bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Resolution T2 Association Tests of Complex Diseases Based on Family Data
Authors: Fan Ruzong , Knapp Michael , Wjst Matthias , Zhao Caixia , Xiong Momiao 
Published: November 2005

SummaryThis paper proposes family based Hotelling's T2 tests for high resolution linkage disequilibrium (LD) mapping or association studies of complex diseases. Assume that genotype data of multiple markers or haplotype blocks are available for a sample of nuclear families, in which some offspring are affected. Paired Hotelling's T2 test statistics are proposed for a high resolution association study using parents as controls for affected offspring, based on two coding methods: haplotype/allele coding and genotype coding. The paired Hotelling's T2 tests take not only the correlation between the haplotype blocks or markers into account, but also take the correlation within each parent‐offspring pair into account. The method extends two sample Hotelling's T2 test statistics for population case control association studies, which are not valid for family data due to correlation of genetic data among family members. The validity of the proposed method is justified by rigorous mathematical and statistical proof under the large sample theory. The non‐centrality parameter approximations of the test statistics are calculated for power and sample size calculations. From power comparison and type I error calculations, it is shown that the test statistic based on haplotype/allele coding is advantageous over the test statistic of genotype coding. Analysis using multiple markers may provide higher power than single marker analysis. If only one marker is utilized the power of the test statistic based on haplotype/allele coding is nearly identical to that of 1‐TDT. Moreover, a permutation procedure is provided for data analysis. The method is applied to data from a German asthma family study. The results based on the paired Hotelling's T2 statistic tests confirm the previous findings. However, the paired Hotelling's T2 tests produce much smaller P‐values than those of the previous study. The permutation tests produce similar results to those of the previous study; moreover, additional marker combinations are shown to be significant by permutation tests. The proposed paired Hotelling's T2 statistic tests are potentially powerful in mapping complex diseases. A SAS Macro, Hotel_fam.sas, has been written to implement the method for data analysis.
The Internet, Organisational Change and Community Engagement: The Case of Birmingham City Council
1
Authors: Goodwin Ian 
Published: November 2005

Abstract
This article examines the extent to which the implementation of Internet technology by Birmingham City Council (BCC) is facilitating new forms of engagement with the communities it serves. The case study presented reveals BCC to be an organisation in complex, conflict‐ridden transition. Networked uses of Internet technologies have resulted in shifts being made towards a new form of ‘citizen‐facing’ organisation. However older, more traditional forms of hierarchical command and control persist. These are being sustained, in part, by adaptive uses of the same technologies that facilitate networking. Ultimately, this situation limits the extent to which new forms of community engagement have been achieved.
An Ethno‐linguistic Approach to the Role of Services in Knowledge Transfer: The Case of the Innovation Relay Centre of Southern Italy
1
Authors: Quatraro Francesco 
Published: November 2005

Abstract
Given the recent resurgence of interest in the economics of language, this paper develops an original model addressing the issue of services role in knowledge transfer by merging economic literature regarding services and technology transfer with linguistic and semiotic theories. The heuristic virtues of the model are then tested by analyzing the case of the Innovation Relay Centre (IRC) of the Apulian region in Southern Italy. This choice was due both to the strong presence in the region of small and medium sized enterprises, and to the well known lack of social capital among local firms. The model has proved to be effective in explaining IRC activity. Moreover it has allowed for the identification of strengths and weaknesses which could be useful for the elaboration of future innovation policies.
Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients
Authors: Hillemacher Thomas , Bayerlein Kristina , Wilhelm Julia , Reulbach Udo , Frieling Helge , Bönsch Dominikus , Kornhuber Johannes , Bleich Stefan 
Published: November 2005

AbstractDopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (‐EW: day 0 or day 1) and late withdrawal (‐LW: day 7–day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS‐EW: r =−0.607, p =0.001; OCDS‐LW: r =−0.730, p2 =0.530; OCDS‐LW: F =17.091, p2 =0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic–pituitary–adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.
Dextromethorphan psychosis, dependence and physical withdrawal
Authors: Miller Shannon 
Published: November 2005

AbstractAs part of a synthesis of evidence regarding the abuse and addiction liability of dextromethorphan (DM), an over‐the‐counter cough medicine available in over 140 preparations, an uncommonly published case of dextromethorphan dependence (addiction) is described, with specific, rarely published complications. The individual was interviewed and several medical databases were also reviewed (Medline, 1966–present; PubMed) for all content relating to the Keywords: dextromethorphan, abuse, dependence, cough medicine, addiction, withdrawal, psychosis. The patient evidenced history suggesting substance dependence, substance‐induced psychosis and substance withdrawal in relation to DM. A literature review revealed that DM has specific serotonergic and sigma‐1 opioidergic properties. Dextrorphan (DOR), the active metabolite of DM, has similar properties; however, DOR is a weaker sigma opioid receptor agonist, and a stronger NMDA receptor antagonist. DM and DOR display specific biological features of addiction, and are capable of inducing specific psychiatric sequelae. A specific, reproducible toxidrome with significant psychiatric effects occurred, when DM was abused at greater than indicated doses, with more profound and potentially life‐threatening effects at even higher doses. DM withdrawal appears evident. DM's active metabolite, DOR, has pharmacodynamic properties and intoxication effects similar to dissociatives, and may be more responsible for the dissociative effect that this DM abuser sought. However, it is this same metabolite that may be fraught with the potentially life‐threatening psychoses and dissociative‐induced accidents, as well as addiction. While DM has been hypothesized as the most commonly abused dissociative, health‐care providers seem largely unaware of its toxidrome and addiction liability.
Concentration changes of methanol in blood samples during an experimentally induced alcohol hangover state
Authors: Woo Young‐Sup , Yoon Su‐Jung , Lee Hae‐Kook , Lee Chang‐Uk , Chae Jeong‐Ho , Lee Chung , Kim Dai‐Jin 
Published: November 2005

AbstractA hangover is characterized by the unpleasant physical and mental symptoms that occur between 8 and 16 hours after drinking alcohol. After inducing experimental hangover in normal individuals, we measured the methanol concentration prior to and after alcohol consumption and we assessed the association between the hangover condition and the blood methanol level. A total of 18 normal adult males participated in this study. They did not have any previous histories of psychiatric or medical disorders. The blood ethanol concentration prior to the alcohol intake (2.26?2.08) was not significantly different from that 13 hours after the alcohol consumption (3.12?2.38). However, the difference of methanol concentration between the day of experiment (prior to the alcohol intake) and the next day (13 hours after the alcohol intake) was significant (2.62?1.33/l vs. 3.88?2.10/l, respectively). A significant positive correlation was observed between the changes of blood methanol concentration and hangover subjective scale score increment when covarying for the changes of blood ethanol level (r =0.498, p
Protective effect of cyclooxygenase‐2 (COX‐2) inhibitors but not non‐selective cyclooxygenase (COX)‐inhibitors on ethanol withdrawal‐induced behavioural changes
Authors: Dhir Ashish , Naidu Pattipati , Kulkarni Shrinivas 
Published: November 2005

AbstractCyclooxygenase (COX) is reported to play a significant role in neurodegeneration. Recent studies have shown that chronic ethanol administration up‐regulates cyclooxygenase expression. In the present study we examined the effect of nimesulide (a preferential COX‐2 inhibitor), rofecoxib (a highly selective COX‐2 inhibitor) or naproxen (a non‐selective COX‐inhibitor displaying high affinity towards the COX‐1 isoenzyme) on alcohol‐induced withdrawal symptoms. Mice were made physically dependent on alcohol by the chronic administration of ethanol (2g/kg of 10% v/v), intragastrically, twice on day 1 and then once‐daily on successive days for a total of 7 days. Nimesulide [2.5mg/kg, intraperitoneally (i.p.)], rofecoxib (2mg/kg, i.p.) or naproxen (7mg/kg, i.p.) were administered daily for 7 days before administering alcohol intragastrically. After 24 hours of the last alcohol administration, the treatments were reversed and the mice were tested for withdrawal, so that the animals that had received COX‐inhibitors followed 30 minutes later by ethanol on days 1–7 were challenged with saline. Similarly, the animals which received saline followed 30 minutes later by ethanol received only saline. Behavioural analysis revealed hyperlocomotor activity, increased anxious response and increased hyperalgesia in mice. Also, alcohol withdrawal decreased the threshold for Pentylenetetrazole‐(PTZ)‐induced convulsions. Pretreatment with COX‐inhibitors rofecoxib (2mg/kg, i.p.) or nimesulide (2.5mg/kg, i.p.) displayed significant protection against ethanol‐induced withdrawal symptoms, while naproxen (7mg/kg, i.p.) was not effective in reversing alcohol‐induced withdrawal symptoms. The results of the present study suggest strongly the possible role of cyclooxygenases, particularly COX‐2 inhibitors, on ethanol‐induced withdrawal symptoms and the potential use of COX‐2 inhibitors in their prevention and treatment.
Khat (Catha edulis)—an updated review
Authors: Al‐Hebshi Nezar , Skaug Nils 
Published: November 2005

AbstractThe habit of chewing fresh leaves and twigs of khat (Catha edulis) for their stimulating amphetamine‐like effects is highly prevalent in East Africa and southwest on the Arabic peninsula. There is an extensive literature on khat providing information about its history, botany, production, geographical distribution, chemistry and pharmacology, and exploring the social, economic, medical, psychological and oral aspects related to its use. Some of this literature dates as early as the 11th century; however, most of it appeared after the first scientific description of khat by Peter Forskal in 1775. This review provides a panorama of khat and the various aspects of its use. A non‐technical description of the plant chemistry and pharmacology is included. The medical, psychological and oral aspects are emphasized, and the current knowledge about the microbiological effects of khat is also presented.
Polar Localizing Class V Myosin Chitin Synthases Are Essential during Early Plant Infection in the Plant Pathogenic FungusUstilago maydis
Authors: Weber Isabella , Aßmann Daniela , Thines Eckhard , Steinberg Gero 
Published: November 2005

AbstractFungal chitin synthases (CHSs) form fibers of the cell wall and are crucial for substrate invasion and pathogenicity. Filamentous fungi contain up to 10 CHSs, which might reflect redundant functions or the complex biology of these fungi. Here, we investigate the complete repertoire of eight CHSs in the dimorphic plant pathogen Ustilago maydis. We demonstrate that all CHSs are expressed in yeast cells and hyphae. Green fluorescent protein (GFP) fusions to all CHSs localize to septa, whereas Chs5-GFP, Chs6-GFP, Chs7-yellow fluorescent protein (YFP), and Myosin chitin synthase1 (Mcs1)-YFP were found at growth regions of yeast-like cells and hyphae, indicating that they participate in tip growth. However, only the class IV CHS genes chs7 and chs5 are crucial for shaping yeast cells and hyphae ex planta. Although most CHS mutants were attenuated in plant pathogenicity, Δchs6, Δchs7, and Δmcs1 mutants were drastically reduced in virulence. Δmcs1 showed no morphological defects in hyphae, but Mcs1 became essential during invasion of the plant epidermis. Δmcs1 hyphae entered the plant but immediately lost growth polarity and formed large aggregates of spherical cells. Our data show that the polar class IV CHSs are essential for morphogenesis ex planta, whereas the class V myosin-CHS is essential during plant infection.
Relay ramp evolution and mass flow deposition (Upper Kimmeridgian–Lower Volgian) in the Tail End Graben, Danish North Sea
Authors: Bruhn Rikke , Vagle Kåre 
Published: November 2005

ABSTRACTThe Central Graben in the Danish North Sea sector consists of a series of N–S to NW–SE trending, eastward‐tilted half‐grabens, bound to the east by the Coffee Soil Fault zone. This fault zone has a complex Jurassic history that encompasses at least two fault populations; N–S to NNW–SSE striking faults active in the Late Aalenian–Early Oxfordian, and NNW–SSE to WNW–ESE striking faults forming in Late Kimmeridgian time (sensu gallico), following a short period of tectonic quiescence. Sediment transport across the Coffee Soil Fault zone was controlled by fault array evolution, and in particular the development of relay ramps that formed potential entry points for antecedent drainage systems from the Ringkøbing–Fyn High east of the rift. Fault and isochore trends of the Upper Kimmeridgian–Lower Volgian succession in the northeast Danish Central Graben show that accommodation space was initially generated close to several minor, isolated or overlapping faults. Subsidence became focused along a few master faults in the Early Volgian through progressive linkage of selected faults. Seismic time isochore geometries, seismic facies, amplitude trends and well ties indicate the presence of coarse clastic lithologies locally along the fault zone. The deposits probably represent submarine mass flow deposits supplied from footwall degradation and possibly also from the graben hinterland via a relay ramp. The latter source appears to have been cut off as the relay ramp was breached and the footwall block are uplifted. Fault growth and linkage processes thus controlled the spatial and temporal trends of accommodation space generation and sediment supply to the rift basin.
Construction of detrital mineral populations: insights from mixing of U–Pb zircon ages in Himalayan rivers
Authors: Amidon William H. , Burbank Douglas W. , Gehrels George E. 
Published: November 2005

ABSTRACTFission‐track, U–Pb and Pb–Pb analyses of detrital heavy mineral populations in depositional basins and modern river sediments are widely used to infer the exhumational history of mountain belts. However, relatively few studies address the underlying assumption that detrital mineral populations provide an accurate representation of their entire source region. Implicit in this assumption is the idea that all units have equal potential to contribute heavy minerals in proportion to their exposure area in the source region. In reality, the detrital mineral population may be biased by variable concentrations of minerals in bedrock and differential erosion rates within the source region. This study evaluates the relative importance of these two variables by using mixing of U–Pb zircon ages to trace zircon populations from source units, through the fluvial system, and into the foreland.The first part of the study focuses on the Marsyandi drainage in central Nepal, using tributaries that drain single formations to define the U–Pb age distributions of individual units and using trunk river samples to evaluate the relative contributions from each lithology. Observed mixing proportions are compared with proportions predicted by a simple model incorporating lithologic exposure area and zircon concentration. The relative erosion rates that account for the discrepancy between the observed and predicted mixing proportions are then modelled and compared with independent erosional proxies. The study also compares U–Pb age distributions from four adjacent drainages spanning ∼250 km along the Himalayan front using the Kolmogorov–Smirnov statistic and statistical estimates of the proportion of zircon derived from each upstream lithology. Results show that, along this broad swath of rugged mountains, the U–Pb age distributions are remarkably similar, thereby allowing data from more localized sources to be extrapolated along strike.
Seal capacity estimation from subsurface pore pressures
Authors: Nordgård Bolås Hege M. , Hermanrud Christian , Teige Gunn M. G. 
Published: November 2005

ABSTRACTA cap rock's capacity to seal hydrocarbons depends on its wettability and the sizes of the pore throats within the interconnected pore system that the leaking hydrocarbons must penetrate. These critical pore throat sizes are often poorly constrained in hydrocarbon exploration, partly because measurements of pore throat sizes have not been performed, and partly because pore throat measurements on a few individual samples in the cap rock may not be representative for the seal capacity of the top seal as a whole.To the contrary, the presence of formation overpressure can normally be estimated in drilled exploration targets. The presence of overpressure in reservoirs testifies to small pore throats in the cap rocks, as large pore throats will result in sufficiently high cap rock permeability to bleed off the overpressure.We suggest a stepwise procedure that enables quantification of top seal capacities of overpressured traps, based on subsurface pressure information. This procedure starts with the estimation of cap rock permeabilities, which are consistent with observed overpressure gradients across the top seals. Knowledge of burial histories is essential for these estimations. Relationships between pore throat size and permeability from laboratory experiments are then applied to estimate critical pore throat diameters in cap rocks. These critical pore throat diameters, combined with information of the physical properties of the pore fluids, are then used to calculate membrane seal capacity of cap rocks.Estimates of top seal capacity based on this procedure are rather sensitive to the vertical fluid velocity, but they are also to some extent sensitive to inaccuracies of the pore throat/permeability relationship, overpressure gradient, interfacial tensions between pore fluids, hydrocarbon density and water viscosity values. Despite these uncertainties, applications of the above‐mentioned procedure demonstrated that the mere presence of reservoir overpressures testifies to sufficient membrane seal capacity of cap rocks for most geological histories. Exempt from this statement are basins with rapid and substantial sediment compaction in the recent past.
P210 Bcr‐abl tyrosine kinase interaction with histone deacetylase 1 modifies histone H4 acetylation and chromatin structure of chronic myeloid leukaemia haematopoietic progenitors
Authors: Brusa Gianluca , Zuffa Elisa , Mancini Manuela , Benvenuti Michela , Calonghi Natalia , Barbieri Enza , Santucci Maria Alessandra 
Published: November 2005

SummaryThe BCR‐ABL fusion gene, originating from the balanced (9;22) translocation, is the molecular hallmark and the causative event of chronic myeloid leukaemia (CML). The interactions of its p210 protein constitutively activated and improperly confined to the cytoplasm with multiple regulatory signals of cell cycle progression, apoptosis and self‐renewal, induce the illegitimate enlargement of clonal haematopoiesis and genetic instability that drives its progression towards the fully transformed phenotype of blast crisis. However, its effects on the basic transcription machinery and chromatin remodelling are unknown. Our study underscored histone H4 hyperacetylation associated with p210 tyrosine kinase in vitro and in vivo and its role in BCR‐ABL transcription. Histone H4 hyperacetylation proceeds, at least partly, from the ‘loss of function’ of histone deacetylase 1 protein, a critical component of Rb‐mediated transcriptional repression, in consequence of its cytoplasmatic compartmentalisation.
Tissue factor pathway inhibitor anticoagulant activity: risk for venous thrombosis and effect of hormonal state
Authors: Dahm Anders , R. Rosendaal Frits , Andersen Trine O. , Sandset Per M. 
Published: November 2005

SummaryFull‐length tissue factor pathway inhibitor (TFPI) is assumed to be biologically more important than truncated TFPI because of its stronger anticoagulant effect in the diluted prothrombin time (dPT) assay. We have developed a dPT‐based assay for TFPI anticoagulant activity. Here, we report the effect of hormonal state on TFPI anticoagulant activity and whether TFPI anticoagulant activity assesses the risk for deep‐vein thrombosis (DVT) better than conventional TFPI assays. We undertook a case‐control study of 474 patients with DVT and 474 controls and compared the odds ratio (OR) for DVT for those with low TFPI anticoagulant activity with the ORs obtained for TFPI free and total antigen, and TFPI chromogenic substrate activity. Hormonal state affected clot time in dPT, but this effect was ameliorated by anti‐TFPI antibodies. Low TFPI anticoagulant activity gave an OR of 1·5 (0·97–2·1) for DVT, similar to the ORs obtained with conventional TFPI assays, ranging from 1·2 to 1·4. Individuals low in both the activity assays obtained an OR of 5·9 (1·7–20). We concluded that the effect of hormonal state on dPT was mediated through TFPI, and a dPT‐based assay of TFPI anticoagulant activity did not assess the risk for DVT better than conventional TFPI assays.