bluuebunny/crossref_metadata_2025 huggingface dataset:
Briefing: The psychology of managing project cost
Authors: Aikens T.
Published: August 2007

Managing cost is an integral part of any engineering project. The impact of overspending can be significant in both private and public sectors. Despite better cost management systems and training, major projects are still suffering large cost overruns. In this article, the author examines the impact of how we think and the project environment on how we manage cost. From the early profit motive, or budget ceiling, to the delivery pressure during construction, managers are often pushed either to reduce budgets or spend unwisely. Contracts such as rates-based design can encourage the wrong behaviours and increase cost dramatically. There is no single answer. We need to consider how our thoughts affect our behaviour and look at the bigger picture of the overall (business) project beyond a short-term cost issue. Communication is how we convey are thoughts, so needless to say it is vital to effective cost management.
Briefing: Engineering skills shortages in China — a personal view
Authors: Mills G.
Published: August 2007

Two challenges from history illustrate how to mobilise an industry to face a major challenge: the engineering infrastructure for the Normandy landings and the establishment of the UK's motorway network. China has already applied the lessons learned from these challenges to undergraduate education, but the focus is now moving to professional development. A group of leading firms, academics and ICE is cooperating to tackle this problem. This is a small step on an arduous journey but to those who judge Chinese engineers only by where they are today and not where they have come from it would be worth remembering the following Zhuang Zi quotation from the 5th century BC. ‘When Heaven is about to place a great responsibility on a man, it always first frustrates his spirit and will, exhausts his muscles and bones, exposes him to starvation and poverty, harasses him by troubles and setbacks so as to stimulate his spirit, toughen his nature and enhance his abilities.’
Risk management and value management in project appraisal
Authors: Afila D. , Smith N. J.
Published: August 2007

The appraisal phase of the project life cycle commences with the inception of the project and ends with the sanction of the project for implementation. During the appraisal phase the key decisions on the viability of the project and the most feasible project option are made in sequence. To enable good ideas and realistic projects to be recognised, both risk management and value management techniques are used, among others. This paper examines current industrial practice in project appraisal and indicates why some practitioners expressed a preference for one of these techniques and some for the other. Those preferring value management prior to risk management stated that the objectives of the project and the definition of options must be examined first, whereas those implementing risk management first considered that assessing the risks of the plan developed to achieve project objectives must take priority over maximising opportunities. Both techniques are important in decision making under uncertainty during project appraisal but greater knowledge of their application will reduce future costs incurred through failure to correctly identify viable projects at an early stage.
Predicting construction disputes: an aetiological approach
Authors: Fenn P.
Published: August 2007

There is considerable interest in construction disputes among both researchers and practitioners; however, most of that interest is in the techniques used to resolve disputes. Practitioners are understandably interested in efficiency in resolution; human nature perhaps allows them to expect that disputes are inevitable. However, there seems to be little interest among researchers in considering the wider issues associated with disputes, which might allow explanation and prediction. There is little empirical evidence in the literature and anecdote abounds. This paper aims to generate debate by proposing that an aetiological approach to construction disputes is to be welcomed since it may lead to explanation or prediction of construction disputes. The work is theoretical and it is argued that the lack of an empirical base means that there has been little scientific consideration of construction disputes. Although it is commonly accepted that disputes need to be avoided, the absence of any empirical data dictates that structured prediction and avoidance are unlikely. An aetiological approach to construction disputes will help develop a mature and sophisticated research base, which may help industry performance. Prediction allows avoidance or at least informed management action if avoidance is not preferred.
Design management: changing roles of the professions
Authors: Male S. , Bower D. , Aritua B.
Published: August 2007

This paper sets out to explore how recent changes in procurement in construction have affected the roles that professions play in the design process. It discusses how professions that traditionally took the role of design manager now find themselves participating within previously unforeseen contexts, working in multi-disciplinary teams led by contractors and with changed responsibilities at the design stage. Supply chain members who were not previously involved during the early project phases are being engaged at the earliest phases of the project life cycle and even taking leadership roles while designers sometimes work as supply chain partners. A study of design in construction and other sectors shows that in dealing with design management issues it is critical to deepen appreciation for the unique characteristics of design and the design process. The paper argues that contractors and designers taking on design management roles in a dynamic industry seeking to explore best practice and innovative approaches to procurement and in the delivery of projects need to acquire new skills, management education and develop the necessary qualities.
Influence of El Niño on rainfall in Guyana and Uganda
Authors: Wardlaw R. , Jaigopaul D. , Rahaman Z.
Published: August 2007

El Niño/southern oscillation (ENSO) activity is known to affect weather patterns in many parts of the world. This paper develops an approach to identifying signals and incorporating associated impacts on hydrological risk into water resources planning and management. The paper builds on earlier research reported in the climatology literature, and brings this to the engineering domain. An evaluation of seasonal rainfall in Guyana clearly demonstrates that distinct rainfall distributions are associated with La Niña and El Niño events. Forecasts of these events are made by a number of organisations at lead times of up to eight months. If these are coupled with the precipitation analysis presented in this paper, an objective hydrological risk assessment can be made. The methodology applied in Guyana has been repeated with data on net basin supply to Lake Victoria. There is a clear indication of a link between ENSO activity and net basin supply to Lake Victoria.
Linking one- and two-dimensional models for free surface flows
Authors: Liang D. , Falconer R. A. , Lin B.
Published: August 2007

This paper presents integration of a one-dimensional (1D) numerical model with a two-dimensional (2D) numerical model for simulating shallow water flows. The dynamic link library (DLL) technique is used to link a 2D research code with a 1D commercial program. The 2D model has been refined to represent ground topography better and the flooding and drying process. Both mass and momentum transfers are allowed between the 1D and 2D solutions. Two test cases were used to verify the linked model. Smooth transitions between wet and dry areas were observed, with accurate mass conservation being achieved during wetting and drying. It has also been shown that the inclusion of momentum transfer between the two models leads to improved results by eliminating the unrealistic variations in the free surface, close to the common boundaries of the models. The combined 1D and 2D model has the capability to simulate hydraulic processes at different spatial scales simultaneously.
Prioritising sewerage maintenance using serviceability criteria
Authors: Arthur S. , Crow H.
Published: August 2007

In the UK and elsewhere, there has been a concerted move away from primarily assessing sewer system capacity to focus on ‘serviceability’ as a key performance indicator in sewerage provision. Increasingly, water regulators are recognising that a prime concern of customers is avoiding flooding of their property, as environmental improvements can often be intangible. However, regulators insist that environmental factors are also given strenuous attention. Based on these considerations, it is evident that sewerage providers will increasingly consider undertaking proactive maintenance on sub-critical and non-critical sewers in order to reduce the risk of customers experiencing reduced levels of serviceability. This paper documents the development of a methodology to manage capital maintenance expenditure within the context of ‘serviceability’ to customers, the public and the environment. The methodology has been applied alongside Infoworks-CS software to determine critical points in a small coastal catchment in Edinburgh, Scotland. The paper also discusses how these results are linked to customer complaints held in a geographic information system (GIS) database, and how the approach developed was able to recommend which assets should be proactively maintained to minimise the risk of serviceability loss. For the catchment considered, key serviceability performance indicators were found to be combined sewer overflow (CSO) spills, flooding in residential areas, flooding in commercial zones and disruption to traffic.
Winterhardiness and Turf Quality of Accessions of Perennial Ryegrass (Lolium perenne L.) from Public Collections
Authors: Hulke Brent S. , Watkins Eric , Wyse Donald , Ehlke Nancy
Published: August 2007

The lack of winterhardiness of some cool‐season grasses limit their usefulness in northern climates. Perennial ryegrass (Lolium perenne L.) lacks winterhardiness in Minnesota but has desirable qualities, such as wear tolerance and rapid establishment, that are useful in many turf applications. While domesticated germplasm may lack winterhardiness, undomesticated wild or landrace germplasm may have genes for better winterhardiness in environments like Minnesota's. In 2004, 300 accessions from two public sources in the USA were planted with eight check varieties and populations in two environments in central Minnesota, St. Paul and Becker. Thirty individuals of each accession were evaluated for seedling vigor and tiller survival after the first winter. Other turf‐quality traits and tiller survival after the second winter were evaluated on those plants that survived the first winter. The first winter was extremely harsh and resulted in the death of all accessions and checks at Becker. There was good differentiation among accessions at St. Paul for tiller survival, with 8 of the 300 accessions performing better than NK200, the most winterhardy check variety. The second winter was considerably less harsh, with less death of tillers and whole plants. While the accessions do not have suitable turf quality for direct domestication, turf quality can be improved through breeding.
Apomictic Bahiagrass Expressing the bar Gene Is Highly Resistant to Glufosinate under Field Conditions
Authors: Sandhu Sukhpreet , Altpeter Fredy , Blount Ann R.
Published: August 2007

Bahiagrass (Paspalum notatum Flugge) is one of the most important low‐input turf and forage grasses in the southeastern USA and in other subtropical regions. Its open growth habit, however, facilitates weed encroachment and its low tolerance to commercially available herbicides complicates weed management. Genetic transformation protocols were recently developed for bahiagrass that allow now, among other approaches, the introduction of herbicide resistance genes. Integration of the bar gene expression cassette into the genomic DNA of the apomictic bahiagrass cultivar Argentine was confirmed by Southern blot analysis. Stable expression of the bar gene was detected by an immunochromatographic assay in primary transgenic lines and the seed‐derived progeny plants. Several independent transgenic lines showed no growth inhibition, chlorosis, or necrosis following a spray application of 1.0% glufosinate ammonium [2‐amino‐4‐(hydroxymethylphosphinyl)butanoic acid] under greenhouse conditions. The selected transgenic plants did not differ morphologically from wild‐type plants and produced viable seeds in the greenhouse and field. All weeds that coestablished during the field experiment, as well as wild‐type bahiagrass, displayed full leaf necrosis after application of 0.3% glufosinate ammonium. Transgenic bahiagrass plants were resistant to a field application of 0.6% glufosinate ammonium, which is twice the recommended rate for weed control, without any symptoms of phytotoxicity.
Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia
Authors: Beech Jill , Boston Raymond , Lindborg Sue , Russell Gail E.
Published: August 2007

Objective—To compare the effect of thyrotropin-releasing hormone (TRH) administration on endogenous ACTH concentrations in healthy horses and those with pituitary pars inter-media hyperplasia and compare the test with the dexamethasone suppression test (DST).

Design—Prospective case series.

Animals—15 horses with clinical signs of pituitary pars intermedia dysfunction (PPID), 4 horses with equivocal signs of PPID, and 29 horses without signs of PPID.

Procedures—ACTH concentrations prior to and after administration of TRH were measured 61 times in 48 horses. Results of the DST (cortisol response) were compared with those of the TRH test in 29 horses. Thirty-three horses (24 with no clinical signs of PPID, 5 with clinical signs of PPID, and 4 with equivocal clinical signs of PPID) were euthanized and necropsied and their pituitary glands evaluated.

Results—ACTH concentrations increased in all horses, but magnitude and duration of increase were significantly higher in horses with PPID. Endogenous ACTH concentrations were influenced by season. The ACTH baseline concentrations and response to TRH were not correlated with results of the DST. Results of DST were abnormal only in clinically abnormal horses or those with pars intermedia hyperplasia, but were within reference range in 17 of 26 tests in these horses.

Conclusions and Clinical Relevance—The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range. The DST was specific but not sensitive and was inconsistent for individuals, and results often did not agree with the TRH test response.
Bubble trapping and coalescence at the baffles in stirred tank reactors
Authors: Sudiyo Rahman , Andersson Bengt
Published: August 2007

Turbulent flow and bubble coalescence in water at the leeward side of a baffle in a stirred tank reactor have been studied with PIV and a high‐speed CCD camera. A large stationary vortex was revealed at the leeward side of the baffle. At impeller speeds of 400–600 RPM, the maximum tangential velocity at the vortex was proportional to the impeller tip speed (uθ ≈ 0.27 Utip), giving a pressure difference in the vortex of as much as a few hundred pascal. The main mechanism for coalescence in this area was trapping of bubbles in the vortex, increasing the local hold‐up and coalescence probability by forcing the bubbles together. The force on the bubbles resulting from the local pressure gradient makes the bubbles move fast to the centre, within 10–20 ms. The coalescence efficiency was very high and more than 85% of the coalescence occurred within 2 ms. Bouncing of bubbles was mainly seen for large bubbles moving up in the centre of the vortex. The trapping of the bubbles was modeled successfully by a drag coefficient model corrected for nonspherical bubbles and turbulent continuous phase. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Optimization of desalination location problem using MILP
Authors: Emhamed A. M. , Czuczai B. , Horvath L. , Rev E. , Lelkes Z.
Published: August 2007

A new mixed‐integer linear programming model for location problem is developed in this work in order to find the optimal co‐ordinates of the desalination plants. The model takes into account the given locations and capacities of the water incomes, the demands, and the costs of plants and pipelining. Feasible and infeasible plant regions are distinguished for locating the plants. The model has been developed in two consecutive phases. First, a basic model is developed that provides a solution within short time but does not take into account the possibility of pipeline branching. Application of this model gives rise to redundant pipelines to some connections, involving extra costs. Pipeline branching is dealt with an improved model developed in the second phase. This improved model provides realistic solution but with much longer computation time. The results of applying the different models on motivated examples of different sizes are detailed. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Process trend monitoring using key sensitive index
Authors: Jeng Jyh‐Cheng , Su An‐Jhih , Yu Cheng‐Ching , Huang Hsiao‐Ping
Published: August 2007

Process monitoring is essential to maintain product quality in semiconductor manufacturing. However, unlike chemical processes, semiconductor manufacturing processes exhibit the following characteristics: (1) much shorter (minutes) and often variable (deliberately adjusted) batch time, (2) multiple processing steps (10–20) in each batch, (3) only some particular processing steps constituting the quality‐determining steps, and (4) mixed products for the same batch processing. In this work, instead of incorporating a large number of trajectory data with variable batch time and possibly “missing” data for some process variables using multivariate statistics, a process‐insight‐based approach, key sensitive index (KSI), is taken. From process knowledge, the key sensitive time‐slot in the recipe is identified. Next, possible key sensitive process variables (KSV) are selected and validated according to the process trend correlation. A simple batch reactor example is used to illustrate the KSV selection procedure. Then, an index for these variables is sought. Two integrated circuit processing examples from real fab data are used to illustrate the KSI‐based approach and results clearly indicate that process trend is captured using KSI‐based approach. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Analysis of flux decline behaviors in filtration of very dilute suspensions
Authors: Iritani Eiji , Katagiri Nobuyuki , Sugiyama Yuuki , Yagishita Koichi
Published: August 2007

The gradual decrease in the filtration flux rate with time, which occurred due to the capture of solid particles and/or organic substances onto the surfaces of pores in a thin filter medium, was measured in constant‐pressure filtration of both pool water and pond water. A new theoretical background of the conventional characteristic filtration equation describing the variation of the filtration resistance of the clogged filter medium with time was afforded based on a consideration of the variation of both the porosity and the specific surface area of the filter medium caused by the capture of the solids in the Kozeny‐Carman equation. The flux decline behavior depended solely on the initial filtration rate, influenced by the pore size of the filter medium and the filtration pressure. The variations of the filtration rate and the filtrate volume with the filtration time were very accurately described by the analytical solution based on the characteristic filtration equation. In the case of pond water with a relatively high turbidity compared to pool water, the transition point from depth to cake filtration was determined based on the pressure dependence of the specific filtration resistance of the filter cake, and then the flux attenuation behavior was evaluated by considering the transition from depth to cake filtration. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Autism in African American Families: Clinical‐phenotypic findings
Authors: Cuccaro Michael L. , Brinkley Jason , Abramson Ruth K. , Hall Alicia , Wright Harry H. , Hussman John P. , Gilbert John R. , Pericak‐Vance Margaret A.
Published: August 2007

Unlike other complex diseases, the study of autism has been almost exclusively limited to Caucasian families. This study represents a first effort to examine clinical and phenotypic findings in individuals with autism from African American families. Drawing from an ongoing genetic study of autism we compared African American (N = 46, mean age = 118 months) and Caucasian (N = 298, mean age = 105 months) groups on autism symptoms and developmental language symptoms. The African American group showed greater delays in language but did not differ from the Caucasian group on core autism symptoms. These findings, while suggestive of a more severe phenotype, may reflect an ascertainment bias. Nonetheless, we believe that more studies of racial‐ethnic groups should be conducted with several goals in mind including strengthening recruiting strategies to include more ethnic‐racial groups and more thoughtful evaluation of phenotypic traits. Such considerations will aid greatly in the search for genetic variants in autism. © 2007 Wiley‐Liss, Inc.
Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3′ UTR VNTR of the DAT: Association with childhood ADHD in male African‐Caribbean cocaine dependents?
Authors: Ballon Nicolas , Leroy Sophie , Roy Christianne , Bourdel Marie‐Chantal , Olie Jean‐Pierre , Charles‐Nicolas Aimé , Krebs Marie‐Odile , Poirier Marie‐France
Published: August 2007

The conflicting results reported by genetic studies with the variants of the genes coding for the dopaminergic system in cocaine addicts could be partially explained by the difficulties to constitute homogenous sample of patients. Childhood attention‐deficit/hyperactivity disorder (ADHD), and/or impulsivity are frequently associated with cocaine addiction and could participate in the heterogeneity of the samples in cocaine addicts. Accordingly, it is hypothesized that cocaine addiction would be associated with the variants of the genes coding for the dopamine system in an homogenized sample of cocaine addicts, especially in individuals with childhood ADHD comorbidity, or with a high impulsivity score. The potential association of the variants TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3′ UTR VNTR of the DAT was examined in African‐Caribbean males, smoked‐cocaine dependents. All the subjects were assessed with the Diagnostic Interview of Genetic Studies, the Barratt's impulsivity scale, and the Wender Utah rating scale for childhood ADHD. A positive association was found with the DRD2 and DRD4 polymorphisms in the subgroups of patients with childhood ADHD, or with a high impulsivity score, which represented, respectively, 53.3 and 73.0% of the patients. Conversely, no positive association was found for any of the polymorphisms studied when the group of patients was examined as a whole. Therefore, our results suggest that the clinical dimensions of childhood ADHD and of impulsivity could be taken into account to homogenize the samples of patients in cocaine association studies. © 2007 Wiley‐Liss, Inc.
Gene‐based SNP mapping of a psychotic bipolar affective disorder linkage region on 22q12.3: Association with HMG2L1 and TOM1
Authors: Potash James B. , Buervenich Silvia , Cox Nancy J. , Zandi Peter P. , Akula Nirmala , Steele Jo , Rathe Jennifer A. , Avramopoulos Dimitrios , Detera‐Wadleigh Sevilla D. , Gershon Elliot S. , DePaulo J. Raymond , Feinberg Andrew P. , McMahon Francis J.
Published: August 2007

Genetic linkage studies in both bipolar affective disorder (BPAD) and schizophrenia have implicated overlapping regions of chromosome 22q. We previously reported that BPAD pedigrees containing multiple members with psychotic symptoms showed suggestive linkage to chromosome 22q12.3. Now we have tested 189 single nucleotide polymorphisms (SNPs) spanning a 3 Mb region around the linkage peak for association with BPAD in 305 families, unrelated cases, and controls. SNPs were selected in or near genes, resulting in coverage at a density of 1 SNP per 6.7 kb across the 22 annotated genes in the region. The strongest signal emerged from family‐based association analysis of an 11‐SNP, 54 kb haplotype straddling the gene HMG2L1 and part of TOM1. A 3‐marker haplotype of SNPs within TOM1 was associated with BPAD (allele‐wise P = 0.0011) and with psychotic BPAD (allele‐wise P = 0.00049). As hypothesized, the mean odds ratio for the risk alleles across the region was 1.39 in the psychotic but only 0.96 in the non‐psychotic subset. Genotype‐wise analyses yielded similar results, but the psychotic/non‐psychotic distinction was more pronounced with mean odds ratios of 1.91 versus 0.8. Permutation of genotype‐wise results for rs2413338 in HMG2L1 showed an empirical P = 0.037 for the difference between subsets. HMG2L1 is a negative regulator of Wnt signaling, a pathway of interest in psychotic BPAD as it is activated by both mood stabilizer and anti‐psychotic medications. Further work is needed to confirm these results and uncover the functional variation underlying the association signal. © 2007 Wiley‐Liss, Inc.
Crystalline structure of poly(ethylene terephthalate) filaments
Authors: Youssefi M. , Morshed M. , Kish M. H.
Published: August 2007

Fully oriented, partially oriented, drawn, and quenched samples of poly (ethylene terephthalate) (PET) filaments were examined. Crystalline fraction and the average size of crystallites were measured by a wide angle X‐ray scattering diffractometer. Sample geometry in X‐ray diffraction was found to affect the intensity of the diffraction patterns. The crystalline fraction of the samples can be measured by X‐ray diffraction in a symmetrical reflection geometry accompanied with curve fitting computer software. Annealing improves the average size of crystallites in a direction perpendicular to (010) plane more than the two other directions, namely perpendicular to (100) and (−105) planes. Fourier transform infrared spectroscopy was used to determine the percentage of trans configuration, and the volume crystalline fraction was determined from density measurements. A good correlation was obtained between the percentage of trans configuration and weight percentage of crystalline fraction determined by density measurements. The molecular orientation of the samples was measured by a polarizing microscope and its results conform to the other findings. The presence of extended chains in the noncrystalline regions supports the idea of the presence of oriented amorphous (amorphous with correlation) and nonoriented amorphous domains in PET drawn filaments. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer
Authors: Hecht J. Randolph , Patnaik Amita , Berlin Jordan , Venook Alan , Malik Imtiaz , Tchekmedyian Simon , Navale Lynn , Amado Rafael G. , Meropol Neal J.
Published: August 2007

BACKGROUND.

The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies.

METHODS.

This phase 2 open‐label, multicenter study of panitumumab enrolled patients with metastatic colorectal cancer who had progressed on chemotherapy that included a fluoropyrimidine and irinotecan or oxaliplatin, or both. All patients had tumors with ≥10% 1+ epidermal growth factor receptor (EGFr) staining by immunohistochemistry. Patients were stratified into 2 strata (high or low staining intensity) and received intravenous panitumumab 2.5 mg/kg weekly 8 of every 9 weeks until disease progression or unacceptable toxicity.

RESULTS.

In all, 148 patients received panitumumab, 105 in the high EGFr stratum, 43 in the low EGFr stratum. Overall response by central review was 9% (95% confidence interval [CI], 5%–15%) and was similar between strata. An additional 29% of patients had stable disease. Median progression‐free survival was 14 weeks (95% CI, 8–16) and median overall survival was 9 months (95% CI, 6–10). Toxicities were manageable, with skin toxicity reported in 95% of patients (5% grade 3 or 4). Four patients discontinued therapy because of toxicity. No antipanitumumab antibodies were detected. One patient had an infusion reaction but was able to continue therapy.

CONCLUSIONS.

Panitumumab given weekly was well tolerated and had single‐agent activity in previously treated patients with colorectal cancer. Dermatologic toxicity was common but rarely severe. Ongoing studies will determine panitumumab activity earlier in the course of treatment for colorectal cancer and in combination with other antineoplastic agents. Cancer 2007. © 2007 American Cancer Society.
Collocated discrete least‐squares (CDLS) meshless method: Error estimate and adaptive refinement
Authors: Afshar M. H. , Lashckarbolok M.
Published: August 2007

Meshless methods are new approaches for solving partial differential equations. The main characteristic of all these methods is that they do not require the traditional mesh to construct a numerical formulation. They require node generation instead of mesh generation. In other words, there is no pre‐specified connectivity or relationships among the nodes. This characteristic make these methods powerful. For example, an adaptive process which requires high computational effort in mesh‐dependent methods can be very economically solved with meshless methods. In this paper, a posteriori error estimate and adaptive refinement strategy is developed in conjunction with the collocated discrete least‐squares (CDLS) meshless method. For this, an error estimate is first developed for a CDLS meshless method. The proposed error estimator is shown to be naturally related to the least‐squares functional, providing a suitable posterior measure of the error in the solution. A mesh moving strategy is then used to displace the nodal points such that the errors are evenly distributed in the solution domain. Efficiency and effectiveness of the proposed error estimator and adaptive refinement process are tested against two hyperbolic benchmark problems, one with shocked and the other with low gradient smooth solutions. These experiments show that the proposed adaptive process is capable of producing stable and accurate results for the difficult problems considered. Copyright © 2007 John Wiley & Sons, Ltd.
Novel aphidicolin‐inducible common fragile site FRA9G maps to 9p22.2, within the C9orf39 gene
Authors: Sawińska Małgorzata , Schmitt Jens Guido , Sagulenko Evgeny , Westermann Frank , Schwab Manfred , Savelyeva Larissa
Published: August 2007

Common fragile sites represent a component of normal chromosome structure that form gaps and breaks on metaphase chromosomes after partial inhibition of DNA synthesis. In humans, cytogenetic locations of 89 common fragile sites are listed in the Genome Database; however, the exact number of fragile sites remains unknown. The application of high resolution mapping approaches continues to reveal new common fragile sites in the human genome. Here, we identified a novel aphidicolin‐inducible common fragile site FRA9G, which maps to chromosomal band 9p22.2. We have characterized the structure of the fragile DNA sequence that extends over a genomic region of ∼300 kb within the C9orf39 (chromosome 9 open reading frame 39) gene. Analysis of incidence in healthy individuals showed that FRA9G is commonly expressed in the population. Heterozygous BRCA2 mutation carriers exhibit an almost sevenfold increase of FRA9G expression compared to an unrelated control population group. Identification of a novel aphidicolin‐inducible common fragile site at 9p22 may have implications for understanding the mechanism of genetic instability in tumorigenesis and other genetic disorders. © 2007 Wiley‐Liss, Inc.
Lack of response to exogenous interferon-α in the liver of chimpanzees chronically infected with hepatitis C virus
Authors: Lanford Robert E. , Guerra Bernadette , Bigger Catherine B. , Lee Helen , Chavez Deborah , Brasky Kathleen M.
Published: August 2007

The mechanism of the interferon-alpha (IFNα)–induced antiviral response is not completely understood. We recently examined the transcriptional response to IFNα in uninfected chimpanzees. The transcriptional response to IFNα in the liver and peripheral blood mononuclear cells (PBMCs) was rapidly induced but was also rapidly down-regulated, with most interferon-alpha–stimulated genes (ISGs) returning to the baseline within 24 hours. We have extended these observations to include chimpanzees chronically infected with hepatitis C virus (HCV). Remarkably, using total genome microarray analysis, we observed almost no induction of ISG transcripts in the livers of chronically infected animals following IFNα dosing, whereas the response in PBMCs was similar to that in uninfected animals. In agreement with this finding, no decrease in the viral load occurred with up to 12 weeks of pegylated IFNα therapy. The block in the response to exogenous IFNα appeared to be HCV-specific because the response in a hepatitis B virus–infected animal was similar to that of uninfected animals. The lack of a response to exogenous IFNα may be due to an already maximally induced ISG response because chronically HCV-infected chimpanzees already have a highly up-regulated hepatic ISG response. Alternatively, negative regulation may block the response to exogenous IFNα, yet it does not prevent the continued response to endogenous ISG stimuli. The IFNα response in chronically HCV-infected chimpanzees may be mechanistically similar to the null response in the human population.

Conclusion:

In chimpanzees infected with HCV, the highly elevated hepatic ISG expression may prevent the further induction of ISGs and antiviral efficacy following an IFNα treatment. (HEPATOLOGY 2007.)
Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy
Authors: Binder Marco , Kochs Georg , Bartenschlager Ralf , Lohmann Volker
Published: August 2007

Hepatitis C virus (HCV) has been known to replicate with extremely varying efficiencies in different host cells, even within different populations of a single human hepatoma cell line, termed Huh-7. Several reports have implicated the retinoic-acid inducible gene I (RIG-I)/ interferon regulatory factor 3 (IRF-3) pathway of the innate antiviral response with differences in host cell permissiveness to HCV. To investigate the general impact of the IRF-3 response onto HCV replication in cell culture, we generated an ample array of stable Huh-7 cell lines with altered IRF-3 responsiveness. Neither blocking IRF-3 activation in various host cells by expression of dominant negative RIG-I or HCV NS3/4A protease nor reconstitution of RIG-I signaling in Huh7.5, a cell clone known to be defective in this pathway, had any impact on HCV replication. Only by overexpressing constitutively active RIG-I or the signaling adaptor Cardif (also known as interferon-beta promoter stimulator 1, mitochondrial anti-viral signaling protein, or virus-induced signaling adaptor), both leading to a stimulation of the IRF-3 pathway in the absence of inducers, was HCV replication significantly inhibited. We therefore assessed the extent of RIG-I– dependent IRF-3 activation by different species of RNA, including full-length HCV genomes and HCV RNA duplexes, and observed strong induction only in response to double-stranded RNAs.

Conclusion:

Based on these findings, we propose a refined model of innate immune escape by HCV involving limited initial induction and stringent subsequent control of the IRF-3 response.
Variations in astrocyte and fibroblast response due to biomaterial particulates in vitro
Authors: de Guzman Roche C. , VandeVord Pamela J.
Published: August 2007

The possible involvement of orthopedic biomaterial particles such as cobalt–chrome alloy (Co–Cr), ultrahigh molecular weight polyethylene (UHMWPE), titanium alloy (Ti‐6Al‐4V), and polymethyl methacrylate (PMMA) in the formation of glial and meningeal scars was investigated using an in vitro system. Cell lines were used as models for astrocytes and meningeal fibroblasts. They were incubated with varying concentrations of particle suspensions, after which proliferative and cytotoxic responses were quantified using MTT assay and Live/Dead microscopy. It was determined that relative particulate toxicity (arranged in decreasing order) to astrocytes is Co–Cr > Ti‐6Al‐4V > PMMA > UHMWPE, and toxicity to fibroblasts is PMMA > Co–Cr > Ti‐6Al‐4V > UHMWPE. Cell death caused by PMMA was mainly due to necrosis, while the rest of the particles induced apoptosis. Low quantities of Co–Cr and Ti‐6Al‐4V stimulate increased astrocyte proliferation rate. However, only the cells treated with titanium alloy caused upregulated transcription of reactive astrocyte markers such as glial fibrillary acidic protein, vimentin, nestin, and type IV collagen, suggesting the potential of titanium alloy alone to trigger glial scarring. None of the biomaterials tested promoted proliferation in fibroblasts implying that biomaterial particles are not directly involved in meningeal scar development. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Prey envenomation does not improve digestive performance in western diamondback rattlesnakes (Crotalus atrox)
Authors: McCue Marshall D.
Published: August 2007

Although the toxic properties of snake venoms have been recognized throughout history, very little is known about the adaptive significance of these powerful mixtures. This study examined the popular hypothesis that prey envenomation enhances digestion by influencing the energetic costs of digestion and assimilation, gut passage time, and apparent assimilation efficiency (ASSIM) in western diamondback rattlesnakes (Crotalus atrox), a species whose venom is recognized for its comparatively high proteolytic activities. A complete randomized block design allowed repeated measures of specific dynamic action and gut passage time to be measured in eight snakes ingesting four feeding treatments (i.e., artificially envenomated live mice, artificially envenomated prekilled mice, saline injected live mice, and saline injected prekilled mice). A second experiment measured ASSIM in eight snakes ingesting a series of six artificially envenomated or six saline injected mice meals over an 8‐week period. Contrary to expectations, the results of both these experiments revealed that envenomation had no significant influence on any of the measured digestive performance variables. Gut passage time averaged 6 days and ASSIM averaged 79.1%. Twenty‐one hours following ingestion, postprandial metabolic rates exhibited factorial increases that averaged 3.9‐fold greater than resting metabolic rate. Specific dynamic action lasted on average 88 hr and accounted for 26% of the total ingested energy. The results of this study reinforce the need to systematically examine the potential adaptive advantages that venoms confer on the snakes that produce them. J. Exp. Zool. 307A:568–577, 2007. © 2007 Wiley‐Liss, Inc.
Gene transfer to the spinal cord neural scar with lentiviral vectors: predominant transgene expression in astrocytes but not in meningeal cells
Authors: Hendriks W. T. J. , Eggers R. , Verhaagen J. , Boer G. J.
Published: August 2007

Viral vector–mediated overexpression of neurotrophins in cells constituting the neural scar may represent a powerful approach to rendering scar tissue of a central nervous system (CNS) lesion permissive for neuronal regrowth. In this study a lentiviral vector encoding green fluorescent protein (LV‐GFP) was injected in and around the neural scar 2 weeks after a dorsal column lesion in the rat spinal cord in order to analyze transduction characteristics of the neural scar after 4, 7, and 14 days. GFP expression was found at all points after injection and increased from 4 to 7 days, with no apparent difference observed between 7 and 14 days. The core of the lesion was virtually devoid of GFP signal despite direct vector injections in this area. The colocalization of GFP with specific cell markers (GFAP, vimentin, Raldh2, NeuN, OX‐42, ED‐1, and NG‐2) indicated that the predominant cells transduced in the rim of the lesion were astrocytes, with neurons, microglia, oligodendrocyte precursors, and macrophages transduced to a lesser extent. None of the Raldh2‐positive meningeal cells, present in the core of the scar, expressed GFP. In vitro meningeal cells were readily transduced, indicating that in vivo the formation of an extracellular matrix might prevent LV particles from transducing cells in the core of the scar. Because astrocytes are important cellular constituents of the glial scar after CNS injury, transduction of astrocytes with LV vectors encoding neurotrophic factors like BDNF or NT‐3 may be used to enhance regeneration of severed axonal tracts through or along boundaries of a CNS lesion. © 2007 Wiley‐Liss, Inc.
Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats
Authors: Cruz Adolfo , Túnez Isaac , Martínez Rubén , Muñoz‐Castañeda Juan Rafael , Ramírez Luz María , Recio Marta , Ochoa Luís , Arjona Alvaro , Montilla Pedro , Muntané Jordi , Padillo Francisco J.
Published: August 2007

The aim of the study was to analyze the impact of melatonin on brain oxidative stress in experimental biliary obstruction. Cholestasis was done by a double ligature and section of the extrahepatic biliary duct. Melatonin was injected intraperitoneally (500 μg/kg/day). Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) contents were determined in the brain tissue. Biliary obstruction raised MDA and reduced GSH contents in the cortex, cerebellum, and hypothalamus areas. Moreover, the scavenger enzyme activity significantly dropped in all areas of the brain. Melatonin drastically reduced MDA concentration and enhanced GSH concentration, as well as all antioxidant enzyme activity in all brain areas obtained from the bile duct–ligated animals. In conclusion, the treatment with melatonin decreased lipid peroxidation and recovered the antioxidant status in the brain from cholestatic animals. © 2007 Wiley‐Liss, Inc.
Intrinsic membrane properties and morphological characteristics of interneurons in the rat supratrigeminal region
Authors: Hsiao Chie‐Fang , Gougar Kelly , Asai J. , Chandler Scott H.
Published: August 2007

The membrane properties and morphological features of interneurons in the supratrigeminal area (SupV) were studied in rat brain slices using whole‐cell patch clamp recording techniques. We classified three morphological types of neurons as fusiform, pyramidal, and multipolar and four physiological types of neurons according to their discharge pattern in response to a 1‐sec depolarizing current pulse from −80 mV. Single‐spike neurons responded with a single spike, phasic neurons showed an initial burst of spikes and were silent during the remainder of the stimulus, delayed‐firing (DF) neurons exhibited a slow depolarization and delay to initial spike onset, and tonic (T) neurons showed maintained a discharge throughout the stimulus pulse. In a subpopulation of neurons (10%), membrane depolarization to around −44 mV produced a rhythmic burst discharge (RB) that was associated with voltage‐dependent subthreshold membrane oscillations. Both these phenomena were blocked by the sodium channel blocker riluzole at a concentration that did not affect the fast transient spike. Low doses of 4‐AP, which blocks low‐threshold K+ currents, transformed bursting into low‐frequency tonic discharge. In contrast, bursting occurred with exposure to cadium, a calcium‐channel blocker. This suggests that persistent sodium currents and low‐threshold K+ currents have a role in intrinsic burst generation. Importantly, RB cells were most often associated with multipolar neurons that exhibited either a DF or a T discharge. Thus, the SupV contains a variety of physiological cell types with unique morphologies and discharge characteristics. Intrinsic bursting neurons form a unique group in this region. © 2007 Wiley‐Liss, Inc.
Mechanisms of neurodegenerative diseases: Insights from live cell imaging
Authors: Weissmann Carina , Brandt Roland
Published: August 2007

Pathologic alterations in protein dynamics such as changes in protein degradation, accumulation of misfolded proteins, and deficits in cellular transport mechanisms are a common feature of most if not all neurodegenerative diseases. Live cell imaging studies promise to contribute to a better understanding of the molecular mechanisms underlying these diseases by visualizing the turnover, accumulation, and transport of proteins in a living cellular context in real time. In this review, we discuss recent work in which different live cell imaging approaches are applied in cellular models of amyotrophic lateral sclerosis, polyQ diseases, and tauopathies as paradigmatic examples of diseases with different types of alterations in protein dynamics. It becomes evident that live cell imaging studies provide new insights into different aspects of protein dynamics, such as the understanding that aggregates are not as static as concluded from previous studies but exhibit a remarkable molecular exchange and that the dynamicity state of the neuronal cytoskeleton might have a critical role in neuronal degeneration. It can be anticipated that live cell imaging studies will lead to a more dynamic view of protein turnover and aggregation, which may aid in identifying drugs that specifically interfere with disease‐related changes. © 2007 Wiley‐Liss, Inc.
Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress
Authors: Hitoshi Seiji , Maruta Noriko , Higashi Mikito , Kumar Akhilesh , Kato Nobumasa , Ikenaka Kazuhiro
Published: August 2007

In rodents, adult neurogenesis occurs in the olfactory bulb and the dentate gyrus of the hippocampus. It has been shown that exposure to psychosocial stress reduces cell proliferation in the dentate gyrus. However, little is known about how stress affects the proliferation kinetics of neural stem cells (NSCs) in the subventricular zone (SVZ), which provide new neurons to the olfactory bulb. We utilized a forced‐swim model of stress in the mouse and found that chronic stress decreased the number of NSCs in the SVZ. The reduction of NSC number persisted for weeks after the cessation of stress but was reversed by treatment with the antidepressant drugs fluoxetine and imipramine. We demonstrated by in vitro colony‐forming neurosphere assay that corticosterone attenuated neurosphere formation by adult NSCs and, in contrast, that serotonin increased the survival of NSCs. In addition, serotonin expanded the size of the NSC pool in the SVZ when it was infused into the lateral ventricle in vivo. These results suggest that, under chronic stress conditions, the number of NSCs is regulated by the actions of glucocorticoids and serotonin. These data provide insights into the molecular mechanisms underlying the pharmacological actions of antidepressant drugs. © 2007 Wiley‐Liss, Inc.