bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behaviour of an artificially replenished shingle beach at Hayling Island, UK
Authors: Whitcombe L. J. 
Published: November 2007

Abstract
Many coastal areas throughout the world are suffering from erosion, so numerous attempts are made, by constructing various forms of sea defences, to stabilize a retreating beach or reduce its rate of erosion. In recent years, artificial beach replenishment has become an established method in helping to restore a deteriorating beach. However, there has been a relative lack of information regarding the post-replenishment behaviour of many artificially renourished beaches. Results of a study of a replenished beach at Hayling Island suggest that the apparent depositional and erosional trends measured along a typical beach profile can be due to the longshore movement of a single, trapezium-shaped, mass of shingle, at a constant rate, rather than variations in the longshore transport rate.
Modelling groundwater flow in the Sellafield area
Authors: Heathcote J. A. , Jones M. A. , Herbert A. W. 
Published: November 2007

Abstract
This paper presents a snapshot of how numerical modelling of groundwater is being used in the interpretation of hydrogeological data for the proposed Sellafield radioactive waste repository. The main objective of the modelling at the present stage of the investigation is to help develop a conceptual understanding of the site hydrogeology, by testing whether particular concepts are quantitatively feasible and whether they are able to explain observations.
Models have been constructed with differing levels of detail: they each contribute to building a consistent conceptual model of the behaviour of the site as a whole, but they do not individually provide such an integrated conceptual model. They are presented here to illustrate the approach to developing the conceptual understanding, and to illustrate the range of quantitative approaches being applied to different aspects of the site hydrogeology.
Four groups of models are described in outline, incorporating variously porous medium and fracture flow, complex geology, anisotropic formations, and dense solutes from more than one source. These are modelled in two and three dimensions.
A two-dimensional areal model reproduces head variation observed in shallow wells penetrating the Sherwood Sandstone Group, identifying recharge and discharge areas, and constraining the hydraulic conductivity of the sandstone. Vertical section models through the geological sequence, incorporating one or two sources of dense saline water were able to reproduce qualitatively the main features observed in deep boreholes, in terms of pressure and salinity. The two-source model produces the better match to the salinity distribution.
A three-dimensional model, using simplified geology, was able to demonstrate the interaction of salinity and geology, and demonstrate how pressures and salinity may evolve with time. Three-dimensional fracture network models of the Borrowdale Volcanic Group show head variability with depth similar to that observed in some deep boreholes. A number of fracture concepts and parameter distributions are compatible with the data. The modelling work presented shows progress towards a numerically consistent conceptual hydrogeological model of the Sellafield region that can accommodate the site characterization data, and further work is under way to continue this progress.
Slope instability in historic hilltop towns of Basilicata, southern Italy
Authors: Gostelow T. P. , Del Prete M. , Simoni A. 
Published: November 2007

Abstract
The importance of preserving Italian hilltop towns through a general geotechnical strategy is discussed and is followed by a specificreview of the hydrogeologicalconditions responsible for regional mass movements at ancient hilltop towns in Basilicata. A historical survey of reactivations in colluvial deposits at selected sitesin the region suggested that increased activity was taking place in response to extreme rainfall events, possibly related to long-term climatic changes. The importance of natural and anthropogenic processes along critical hydrogeological boundary conditions in relation to this activity is then reviewed and one example of urban landsliding from Grassano in the Basento valley is described. Local structure, such as faulting, was shown to be especially important in the location of both groundwater discharge (springs) and the landsliding. The landslide activity in the town was also shown to be related to a period of population expansion and possible domestic water leakages following the provision of a pumped supply. It is suggested that these anthropogenic processes reduce the usefulness of empirical links between landslide frequency, rainfall extremes or other explanations involving climatic change. Finally, a strategy for landslide management based on the use of hydrogeological conceptual models and GIS technology is proposed.
Tectonically influenced glacial erosion, and ensuing valley infill: a geophysical survey
Authors: Taylor W. P. , Wilson C. D. V. 
Published: November 2007

Abstract
A geophysical survey has been made of the buried floor and infill of the Gilpin-Kent Valley, south Cumbria. The 18 km valley has been investigated using 50 seismic refraction spreads and 140 gravity stations. The survey has been integrated with data from boreholes and with the adjoining Morecambe Bay Barrage feasibility survey.
Five geophysical cross-sections of the valley are given, together with one from a former site investigation near Arnside. Maximum depth to bedrock on each profile lies between 40 and 90 m. The rock floor is dissected by faulting into segments of Silurian and Dinantian (Carboniferous) strata; the softer Silurian rocks have been preferentially eroded to form subglacial tunnel valleys with relief of up to 40 m. In the south the strike of the Carboniferous beds and the trend of some of the faults swing from north-south into a NE-SW direction, which governs the course of the River Kent to its mouth at Grange-over-Sands.
The valley fill consists mostly of silty clay, with some peat; beneath the clay is a horizon of gravel/cobbles that is up to 40 m thick in some of the tunnel valleys. Till has not been recognized in the survey; the gravel may be its reworked remains. The deep and irregular rock floor of the valley points to a glacial regime of vigorous erosion, both by ice and by melt water.
Geotechnical data from boreholes have been correlated, where possible, with seismic velocities and density.
Drainage characteristics of a cut soil slope with horizontal drains
Authors: Whiteside P. G. D. 
Published: November 2007

Abstract
Groundwater in a regraded, previously unstable slope was controlled by installation of a parallel array of horizontal drains. During a major rainstorm, the discharge from these drains was measured continuously over a period of 65 hours. The results showed that groundwater flow was taking place preferentially along highly permeable subsurface drainage paths and that the overall piezometric level was being controlled by the drains. The characteristics of the drainage curve indicate that some drainage paths only operate at times of high flow.
Is Region-of-Interest Overlap Comparison a Reliable Measure of Category Specificity?
Authors: Kung Chun-Chia , Peissig Jessie J. , Tarr Michael J. 
Published: November 2007

Abstract
Analysis of the degree of overlap between functional magnetic resonance imaging–derived regions of interest (ROIs) has been used to assess the functional convergence and/or segregation of category-selective brain areas. An examination of the extant literature reveals no consistent usage for how such overlap is calculated, nor any systematic comparison between different methods. We argue that how ROI overlap is computed, especially the choice of the denominator in the formula, can profoundly affect the results and interpretation of such an analysis. To do this, we compared the overlap of the FFA-FFA (fusiform face area) and FFA-FGA (fusiform Greeble-selective area) in a localizer study testing both Greeble novices and experts. When using a single ROI as the denominator, we found a significant difference in FFA-FFA versus FFA-FGA overlap, consistent with the result of a previous study arguing for face specificity of the FFA [Rhodes, G., Byatt, G., Michie, P. T., & Puce, A. Is the fusiform face area specialized for faces, individuation, or expert individuation? J Cogn Neurosci, 16, 189–203, 2004]. However, these ROI overlap differences disappeared when the denominator combined both of the involved ROIs, and the patterns of such overlap comparisons were dependent on given statistical thresholds. We also found proportionally decreasing FFA-FFA overlap with increasing center-of-FFA distance, resolving an apparent contradiction between the consistency of the location of the FFA and the seemingly low FFA-FFA overlap. Finally, Monte Carlo simulations revealed the most stable formula—the most resistant to ROI size variations—to be the average of the two single-ROI-denominator-based overlap indices. In sum, ROI overlap analysis is not a reliable tool for assessing category specificity, and caution should be exercised with regard to ROI overlap definition, underlying assumptions, and interpretation.
Functional Magnetic Resonance Imaging Evidence for a Hierarchical Organization of the Prefrontal Cortex
Authors: Badre David , D'Esposito Mark 
Published: November 2007

AbstractThe prefrontal cortex (PFC) is central to flexible and organized action. Recent theoretical and empirical results suggest that the rostro-caudal axis of the frontal lobes may reflect a hierarchical organization of control. Here, we test whether the rostro-caudal axis of the PFC is organized hierarchically, based on the level of abstraction at which multiple representations compete to guide selection of action. Four functional magnetic resonance imaging (fMRI) experiments parametrically manipulated the set of task-relevant (a) responses, (b) features, (c) dimensions, and (d) overlapping cue-to-dimension mappings. A systematic posterior to anterior gradient was evident within the PFC depending on the manipulated level of representation. Furthermore, across four fMRI experiments, activation in PFC subregions was consistent with the sub- and superordinate relationships that define an abstract representational hierarchy. In addition to providing further support for a representational hierarchy account of the rostro-caudal gradient in the PFC, these data provide important empirical constraints on current theorizing about control hierarchies and the PFC.
Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells
Authors: Secchiero Paola , Corallini Federica , Rimondi Erika , Chiaruttini Cristina , di Iasio Maria Grazia , Rustighi Alessandra , Del Sal Giannino , Zauli Giorgio 
Published: November 2007

Abstract
It has been shown that the expression of osteoprotegerin (OPG) is up-regulated in tumor-associated endothelial cells as well as in the sera of patients affected by both solid tumors and hematologic malignancies. We now report that sera of p53−/− mice contain higher levels of OPG with respect to p53+/+ mice and that endothelial cells, in which p53 was knocked down by siRNA, release increased levels of OPG with respect to mock-transfected cells. Conversely, activation of the p53 pathway by the MDM2 small molecule antagonist Nutlin-3 significantly attenuated both spontaneous and tumor necrosis factor-α (TNF-α)–induced OPG mRNA and protein release in endothelial cell cultures. OPG promoter functional assays and chromatin immunoprecipitation experiments revealed inhibitory effects of Nutlin-3 on the TNF-α-induced NF-κB DNA binding activity to the OPG promoter. Because OPG inhibits the pro-tumoricidal activity of TNF-related apoptosis-inducing ligand, our findings suggest that, besides its well-documented functions within the malignant cancer cells, the ability of p53 to down-modulate OPG production by endothelial cells may be an additional important mechanism whereby it exerts non–cell-autonomous tumor suppression function.
Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation
Authors: Zhang Linsheng , Fried Florence B. , Guo Hong , Friedman Alan D. 
Published: November 2007

Abstract
RUNX1/AML1 regulates lineage-specific genes during hematopoiesis and stimulates G1 cell-cycle progression. Within RUNX1, S48, S303, and S424 fit the cyclin-dependent kinase (cdk) phosphorylation consensus, (S/T)PX(R/K). Phosphorylation of RUNX1 by cdks on serine 303 was shown to mediate destabilization of RUNX1 in G2/M. We now use an in vitro kinase assay, phosphopeptide-specific antiserum, and the cdk inhibitor roscovitine to demonstrate that S48 and S424 are also phosphorylated by cdk1 or cdk6 in hematopoietic cells. S48 phosphorylation of RUNX1 paralleled total RUNX1 levels during cell-cycle progression, S303 was more effectively phosphorylated in G2/M, and S424 in G1. Single, double, and triple mutation of the cdk sites to the partially phosphomimetic aspartic acid mildly reduced DNA affinity while progressively increasing transactivation of a model reporter. Mutation to alanine increased DNA affinity, suggesting that in other gene or cellular contexts phosphorylation of RUNX1 by cdks may reduce transactivation. The tripleD RUNX1 mutant rescued Ba/F3 cells from inhibition of proliferation by CBFβ-SMMHC more effectively than the tripleA mutant. Together these findings indicate that cdk phosphorylation of RUNX1 potentially couples stem/progenitor proliferation and lineage progression.
Identification of tissue-specific cis-regulatory modules based on interactions between transcription factors
Authors: Yu Xueping , Lin Jimmy , Zack Donald J , Qian Jiang 
Published: November 2007

AbstractBackgroundEvolutionary conservation has been used successfully to help identify cis-acting DNA regions that are important in regulating tissue-specific gene expression. Motivated by increasing evidence that some DNA regulatory regions are not evolutionary conserved, we have developed an approach for cis-regulatory region identification that does not rely upon evolutionary sequence conservation.ResultsThe conservation-independent approach is based on an empirical potential energy between interacting transcription factors (TFs). In this analysis, the potential energy is defined as a function of the number of TF interactions in a genomic region and the strength of the interactions. By identifying sets of interacting TFs, the analysis locates regions enriched with the binding sites of these interacting TFs. We applied this approach to 30 human tissues and identified 6232 putative cis-regulatory modules (CRMs) regulating 2130 tissue-specific genes. Interestingly, some genes appear to be regulated by different CRMs in different tissues. Known regulatory regions are highly enriched in our predicted CRMs. In addition, DNase I hypersensitive sites, which tend to be associated with active regulatory regions, significantly overlap with the predicted CRMs, but not with more conserved regions. We also find that conserved and non-conserved CRMs regulate distinct gene groups. Conserved CRMs control more essential genes and genes involved in fundamental cellular activities such as transcription. In contrast, non-conserved CRMs, in general, regulate more non-essential genes, such as genes related to neural activity.ConclusionThese results demonstrate that identifying relevant sets of binding motifs can help in the mapping of DNA regulatory regions, and suggest that non-conserved CRMs play an important role in gene regulation.
Immobility, inheritance and plasticity of shape of the yeast nucleus
Authors: Hattier Thomas , Andrulis Erik D , Tartakoff Alan M 
Published: November 2007

Abstract

Background
Since S. cerevisiae undergoes closed mitosis, the nuclear envelope of the daughter nucleus is continuous with that of the maternal nucleus at anaphase. Nevertheless, several constitutents of the maternal nucleus are not present in the daughter nucleus. The present study aims to identify proteins which impact the shape of the yeast nucleus and to learn whether modifications of shape are passed on to the next mitotic generation. The Esc1p protein of S. cerevisiae localizes to the periphery of the nucleoplasm, can anchor chromatin, and has been implicated in targeted silencing both at telomeres and at HMR.

Results
Upon increased Esc1p expression, cell division continues and dramatic elaborations of the nuclear envelope extend into the cytoplasm. These "esc apades" include nuclear pores and associate with the nucleolus, but exclude chromatin. Escapades are not inherited by daughter nuclei. This exclusion reflects their relative immobility, which we document in studies of prezygotes. Moreover, excess Esc1p affects the levels of multiple transcripts, not all of which originate at telomere-proximal loci. Unlike Esc1p and the colocalizing protein, Mlp1p, overexpression of selected proteins of the inner nuclear membrane is toxic.

Conclusion
Esc1p is the first non-membrane protein of the nuclear periphery which – like proteins of the nuclear lamina of higher eukaryotes – can modify the shape of the yeast nucleus. The elaborations of the nuclear envelope ("escapades") which appear upon induction of excess Esc1p are not inherited during mitotic growth. The lack of inheritance of such components could help sustain cell growth when parental nuclei have acquired potentially deleterious characteristics.
Global patterns of sequence evolution in Drosophila
Authors: Gallach Miguel , Arnau Vicente , Marín Ignacio 
Published: November 2007

Abstract

Background
Sequencing of the genomes of several Drosophila allows for the first precise analyses of how global sequence patterns change among multiple, closely related animal species. A basic question is whether there are characteristic features that differentiate chromosomes within a species or between different species.

Results
We explored the euchromatin of the chromosomes of seven Drosophila species to establish their global patterns of DNA sequence diversity. Between species, differences in the types and amounts of simple sequence repeats were found. Within each species, the autosomes have almost identical oligonucleotide profiles. However, X chromosomes and autosomes have, in all species, a qualitatively different composition. The X chromosomes are less complex than the autosomes, containing both a higher amount of simple DNA sequences and, in several cases, chromosome-specific repetitive sequences. Moreover, we show that the right arm of the X chromosome of Drosophila pseudoobscura, which evolved from an autosome 10 – 18 millions of years ago, has a composition which is identical to that of the original, left arm of the X chromosome.

Conclusion
The consistent differences among species, differences among X chromosomes and autosomes and the convergent evolution of X and neo-X chromosomes demonstrate that strong forces are acting on drosophilid genomes to generate peculiar chromosomal landscapes. We discuss the relationships of the patterns observed with differential recombination and mutation rates and with the process of dosage compensation.
A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion
Authors: Mitsios Nick , Saka Mohamad , Krupinski Jerzy , Pennucci Roberta , Sanfeliu Coral , Wang Qiuyu , Rubio Francisco , Gaffney John , Kumar Pat , Kumar Shant , Sullivan Matthew , Slevin Mark 
Published: November 2007

Abstract

Background
Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain.

Results
Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11.

Conclusion
Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.
Expression of a Cu,Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of neuroblastoma cells to infectious injury
Authors: Goos Miriam , Zech Wolf-Dieter , Jaiswal Manoj Kumar , Balakrishnan Saju , Ebert Sandra , Mitchell Timothy , Carrì Maria Teresa , Keller Bernhard U , Nau Roland 
Published: November 2007

AbstractBackgroundInfections can aggravate the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in the anti-oxidant enzyme Cu,Zn superoxide dismutase (EC 1.15.1.1, SOD1) are associated with familial ALS. Streptococcus pneumoniae, the most frequent respiratory pathogen, causes damage by the action of the cholesterol-binding virulence factor pneumolysin and by stimulation of the innate immune system, particularly via Toll-like-receptor 2.MethodsSH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 were both exposed to pneumolysin and in co-cultures with cultured human macrophages treated with the Toll like receptor 2 agonist N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine × 3 HCl (Pam3CSK4). Cell viability and apoptotic cell death were compared morphologically and by in-situ tailing. With the help of the WST-1 test, cell viability was quantified, and by measurement of neuron-specific enolase in the culture supernatant neuronal damage in co-cultures was investigated. Intracellular calcium levels were measured by fluorescence analysis using fura-2 AM.ResultsSH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam3CSK4than SH-SY5Y cells transfected with wild-type human SOD1. The enhanced pneumolysin toxicity in G93A-SOD1 neuronal cells depended on the inability of these cells to cope with an increased calcium influx caused by pores formed by pneumolysin. This inability was caused by an impaired capacity of the mitochondria to remove cytoplasmic calcium. Treatment of G93A-SOD1 SH-SY5Y neuroblastoma cells with the antioxidant N-acetylcysteine reduced the toxicity of pneumolysin.ConclusionThe particular vulnerability of G93A-SOD1 neuronal cells to hemolysins and inflammation may be partly responsible for the clinical deterioration of ALS patients during infections. These findings link infection and motor neuron disease and suggest early treatment of respiratory infections in ALS patients.