bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognising Humanity
Authors: HALDANE JOHN
Published: October 2008

abstract  Martha Nussbaum's Hiding from Humanity, links the philosophical understanding of emotion with important issues in ethics, law and political philosophy, and engages with empirical material in a manner that provides a model for open and practically oriented moral philosophy. Here I explore four areas in which I believe the discussion now needs to be carried forward. First, the connections between Nussbaum's work and other contributions to recent moral philosophy, principally that of Alasdair MacIntyre in Dependent Rational Animals (1999) but also that of David Wiggins in Ethics (2006). Second, the conceptual understanding of notions of disability, impairment and normal human functioning, and the standards against which these are determined and judged. Third, the nature of mental disorder and the harm done to sufferers by the stigma attaching to it. Fourth, the implications of following Nussbaum's lead in recognising humanity in the vulnerable, as these bear upon ‘ending life’ issues, especially that of abortion. Nussbaum's book serves to orient readers towards a cluster of important philosophical issues and specific policy areas; but it also raises questions that she might now wish to consider further.
Five‐Year Evaluation of Lifecore Restore® Implants: A Retrospective Comparison with Nobel Biocare MK II® Implants
Authors: Kallus Thomas , Bessing Christer , Homsi George , Eklund Inger
Published: October 2008

Purpose: The purpose of this study was to compare survival rates and marginal bone resorption of the Lifecore (LC) Restore® Implant System with the benchmark Nobel Biocare (NB) MK II® Implant System.

Materials and Methods: All implants were inserted by the same surgeon and all radiological analyses were performed by the same radiologist. Two hundred ninety LC implants were analyzed radiologically after 1 year and compared with the same number of NB implants serving as a historical reference group. After 5 years, 200 LC implants could be compared with 224 NB implants. Each implant was monitored for exposed threads, as compared with the baseline registrations.

Results: No significant differences were found between the two implant systems regarding survival rates (LC 100% and NB 99.2%). Considering the findings of this study, the two implant systems compared might be regarded as clones. Nevertheless, because of dissimilar onset of threads, about 1 mm more implant‐retaining bone anchorage is gained with the Lifecore Restore Implants as compared with NB MK II Implants.

Conclusions: Based on the assumption that >3 exposed NB threads correspond to >4 exposed LC threads, significantly more bone loss (p < .01) could be demonstrated for the NB implants after 5 years. Thus, it may be justified to consider the differences in implant design to have a decisive clinical relevance.
Engineered Security Measures of Nuclear Power Plants
Authors: Moody F. J.
Published: October 2008

Even in the absence of depraved terrorist threats, nuclear plants have been designed to respond safely to postulated accidents. Redundant safety features are built into plants to trigger safe shutdown and containment of possible accidents. The defined accidents range from minor leakage and operator errors to a complete loss of coolant from the reactor. Post-accident scenarios are postulated by experts in reactor and containment thermal-hydraulics, and all other sciences embraced by nuclear power plant design. The probability of failure is determined for all engineered safety systems. Then analytical and experimental programs are employed to predict the long term post-accident thermal-hydraulic state of a plant and its effect on the environment. The postulated accidents and safety system responses include effects resulting from mechanical damage and component malfunctions, such as pipe ruptures and the failure of pumps and valves. The initiating causes can be material failure, human error, and environmental effects from earthquakes, floods, and other severe acts of nature. It is prudent to build on an already established safety and accident technology to include the effects of external, planned attacks on a nuclear plant. This process includes “matching wits” with the minds of those who plot evil, and reinforcing protective security barriers where potential vulnerabilities are detected. Hard questions to ask and answer are, “What are the greatest potential security threats to a nuclear power plant? What possible human activity could make them happen? How can they be prevented?” Reactor and containment thermal-hydraulics contributes significantly to answering these questions.
Effect of Blend Radius on Stress Concentration Factor of Crossbored Holes in Thick Walled Pressure Vessels
Authors: Peters Daniel T.
Published: October 2008

Many studies have been performed on the effect of stress concentration factor in thick walled cylinders caused by holes drilled to the wall perpendicular to the vessel ID, commonly called crossbores. Recent developments in FEA analysis and computer technology have allowed detailed analysis in their effect on the stresses in pressure vessels. This allows the reevaluation of many theories developed in the past. The following is a study of how applying a blend radius to the inside intersection of a vessel bore and a crossbore affects the stresses in vicinity of the hole and the stress concentrations developed near the hole.
An Experimental Investigation on Self-Loosening of Bolted Joints
Authors: Jiang Yanyao , Zhang Ming , Park Tae-Won , Lee Chu-Hwa
Published: October 2008

The self-loosening process of a bolted joint consists of two distinct stages. The early stage of self-loosening is due to the cyclic plastic deformation of the materials. The second stage of self-loosening is characterized by the backing off of the nut. The current study is concentrated on the experimental investigation of the second stage of self-loosening with the aim to explore the mechanisms responsible for the phenomenon. Over a hundred bolted joints were experimentally tested using a specially designed testing apparatus. M12×1.75 bolts and nuts were used. The experiments mimicked two plates jointed by a bolt and a nut and were subjected to cyclic transverse shear loading. During an experiment, the relative displacement between the two clamped plates, denoted by δ, was a control parameter. The clamping force, the relative rotation between the nut and the bolt, and the applied transverse load were monitored and recorded for each loading cycle. For a given preload, the relationship between, Δδ/2, the amplitude of the relative displacement between the two clamped plates, and, NL, the number of loading cycles to loosening followed a pattern similar to a fatigue curve. There existed an endurance limit below which self-loosening would not persist. A larger preload resulted in a larger endurance limit. However, a large preload increased the possibility for the bolt to fail in fatigue. It was found that the surface condition, which influenced the friction coefficient, had a significant influence on self-loosening resistance. The results also reveal that the use of a regular nut is superior to the use of a flange nut in terms of self-loosening resistance. An “endurance diagram” concept was developed that can be used directly for the design and evaluation of the bolted joints.
Achieving a Leak Free Start Up: Impossible Dream or Achievable Project?
Authors: McQuillan Kevin W. , Milne Gary L. , Smith Gavin
Published: October 2008

Large petrochemical plants are shutdown periodically for maintenance and inspection. During the shutdowns a large number of gasketted joints are dismantled in order to gain access to the equipment, and subsequently remade at the end of the shutdown. In order to ensure the integrity of the pressure envelope, the plant systems are leak tested with high-pressure nitrogen prior to the introduction of hydrocarbons. If leaks from gasketted joints are discovered during this process, it becomes necessary to de-pressure the systems in order that the joints can be remade. During the 1990 Shutdown of the Huntsman Olefins6 plant at Wilton, approximately 200 gasketted joints were required to be remade during leak testing. This caused significant and costly delays to the start up of the plant. Later analysis showed that the leaks were the result of poor standards in the making and checking of the gasketted joints. A new joint making procedure was written for the 1993 and 1997 shutdowns, and this included a requirement for joints to be traceable by a tagging system to the technician who made the joint. The number of remakes reduced dramatically, to approximately 10 in each of the two shutdowns. In preparation for the 2002 shutdown engineers at Wilton set a target of achieving ZERO remakes during leak testing after the shutdown. This was a great challenge, especially given that approximately 7000 joints were to be remade by 400 technicians. The project was developed in partnership with Hedley Purvis Limited, who supplied design services for calculating residual bolt loads, and Klinger UK Limited, who supplied gaskets for use during the shutdown. The Olefins Joint Making procedure was further developed, requiring full traceability and the use of controlled tightening of joints to a pre-defined load. Great emphasis was placed on the role of people in effective joint making, and in ensuring that each technician was carefully briefed and validated in his understanding of the importance to the business of high standards in joint making. A training video was prepared to help in the process of gaining the understanding and involvement of the technicians and their supervisors. Hedley Purvis and Klinger supported Huntsman in the development of the video, and in the delivery of the training and validation exercise. The project was a great success, and resulted in the first “leak free” start up of the Olefins6 plant. The paper will described the project in detail, and will include a showing of the training video.
Effects of Scatter in Bolt Preload of Pipe Flange Connections With Gaskets on Sealing Performance
Authors: Sawa Toshiyuki , Matsumoto Mitsuhiro , Nagata Satoshi
Published: October 2008

It has been well known that a scatter in axial bolt forces of pipe flange connections tightened by the torque control method is substantial. It is necessary for evaluating the sealing performance of the pipe flange connections with the gaskets subjected to intemal pressure to know the contact gasket stress distributions due to the scatter of the axial bolt forces in the connections tightened by the torque control method. This paper deals with the leakage of the pipe flange connections with a spiral wound gasket and that with a compressed sheet gasket tightened by the torque control method. The scatter in the axial bolt forces was measured in the experiments. The contact gasket stress distributions at the interfaces of the pipe flange connections with the gaskets were calculated under the measured axial bolt forces by using elasto-plastic finite element method (FEM) taking into account hysteresis and non-linearity in the stress-strain curves of the gaskets. The effects of the scatter in the axial bolt forces tightened by the torque control method on the gas leakage were also examined by using the actual pipe flange connections. As the result, a difference in an amount of gas leakage measured was found to be substantial between our study and PVRC procedure. By using the calculated contact gasket stress distributions under the internal pressure and the results of the leakage tests, the sealing performance was evaluated. It is found that the sealing performance is worse in the actual pipe flange connection than that evaluated by PVRC procedure.
Limit States Design—A Probabilistic Study
Authors: Allen D. E.
Published: October 2008

Canadian structural standards for buildings are moving toward a unified limit states philosophy with common safety and serviceability criteria for all materials and types of construction. Structural steel and cold formed steel will have limit states design rules by 1975 and concrete, masonry, and wood will follow later.This paper compares the new rules with existing NBC/CSA requirements on the basis of probability of failure calculated by simplified theory. The main emphasis is on load combinations of dead, floor, and wind loads for office and residential buildings where failure occurs by yielding of steel. Other aspects of the new limit states design rules—column formula for structural steel, performance factors for composite structures, the importance factor which reflects the seriousness of failure, and safety factors during construction, are also considered.The results indicate that the new rules provide more consistent safety than existing rules for different combinations of loads and materials; and that simple rules are sufficiently accurate, keeping in mind the predominating influence of human error on failures and the simplifications used in analyzing complex building structures.
Dikes on permafrost foundations in northern Manitoba
Authors: Macpherson J. G. , Watson G. H. , Koropatnick A.
Published: October 2008

The development of hydro-electric power within the areas of low relief of northern Canada often requires long dikes to impound a reservoir. Much of this region lies within a zone of discontinuous permafrost, and dike design must allow for foundations varying from soft alluvial materials which will settle during or shortly after construction, to frozen strata with a high ice content which will settle as the ice thaws due to heat loss from the reservoir.This paper describes the approach to design and construction of dikes for the Kettle Generating Station in northern Manitoba, and includes a description of the instrumentation installed in an attempt to correlate the relationship between the rate of thawing of the permafrost and the rate of drainage of free water from the foundation.
AN INTELLIGENT AGENT MOBILE EMISSIONS MODEL FOR URBAN ENVIRONMENTAL MANAGEMENT
Authors: WU C. Z. , YAN X. P. , HUANG G. H. , LI Y. P.
Published: October 2008

In this study, we developed a microcosmic mobile emissions model based on an intelligent agent model of vehicles. The intelligent agent was first introduced into a micro-traffic flow system. Individual differences in driver behavior were considered, and the theory of probability was applied to reflect the distribution of drivers' stochastic characteristic dispositions. Each vehicle expressed its intelligence through its own character by perceiving the leading vehicle. From an operational perspective, differences in drivers' dispositions were reflected by a weighted coefficient. Finally, a hybrid microcosmic mobile emissions model was proposed. Its coefficients were determined using traffic data and experiments. Because it addresses more aspects of the car-following process, this model is theoretically superior to previous models, as verified by a numerical simulation. The proposed model was applied to a case study of the emissions from ten vehicles in an urban setting. The model effectively estimated mobile emissions rates. The results indicate that the model can reflect individual differences among drivers and demonstrate that reckless drivers generate more emissions.
A mid-Cretaceous age for the Palmer Land event, Antarctic Peninsula: implications for terrane accretion timing and Gondwana palaeolatitudes
Authors: VAUGHAN ALAN P. M. , PANKHURST ROBERT J. , FANNING C. MARK
Published: October 2008

New structural and age data suggest that West Gondwana may have been at lower palaeolatitudes than previously interpreted from Albian sequences in Gondwana marginal suspect terranes. The Palmer Land event, which juxtaposed Mesozoic terranes on the Gondwana margin, deformed granitoids in the southern Antarctic Peninsula. U–Pb SHRIMP dating of zircons from a microgranite dyke yields a crystallization age of 106.9± 1.1 Ma. This result and re-interpretation of the structural position of another granite pluton date the Palmer Land event, and probable terrane collision, as late Early Cretaceous, and not latest Jurassic as formerly interpreted.
Growth and linkage of the East Tanka fault zone, Suez rift: structural style and syn-rift stratigraphic response
Authors: JACKSON CHRIS A.-L. , GAWTHORPE ROB L. , SHARP IAN R.
Published: October 2008

Abstract: An integrated tectono-stratigraphic analysis of the East Tanka fault zone, Suez rift, indicates fault growth by linkage of initially isolated fault segments that is consistent with fault growth models based on displacement–length (D-L) scaling laws. During the initial 2.4 Ma of rifting, the East Tanka fault zone was composed of two en-echelon fault segments
c.
1–1.5 km long, separated by a hanging-wall intrabasin high that controlled the geometry of depocentres filled with continental deposits. Alluvial fan conglomerates were fed through the region between the two fault segments, and form a discrete coarse-grained body, preserved in the immediate hanging wall of the fault zone. Subsequent stratigraphic patterns indicate that the two faults hard-linked to form a single fault zone
c.
3.5 km long. Hard linkage of the segments resulted in migration of the zone of maximum displacement and subsidence into the zone of linkage. Uplift due to the migration of activity caused modification of drainage in the footwall of the fault zone that terminated the growth of the alluvial fan. This study demonstrates the need to integrate structural and stratigraphic data when attempting to reconstruct the temporal and spatial evolution of normal fault zones. Additionally, the fault dynamics illustrated have implications for tectono-stratigraphic models of rift basins, and syn-rift stratigraphic evolution.
The weak and superfast Cretan detachment, Greece: exhumation at subduction rates in extruding wedges
Authors: RING U. , REISCHMANN T.
Published: October 2008

Low-angle normal faults (detachments) are only efficient agents for bringing rocks from 40–>100 km depth back to the Earth’s surface if they operate with extreme slip rates exceeding 20 km Ma
−1
. Here we propose a slip rate of ≧20–30 km Ma
−1
for the Cretan detachment in the Aegean, Greece. The Cretan detachment and the subjacent subduction thrust bounded an extruding wedge above the Miocene Hellenic subduction zone. During exhumation the high-pressure rocks in the wedge were not significantly deformed. Very low shear coupling at the bounding faults (which are therefore weak) is needed to prevent significant deformation in the extruding wedge. The proposed slip rate of ≧20–30 km Ma
−1
is similar to the subduction rate of 35–45 km Ma
−1
at the Hellenic subduction zone. We argue that extruding wedges can only slip at rates similar to subduction rates if there is very low shear coupling at the bounding faults, which may also explain the paradox of almost non-deformed but very rapidly exhumed rocks.
Extension, crustal structure and magmatism at the outer Vøring Basin, Norwegian margin
Authors: Gernigon L. , Ringenbach J.C. , Planke S. , Gall B.Le , Jonquet-KolstØ H.
Published: October 2008

Regional analysis of new 2D and 3D multichannel seismic data has improved interpretation of the crustal configuration and structural style along the Norwegian margin. Five domains with different structural styles and evolutions are defined along the outer Vøring Basin: (1) the Nyk High–Naglfar Dome; (2) the north Gjallar Ridge; (3) the Gleipne saddle; (4) the south Gjallar Ridge; (5) the Rån ridge. Early Campanian–Early Paleocene and Early to mid-Cretaceous extensional events are evidenced. Timing of deformation and structural styles observed along each segment reflect a lateral variation of the rifted system, probably affected by magma-tectonic processes. Correlation with the deep structures of the outer Vøring Basin shows that the shallow structure in that basin is directly controlled by a deep-seated, strong, high-amplitude reflection (the T reflection), marking the top of a high-velocity body (
V
p
>7 km s
−1
). The relation between the lower-crustal architecture and the subsurface basin structures has implications for the margin evolution and for the nature of the high-velocity body.
Granite laccolith emplacement in the Iberian arc: AMS and gravity study of the La Tojiza pluton (NW Spain)
Authors: Aranguren A. , Cuevas J. , TubÍa J.M. , RomÁn-Berdiel T. , Casas-Sainz A. , Casas-Ponsati A.
Published: October 2008

A laccolithic geometry is inferred from geological and geophysical data for the La Tojiza granitic body emplaced in an extensional regime. Nearly circular in outcrop, this 16 km diameter pluton, one of the so-called ‘post-tectonic granodioritic plutons’ of Galicia, is located in the northern Variscan arc of Iberia, within the Mondoñedo Nappe (Western Asturian–Leonese Zone). From anisotropy of magnetic susceptibility measurements and extensive microstructural data, the magnetic fabric of this pluton has been inferred to correlate with the magmatic fabric. Magnetic foliations strike NE–SW and dip gently SE. Magnetic lineations trend NW–SE and plunge gently SE. Gravity data suggest that the pluton has the shape of a sheet with a maximum preserved thickness of 1 km and a root zone located at its eastern border. This pluton is reinterpreted as late kinematic and emplaced during an extensional tectonic regime related to the ductile Vivero normal fault. It is suggested that the emplacement of most post-tectonic plutons of this part of the Variscan orogenic belt may have been controlled by the late extensional collapse of the Iberian Massif.
Exhumation history of eastern Ladakh revealed by
40
Ar/
39
Ar and fission-track ages: the Indus River–Tso Morari transect, NW Himalaya
Authors: Schlup M. , Carter A. , Cosca M. , Steck A.
Published: October 2008

Fission-track and
40
Ar/
39
Ar ages place time constraints on the exhumation of the North Himalayan nappe stack, the Indus Suture Zone and Molasse, and the Transhimalayan Batholith in eastern Ladakh (NW India). Results from this and previous studies on a north–south transect passing near Tso Morari Lake suggest that the SW-directed North Himalayan nappe stack (comprising the Mata, Tetraogal and Tso Morari nappes) was emplaced and metamorphosed by
c
. 50–45 Ma, and exhumed to moderately shallow depths (
c
. 10 km) by
c
. 45–40 Ma. From the mid-Eocene to the present, exhumation continued at a steady and slow rate except for the root zone of the Tso Morari nappe, which cooled faster than the rest of the nappe stack. Rapid cooling occurred at
c
. 20 Ma and is linked to brittle deformation along the normal Ribil–Zildat Fault concomitant with extrusion of the Crystalline nappe in the south. Data from the Indus Molasse suggest that sediments were still being deposited during the Miocene.
Faeces, clay minerals and reservoir potential
Authors: McIlroy D. , Worden R.H. , Needham S.J.
Published: October 2008

By controlled experiments that simulate marine conditions, it is shown that accelerated weathering and mineral authigenesis occur during the combined process of digestion, ingestion and excretion of sediment by worms. Previously characterized synthetic mud, composed of finely ground, low-grade metamorphic slate dominated by highly crystalline chlorite and muscovite, was unchanged in control tanks over a 20 week time scale, but was significantly different in faecal samples from an experimental tank populated with the annelid
Arenicola marina
. Chlorite was preferentially destroyed during digestion and both chlorite and muscovite underwent peak broadening with a skew developing towards higher lattice spacings. Neoformed minerals with very high
d
-spacings and a mineral with 0.75 nm basal lattice spacing (possibly berthierine) were detected in the cast samples. It is postulated that the lowered pH microenvironment in the guts of organisms may accelerate mineral dissolution and precipitation processes during ingestion. These results show that macrobiotic activity significantly accelerates weathering and mineral degradation along with mineral authigenesis. Neoformed minerals produced in this way would be likely to form the precursors of diagenetic clay mineral cements and thus have an impact on sandstone reservoir quality.
Emerging Pharmacology: Inhibitors of Human Immunodeficiency Virus Integration
Authors: Hazuda Daria , Iwamoto Marian , Wenning Larissa
Published: October 2008

The first integrase inhibitor licensed to treat HIV-1 infection was approved in late 2007, more than a decade after the introduction of the first inhibitors of the HIV-1 reverse transcriptase and protease. The unique biochemical and molecular mechanism of action of this novel class of antiretroviral drugs is the fundamental basis for their activity in treating multidrug-resistant HIV-1 infection and is important for understanding both the cellular and in vivo pharmacology and metabolism of these agents. In addition, available pharmacokinetic and drug interaction data for raltegravir and elvitegravir, the two integrase inhibitors that are the most advanced in clinical development to date, are reviewed.
Renal Cell Carcinoma in Two Patients with Crossed Fused Ectopic Kidneys
Authors: Davis Carley M. , Rao Manoj V. , Flanigan Robert C. , Quek Marcus L.
Published: October 2008

Primary renal malignancies involving crossed fused ectopic kidneys have rarely been reported. We describe two cases of renal cell carcinoma involving the orthotopic renal moiety in one patient and the heterotopic crossed renal moiety in another patient. Both patients were treated with surgical excision and preservation of the uninvolved renal unit.
The Role of Endothelial Progenitor Cells in Tumour Vasculogenesis
Authors: Ding Yi-tao , Kumar Shant , Yu De-cai
Published: October 2008

Objective: To review the biological behaviour of endothelial progenitor cells and their role and significance in tumour vasculogenesis. Data Sources: The data in this review were mainly from Medline and PubMed for the relevant articles in English published from March, 1997, to March, 2008. The search terms were ‘endothelial progenitor cells’ (EPCs) and ‘neoplasm’. Articles about the biological behaviour of EPCs and their roles in tumour vasculogenesis were included. Results: EPCs, whose characteristics are similar to those of endothelial cells (ECs) and stem cells, contribute to tumour vasculogenesis during tumour progression. The mobilisation, recruitment, homing and incorporation of EPCs into tumours are multi-step and multi-factor events during tumour vasculogenesis. This complex process requires the participation of many growth factors and cells, such as tumour cells, ECs, stromal cells and EPCs in the tumour microenvironment. However, there is still some debate about EPC distribution, contribution, origin and differentiation in tumour vasculogenesis. Conclusions: The characterisation of tumour-associated EPCs may provide valuable clues for more specific anti-angiogenesis therapy and/or tumour diagnosis. Many challenges remain in understanding definition, differentiation, mobilisation and recruitment of EPCs.
EphB1 Is Underexpressed in Poorly Differentiated Colorectal Cancers
Authors: Sheng Zhen , Wang Jiandong , Dong Yingchun , Ma Henghui , Zhou Hangbo , Sugimura Haruhiko , Lu Guangming , Zhou Xiaojun
Published: October 2008

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.
Detection of Parent-of-Origin Effects Based on Complete and Incomplete Nuclear Families with Multiple Affected Children
Authors: Zhou Ji-Yuan , Hu Yue-Qing , Lin Shili , Fung Wing K.
Published: October 2008

Parent-of-origin effects are important in studying genetic traits. More than 1% of all mammalian genes are believed to show parent-of-origin effects. Some statistical methods may be ineffective or fail to detect linkage or association for a gene with parent-of-origin effects. Based on case-parents trios, the parental-asymmetry test (PAT) is simple and powerful in detecting parent-of-origin effects. However, it is common in practice to collect nuclear families with both parents as well as nuclear families with only one parent. In this paper, when only one parent is available for each family with an arbitrary number of affected children, we firstly develop a new test statistic 1-PAT to test for parent-of-origin effects in the presence of association between an allele at the marker locus under study and a disease gene. Then we extend the PAT to accommodate complete nuclear families each with one or more affected children. Combining families with both parents and families with only one parent, the C-PAT is proposed to detect parent-of-origin effects. The validity of the test statistics is verified by simulation in various scenarios of parameter values. A power study shows that using the additional information from incomplete nuclear families in the analysis greatly improves the power of the tests, compared to that based on only complete nuclear families. Also, utilizing all affected children in each family, the proposed tests have a higher power than when only one affected child from each family is selected. Additional power comparison also demonstrates that the C-PAT is more powerful than a number of other tests for detecting parent-of-origin effects.
What Do We Mean by ‘Replication’ and ‘Validation’ in Genome-Wide Association Studies?
Authors: Igl Bernd-Wolfgang , König Inke R. , Ziegler Andreas
Published: October 2008

It has been acknowledged that results from genome-wide association studies need to be reproduced in further independent samples. This includes both aspects of replication and validation. Although often used interchangeably, both of these terms have a specific unique meaning and are not synonyms. Based on a number of applications from the literature producing a certain amount of confusion, our aim therefore is to clarify the definition of ‘replication’ and ‘validation’ and propose standards of their usage.
At the Cutting Edge: Ghrelin Gene Products in Food Intake and Gut Motility
Authors: Chen Chih-Yen , Fujimiya Mineko , Asakawa Akihiro , Chang Full-Young , Cheng Juei-Tang , Lee Shou-Dong , Inui Akio
Published: October 2008

Ghrelin, a 28-amino acid peptide, was recently identified from the stomach as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Ghrelin was discovered by ‘reverse pharmacology’. The acyl ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is the only gastrointestinal signal that increases meal size. However, des-acyl ghrelin accounts for the major forms in the plasma. Most recently, obestatin, a novel 23-amino acid peptide, was derived from the mammalian preproghrelin gene, which also encodes ghrelin, by a bioinformatic approach. This at-the-cutting-edge review focuses on three ghrelin gene products: acyl ghrelin, des-acyl ghrelin, and the newly identified obestatin. Their updated orexigenic and anorexigenic effects on food intake, their signal transduction pathways from the periphery to the brain, as well as their roles in modulating gastrointestinal motility, and potential applications in the many fields of medicine such as eating disorders, obesity/anorexia-cachexia, and gastrointestinal dysmotility under different conditions, are critically addressed.
Formation of STAT5/PPARγ Transcriptional Complex Modulates Angiogenic Cell Bioavailability in Diabetes
Authors: Dentelli Patrizia , Trombetta Antonella , Togliatto Gabriele , Zeoli Annarita , Rosso Arturo , Uberti Barbara , Orso Francesca , Taverna Daniela , Pegoraro Luigi , Brizzi Maria Felice
Published: October 2008

Objective—

Circulating angiogenic cells (CACs) expansion is a multistage process requiring sequential activation of transcriptional factors, including STAT5. STAT5, in concert with peroxisome proliferator-activated receptors (PPARs), seems to induce discrete biological responses in different tissues. In the present study we investigated the role of STAT5 and PPARγ in regulating CAC expansion in normal and diabetic settings.

Methods and Results—

Normal and diabetic CACs were used. siRNA technology, EMSA, and chromatin immunoprecipitation (ChIP) assay as well as site-directed mutagenesis of the STAT5 response element in the PPARγ promoter enabled us to demonstrate that STAT5 transcriptional activity controls PPARγ expression. Moreover, FACS analysis, coimmunoprecipitation experiments, and ChIP assay revealed that a STAT5/PPARγ transcriptional complex controls cyclin D1 expression and CAC progression into the cell-cycle. Conversely, PPARγ agonists, by preventing the expression of STAT5 and the formation of the STAT5/PPARγ heterodimeric complex failed to promote CAC expansion. Finally, we demonstrated that diabetic CAC functional capability can be recovered by molecules able to activate the STAT5/PPARγ transcriptional complex.

Conclusions—

Our data identify the STAT5/PPARγ heterodimers as landmark of CAC expansion and provide evidences for a mechanism that partially rescues CAC bioavailability in diabetic setting.
Temporary Reduction of Blood Pressure and Sympathetic Nerve Activity in Hypertensive Patients After Microvascular Decompression
Authors: Frank Helga , Heusser Karsten , Geiger Helmut , Fahlbusch Rudolf , Naraghi Ramin , Schobel Hans P.
Published: October 2008

Background and Purpose—

Experimental studies suggested neurovascular compression of the brain stem as a cause of hypertension. The aim of our prospective study was to investigate the effect of microvascular decompression in patients with severe hypertension with neurovascular compression on blood pressure and central sympathetic nerve activity in the long-term.

Methods—

Fourteen patients (4 males; mean age, 46±8 years) with essential hypertension underwent microvascular decompression of the brain stem. Vasoconstrictor muscle sympathetic nerve activity (recorded by microneurography: burst frequency, bursts/min) and blood pressure (24-hour profiles) were investigated before surgery and 7 days, 3 months, and every 6 months postoperatively.

Results—

Muscle sympathetic nerve activity was preoperatively elevated and decreased significantly postoperatively (35±13 bursts/min vs 20±9 bursts/min;
P
<0.01). Sympathetic activity remained reduced 3 months (19±8bursts/min;
P
<0.01), 6 months (19±7 bursts/min;
P
<0.01), and 12 months (23±9 bursts/min;
P
<0.01) postoperatively. However, in the long-term, sympathetic nerve activity increased again (18 months after surgery: 28±10 bursts, not significant; 24 months postoperatively: 34±12 bursts/min, not significant). Systolic and diastolic blood pressure decreased from 162±6/98±5 mm Hg preoperatively to 133±6/85±4 mm Hg (7 days postoperatively;
P
<0.01); 136±5/86±4 mm Hg (3 months postoperatively;
P
<0.01); 132±4/85±4 mm Hg (6 months postoperatively;
P
<0.01); 132±3/85±5 mm Hg (12 months postoperatively;
P
<0.01); 132±5/84±5 mm Hg;
P
<0.01). Twenty-four months after microvascular decompression, blood pressure increased again up to 158±7/96±6 mm Hg, corresponding to the sympathetic nerve activity course.

Conclusion—

Sympathetic nerve activity and blood pressure are temporary reduced by microvascular decompression in patients with severe hypertension with neurovascular compression. The data are a hint for sympathetic overactivity as a pathomechanism in this subgroup of patients.
Information in the Nonstationary Case
Authors: Vu Vincent Q. , Yu Bin , Kass Robert E.
Published: October 2008

Information estimates such as the direct method of Strong, Koberle, de Ruyter van Steveninck, and Bialek (1998) sidestep the difficult problem of estimating the joint distribution of response and stimulus by instead estimating the difference between the marginal and conditional entropies of the response. While this is an effective estimation strategy, it tempts the practitioner to ignore the role of the stimulus and the meaning of mutual information. We show here that as the number of trials increases indefinitely, the direct (or plug-in) estimate of marginal entropy converges (with probability 1) to the entropy of the time-averaged conditional distribution of the response, and the direct estimate of the conditional entropy converges to the time-averaged entropy of the conditional distribution of the response. Under joint stationarity and ergodicity of the response and stimulus, the difference of these quantities converges to the mutual information. When the stimulus is deterministic or nonstationary the direct estimate of information no longer estimates mutual information, which is no longer meaningful, but it remains a measure of variability of the response distribution across time.
Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia
Authors: Becker Pamela S. , Kopecky Kenneth J. , Wilks Adrianne N. , Chien Sylvia , Harlan John M. , Willman Cheryl L. , Petersdorf Stephen H. , Stirewalt Derek L. , Papayannopoulou Thalia , Appelbaum Frederick R.
Published: October 2008

Adhesion of acute myeloid leukemia (AML) blasts in the bone marrow microenvironment confers protection from chemotherapy-induced apoptosis. One mechanism for retention of blasts within the bone marrow is adhesion via very late antigen-4 (VLA-4), the α4β1 integrin heterodimer that binds to its main ligands, fibronectin, and vascular cell adhesion molecule-1 (VCAM-1). To examine the relationship of functional expression of VLA-4 to prognosis in AML, we studied marrow samples from 175 adult AML patients who underwent induction chemotherapy with anthracycline and cytarabine on Southwest Oncology Group trials. The studies included flow cytometry and functional in vitro assays for ligand binding and maximal β1 activation. VLA-4 expression varied widely, with mean expression 60.6% for α4, and was not significantly associated with response to chemotherapy, relapse-free, or overall survival (OS). However, increased binding of soluble VCAM-1 via VLA-4 was significantly associated with longer OS, corrected for age (P = .033). Estimated 5-year OS was 31% (95% confidence interval, 14%-48%) in 30 patients with soluble VCAM-1 binding greater than or equal to 40%, compared with 10% (confidence interval, 3%-17%) in 72 patients with lower binding. Adhesion and migratory properties of AML blasts thus appear to influence chemosensitivity and therefore may be therapeutic targets.
Geographic variation and effect of area-level poverty rate on colorectal cancer screening
Authors: Lian Min , Schootman Mario , Yun Shumei
Published: October 2008

Background

With a secular trend of increasing colorectal cancer (CRC) screening, concerns about disparities in CRC screening also have been rising. It is unclear if CRC screening varies geographically, if area-level poverty rate affects CRC screening, and if individual-level characteristics mediate the area-level effects on CRC screening.

Methods

Using 2006 Missouri Behavioral Risk Factor Surveillance System (BRFSS) data, a multilevel study was conducted to examine geographic variation and the effect of area-level poverty rate on CRC screening use among persons age 50 or older. Individuals were nested within ZIP codes (ZIP5 areas), which in turn, were nested within aggregations of ZIP codes (ZIP3 areas). Six groups of individual-level covariates were considered as potential mediators.

Results

An estimated 51.8% of Missourians aged 50 or older adhered to CRC screening recommendations. Nearly 15% of the total variation in CRC screening lay between ZIP5 areas. Persons residing in ZIP5 areas with ≥ 10% of poverty rate had lower odds of CRC screening use than those residing in ZIP5 areas with <10% poverty rate (unadjusted odds ratio [OR], 0.69; 95% confidence interval [95% CI], 0.58–0.81; adjusted OR, 0.81; 95% CI, 0.67–0.98). Persons who resided in ZIP3 areas with ≥ 20% poverty rate also had lower odds of following CRC screening guidelines than those residing in ZIP3 areas with <20% poverty rate (unadjusted OR, 0.66; 95% CI, 0.52–0.83; adjusted OR, 0.64; 95% CI, 0.50–0.83). Obesity, history of depression/anxiety and access to care were associated with CRC screening, but did not mediate the effect of area-level poverty on CRC screening.

Conclusion

Large geographic variation of CRC screening exists in Missouri. Area-level poverty rate, independent of individual-level characteristics, is a significant predictor of CRC screening, but it only explains a small portion of the geographic heterogeneity of CRC screening. Individual-level factors we examined do not mediate the effect of the area-level poverty rate on CRC screening. Future studies should identify other area- and individual-level characteristics associated with CRC screening in Missouri.
A Dual Role for Oncostatin M Signaling in the Differentiation and Death of Mammary Epithelial Cells in Vivo
Authors: Tiffen Paul G. , Omidvar Nader , Marquez-Almuina Nuria , Croston Dawn , Watson Christine J. , Clarkson Richard W. E.
Published: October 2008

Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes β-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed β-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.
Kinematics of slow turn maneuvering in the fruit batCynopterus brachyotis
Authors: Iriarte-Díaz José , Swartz Sharon M.
Published: October 2008

Maneuvering abilities have long been considered key factors that influence habitat selection and foraging strategies in bats. To date, however, very little experimental work has been carried out to understand the mechanisms that bats use to perform maneuvers. In the present study, we examined the kinematics of slow-speed turning flight in the lesser short-nosed fruit bat, Cynopterus brachyotis, to understand the basic mechanics employed to perform maneuvers and to compare them with previous findings in bats and other flying organisms. Four individuals were trained to fly in L-shaped flight enclosure that required them to make a 90 deg. turn midway through each flight. Flights were recorded with three low-light, high-speed videocameras,allowing the three-dimensional reconstruction of the body and wing kinematics. For any flying organisms, turning requires changes of the direction of travel and the reorientation of the body around the center of mass to maintain the alignment with the flight direction. In C. brachyotis, changes in body orientation (i.e. heading) took place during upstroke and preceded the changes in flight direction, which were restricted to the downstroke portion of the wingbeat cycle. Mean change in flight direction was significantly correlated to the mean heading angular velocity at the beginning of the downstroke and to the mean bank angle during downstroke, although only heading velocity was significant when both variables were considered. Body reorientation prior to changes in direction might be a mechanism to maintain the head and body aligned with the direction of travel and, thus, maximizing spatial accuracy in three-dimensionally complex environments.
Design of Laterally Loaded Driven Piles Using the Flat Dilatometer
Authors: Robertson PK , Davies MP , Campanella RG
Published: October 2008

The nonlinear subgrade reaction method (P-y curves) is widely used for the design of laterally loaded piles. This method replaces the soil reaction with a series of independent nonlinear Winkler springs.

A preliminary semi-empirical approach for the determination of P-y curves using data obtained from a flat dilatometer test (DMT) is presented and evaluated. A brief description of the equipment, testing procedures, and the theory that enables the family of P-y curves to be determined are presented. The P-y curves are used as input for an existing finite-difference program, which calculates pile deflection versus depth at various lateral loads.

An evaluation of the proposed method is presented using data from three full-scale laterally loaded test piles. A comparison and discussion are provided between the predicted and measured behavior of the piles during lateral loading.
Effect of Rigid Boundaries on Measurement of Particle Concentration
Authors: Hardin B
Published: October 2008

Soil specimens are often formed by placement in a mold with rigid boundaries, followed by striking off a plane surface with a rigid straightedge. These rigid boundaries and plane surfaces interrupt the packing of particles causing the measured void ratio to be greater than the value away from the boundary. A theory for boundary effects has been derived considering regular packings of uniform sized particles. For a cubical container, the difference between measured and true void ratios is proportional to the ratio of particle size to cube side length. Definition of an equivalent side length permits application of the theory to volumes with boundaries of arbitrary shape. Tests indicate that the theory works for angular particles and for graded materials providing particle size is represented by the size for which 10% of the particles (by mass) are finer. For container sizes normally used in practice, boundary effects are negligible for silt and clay soils and for cohesionless soils containing more than 10% finer than 0.074 mm.