 pathways but through increased reactive oxygen species
Authors: Gordon John , Wu Ching‐Huang , Rastegar Mojgan , Safa Ahmad R. 
Published: December 2002

AbstractExogenous β2‐microglobulin (β2m) induces significant apoptosis in the CCRF‐HSB‐2 human lymphoblastic leukemia cell line as detected by DNA fragmentation, DAPI staining and annexin V binding assay. β2m treatment induced the release of cytochrome c and apoptosis‐inducing factor (AIF) from the mitochondria, but no change in mitochondrial membrane potential (ΔΨm) was observed during apoptosis, suggesting that cytochrome c may be released through a mechanism independent of mitochondrial permeability transition (MPT) pore formation. Moreover, the β2m‐induced release of cytochrome c and AIF from the mitochondria in CCRF‐HSB‐2 cells was caspase‐independent, since Z‐VAD‐fmk, a general inhibitor of caspases, did not block the release of these factors. However, Z‐VAD‐fmk treatment significantly blocked β2m‐induced apoptosis, while Western blot analysis revealed that caspases‐1, ‐2, ‐3, ‐6, ‐7, ‐8 and ‐9 are not activated during β2m‐induced apoptosis in these cells. These results collectively indicate that a post‐mitochondrial caspase‐dependent mechanism is involved in β2m‐induced apoptosis. Moreover, β2m significantly enhanced the production of reactive oxygen species (ROS) during 12–48 hr treatment, and β2m‐induced apoptosis was almost totally inhibited in cells pre‐treated with the antioxidant N‐acetylcysteine (NAC), providing evidence that β2m‐induced apoptosis in CCRF‐HSB‐2 cells is ROS‐dependent. Therefore, these results reveal that β2m‐induced apoptosis in CCRF‐HSB‐2 cells may occur through an unknown caspase‐dependent and ROS‐dependent mechanism(s) that is associated with cytochrome c and AIF release from mitochondria, but is independent of the caspase ‐3, ‐8 and ‐9 pathways. © 2002 Wiley‐Liss, Inc.
Prospective and randomised public‐health trial on neural network‐assisted screening for cervical cancer in Finland: Results of the first year
Authors: Nieminen Pekka , Hakama Matti , Viikki Merja , Tarkkanen Jussi , Anttila Ahti 
Published: December 2002

AbstractOur objective was to evaluate the feasibility and relative validity of interactive neural network assisted screening (Papnet) in primary mass screening for cervical cancer as a public health policy (routine screening). A randomized, ongoing trial involved 152,969 invitees and 108,686 attendees in the organized mass screening in Finland in 1999. Drawing invitations from the population registry, women were randomized 2:1 at an individual level to have their smear analyzed either conventionally or with Papnet. The distribution of smears to different cytological categories, detection rates of dysplasias, in situ carcinomas and cancers were estimated with smears analyzed either conventionally (72,461) or by Papnet (36,225). A total of 108,686 smears were screened and 449 were histologically confirmed as dysplasias and carcinomas. The detection rates for histologically verified carcinoma in situ/severe dysplasia, moderate and mild dysplasias were 0.14%, 0.14% and 0.13% with conventional and 0.14%, 0.14% and 0.11% with Papnet, respectively. The detection rate of invasive cancer was 0.06‰ (n = 4) with conventional method and 0.08‰ (n = 3) with Papnet. None of the differences were statistically significant (p > 0.05). Papnet was able to identify 92.5% of healthy women (normal cytology), and the specificity of conventional smear was 92.9%. The positive predictive value (Pap Classes III–V) of Papnet was slightly but not significantly better (55% vs. 51%). Papnet screening was feasible as a part of routine screening and performed equally well compared to conventional one methods used in Finland. Organized mass screening was practiced very successfully in the last 38 years. We are going to continue the trial to study the potential trends in cervical cancer incidence in both study arms. © 2002 Wiley‐Liss, Inc.
Quantitative analysis of follicle‐stimulating hormone receptor in ovarian epithelial tumors: A novel approach to explain the field effect of ovarian cancer development in secondary mullerian systems
Authors: Wang Jun , Lin Lynne , Parkash Vinita , Schwartz Peter E. , Lauchlan Stuart C. , Zheng Wenxin 
Published: December 2002

AbstractThe role of FSHR expression in ovarian cancer development is not clear. We examined quantitative expression of FSHR in different types of OET, presumed precursor lesions and peritoneal implants and further discussed FSH as a key growth‐promotion factor for the process of ovarian epithelial tumorigenesis. Thirty‐five primary OET specimens, including 5 serous cystadenomas, 4 papillary serous cystadenomas, 9 SBTs and 17 serous carcinomas, were examined for quantitative FSHR expression. Ten paired samples (3 benign cystadenomas, 5 SBTs and 2 carcinomas) were obtained from several morphologically different areas, including benign‐looking, borderline and cancerous areas in the same OETs, and from the remaining ovarian tissue and contralateral ovaries. Competitive RT‐PCR was performed to measure the quantitative expression of FSHR in each tissue sample. FSHR expression levels were compared among nonpaired samples and within paired samples. We found that OSE had the lowest FSHR expression, whereas antral follicles had the highest level. Within benign OETs, papillary serous cystadenomas have 4.9‐fold higher FSHR levels than nonpapillary serous cystadenomas. SBTs had the highest level of FSHR expression, which was 12.8‐fold, 2.7‐fold and 2.4‐fold higher than that of serous cystadenomas, papillary serous cystadenomas and grade 1 carcinomas, respectively. A similarly high level of FSHR mRNA was found in peritoneal implants, which were associated with SBTs. FSHR levels among serous carcinomas decreased with an increase in carcinoma grade. Grade 3 carcinomas had the lowest FSHR level, which was similar to that of serous cystadenomas, while grade 1 carcinomas had 6.5‐fold higher FSHR levels than those in serous cystadenomas. Our results suggest that not only serum FSH but also FSHR in ovarian epithelium may play important roles in ovarian OET development. Both the receptor and ligand may act in a synergistic way to promote tumor growth. The observation that high FSHR levels are present in peritoneal implants suggests that FSH may also play a similar role in the development of peritoneal serous tumors. From this perspective, circulating FSH may be considered a driving force in the field effect theory for the development of both ovarian neoplasms and their associated peritoneal implants. However, the exact role of FSH and/or FSHR in the development of epithelial tumors arising in both the ovary and peritoneum needs further investigation. © 2002 Wiley‐Liss, Inc.
Cyclopentenyl cytosine primes SK‐N‐BE(2)c neuroblastoma cells for cytarabine toxicity
Authors: Bierau Jörgen , van Gennip Albert H. , Leen René , Helleman Jozien , Caron Huib N. , van Kuilenburg André B.P. 
Published: December 2002

AbstractCPEC is a potent inhibitor of CTP synthetase and causes depletion of CTP and dCTP pools. AraC is an analog of dCyd and a chemotherapeutic agent. Here, we demonstrate that, upon incubation with CPEC, both the anabolism and cytostatic effect of AraC in SK‐N‐BE(2)c neuroblastoma cells were increased. Cotreatment of CPEC (50–250 nM) and AraC (37.5–500 nM) decreased the 4‐day ED50 value for AraC 2‐ to 8‐fold in the SK‐N‐BE(2)c cell line, while pretreatment with CPEC followed by incubation with AraC alone decreased the 4‐day ED50 value for AraC 1‐ to 19‐fold. Preincubation of SK‐N‐BE(2)c cells with 100 nM CPEC followed by incubation with 500 nM [3H]AraC increased the total amount of AraC nucleotides and incorporation of [3H]AraC into DNA by 392% and 337%, respectively, compared to non‐CPEC‐treated cells. When 20 nM [3H]AraC was used, the maximum incorporation of [3H]AraC into DNA was 1,378% compared to non‐CPEC‐treated cells. Incorporation of AraC into DNA correlated well with the accumulation of cells in S phase of the cell cycle caused by CPEC. DNA synthesis was almost completely inhibited (>91%) when 100 nM CPEC and 500 nM AraC were combined. CPEC alone and the combination of CPEC and AraC increased caspase‐3 activity 3‐fold, indicating induction of apoptosis in SK‐N‐BE(2)c cells. In contrast, AraC alone did not induce caspase‐3 activity. Our results demonstrate that low concentrations of CPEC profoundly increase the cytostatic properties of AraC toward SK‐N‐BE(2)c human neuroblastoma cells. © 2002 Wiley‐Liss, Inc.
Big firms waiting to grow? Franchisees in the pub sector
Authors: Lashley Conrad , Rowson Bill 
Published: December 2002

Abstract
Pub‐operating companies have undergone major changes in their business organization over recent years. One of the effects of the ‘Beer Orders’ has been to break up the large estates of pubs directly tied to a beer producer.
In many cases, the larger brewers have directly managed their estate of large high‐volume pubs and bars. More typically, however, companies control pubs in indirectly managed forms. Tenancies and leases offer the pub operator strategies that allow them to operate on a larger scale with less risk because the smaller firm takes the risk and also has the entrepreneurial motives to build the business.
In many ways, this limited form of franchising appears to offer many benefits as a business strategy because it enables the pub operator to trade at a higher scale and at lower risk. The problem is that many companies have a limited understanding of the motives of the small‐firm operators who are running their pubs as tenants or lessees.
Whilst the key motive for indirect forms of pub control was to maintain outlets for the beer product, these strategies are flawed when properties need to be run as retail outlets, intent on maximizing sales and business growth.
This paper explores some of the motives of the small firms who operate pubs via tenancy and lessee arrangements and the difficulties that exist between the pub‐operating companies and their small‐firm partners.
Copyright © 2002 John Wiley & Sons, Ltd.
Evidence of worth in not‐for‐profit sector organizations
Authors: Harris Ian , Mainelli Michael , O'Callaghan Mary 
Published: December 2002

Abstract
The not‐for‐profit sector is a significant part of the economy. Such organizations have a duty to their stakeholders to provide evidence that they are using resources well.
The authors have substantial client work in this area and have conducted research among leaders of UK not‐for‐profit organizations in order to see to what extent such organizations provide evidence of worth. Indeed, this research presented here confirms the prominence of this objective.
Four themes emerge in discharging this goal as not‐for profit organizations strive to balance internal aspiration versus external imposition, outcomes not outputs, gathering evidence and communication, contribution, consensus and commitment.
There are four basic types of not‐for‐profit evidence based on the primary outcome; these are expanding frontiers, changing systems, service delivery and communitarian.
Information to validate evidence of worth may be categorized as risk control, reward enhancement or volatility‐reduction targets and outcomes. Copyright © 2002 John Wiley & Sons, Ltd.
Long‐ and short‐range interactions in native protein structures are consistent/minimally frustrated in sequence space
Authors: Miyazawa Sanzo , Jernigan Robert L. 
Published: December 2002

AbstractWe show that long‐ and short‐range interactions in almost all protein native structures are actually consistent with each other for coarse‐grained energy scales; specifically we mean the long‐range inter‐residue contact energies and the short‐range secondary structure energies based on peptide dihedral angles, which are potentials of mean force evaluated from residue distributions observed in protein native structures. This consistency is observed at equilibrium in sequence space rather than in conformational space. Statistical ensembles of sequences are generated by exchanging residues for each of 797 protein native structures with the Metropolis method. It is shown that adding the other category of interaction to either the short‐ or long‐range interactions decreases the means and variances of those energies for essentially all protein native structures, indicating that both interactions consistently work by more‐or‐less restricting sequence spaces available to one of the interactions. In addition to this consistency, independence by these interaction classes is also indicated by the fact that there are almost no correlations between them when equilibrated using both interactions and significant but small, positive correlations at equilibrium using only one of the interactions. Evidence is provided that protein native sequences can be regarded approximately as samples from the statistical ensembles of sequences with these energy scales and that all proteins have the same effective conformational temperature. Designing protein structures and sequences to be consistent and minimally frustrated among the various interactions is a most effective way to increase protein stability and foldability. Proteins 2003;50:35–43. © 2002 Wiley‐Liss, Inc.
A knowledge‐based scale for amino acid membrane propensity
Authors: Punta Marco , Maritan Amos 
Published: December 2002

AbstractIn this article, a membrane‐propensity scale for amino acids is derived using only two ingredients: (i) a set of transmembrane helices segments from membrane protein crystal structures and (ii) the request that each component of the set has a free energy lower than that of a typical soluble protein sequence of the same length. Although the most widely used hydropathy scales satisfy this request, we use an optimization procedure that allows for extraction of an optimal scale, which correlates equally well with those scales. We show that, if the choice of the sequence database is accurate, significant knowledge‐based scales, which are robust with respect to changes in the learning set, can be easily derived. The obtained scales can be used for transmembrane helices prediction. The predictive power of one of these scales is tested on membrane proteins, soluble proteins, and signal peptides databases, finding that its performances is comparable with those of the hydropathy scales. Proteins 2003;50:114–121. © 2002 Wiley‐Liss, Inc.
Ion permeation through the gramicidin channel: Atomically detailed modeling by the stochastic difference equation
Authors: Siva Koneshan , Elber Ron 
Published: December 2002

AbstractAtomically detailed descriptions of ionic solution, membrane, and the gramicidin channel are used to compute molecular dynamics trajectories of ion permeation. The microsecond trajectories are calculated with the Stochastic Difference Equation (SDE), which provides approximate solutions to the equations of motions (with filtered high‐frequency modes) of extended timescales. The relative permeations of lithium, sodium, and potassium are estimated by using a novel, kinetic cycle protocol and are compared with experiment. The transport through native gramicidin and one fluoro‐valine variant is considered as well. Qualitative agreement between theory and experiment is obtained. The faster permeation rate of sodium compared to lithium is reproduced in the calculations. The calculations also reproduce the slower diffusion through a gramicidin with fluorinated valine compared to native gramicidin. The calculations are inconclusive about the relative rates of potassium and sodium. The experiment suggests that potassium permeates more quickly. We directly probe the kinetics of a biophysical process at a relevant time window without reducing the atomically detailed description of the system. The calculations were able to capture subtle balances between binding and diffusion that determine permeation rates. The same model gave the correct ordering of diffusion rates for cases in which electrostatic binding has opposite effects and must be supplemented by dynamic factors. Diffusion rates are faster when favorable electrostatic interactions of ions in the channel (compared to the solvent) are observed. Studies of a gramicidin variant suggest an opposite effect, in which permeation is faster for the less polar channel, indicating dynamic effects. Although both trends can be explained qualitatively, it is not possible to predict (before doing the SDE calculations) which factor is more important. Proteins 2003;50:63–80. © 2002 Wiley‐Liss, Inc.
Exponential decay kinetics in “downhill” protein folding
Authors: Hagen Stephen J. 
Published: December 2002

AbstractThe observation of single‐exponential kinetic phases in early stages of protein folding is often interpreted as evidence that these phases are rate limited by significant energy or entropy barriers. However, although the existence of large barriers reliably implies exponential kinetics, the reverse is not necessarily true. A simple model for the hydrophobic collapse of a chain molecule demonstrates that a barrierless or “downhill” diffusional relaxation can give rise to kinetics that are practically indistinguishable from a pure exponential. Within this model, even a highly nonlinear experimental probe such as resonance energy transfer (Förster transfer) could exhibit a large amplitude decay (greater than 90% in fluorescence) that deviates from a simple exponential by less than 0.5%. Only a detailed analysis of the dynamics is likely to reveal that a free energy barrier is absent. Proteins 2003;50:1–4. © 2002 Wiley‐Liss, Inc.