bluuebunny/crossref_metadata_2025 huggingface dataset:
Global analysis of
trans
-splicing in
Drosophila
Authors: McManus C. Joel , Duff Michael O. , Eipper-Mains Jodi , Graveley Brenton R.
Published: July 2010

Precursor mRNA (pre-mRNA) splicing can join exons contained on either a single pre-mRNA (
cis
) or on separate pre-mRNAs (
trans
). It is exceedingly rare to have
trans
-splicing between protein-coding exons and has been demonstrated for only two
Drosophila
genes:
mod(mdg4)
and
lola
. It has also been suggested that
trans
-splicing is a mechanism for the generation of chimeric RNA products containing sequence from multiple distant genomic sites. Because most high-throughput approaches cannot distinguish
cis
- and
trans
-splicing events, the extent to which
trans
-splicing occurs between protein-coding exons in any organism is unknown. Here, we used paired-end deep sequencing of mRNA to identify genes that undergo
trans
-splicing in
Drosophila
interspecies hybrids. We did not observe credible evidence for the existence of chimeric RNAs generated by
trans
-splicing of RNAs transcribed from distant genomic loci. Rather, our data suggest that experimental artifacts are the source of most, if not all, apparent chimeric RNA products. We did, however, identify 80 genes that appear to undergo
trans
-splicing between homologous alleles and can be classified into three categories based on their organization: (
i
) genes with multiple 3′ terminal exons, (
ii
) genes with multiple first exons, and (
iii
) genes with very large introns, often containing other genes. Our results suggest that
trans
-splicing between homologous alleles occurs more commonly in
Drosophila
than previously believed and may facilitate expression of architecturally complex genes.
Interpolation and quadrature methods for ordinary differential equations
Authors: Cooper G. J.
Published: July 2010

A class of single-step methods is constructed for solving systems of differential equations. These methods are based on the use of interpolation and quadrature formulae, and are related to some implicit methods of Runge-Kutta type. Weight functions may be used to cope with difficult behaviour.
Chebyshev approximations for Dawson’s integral
Authors: Cody W. J. , Paciorek Kathleen A. , Thacher Henry C.
Published: July 2010

Rational Chebyshev approximations to Dawson’s integral are presented in well-conditioned forms for
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartAbsoluteValue x EndAbsoluteValue less-than-over-equals 2.5 comma 2.5 less-than-over-equals StartAbsoluteValue x EndAbsoluteValue less-than-over-equals 3.5 comma 3.5 less-than-over-equals StartAbsoluteValue x EndAbsoluteValue less-than-over-equals 5.0">

|

x

|

≦
2.5
,
2.5
≦

|

x

|

≦
3.5
,
3.5
≦

|

x

|

≦
5.0

|x| \leqq 2.5, 2.5 \leqq |x| \leqq 3.5, 3.5 \leqq |x| \leqq 5.0

and

5.0
≦

|

x

|

5.0 \leqq |x|

. Maximal relative errors range down to between

2
×

10

−
20

2 \times {10^{ - 20}}

and

7
×

10

−
22

7 \times {10^{ - 22}}

.
Further approximations for elliptic integrals
Authors: Luke Yudell L.
Published: July 2010

The present paper develops approximations for the three kinds of elliptic integrals based on the Padé approximations for the square root. The work includes and extends our previous work on the subject to provide efficient approximations over a larger part of the complex

k
k

and

ϕ
\phi

planes.
Symmetric quadrature formulae for simplexes
Authors: Silvester P.
Published: July 2010

Symmetrie interpolation polynomials are defined for

N
N

-dimensional simplexes with the aid of a symmetric coordinate notation. These polynomials are used to produce symmetric interpolatory quadrature formulae of arbitrary degree of precision over simplexes of arbitrary dimensionality. Tabulated values of weight coefficients are given for triangles and tetrahedra.
Difference methods for nonlinear first-order hyperbolic systems of equations
Authors: Shampine L. F. , Thompson R. J.
Published: July 2010

Two difference methods for approximating some first-order nonlinear hyperbolic differential equations are considered. The methods apply to problems arising in a number of physical applications. Each of the methods is explicit and can be implemented on a computer easily. It is proved that the methods are first-order convergent in the maximum norm. For one of the methods in order to obtain convergence it is necessary to monitor, and perhaps change, the size of the time step as the computation proceeds. The other method is unconditionally convergent.
The obligate aerobe Streptomyces coelicolor A3(2) synthesizes three active respiratory nitrate reductases
Authors: Fischer Marco , Alderson Jesse , van Keulen Geertje , White Janet , Sawers R. Gary
Published: July 2010

Streptomyces coelicolorA3(2) synthesizes three membrane-associated respiratory nitrate reductases (Nars). During aerobic growth in liquid medium the bacterium was able to reduce 50 mM nitrate stoichiometrically to nitrite. Construction and analysis of a mutant in which all threenarGHJIoperons were deleted showed that it failed to reduce nitrate. Deletion of the gene encoding MoaA, which catalyses the first step in molybdenum cofactor biosynthesis, also prevented nitrate reduction, consistent with the Nars being molybdoenzymes. In contrast to the triplenarGHJImutant, themoaAmutant was also unable to use nitrate as sole nitrogen source, which indicates that the assimilatory nitrate reductases inS. coelicolorare also molybdenum-dependent. Analysis ofS. coelicolorgrowth on solid medium demonstrated that Nar activity is present in both spores and mycelium (hypha). Development of a survival assay with the nitrate analogue chlorate revealed that wild-typeS. coelicolorspores and mycelium were sensitive to chlorate after anaerobic incubation, independent of the presence of nitrate, while both themoaAand triplenarmutants were chlorate-resistant. Complementation of the triplenarmutant with the individualnarGHJIoperons delivered on cosmids revealed that each operon encoded an enzyme that was synthesized and active in nitrate or chlorate reduction. The data obtained from these studies allow a tentative assignment of Nar1 activity to spores, Nar2 to spores and mycelium, and Nar3 exclusively to mycelium.
Anterior–posterior patterning of neural differentiated embryonic stem cells by canonical Wnts, Fgfs, Bmp4 and their respective antagonists
Authors: Hendrickx Marijke , Van Xong Hoang , Leyns Luc
Published: July 2010

Embryonic stem (ES) cells are pluripotent and can differentiate into every cell type of the body. Next to their potential in regenerative medicine, they are excellent tools to study embryonic development. In this work the processes of neural induction and neural patterning along the antero‐posterior (A/P) body axis are studied and evidence suggests a two step mechanism for these events. First, neural induction occurs by default in the primitive ectoderm, forming anterior neural tissue and thereafter, a series of factors can posteriorize this anterior neurectoderm. In a gain‐of‐function/loss‐of‐function approach using mouse ES cells, we show that Fgf2 has the strongest caudalizing potential of all Fgfs tested. Furthermore, Bmp4 and Wnt3a, but not Wnt1, can caudalize the neurectodermal cells. The effect of the antagonists of these factors was also examined and though Dkk1 and Noggin clearly have an effect that opposes that of Wnt3a and Bmp4 respectively, they fail to anteriorize the neurectoderm. The patterning effect of SU5402, an Fgf receptor inhibitor, was rather limited. These data confirm that in the mouse, two steps are involved in neural patterning and we show that while Fgf4, Fgf8 and Wnt1 have no strong patterning effect, Fgf2, Wnt3a and Bmp4 are strong posteriorizing factors.
Stem cells in mammalian spermatogenesis
Authors: Yoshida Shosei
Published: July 2010

Mammalian testes continually produce a huge number of sperm over a long reproductive period. This constant spermatogenesis is supported by a highly robust stem cell system. Morphological analyses in the 1960s and 70s established the basis of mammalian spermatogenesis and the associated stem cell research. Subsequently, from the 1990s on, functional analyses, which have included post‐transplantation colony formation,in vitrospermatogonial culture with persisting stem cell activity,in vivolineage tracing, and live imaging, and also lines of molecular‐genetic analyses, have contributed greatly to our understanding of mammalian spermatogenic stem cells. This review will provide a brief overview of the history of this field and then go on to describe in detail the progress made in recent years.
ModEco: an integrated software package for ecological niche modeling
Authors: Guo Qinghua , Liu Yu
Published: July 2010

ModEco is a software package for ecological niche modeling. It integrates a range of niche modeling methods within a geographical information system. ModEco provides a user friendly platform that enables users to explore, analyze, and model species distribution data with relative ease. ModEco has several unique features: 1) it deals with different types of ecological observation data, such as presence and absence data, presence‐only data, and abundance data; 2) it provides a range of models when dealing with presence‐only data, such as presence‐only models, pseudo‐absence models, background vs presence data models, and ensemble models; and 3) it includes relatively comprehensive tools for data visualization, feature selection, and accuracy assessment.
Neurobiological Foundations for the Theory of Harmony in Western Tonal Music
Authors: TRAMO MARK JUDE , CARIANI PETER A. , DELGUTTE BERTRAND , BRAIDA LOUIS D.
Published: July 2010

Abstract: Basic principles of the theory of harmony reflect physiological and anatomical properties of the auditory nervous system and related cognitive systems. This hypothesis is motivated by observations from several different disciplines, including ethnomusicology, developmental psychology, and animal behavior. Over the past several years, we and our colleagues have been investigating the vertical dimension of harmony from the perspective of neurobiology using physiological, psychoacoustic, and neurological methods. Properties of the auditory system that govern harmony perception include (1) the capacity of peripheral auditory neurons to encode temporal regularities in acoustic fine structure and (2) the differential tuning of many neurons throughout the auditory system to a narrow range of frequencies in the audible spectrum. Biologically determined limits on these properties constrain the range of notes used in music throughout the world and the way notes are combined to form intervals and chords in popular Western music. When a harmonic interval is played, neurons throughout the auditory system that are sensitive to one or more frequencies (partials) contained in the interval respond by firing action potentials. For consonant intervals, the fine timing of auditory nerve fiber responses contains strong representations of harmonically related pitches implied by the interval (e.g., Rameau's fundamental bass) in addition to the pitches of notes actually present in the interval. Moreover, all or most of the partials can be resolved by finely tuned neurons throughout the auditory system. By contrast, dissonant intervals evoke auditory nerve fiber activity that does not contain strong representations of constituent notes or related bass notes. Furthermore, many partials are too close together to be resolved. Consequently, they interfere with one another, cause coarse fluctuations in the firing of peripheral and central auditory neurons, and give rise to perception of roughness and dissonance. The effects of auditory cortex lesions on the perception of consonance, pitch, and roughness, combined with a critical reappraisal of published psychoacoustic data on the relationship between consonance and roughness, lead us to conclude that consonance is first and foremost a function of the pitch relationships among notes. Harmony in the vertical dimension is a positive phenomenon, not just a negative phenomenon that depends on the absence of roughness—a view currently held by many psychologists, musicologists, and physiologists.
Magmatic layering and intrusive plumbing in the Jurassic Morgantown Sheet, Central Atlantic Magmatic Province
Authors: Srogi LeeAnn , Lutz Tim , Dickson Loretta D. , Pollock Meagen , Gimson Kirby , Lynde Nicole
Published: July 2010

This field trip explores igneous layering in the Morgantown Sheet, southeastern Pennsylvania, a Jurassic diabase intrusion that is part of the Central Atlantic Magmatic Province, formed during rifting of Pangea. The Pennsylvania Granite Quarry (Stop 1) is a dimension stone quarry in the southern side of the sheet, in which the cut walls display intermittent modal layering crosscut by channels of mafic diabase. Plagioclase-rich layers overlie pyroxene-rich layers in packages with slightly concave-up “wok” shapes ~ 0.3–0.4 m in dimension and ~ 0.35–0.5 m thick. Mafic diabase — both layers and crosscutting channels—contain 15–25 modal percent orthopyroxene phenocrysts and are interpreted as basaltic magma replenishments. Orientations of layering and channels suggest this part of the sheet was originally a horizontal sill ~ 400 m thick, at about six kilometers depth, and that the sheet was tilted 20° – 25° to the north after crystallization. The Dyer aggregate quarry (Stop 2) is in the northeast side of the sheet that dips ~ 80° southeast (Birdsboro dike). Here, rhythmic plagioclase-pyroxene layering also dipping ~ 80° is found in the interior and near the margin of the ~ 255-m-wide dike. Augite and plagioclase compositions are very similar in samples from different vertical heights in the sheet, suggesting localized rather than sheet-wide fractionation. We compare the Morgantown Sheet layering to similar features in the Palisades sill, New Jersey, and Basement sill, Antarctica, and discuss models for their formation.
The early through late Pleistocene record in the Susquehanna River Basin
Authors: Braun Duane D.
Published: July 2010

A transect of the Coastal Plain, Piedmont, Ridge and Valley, and Appalachian Plateau physiographic provinces valley will be made by going up the Susquehanna Valley. Early to late Pleistocene features will be examined at eleven sites. The pre-Pleistocene evolution of the Appalachian landscape will also be discussed at two sites. The journey will start on the Coastal Plain and travel to the lower Susquehanna bedrock gorge across the High Piedmont, where strath terraces will be examined. From there the Susquehanna River will be followed upstream to the Low Piedmont where broad outwash terraces, of early to late Pleistocene-age, flank the River. Continuing up-river into Ridge and Valley Province, the water gaps at Harrisburg, Pennsylvania, will be viewed and their origin discussed. The Susquehanna River will be followed across the remainder of the Ridge and Valley with stops to view early and mid-Pleistocene-aged features. Emphasis will be placed on the amount of erosion that has occurred since the early Pleistocene and the development of a pseudo-moraine landscape. At the wind gap through Bald Eagle Mountain, the mid-Miocene to present evolution of the overall Appalachian landscape will be discussed. The evidence for the early Pleistocene-age for Glacial Lake Lesley will be examined in the West Branch Susquehanna valley. In the deep valleys section of the Appalachian Plateau, the mid- and late Pleistocene glacial termini will be examined. Turning south into the Ridge and Valley, the trip will conclude with examination of glaciofluvial deposits of probable mid-Pleistocene-age.
Evaluation of patient rights practices in a developing country: the Edirne model for the implementation of patient rights in Turkey
Authors: Saraçoğlu G V , Tokuç B , Güler F , Gül H
Published: July 2010

Objective

The aim of this study was to examine the development of the implementation of patient rights and the practical course of patient rights legislation in Edirne, as well as the verbal and written applications to relevant departments between 2004 and 2008.

Methods

The present study was a descriptive, retrospective and cross-sectional study. The data of the study were obtained by retrospectively reviewing records of written complaints to patient rights units and on-site solutions between 2004, the year of establishment of these units, and 2008.

Results

The incidence of written and verbal complaints were calculated to be 23.1 in 100 000 and 137.9 in 100 000, respectively. The increase was 102.2% for on-site solutions, whereas it was calculated as 97.8% for written applications. It was noticed that the rate of violation judgements was high (42.5% (17/40)) in the first year the Edirne State Hospital patient rights committee was established.

Conclusions

Possible problems encountered during the presentation of health services can be solved by the implementation of patient rights under the legislative guarantee. The implementation of patient rights should be considered as reflections of a socialised government on health services.
Seclusion and its context in acute inpatient psychiatric care
Authors: Cleary Michelle , Hunt Glenn E , Walter Garry
Published: July 2010

In acute inpatient mental health services, patients commonly demonstrate extreme behaviours. A number of coercive practices, such as locked doors, enforced medication and seclusion, are used in these settings to control such behaviours. The aim of this report is to explore briefly some of the contemporary debates pertaining to seclusion. A perusal of the literature reveals a clarion call to end the practice of seclusion, without consideration of feasible alternatives. It is hoped that this brief report will encourage further evidence-based discussion and research initiatives on this important ethical topic.
The Structure of Grain Boundaries in Strontium Titanate: Theory, Simulation, and Electron Microscopy
Authors: von Alfthan Sebastian , Benedek Nicole A. , Chen Lin , Chua Alvin , Cockayne David , Dudeck Karleen J. , Elsässer Christian , Finnis Michael W. , Koch Christoph T. , Rahmati Behnaz , Rühle Manfred , Shih Shao-Ju , Sutton Adrian P.
Published: July 2010

We review a combination of theoretical and experimental techniques that have been applied to the study of grain boundaries in SrTiO3, with particular attention to Σ3 and ( 100 )-oriented grain boundaries. Electron microscopy, which includes high-resolution transmission and high-angle annular dark-field methods, is discussed, with successful applications to mapping atomic columns and testing theoretical models. Then, we compare and contrast different techniques of electron holography that may be used to map electrostatic potentials. Problems with the current methods of interpretation in holography and impedance spectroscopy are highlighted in an attempt to reconcile their respective estimates of electrostatic potentials at grain boundaries. Then, standard theoretical tools for the atomistic simulation of boundary structures are critically reviewed, which include classical potentials and density functional theory. A promising genetic algorithm for discovering low-energy grain boundary structures is described and tested. Finally, the synergy of experiment, theory, and simulation that is required to understand boundaries is demonstrated, and we identify major challenges to understanding multicomponent systems.
On the Mechanistic Origins of Toughness in Bone
Authors: Launey Maximilien E. , Buehler Markus J. , Ritchie Robert O.
Published: July 2010

One of the most intriguing protein materials found in nature is bone, a material composed of assemblies of tropocollagen molecules and tiny hydroxyapatite mineral crystals that form an extremely tough, yet lightweight, adaptive and multifunctional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are of great physiological relevance. In this article, we review the structure and properties of bone, focusing on mechanical deformation and fracture behavior from the perspective of the multidimensional hierarchical nature of its structure. In fact, bone derives its resistance to fracture with a multitude of deformation and toughening mechanisms at many size scales ranging from the nanoscale structure of its protein molecules to the macroscopic physiological scale.
Electrochemically Driven Phase Transitions in Insertion Electrodes for Lithium-Ion Batteries: Examples in Lithium Metal Phosphate Olivines
Authors: Tang Ming , Carter W. Craig , Chiang Yet-Ming
Published: July 2010

The thermodynamics and kinetics of phase transformations in electrochemical systems are reviewed. Phase transitions in LiMPO4(M = Fe, Mn, Ni, Co) olivines are highlighted. The phase transformation phenomena in LiMPO4are diverse and include thermodynamic effects of particle size and applied overpotential, the appearance of metastable phases, and the effects of defects from atomic disorder and aliovalent doping. Such phenomena also include kinetic effects such as interface motion and diffusion of Li-electron complexes. The nature of phase transitions directly influences electrode performance in battery applications. Reduced particle size and doping can reduce or eliminate room-temperature Li miscibility gaps, which in turn affect characteristics of state of charge versus voltage and the elastic energy due to volume mismatches between phases. Near the conditions for a phase transition, Li diffusion coefficients are reduced. Nucleation and growth kinetics produce a series of phase transition sequences, which can result in the accumulation of noncrystalline phases during electrochemical cycling.
Saturation of Fragmentation During Severe Plastic Deformation
Authors: Pippan R. , Scheriau S. , Taylor A. , Hafok M. , Hohenwarter A. , Bachmaier A.
Published: July 2010

In this review, we focus on the saturation microstructure that evolves during severe plastic deformation (SPD). These nanocrystalline or ultrafine-grained microstructures consist predominantly of high-angle boundaries, although low-angle boundaries are also present. Deformation temperature, alloying, and strain path are the dominant factors controlling the saturation grain size in single-phase materials. The saturation grain size decreases significantly with decreasing deformation temperature, although the dependency is stronger at medium homologous temperatures and less in the low-temperature regime. The saturation microstructure is sensitive to strain rate at medium temperatures and less so at low temperatures. The addition of alloying elements to pure metals also reduces the saturation grain size. The results indicate that grain boundary migration is the dominant process responsible for the limitation in refinement by SPD. Therefore, second-phase particles of the nanometer scale can stabilize even finer microstructures. This mechanism of stabilization of the microstructure is an effective tool for overcoming the limit in refinement of single-phase materials by SPD. The improved thermal stability of the obtained nanostructures is another benefit of the introduction of second-phase particles.
Association of Cystatin C and Depression in Healthy Elders: The Health, Aging and Body Composition Study
Authors: Minev Evgueni , Unruh Mark , Shlipak Michael G. , Simsonick Eleanor , Yaffe Kristine , Leak Tennille S. , Newman Anne B. , Fried Linda F.
Published: July 2010

Background/Aims: Depression is highly prevalent in individuals with advanced kidney disease, but is less well studied in individuals with milder disease. We evaluated the association between kidney function and depression in the Health, Aging and Body Composition (Health ABC) study. Methods: The study enrolled 3,075 community-dwelling black and white adults aged 70–79 years. Kidney function was measured by cystatin C and estimated glomerular filtration rate (eGFR). The main outcome was incident treated depression. Results: 52% of participants had low (≤1.0), 33% intermediate (>1–1.25) and 15% high cystatin C (>1.25). Kidney function and depression were not associated at baseline. Of 2,731 nondepressed participants at baseline, 95 developed incident depression during follow-up. In unadjusted Cox proportional hazard models, hazard ratios (HR) for incident depression were 1.89 (95% confidence interval (CI) 1.21–2.97) for the intermediate and 2.17 (CI 1.24–3.79) for the high cystatin C group. Intermediate (HR = 1.84) and high (HR = 2.1) serum cystatin C remained associated with incident depression in adjusted models. Chronic kidney disease, defined by an eGFR <60 ml/min/1.73 m2, was not associated with depression. Conclusion: Participants with higher cystatin C had an increased likelihood of developing treated depression. Future studies should target this high-risk group.
Liver Cirrhosis Mortality in Europe, with Special Attention to Central and Eastern Europe
Authors: Zatoński Witold A. , Sulkowska Urszula , Mańczuk Marta , Rehm Jürgen , Boffetta Paolo , Lowenfels Albert B. , La Vecchia Carlo
Published: July 2010

Background and Aims: Over the last decades, Europe has experienced dramatic changes in the geographical variation of liver cirrhosis rates. We attempt to provide a comprehensive analysis of patterns and trends in liver cirrhosis mortality in European countries and regions. Methods: Age-standardized (world standard) liver cirrhosis mortality rates per 100,000 person-years at ages 20–64 for 35 separate countries were computed using the World Health Organization Mortality Database. Results: In the analyzed period (1959–2002), a very strong East-to-West gradient in mortality rates was observed. An increase of the burden of mortality due to liver cirrhosis appeared in Eastern Europe in two specific areas: South-eastern Europe and North-eastern Europe. In the first group of countries, liver cirrhosis mortality was 10–20 times higher than in most other European states, levels never before observed in Europe. In the countries of North-eastern Europe (former Soviet Union countries) liver cirrhosis mortality was characterized by dramatic changes (both positive and negative) in specific periods of time. Conclusions: Despite the fact that the etiology of liver cirrhosis is multifactorial, it seems that alcohol drinking is the factor that best explains the observed patterns in frequency of this disease in Europe. Alcohol control policies in Central and Eastern Europe could lead to an appreciable reduction of premature mortality from liver cirrhosis.
Rates of Infection and Phylogenetic Analysis of GB Virus-C among Kuwaiti and Jordanian Blood Donors
Authors: Abu Odeh Raed , Yasin Salem , Nasrallah Gheyath , Babi Yaman
Published: July 2010

Objectives: GB virus-C/hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, has been reported to be associated with non-A-E hepatitis. The aim of this study was to determine the rate of infection and genotypic characteristics of GBV-C among Kuwaiti and Jordanian blood donors. Methods: A total of 334 plasma/serum samples from healthy blood donors in Kuwait (n = 130) and Jordan (n = 204) were screened using RT-PCR/nested PCR of the 5′-untranslated region (5′-UTR). Phylogenetic analysis was conducted by sequencing the 5′-UTR region of the randomly picked clones representative of the two populations. Results: The results obtained showed that the rate of GBV-C infection in healthy Kuwaiti and Jordanian blood donors was 24.6 and 9.8%, respectively. Sequence analysis of the 5′-UTR using 4 and 6 clones from healthy Kuwaiti and Jordanian blood donors, respectively, revealed the prevalence of the European/North American genotype 2 when compared to the 6 reference genotypes in GenBank. Conclusion: GBV-C/HGV was detectable at rates relatively comparable with other regions in the world in Kuwaiti and Jordanian blood donors, although the significance of which remains controversial. More interesting is the dominance of GBV-C genotype 2 among the two populations, which remains to be explained.
Lead Contributes to Arterial Intimal Hyperplasia Through Nuclear Factor Erythroid 2–Related Factor–Mediated Endothelial Interleukin 8 Synthesis and Subsequent Invasion of Smooth Muscle Cells
Authors: Zeller Iris , Knoflach Michael , Seubert Andreas , Kreutmayer Simone B. , Stelzmüller Marlies E. , Wallnoefer Evelyn , Blunder Stefan , Frotschnig Sandra , Messner Barbara , Willeit Johann , Debbage Paul , Wick Georg , Kiechl Stefan , Laufer Günther , Bernhard David
Published: July 2010

Objective—

To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted.

Methods and Results—

During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (
P
=0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2–related factor–2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell–secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells.

Conclusion—

Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia.
Purkinje Cells From RyR2 Mutant Mice Are Highly Arrhythmogenic But Responsive to Targeted Therapy
Authors: Kang Guoxin , Giovannone Steven F. , Liu Nian , Liu Fang-Yu , Zhang Jie , Priori Silvia G. , Fishman Glenn I.
Published: July 2010

Rationale:

The Purkinje fiber network has been proposed as the source of arrhythmogenic Ca
2+
release events in catecholaminergic polymorphic ventricular tachycardia (CPVT), yet evidence supporting this mechanism at the cellular level is lacking.

Objective:

We sought to determine the frequency and severity of spontaneous Ca
2+
release events and the response to the antiarrhythmic agent flecainide in Purkinje cells and ventricular myocytes from RyR2
R4496C/+
CPVT mutant mice and littermate controls.

Methods and Results:

We crossed RyR2
R4496C/+
knock-in mice with the newly described
Cntn2-EGFP
BAC transgenic mice, which express a fluorescent reporter gene in cells of the cardiac conduction system, including the distal Purkinje fiber network. Isolated ventricular myocytes (EGFP
−
) and Purkinje cells (EGFP
+
) from wild-type hearts and mutant hearts were distinguished by epifluorescence and intracellular Ca
2+
dynamics recorded by microfluorimetry. Both wild-type and RyR2
R4496C/+
mutant Purkinje cells displayed significantly slower kinetics of activation and relaxation compared to ventricular myocytes of the same genotype, and τ
decay
in the mutant Purkinje cells was significantly slower than that observed in wild-type Purkinje cells. Of the 4 groups studied, RyR2
R4496C/+
mutant Purkinje cells were also most likely to develop spontaneous Ca
2+
release events, and the number of events per cell was also significantly greater. Furthermore, with isoproterenol treatment, although all 4 groups showed increases in the frequency of arrhythmogenic Ca

2+
i

events, the RyR2
R4496C/+
Purkinje cells responded with the most profound abnormalities in intracellular Ca
2+
handling, including a significant increase in the frequency of unstimulated Ca

2+
i

events and the development of alternans, as well as isolated and sustained runs of triggered beats. Both Purkinje cells and ventricular myocytes from wild-type mice showed suppression of spontaneous Ca
2+
release events with flecainide, whereas in RyR2
R4496C/+
mice, the Purkinje cells were preferentially responsive to drug. In contrast, the RyR2 blocker tetracaine was equally efficacious in mutant Purkinje cells and ventricular myocytes.

Conclusions:

Purkinje cells display a greater propensity to develop abnormalities in intracellular Ca
2+
handling than ventricular myocytes. This proarrhythmic behavior is enhanced by disease-causing mutations in the RyR2 Ca
2+
release channel and greatly exacerbated by catecholaminergic stimulation, with the development of arrhythmogenic triggered beats. These data support the concept that Purkinje cells are critical contributors to arrhythmic triggers in animal models and humans with CPVT and suggest a broader role for the Purkinje fiber network in the genesis of ventricular arrhythmias.
Endothelial Activation in Lacunar Stroke Subtypes
Authors: Knottnerus Iris L.H. , Govers-Riemslag Jose W.P. , Hamulyak Karly , Rouhl Rob P.W. , Staals Julie , Spronk Henri M.H. , van Oerle Rene , van Raak Elisabeth P.M. , Lodder Jan , ten Cate Hugo , van Oostenbrugge Robert J.
Published: July 2010

Background and Purpose—

Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients.

Methods—

In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA–PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors.

Results—

In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA;
P
=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA;
P
=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98–1.00 per ng/mL change of PAI-1;
P
=0.04).

Conclusions—

We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.
Combining Acute Diffusion-Weighted Imaging and Mean Transmit Time Lesion Volumes With National Institutes of Health Stroke Scale Score Improves the Prediction of Acute Stroke Outcome
Authors: Yoo Albert J. , Barak Elizabeth R. , Copen William A. , Kamalian Shahmir , Gharai Leila Rezai , Pervez Muhammad A. , Schwamm Lee H. , González R. Gilberto , Schaefer Pamela W.
Published: July 2010

Background and Purpose—

The purpose of this study was to determine whether acute diffusion-weighted imaging (DWI) and mean transit time (MTT) lesion volumes and presenting National Institutes of Health Stroke Scale (NIHSS) can identify patients with acute ischemic stroke who will have a high probability of good and poor outcomes.

Methods—

Fifty-four patients with acute ischemic stroke who had MRI within 9 hours of symptom onset and 3-month follow-up with modified Rankin scale were evaluated. Acute DWI and MTT lesion volumes and baseline NIHSS scores were calculated. Clinical outcomes were considered good if the modified Rankin Scale was 0 to 2.

Results—

The 33 of 54 (61%) patients with good outcomes had significantly smaller DWI lesion volumes (
P
=0.0001), smaller MTT lesion volumes (
P
<0.0001), and lower NIHSS scores (
P
<0.0001) compared with those with poor outcomes. Receiver operating characteristic curves for DWI, MTT, and NIHSS relative to poor outcome had areas under the curve of 0.889, 0.854, and 0.930, respectively, which were not significantly different. DWI and MTT lesion volumes predicted outcome better than mismatch volume or percentage mismatch. All patients with a DWI volume >72 mL (13 of 54) and an NIHSS score >20 (6 of 54) had poor outcomes. All patients with an MTT volume of <47 mL (16 of 54) and an NIHSS score <8 (17 of 54) had good outcomes. Combining clinical and imaging thresholds improved prognostic yield (70%) over clinical (43%) or imaging (54%) thresholds alone (
P
=0.01).

Conclusions—

Combining quantitative DWI and MTT with NIHSS predicts good and poor outcomes with high probability and is superior to NIHSS alone.
Psychological Disorders After Stroke Are an Important Influence on Functional Outcomes
Authors: West Robert , Hill Kate , Hewison Jenny , Knapp Peter , House Allan
Published: July 2010

Background and Purpose—

Psychological disorders are recognized as an important and common problem after stroke but little is known about their longer-term effects on functional outcomes. We investigated the trajectory of psychological symptoms after stroke and studied their impact on physical functional recovery.

Methods—

The Stroke Outcomes Study was a prospective cohort study conducted in West Yorkshire, UK, from 2002 to 2006. Baseline assessments were conducted within 2 to 6 weeks of an index stroke event and follow-up at 9, 13, 26, and 52 weeks thereafter. Measures of psychological symptoms (assessed using the 28-item General Health Questionnaire) and function (modified Barthel Index) were completed at each visit. Longitudinal latent class analysis identified psychological symptom trajectories. Logistic regression modeled poor functional outcome. Multiple imputation was used as a sensitivity analysis.

Results—

Five hundred ninety-two (55% of eligible patients) consented to participate. Four hundred forty-four (76%) complete sets of data (5 time points) were obtained for analysis. Four distinct classes of patients emerged from the analyses based on trajectory of psychological symptoms in the first 26 weeks after stroke. There was a strong association between functional outcome and class as defined by psychological symptom trajectory, which was not explained by age, sex, or initial disability after stroke.

Conclusions—

Currently, the assessment of psychological distress is concentrated in the first weeks after stroke. Our results suggest that the timing of assessment and intervention needs to be reconsidered to take into account the trajectory of psychological symptoms rather than assessment at a single time point.
Conflicten Rond Predikantsbenoemingen in Enkele Hollandse Steden, Ca. 1670-1770
Authors: De Jongste Jan A.F.
Published: July 2010

Within the rather complex relationship between State and Church the appointment of ministers has always been of the greatest importance. Attempts to make a regulation, which would be valid in all the towns of the province of Holland, were not successful because of the fundamental disagreement between church and civil authorities on the limits of competence on both sides. The "broad" church council, composed of ministers, elders and deacons and sometimes also former elders and representatives of the town government (commissarissen politiek) officially decided on the selection of ministers. In almost every town however, the church council had to ask the burgomasters for permission to set the procedure in motion. In the end the council had to present a select list of three candidates and finally the name of the candidate the majority of its members thought preferable. This procedure offered the town governments ample opportunities to intervene. They could decline to initiate the selection process, impose conditions or veto unsuitable candidates. Many church councils considered these interventions as unacceptable encroachments on their rights and freedom. The appointments of ministers were always potential causes of discord between the civil authorities and the church councils. The article deals with the many conflicts in a number of towns in the province of Holland between 1670 and 1770. The beginning is marked by the political crisis of 1672 which resulted in the restoration of the stadholderly regime under William III. The Voetians, the Reformed orthodoxy, hoped for support of the stadholder in their theological struggle with the adherents of Coccejus. In the second half of the 18th century this conflict had lost its original character and furthermore the dissension within the Reformed Church was no longer mainly based on disagreement between these two groups but the changed situation had produced a tripartition. Somewhat later political elements began influencing the internal relations. Analysis of the conflicts leads to the conclusion, that local circumstances often played a decisive part. It also demonstrates the complex and comprehensive character of these collisions. Yet it is possible to categorize the various conflicts by distinguishing between different, although closely interconnected, dominating factors: 1. religious antagonism within the Reformed Church (the richtingenstrijd); 2. discord between political factions within the town governments; 3. differing opinions on the relation between church and state at the local level and more specifically the part played by the church council in the selection procedure; 4. nepotism and favouritism; and 5. meddling by the Orange stadholders in the appointments of ministers under William III and after the restoration of the Orangist regime in 1747.
Johannes Braun (1628-1708), Cartesiaan in Groningen
Authors: Steenbakkers Piet
Published: July 2010

Johannes Braun (1628-1708) was professor of theology and Hebrew at the university of Groningen. A disciple of Coccejus in theology, he adhered to Cartesianism in philosophical matters. He published scholarly, didactic and polemic writings. Among his correspondents was Leibniz. He knew at least some of Spinoza's works, and rejected the latter's alleged atheism. Descartes's influence is pervasive, though as a philosopher Braun was rather superficial. For him, Cartesian ism was a tool in a rationalist approach to cheology and (particularly) in demarcating theology from philosophy. In this respect, his position is exemplary for the adaptations taking place in institutional philosophy around 1700.
Latin American Images of Christ
Authors: Irarrazaval Diego
Published: July 2010

In several areas, particularly in Peru and Chile, Catholic communities have developed traditions with rich symbols and wisdom as is expressed in images, rituals, devotions, festivals, and social movements. The faith of the people nurtures church life and theological discourse.
Christ in Popular Culture in Korea
Authors: Hwan Ra Young
Published: July 2010

The purpose of this paper is to explore the way in which the Korean church developed a popular image of Jesus Christ in her own context. Many scholars often refer to Minjung theology in order to find the Korean understanding of Jesus Christ. Yet, if one seeks to understand Korean Christology only through Minjung theology, he or she will not be able to grasp its whole nature. The evangelicals have also developed their own Christology that is rooted in a particular Korean context. As will be discussed in this paper, there are four popular images of Christ in Korean Christianity. These are: Christ as the Gift, the Reconciler, the Transformer, and the Liberator.
Trinity in the Temptation Narrative and the Interpratation of Noordmans, Dostoyevski, and Mbeki
Authors: Theron Johann
Published: July 2010

First, this article gives a biblical theological account of the use of the term 'temptation' through out the Bible and relates it to the temptation narrative in Luke. It proposes to show that there is a trinitarian structure in the temptation narrative in Luke. It is argued that the temptation narrative is primarily concerned with the person and work of Christ from a Christological perspective, while it can be related to the believer only from a secondary Pneumatological perspective.Second, this article will focus on the way the temptation narrative has been interpreted by Oepke Noordmans, Fyodor Dostoyevski, and in the South African context by President Thabo Mbeki in his Nelson Mandela Memorial Lecture. Noordmans, the theologian, emphasizes the Christo logical aspects of the temptation narrative, while Dostoyevski explores the Pneumatological aspects by looking at humankind in its concrete socio-political and religious situation. President Thabo Mbeki refers to the temptation narrative from an anthropological perspective to indicate how a citizen must live responsibly in South Africa.
The Church as the Community of the Shared Story
Authors: Van der Borght Eddy
Published: July 2010

Within this article, three ecumenical documents that discuss reconciliation and healing memories and that were published in the twenty first century are analyzed. The focus is on the way they deal with the past link between church and ethnicity, and how this has contributed to the inability of actual national or ethnic churches to be an expression of the one, catholic church of the ancient creeds. The result of the analysis is disappointing. The texts avoid dealing with this issue.
The Appeal to the Inner Testimony of the Spirit, especially in H. Bavinck
Authors: van der Kooi Cornelius
Published: July 2010

“The Reformation took—deliberately and freely—its position in the religious subject.” In this article, the argument is made that Bavinck has not formulated a strong position with this statement; but rather, a dubious starting point for Reformed theology. The question is whether this thesis, with its focus on the subject, can still be maintained in this manner within the current ecumenical situation, or whether it is imperative that it be adjusted.
The Election of Jesus Christ
Authors: Crisp Oliver
Published: July 2010

In modern theology the election of Christ is often associated with the work of Karl Barth. In this paper, I offer an alternative account of Christ's election in dialogue with the Post-Reformation Reformed tradition. It turns out that, contrary to popular belief, there is no single 'Reformed' doctrine of election; a range of views has been tolerated in the tradition. I set out one particular construal of the election of Christ that stays within the confessional parameters of Reformed theology, while arguing, contrary to some Reformed divines, that Christ is the cause and foundation of election.
A Dutch Response to Nihilism: an Evaluation of K.H. Miskotte's Interaction with Nietzsche
Authors:   Ad Prosman
Published: July 2010

This article discusses the way in which the Dutch theologian K.H. Miskotte interpreted the nihilism of Friedrich Nietzsche. It will be pointed out that religion is the central notion of Miskotte's approach of Nietzsche. Discussing this theme, it will be necessary to pay attention to the concept of Nietzsche's nihilism. From there we receive a clearer insight in the interaction between Miskotte and Nietzsche. It is expected that examining nihilism and the interaction with nihilism will be helpful to contextualize theology. The method of Miskotte is attractive because he does not evaluate nihilism in a philosophical manner, but he counters it by the Thora. Belief stands against belief. Nevertheless we can ask whether Miskotte's concept of religion is adequate enough to tackle the problems we have to deal with in our nihilistic culture. Is Miskotte right when he connects nihilism and religion, and what kind of religion is he connecting with nihilism?
Vulnerable Church in a Vulnerable World? Towards an Ecclesiology of Vulnerability
Authors: Koopman Nico
Published: July 2010

This essay argues that the faithfulness of the church in a world with so many vulnerabilities entails that she acknowledges her own vulnerability and frailty. This ecclesial vulnerability is based in the vulnerability of the triune God to whom she witnesses, as well as in the vulnerability of human beings. On the basis of this trinitarian and anthropological vulnerability, suggestions are made regarding the nature, attitude, and public calling of the church. As witnesses and disciples of Jesus Christ, the church has a threefold presence in public life; namely, to be vulnerable prophets, priests, and royals. A vulnerable church is a faithful church, and therefore, a relevant church.