bluuebunny/crossref_metadata_2025 huggingface dataset:
Sampling Plan Optimization: A Data Review and Sampling Frequency Evaluation Process
Authors: Ridley Maureen , MacQueen Donald
Published: February 2007

Lawrence Livermore National Laboratory (LLNL) uses a cost‐effective sampling (CES) methodology to evaluate and review ground water contaminant data and optimize the site's ground water monitoring plan. The CES methodology is part of LLNL's regulatory approved compliance monitoring plan (Lamarre et al. 1996). It allows LLNL to adjust the ground water sampling plan every quarter in response to changing conditions at the site. Since the use of the CES methodology has been approved by the appropriate regulatory agencies, such adjustments do not need additional regulatory approval. This permits LLNL to respond more quickly to changing conditions. The CES methodology bases the sampling frequency for each location on trend, variability, and magnitude statistics describing the contaminants at that location, and on the input of the technical staff (hydrologists, chemists, statisticians, and project leaders). After initial setup is complete, each application of CES takes only a few days for as many as 400 wells. Effective use of the CES methodology requires sufficient data, an understanding of contaminant transport at the site, and an adequate number of monitoring wells downgradient of the contamination. The initial implementation of CES at LLNL in 1992 produced a 40% reduction in the required number of annual routine ground water samples at LLNL. This has saved LLNL $390,000 annually in sampling, analysis, and data management costs.
Attenuation of Two Estrogen Compounds in Aquifer Materials Supplemented with Sewage Effluent
Authors: Ying Guang‐Guo , Kookana Rai S. , Dillon Peter
Published: February 2007

Aquifer storage and recovery (ASR) is an emerging and effective management technique in reclaiming and reusing waste water. During ASR, attenuation processes such as sorption and degradation may play an important role in removing trace organic contaminants in injected waste water. This study mainly investigated the role of treated sewage effluent injectant (the waste water injected into the aquifer) on degradation of two endocrine disrupting compounds, 17β‐estradiol (E2) and 17α‐ethynylestradiol (EE2), in the laboratory by comparing their behavior in incubation media—aquifer sediment/ground water slurry from the Bolivar experimental ASR site in South Australia and sediment/effluent slurry. Biodegradation of the two compounds in the sediment/ground water media (1:1, w/w) and in the sediment/effluent media (1:1, w/w) were conducted under aerobic and anaerobic conditions at 20°C. In both incubation media, E2 showed a rapid biodegradation with a DT50 value (time for 50% loss) of ∼2 days under aerobic conditions. E2 degraded slowly in both aquifer media under anaerobic conditions; however, the anaerobic degradation was noted to be somewhat faster in the sediment/effluent media. In contrast, EE2 was found to be resistant to biodegradation and remained almost unchanged within 70 days under anaerobic conditions in both incubation media. The mobility of the two compounds in the aquifer would depend on their sorption. The sorption coefficients measured on the aquifer sediment were 7.7 ± 3.4 L/kg for E2 and 10.6 ± 5.1 L/kg for EE2 using batch equilibration methods. The corresponding retardation factors were calculated to be 25 for E2 and 34 for EE2 based on the physical properties of the aquifer material in the Bolivar ASR site. This study showed that while E2 has modest sorption affinity for aquifer material, it is rapidly biodegraded with or without the supplement of effluent under aerobic conditions. Under anaerobic conditions, the relative rate of E2 degradation was slightly enhanced due to the presence of effluent in the incubation media. EE2 on the other hand was found to be persistent in this study under both aerobic and anaerobic conditions, as well as in the presence of effluent.
Layer‐ and cell‐type‐specific suprathreshold stimulus representation in rat primary somatosensory cortex
Authors: De Kock C. P. J. , Bruno R. M. , Spors H. , Sakmann B.
Published: February 2007

Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single‐cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory‐evoked responses were layer‐ and cell‐type‐specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick‐tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours.
Increases in central blood volume modulate carotid baroreflex resetting during dynamic exercise in humans
Authors: Ogoh Shigehiko , Fisher James P. , Fadel Paul J. , Raven Peter B.
Published: February 2007

We sought to determine if resetting of the carotid‐vasomotor baroreflex function curve during exercise is modulated by changes in central blood volume (CBV). CBV was increased during exercise by altering: (1) subject posture (supine versus upright) and (2) pedal frequency (80 versus 60 revolutions min−1 (r.p.m.)); while oxygen uptake () was kept constant. Eight male subjects performed three exercise trials: upright cycling at 60 r.p.m. (control); supine cycling at 60 r.p.m. (SupEX) and upright cycling at 80 r.p.m. to enhance the muscle pump (80EX). During each condition, carotid baroreflex (CBR) function was determined using the rapid neck pressure (NP) and neck suction (NS) protocol. Although mean arterial pressure (MAP) was significantly elevated from rest (88 ± 2 mmHg) during all exercise conditions (P < 0.001), the increase in MAP was lower during SupEX (94 ± 2 mmHg) and 80EX (95 ± 2 mmHg) compared with control (105 ± 2 mmHg, P < 0.05). Importantly, the blood pressure responses to NP and NS were maintained around these changed operating points of MAP. However, in comparison to control, the carotid‐vasomotor baroreflex function curve was relocated downward and leftward when CBV was increased during SupEX and 80EX. These alterations in CBR resetting occurred without any differences in or heart rate between the exercise conditions. Thus, increasing CBV and loading the cardiopulmonary baroreflex reduces the magnitude of exercise‐induced increases in MAP and CBR resetting. These findings suggest that changes in cardiopulmonary baroreceptor load influence carotid baroreflex resetting during dynamic exercise.
Effects of hypoxia on diaphragmatic fatigue in highly trained athletes
Authors: Vogiatzis Ioannis , Georgiadou Olga , Koskolou Maria , Athanasopoulos Dimitrios , Kostikas Konstantinos , Golemati Spyretta , Wagner Harrieth , Roussos Charis , Wagner Peter D. , Zakynthinos Spyros
Published: February 2007

Previous work suggests that exercise‐induced arterial hypoxaemia (EIAH), causing only moderate arterial oxygen desaturation (: 92 ± 1%), does not exaggerate diaphragmatic fatigue exhibited by highly trained endurance athletes. Since changes in arterial O2 tension have a significant effect on the rate of development of locomotor muscle fatigue during strenuous exercise, the present study investigated whether hypoxia superimposed on EIAH exacerbates the exercise‐induced diaphragmatic fatigue in these athletes. Eight trained cyclists (: 67.0 ± 2.6 ml kg−1 min−1; mean ±s.e.m.) completed in balanced order four 5 min exercise tests leading to different levels of end‐exercise (64 ± 2, 83 ± 1, 91 ± 1 and 96 ± 1%) via variations in inspired O2 fraction (: 0.13, 0.17, 0.21 and 0.26, respectively). Measurements were made at corresponding intensities (65 ± 3, 80 ± 3, 85 ± 3 and 90 ± 3% of normoxic maximal work rate, respectively) in order to produce the same tidal volume, breathing frequency and respiratory muscle load at each . The mean pressure time product of the diaphragm did not differ across the four exercise tests and ranged between 312 ± 28 and 382 ± 22 cmH2O s min−1. Ten minutes into recovery, twitch transdiaphragmatic pressure (Pdi,tw) determined by bilateral phrenic nerve stimulation, was significantly (P= 0.0001) reduced after all tests. After both hypoxic tests (: 0.13, 0.17) the degree of fall in Pdi,tw (by 26.9 ± 2.7 and 27.4 ± 2.6%, respectively) was significantly greater (P < 0.05) than after the normoxic test (by 20.1 ± 3.4%). The greater amount of diaphragmatic fatigue in hypoxia at lower leg work rates (presumably requiring smaller leg blood flow compared with normoxia at higher leg work rates), suggests that when ventilatory muscle load is similar between normoxia and hypoxia, hypoxia exaggerates diaphragmatic fatigue in spite of potentially greater respiratory muscle blood flow availability.
Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans
Authors: Amann Markus , Romer Lee M. , Subudhi Andrew W. , Pegelow David F. , Dempsey Jerome A.
Published: February 2007

We examined the effects of hypoxia severity on peripheral versus central determinants of exercise performance. Eight cyclists performed constant‐load exercise to exhaustion at various fractions of inspired O2 fraction (FIO2 0.21/0.15/0.10). At task failure (pedal frequency < 70% target) arterial hypoxaemia was surreptitiously reversed via acute O2 supplementation (FIO2= 0.30) and subjects were encouraged to continue exercising. Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (ΔQtw,pot) as measured pre‐ versus post‐exercise in response to supramaximal femoral nerve stimulation. At task failure in normoxia (haemoglobin saturation (SpO2) ∼94%, 656 ± 82 s) and moderate hypoxia (SpO2∼82%, 278 ± 16 s), hyperoxygenation had no significant effect on prolonging endurance time. However, following task failure in severe hypoxia (SpO2∼67%; 125 ± 6 s), hyperoxygenation elicited a significant prolongation of time to exhaustion (171 ± 61%). The magnitude of ΔQtw,pot at exhaustion was not different among the three trials (−35% to −36%, P= 0.8). Furthermore, quadriceps integrated EMG, blood lactate, heart rate, and effort perceptions all rose significantly throughout exercise, and to a similar extent at exhaustion following hyperoxygenation at all levels of arterial oxygenation. Since hyperoxygenation prolonged exercise time only in severe hypoxia, we repeated this trial and assessed peripheral fatigue following task failure prior to hyperoxygenation (125 ± 6 s). Although Qtw,pot was reduced from pre‐exercise baseline (−23%; P < 0.01), peripheral fatigue was substantially less (P < 0.01) than that observed at task failure in normoxia and moderate hypoxia. We conclude that across the range of normoxia to severe hypoxia, the major determinants of central motor output and exercise performance switches from a predominantly peripheral origin of fatigue to a hypoxia‐sensitive central component of fatigue, probably involving brain hypoxic effects on effort perception.
A New Variational Association Process for the Verification of Geometrical Specifications
Authors: Choley Jean-Yves , Riviere Alain , Clement André , Bourdet Pierre
Published: February 2007

When this new association process of a datum is performed to verify a geometrical specification, measured points are considered as perturbations which generate modifications of the nominal geometry by variation of its location, orientation, and intrinsic dimensional characteristics, without requiring rotation and translation variables as the traditional methods usually do (Bourdet, et al., 1996, Advanced Mathematical Tools in Metrology II, World Scientific) with torsors or matrices. This new association process (Choley, 2005, Ph.D. thesis, Ecole Central, Paris; Choley, et al., 2006, Advanced Mathematical and Computational Tools in Metrology, VII, World Scientific) is based on both a reduced modeling of the geometry, taken out of the computer aided design system database, and a variational distance function. The whole measured points set influence is taken into account as an optimization criterion is applied (Bourdet and Clement, 1988, Ann. CIRP 37(1), p. 503; Srinivasan, DIMACS Workshop on Computer Aided Design and Manufacturing, Rutgers University, NJ, October 7–9). Thus, the least squares optimization is achieved using the pseudo-inverse matrix, whereas the minimax optimization is treated with an algorithm developed by the Physikalisch-Technische Bundesanstalt and adapted for this purpose. In this paper, it is explained how this association process may be applied to planes and cylinders, used as single datum, datum systems, or common datum, with the least squares and minimax criteria.
Perceptions of a Receptor
Authors: Colquhoun David
Published: February 2007

Nicotinic Acetylcholine Receptors
. From Molecular Biology to Cognition.
By Jean-Pierre Changeux and Stuart J. Edelstein
. Odile Jacob, New York. 296 pp. $99. ISBN 9780976890805.

The authors offer a serious, insider's history of research on "the first membrane receptor for a neurotransmitter to be isolated and characterized at the molecular level."
Electrical Activity During the 2006 Mount St. Augustine Volcanic Eruptions
Authors: Thomas R. J. , Krehbiel P. R. , Rison W. , Edens H. E. , Aulich G. D. , Winn W. P. , McNutt S. R. , Tytgat G. , Clark E.
Published: February 2007

By using a combination of radio frequency time-of-arrival and interferometer measurements, we observed a sequence of lightning and electrical activity during one of Mount St. Augustine's eruptions. The observations indicate that the electrical activity had two modes or phases. First, there was an explosive phase in which the ejecta from the explosion appeared to be highly charged upon exiting the volcano, resulting in numerous apparently disorganized discharges and some simple lightning. The net charge exiting the volcano appears to have been positive. The second phase, which followed the most energetic explosion, produced conventional-type discharges that occurred within plume. Although the plume cloud was undoubtedly charged as a result of the explosion itself, the fact that the lightning onset was delayed and continued after and well downwind of the eruption indicates that in situ charging of some kind was occurring, presumably similar in some respects to that which occurs in normal thunderstorms.
The Triple-Ring Nebula Around SN 1987A: Fingerprint of a Binary Merger
Authors: Morris Thomas , Podsiadlowski Philipp
Published: February 2007

Supernova 1987A, the first naked-eye supernova observed since Kepler's supernova in 1604, defies a number of theoretical expectations. Its anomalies have long been attributed to a merger between two massive stars that occurred some 20,000 years before the explosion, but so far there has been no conclusive proof that this merger took place. Here, we present three-dimensional hydrodynamical simulations of the mass ejection associated with such a merger and the subsequent evolution of the ejecta, and we show that this accurately reproduces the properties of the triple-ring nebula surrounding the supernova.
Disrupting the Pairing Between
let-7
and
Hmga2
Enhances Oncogenic Transformation
Authors: Mayr Christine , Hemann Michael T. , Bartel David P.
Published: February 2007

MicroRNAs (miRNAs) are ∼22-nucleotide RNAs that can pair to sites within messenger RNAs to specify posttranscriptional repression of these messages. Aberrant miRNA expression can contribute to tumorigenesis, but which of the many miRNA-target relationships are relevant to this process has been unclear. Here, we report that chromosomal translocations previously associated with human tumors disrupt repression of
High Mobility Group A2
(
Hmga2
) by
let-7
miRNA. This disrupted repression promotes anchorage-independent growth, a characteristic of oncogenic transformation. Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells.
SYNCHRONIZATION AND PEAK-TO-PEAK DYNAMICS IN NETWORKS OF LOW-DIMENSIONAL CHAOTIC OSCILLATORS
Authors: MAGGI STEFANO , RINALDI SERGIO
Published: February 2007

In this paper we study the relationships between local and global properties in networks of dynamical systems by focusing on two global properties, synchronization and peak-to-peak dynamics, and on two local properties, coherence of the components of the network and coupling strength. The analysis is restricted to networks of low-dimensional chaotic oscillators, i.e. oscillators which have peak-to-peak dynamics when they work in isolation. The results are obtained through simulation, first by considering pairs of coupled Lorenz, Rössler and Chua systems, and then by studying the behavior of spatially extended tritrophic food chains described by the Rosenzweig–MacArthur model. The conclusion is that synchronization and peak-to-peak dynamics are different aspects of the same collective behavior, which is easily obtained by enhancing local coupling and coherence. The importance of these findings is briefly discussed within the context of ecological modeling.
GLOBAL ANALYSIS OF SYNCHRONIZATION IN COUPLED MAPS
Authors: JOST JÜRGEN , KOLWANKAR KIRAN M.
Published: February 2007

We introduce a new method for determining the global stability of synchronization in systems of coupled identical maps. The method is based on the study of invariant measures. Besides the simplest nontrivial example, namely two symmetrically coupled tent maps, we also treat the case of two asymmetrically coupled tent maps as well as a globally coupled network. Our main result is the identification of the precise value of the coupling parameter where the synchronizing and desynchronizing transitions take place.
MODULI-FREE NORMAL FORMS AND LINEARIZATION OF VECTOR FIELDS
Authors: LI CHENGZHI , REN ZHIHUA , YANG JIAZHONG
Published: February 2007

In this paper we study C1 linearization and classification of germs of hyperbolic vector fields on Rn. Two sets of algebraic conditions imposed on the eigenvalues of vector fields are given, under either of which strict similarity of the linear parts is necessary and sufficient for C1 conjugacy of two vector fields. Furthermore, one set of the algebraic conditions together with strict similarity also imply linearization.
Pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats
Authors: Albertí E. , Mikkelsen H. B. , Wang X. Y. , Díaz M. , Larsen J. O. , Huizinga J. D. , Jiménez M.
Published: February 2007

The aim of this study was to characterize the pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats, which harbor a mutation in the c- kit gene that affects development of interstitial cells of Cajal (ICC). In Ws/Ws rats, the density of KIT-positive cells was markedly reduced. Wild-type, but not Ws/Ws, rats showed low- and high-frequency cyclic depolarization that were associated with highly regular myogenic motor patterns at the same frequencies. In Ws/Ws rats, irregular patterns of action potentials triggered irregular muscle contractions occurring within a bandwidth of 10–20 cycles/min. Spontaneous activity of nitrergic nerves caused sustained inhibition of muscle activity in both wild-type (+/+) and Ws/Ws rats. Electrical field stimulation of enteric nerves, after blockade of cholinergic and adrenergic activity, elicited inhibition of mechanical activity and biphasic inhibitory junction potentials both in wild-type and Ws/Ws rats. Apamin-sensitive, likely purinergic, inhibitory innervation was not affected by loss of ICC. Variable presence of nitrergic innervation likely reflects the presence of direct nitrergic innervation to smooth muscle cells as well as indirect innervation via ICC. In summary, loss of ICC markedly affects pacemaker and motor activities of the rat colon. Inhibitory innervation is largely maintained but nitrergic innervation is reduced possibly related to the loss of ICC-mediated relaxation.
Frequency-dependent response of the vascular endothelium to pulsatile shear stress
Authors: Himburg Heather A. , Dowd Scot E. , Friedman Morton H.
Published: February 2007

As a result of the complex blood flow patterns that occur in the arterial tree, certain regions of the vessel wall experience fluctuations in shear stress that are dominated by harmonic frequencies higher than the heart rate ( 11 ). To assess whether variations in frequency affect endothelial gene expression, the gene expression patterns of cultured porcine aortic endothelium exposed to three sinusoidal waveforms (1, 2, and 3 Hz; amplitude = 15 dyn/cm2) and one physiological waveform were compared with the expression profiles elicited by steady flow. At each frequency, including steady flow, three levels of mean shear stress (0, 7.5, and 15 dyn/cm2) were used. After 24 h shear exposure, RNA was extracted for microarray analysis against 10,665 Sus scrofa oligonucleotides. A two-way ANOVA identified 232 genes of which their transcription was differentially modulated by frequency, while mean shear significantly affected the expression of ∼3,000 genes. One-way ANOVAs showed that the number of frequency-dependent genes increased as the mean shear stress was reduced. At 1 Hz, several inflammatory transcripts were repressed relative to steady flow, including VCAM and IL-8, whereas several atheroprotective transcripts were induced. The anti-inflammatory response at 1 Hz was reversed at 2 Hz. The proinflammatory response evoked by the higher frequency was most pronounced under reversing and oscillatory shear. This study suggests that arterial regions subject to both shear reversal and dominant frequencies that exceed the normal heart rate are at greater risk for atherosclerotic lesion development.
Rehydration with fluid of varying tonicities: effects on fluid regulatory hormones and exercise performance in the heat
Authors: Kenefick R. W. , Maresh C. M. , Armstrong L. E. , Riebe D. , Echegaray M. E. , Castellani J. W.
Published: February 2007

This study examined the effects of rehydration (Rehy) with fluids of varying tonicities and routes of administration after exercise-induced hypohydration on exercise performance, fluid regulatory hormone responses, and cardiovascular and thermoregulatory strain during subsequent exercise in the heat. On four occasions, eight men performed an exercise-dehydration protocol of ∼185 min (33°C) to establish a 4% reduction in body weight. Following dehydration, 2% of the fluid lost was replaced during the first 45 min of a 100-min rest period by one of three random Rehy treatments (0.9% saline intravenous; 0.45% saline intravenous; 0.45% saline oral) or no Rehy (no fluid) treatment. Subjects then stood for 20 min at 36°C and then walked at 50% maximal oxygen consumption for 90 min. Subsequent to dehydration, plasma Na+, osmolality, aldosterone, and arginine vasopressin concentrations were elevated ( P < 0.05) in each trial, accompanied by a −4% hemoconcentration. Following Rehy, there were no differences ( P > 0.05) in fluid volume restored, post-rehydration (Post-Rehy) body weight, or urine volume. Percent change in plasma volume was 5% above pre-Rehy values, and plasma Na+, osmolality, and fluid regulatory hormones were lower compared with no fluid. During exercise, skin and core temperatures, heart rate, and exercise time were not different ( P > 0.05) among the Rehy treatments. Plasma osmolality, Na+, percent change in plasma volume, and fluid regulatory hormones responded similarly among all Rehy treatments. Neither a fluid of greater tonicity nor the route of administration resulted in a more rapid or greater fluid retention, nor did it enhance heat tolerance or diminish physiological strain during subsequent exercise in the heat.
Array painting using microdissected chromosomes to map chromosomal breakpoints
Authors: Backx L. , van Esch H. , Melotte C. , Kosyakova N. , Starke H. , Frijns J.-P. , Liehr T. , Vermeesch J.R.
Published: February 2007

Molecular characterization of breakpoints of chromosomal rearrangements is a successful strategy for the identification of candidate disease genes. Mapping translocation breakpoints and rearranged chromosomal boundaries is labor intensive and/or time consuming. Here, we present a novel and rapid procedure to map such chromosomal breakpoints by hybridizing amplified microdissection derived DNA of aberrant chromosomes to arrays containing genomic clones. We illustrate the potential of the technique by molecularly delineating the breakpoints in five small supernumerary marker chromosomes (sSMC) and mapping the breakpoints of five different chromosomal translocations.
Isochores and replication time zones: a perfect match
Authors: Schmegner C. , Hameister H. , Vogel W. , Assum G.
Published: February 2007

The mammalian genome is not a random sequence but shows a specific, evolutionarily conserved structure that becomes manifest in its isochore pattern. Isochores, i.e. stretches of DNA with a distinct sequence composition and thus a specific GC content, cause the chromosomal banding pattern. This fundamental level of genome organization is related to several functional features like the replication timing of a DNA sequence. GC richness of genomic regions generally corresponds to an early replication time during S phase. Recently, we demonstrated this interdependency on a molecular level for an abrupt transition from a GC-poor isochore to a GC-rich one in the NF1 gene region; this isochore boundary also separates late from early replicating chromatin. Now, we analyzed another genomic region containing four isochores separated by three sharp isochore transitions. Again, the GC-rich isochores were found to be replicating early, the GC-poor isochores late in S phase; one of the replication time zones was discovered to consist of one single replicon. At the boundaries between isochores, that all show no special sequence elements, the replication machinery stopped for several hours. Thus, our results emphasize the importance of isochores as functional genomic units, and of isochore transitions as genomic landmarks with a key function for chromosome organization and basic biological properties.
Extensive coloured identification of dog chromosomes to support karyotype studies: the colour code
Authors: Courtay-Cahen C. , Griffiths L.A. , Hudson R. , Starkey M.
Published: February 2007

The identification of individual dog chromosomes is problematic because the 38 pairs of autosomes are small and acrocentric. Here we describe the design and application of a FISH tool that enables definitive identification of each dog autosome in a normal karyotype, without relying on subjective interpretation of DAPI banding patterns. From a high-resolution physical map of the canine genome, we have chosen a panel of 80 canine chromosome-specific BAC clones. DNA from each clone is labeled with one of five different fluorochrome-conjugated nucleotides. By selecting one to three spatially separated BACs per chromosome, and labelling them with a distinctive combination of colours, each autosome can be identified objectively and orientated accurately, irrespective of the quality of DAPI chromosome banding. This tool, or part of it, can be used for any purpose where accurate identification of canine autosomes in a normal karyotype is essential. In this study, we demonstrate use of the ‘colour code’ for chromosome identification following CGH analysis of unbalanced genomic aberrations in a canine brain tumour. Our method is an improvement of an earlier procedure, featuring chromosome-specific BACs and sequential FISH hybridisations, as it enables simultaneous identification of all chromosomes in a single hybridisation.
Mapping the distribution of the telomeric sequence (T2AG3)n in the Macropodoidea (Marsupialia) by fluorescence in situ hybridization. II. The ancestral 2n = 22 macropodid karyotype
Authors: Metcalfe C.J. , Eldridge M.D.B. , Johnston P.G.
Published: February 2007

In marsupial karyotypes with little heterochromatin, the telomeric sequence (T2AG3)n, is involved in chromosome rearrangements. Here we compare the distribution of the (T2AG3)n sequence in chromosomes recently derived by fusions and other rearrangements (7–0.5 MYBP) with its distribution in chromosomes derived earlier (24–9 MYBP). We have previously shown that the (T2AG3)n sequence is consistently retained during chromosome rearrangements that are recent (7–0.5 MYBP). We suggest that in less recent rearrangements (24–9 MYBP) the pattern observed is initial retention followed by loss or amplification. We also suggest that the presence of interstitial (T2AG3)n sequence is related to the evolutionary status of single chromosomes rather than entire karyotypes.
The Acute Effect of a Low Dosage of Pramipexole on Severe Idiopathic Restless Legs Syndrome: An Open-Label Trial
Authors: Merlino Giovanni , Dolso Pierluigi , Canesin Roberto , Cancelli Iacopo , Valente Mariarosaria , Gigli Gian Luigi
Published: February 2007

Background: Pramipexole is a D3 dopaminergic agonist that has shown a major effect on both sensory and motor manifestations of restless legs syndrome (RLS) in long-term trials. No data regarding the acute effect of low doses of pramipexole have been reported. Objective: To evaluate the acute effect of a low dosage of pramipexole (0.125 mg) on sensory symptoms and motor signs of RLS and on the macro- and microstructure of sleep. Methods: We initially recruited 13 patients affected by severe idiopathic RLS and included 10 of them in our study. For 2 consecutive nights the selected patients were evaluated. Pramipexole 0.125 mg was administered before the second night at 9:00 p.m. A visual analog scale was used to assess the sensory symptoms of RLS. The motor manifestations of RLS and the architecture of sleep were analyzed by polysomnography. Results: After the acute administration of pramipexole, we observed a significant improvement of the sensory symptoms and motor signs of RLS. Several sleep macrostructure and microstructure parameters improved as well. Conclusions: Our results suggest that low doses of pramipexole are effective in reducing sensory symptoms and motor signs of RLS, even after the first administration.
Exploiting Hardy-Weinberg Equilibrium for Efficient Screening of Single SNP Associations from Case-Control Studies
Authors: Chen Jinbo , Chatterjee Nilanjan
Published: February 2007

In case-control studies, the assessment of the association between a binary disease outcome and a single nucleotide polymorphism (SNP) is often based on comparing the observed genotype distribution for the cases against that for the controls. In this article, we investigate an alternative analytic strategy in which the observed genotype frequencies of cases are compared against the expected genotype frequencies of controls assuming Hardy-Weinberg Equilibrium (HWE). Assuming HWE for controls, we derive closed-form expressions for maximum likelihood estimates of the genotype-specific disease odds ratio (OR) parameters and related variance-covariances. Based on these estimates and their variance-covariance structure, we then propose a two-degree-of-freedom test for disease-SNP association. We show that the proposed test can have substantially higher power than a variety of existing methods, especially when the true effect of the SNP is recessive. We also obtain analytic expressions for the bias of the OR estimates when the underlying HWE assumption is violated. We conclude that the novel test would be particularly useful for analyzing data from the initial ‘screening’ stages of contemporary multi-stage association studies.
Genetic Predisposition to Familial Neuroblastoma: Identification of Two Novel Genomic Regions at 2p and 12p
Authors: Longo Luca , Panza Emanuele , Schena Francesca , Seri Marco , Devoto Marcella , Romeo Giovanni , Bini Carla , Pappalardo Giuseppe , Tonini Gian Paolo , Perri Patrizia
Published: February 2007

Objectives: The rarity of familial neuroblastoma (NB) has allowed only a few linkage studies, most of which did not show any evidence of linkage to regions involved in somatic alterations or to genes implicated in other neurocristopathies seldom associated with NB. We screened a highly informative family with recurrent NB by genome-wide linkage analysis aimed at identifying chromosomal regions for NB predisposing genes. Methods: A genome-wide screen was performed using 382 microsatellite markers. Multipoint model-based linkage analysis was carried out under a dominant mode of inheritance for the disease using the ‘affected only’ approach. Results: Our analysis identified two haplotypes co-segregating with the disease on chromosomes 2p and 12p, and yielded maximum lod-score values of 3.01 (p < 0.0001) for markers on both intervals. Conclusions: Evidence of linkage was reported at 16p in North American families, whereas our studies excluded this interval and indicated other loci for disease predisposition, thus confirming the remarkable genetic heterogeneity of NB. These results suggest an oligogenic inheritance in NB involving more loci in genetic determination of the disease.
Types of Depression More Frequent in Bipolar than in Unipolar Affective Illness: Results of the Polish DEP-BI Study
Authors: Rybakowski Janusz K. , Suwalska Aleksandra , Lojko Dorota , Rymaszewska Joanna , Kiejna Andrzej
Published: February 2007

Background: The aim of the study was to assess the relative frequency of various kinds of depression in patients with bipolar and unipolar affective illness. The study was performed in the framework of the DEP-BI project aimed at assessing the prevalence of bipolar disorders among depressive outpatients treated by psychiatrists in Poland. Methods: Eight-hundred and eighty patients (237 male, 643 female) participated in the study. The patients were classified into the following diagnostic categories: bipolar affective illness type I, type II, bipolar spectrum disorder and unipolar affective illness. The various kinds of depression in each group were assessed by means of a semistructured questionnaire added to the diagnostic interview. Results: In the group of bipolar patients, a significantly higher frequency of psychotic depression in male compared to female patients was observed. Male bipolar patients compared with unipolar depressed ones had significantly more episodes of psychotic depression (odds ratio, OR, 4.29) and atypical depression (hypersomnia and hyperphagia; OR 2.82), and those with bipolar spectrum had more episodes of treatment-resistant depression (OR 2.56). Female bipolar patients compared with unipolar depressed ones had significantly more frequently an early onset of depression (before 25 years; OR 2.95) and postpartum depression (OR 2.48). On the other hand, the percentage of agitation, irritability, distractibility, thought racing and panic attacks during depression was not different in patients with bipolar and unipolar affective illness either in males or females. Conclusions: Some kinds of depression occur with a higher frequency in patients with bipolar compared to unipolar affective illness. The occurrence of a given type of depression may constitute an aid for the diagnosis of bipolar illness. The results of this study did not confirm the concept of bipolar mixed depression based on the presence of anxiety symptoms occurring during the depressive episode. The limitation of our study may be the lack of formal criteria or a structured interview to assess the symptoms occurring during depressive episodes.
Decreased Endothelial Progenitor Cells in Umbilical Cord Blood in Severe Preeclampsia
Authors: Kwon Ja-Young , Maeng Yong-Son , Kwon Young-Guen , Kim Young-Han , Kang Moung-Hwa , Park Yong-Won
Published: February 2007

Background/Aims: We compared the numbers of endothelial progenitor cells (EPCs) in umbilical cord blood in severe preeclampsia and normal pregnancy, along with the cord blood plasma levels of free VEGF and sVEGFR-1. Methods: Umbilical cord blood EPC counts in severe preeclampsia (n = 15) and gestationally matched normal pregnant women (n = 30) were retrospectively analyzed. Cord plasma free VEGF and sVEGFR-1 levels were measured by enzyme immunoassay. Results: Significantly higher systolic blood pressure, lower birth weight, and higher rate of small for gestational age were noted in the severe preeclampsia group. Circulating EPCs in cord blood and umbilical cord plasma free VEGF were significantly decreased in severe preeclampsia compared to the control group (p = 0.009 and 0.04, respectively). Conclusion: In severe preeclampsia, cord blood EPCs were reduced markedly and this was accompanied by a significant decrease in cord plasma free VEGF which is known to play a role in EPC mobilization.
Role of Aldosterone in Left Ventricular Hypertrophy among African-American Patients with End-Stage Renal Disease on Hemodialysis
Authors: Steigerwalt Susan , Zafar Abida , Mesiha Nancy , Gardin Julius , Provenzano Robert
Published: February 2007

Aims: Recently, serum aldosterone levels have been reported to play a significant role in cardiac hypertrophy. One study of Japanese patients correlated aldosterone levels with the degree of left ventricular hypertrophy (LVH) in those undergoing hemodialysis. However, the role of aldosterone in LVH in non-Japanese patients with end-stage renal disease (ESRD) has not been established. Materials and Methods: Researchers evaluated 42 [29 African-Americans (69%), 11 Caucasians (26%), and 2 other (5%)] male ESRD patients on dialysis for more than 6 months. Pre- and postdialysis, blood pressures and aldosterone and renin concentrations were measured. Transthoracic echocardiography was performed and left ventricular mass (LVM) index was calculated using the Devereaux formula. Medications were reviewed. Results: There were no differences noted in medications prescribed for African-Americans and for Caucasians. Additionally, data from diabetic patients showed no statistically significant correlation between LVM index and any of the variables, including pre- and postdialysis blood pressure, serum potassium, renin, and aldosterone levels, for African-Americans compared to Caucasians. Data from nondiabetic patients showed a positive correlation between LVM and plasma aldosterone concentration in African-Americans (n = 10). Data from nondiabetic Caucasians were disregarded because only one was studied. Conclusion: LVM and aldosterone correlate in African-American males with ESRD on hemodialysis without diabetes. This has important implications for the etiology of, and therapy for LVH in this population. Larger studies are needed to determine whether the same associations exist in females and Caucasians.
Protein Kinase D Selectively Targets Cardiac Troponin I and Regulates Myofilament Ca
2+
Sensitivity in Ventricular Myocytes
Authors: Cuello Friederike , Bardswell Sonya C. , Haworth Robert S. , Yin Xiaoke , Lutz Susanne , Wieland Thomas , Mayr Manuel , Kentish Jonathan C. , Avkiran Metin
Published: February 2007

Protein kinase D (PKD) is a serine/threonine kinase with emerging myocardial functions; in skinned adult rat ventricular myocytes (ARVMs), recombinant PKD catalytic domain phosphorylates cardiac troponin I at Ser22/Ser23 and reduces myofilament Ca
2+
sensitivity. We used adenoviral gene transfer to determine the effects of full-length PKD on protein phosphorylation, sarcomere shortening and [Ca
2+
]
i
transients in intact ARVMs. In myocytes transduced to express wild-type PKD, the heterologously expressed enzyme was activated by endothelin 1 (ET1) (5 nmol/L), as reflected by PKD phosphorylation at Ser744/Ser748 (PKC phosphorylation sites) and Ser916 (autophosphorylation site). The ET1-induced increase in cellular PKD activity was accompanied by increased cardiac troponin I phosphorylation at Ser22/Ser23; this measured approximately 60% of that induced by isoproterenol (10 nmol/L), which activates cAMP-dependent protein kinase (PKA) but not PKD. Phosphorylation of other PKA targets, such as phospholamban at Ser16, phospholemman at Ser68 and cardiac myosin-binding protein C at Ser282, was unaltered. Furthermore, heterologous PKD expression had no effect on isoproterenol-induced phosphorylation of these proteins, or on isoproterenol-induced increases in sarcomere shortening and relaxation rate and [Ca
2+
]
i
transient amplitude. In contrast, heterologous PKD expression suppressed the positive inotropic effect of ET1 seen in control cells, without altering ET1-induced increases in relaxation rate and [Ca
2+
]
i
transient amplitude. Complementary experiments in “skinned” myocytes confirmed reduced myofilament Ca
2+
sensitivity by ET1-induced activation of heterologously expressed PKD. We conclude that increased myocardial PKD activity induces cardiac troponin I phosphorylation at Ser22/Ser23 and reduces myofilament Ca
2+
sensitivity, suggesting that altered PKD activity in disease may impact on contractile function.
Monitoring After the Acute Stage of Stroke
Authors: Rocco Andrea , Pasquini Marta , Cecconi Emanuella , Sirimarco Gaia , Ricciardi Maria C. , Vicenzini Edoardo , Altieri Marta , Di Piero Vittorio , Lenzi Gian L.
Published: February 2007

Background and Purposes—

In the early stage of stroke, the occurrence of neurologic and medical complications is associated with clinical deterioration. Previous studies were focused on the first week after stroke onset. The aim of this study was to evaluate the impact of complications on clinical outcome in patients with stroke in the early subacute stage.

Methods—

We prospectively evaluated the influence on the outcome of complications feasible (MC) and not feasible for monitoring (NMC) in all patients with stroke admitted consecutively in our subacute stroke unit. Patients were divided into three classes according to stroke severity evaluated by the National Institutes of Health Stroke Scale score. A change in the National Institutes of Health Stroke Scale score group from admission to discharge was considered clinically significant.

Results—

We included 261 patients. Sixty percent of patients had complications (105 MC, 118 NMC). Hyperthermia (OR=14.12; 95% CI: 6.01 to 33.20), urinary infections (OR=4.92; 95% CI: 2.19 to 11.04), hypertension (OR=2.86; 95% CI: 1.21 to 6.76), hypoxia (OR=15.75; 95% CI: 6.73 to 36.84), and neuroradiologic damage progression (OR=58.31; 95% CI, 19.48 to 174.55) were associated with a change to a more severe class at discharge and with a higher risk of mortality.

Conclusions—

A high percentage of patients can develop both MC and NMC during this subacute stage of stroke. The occurrence of complications influences outcome and raises the question about the need for a prolonged stay in a dedicated ward for patients with stroke.
Preclinical Vascular Cognitive Impairment and Alzheimer Disease
Authors: Ingles Janet L. , Boulton Denise C. , Fisk John D. , Rockwood Kenneth
Published: February 2007

Background and Purpose—

Neuropsychological changes that precede a diagnosis of vascular cognitive impairment (VCI) and the differences between preclinical VCI and Alzheimer disease (AD) are not well understood. We compared the neuropsychological performances of people with incident VCI, incident AD, and no cognitive impairment (NCI) 5 years before their clinical diagnoses.

Methods—

The Canadian Study of Health and Aging is a prospective, cohort study of 10 263 randomly selected persons age 65 years or older. We studied 332 individuals who had completed a battery of neuropsychological tests and were diagnosed with NCI at baseline. After 5 years, 41 were diagnosed with VCI, 25 with AD, and 266 with NCI.

Results—

At baseline, the incident-VCI group performed worse on a wide range of neuropsychological tests compared with the NCI group. A test of abstract reasoning was selectively low in the incident-VCI group, relative to both the incident-AD and NCI groups. The incident-AD group performed worse at baseline on memory tests compared with incident-VCI and NCI groups.

Conclusions—

This study suggests a preclinical phase may exist in VCI that differs from that in AD. Neuropsychological measures may aid the design of preventive strategies for VCI.
Time-Dependent Alterations in Functional and Pharmacological Arteriolar Reactivity After Subarachnoid Hemorrhage
Authors: Britz Gavin W. , Meno Joseph R. , Park Ik-Seong , Abel Taylor J. , Chowdhary Abhineet , Nguyen Thien-Son K. , Winn H. Richard , Ngai Al C.
Published: February 2007

Background and Purpose—

Disturbances in cerebral arteriolar function, in addition to large vessel vasospasm, may be responsible for ischemia after subarachnoid hemorrhage. The purpose of this study was to test the hypothesis that subarachnoid hemorrhage alters cerebral microvascular reactivity.

Methods—

An endovascular filament model was used to induce subarachnoid hemorrhage in halothane-anesthetized male Sprague-Dawley rats. We evaluated pial arteriolar responses to sciatic nerve stimulation, topically applied vasoactive agents (adenosine or sodium nitroprusside), and CO
2
inhalation in rats subjected to subarachnoid hemorrhage at 1 to 5 days after insult.

Results—

In sham-operated rats, sciatic nerve stimulation evoked a 23.5±1.8% increase in arteriolar diameter, which was significantly attenuated to 13.7±0.9%, 12.8±2.5%, and 18.8±2.9% at 24, 48, and 72 hours after subarachnoid hemorrhage, respectively (
P
<0.05; n≥7). At 96 and 120 hours after subarachnoid hemorrhage, sciatic nerve stimulation-induced dilation recovered to sham levels. Somatosensory-evoked potentials were unaltered by subarachnoid hemorrhage. Pial vasodilatation to adenosine (10 μmol/L) and sodium nitroprusside (1 μmol/L) were significantly impaired, by 47% and 41%, respectively, at 48 hours after subarachnoid hemorrhage (
P
<0.05; n=7). In contrast, CO
2
reactivity was unaffected by subarachnoid hemorrhage.

Conclusions—

Pial arteriolar responses to cortical activation may be decreased in the initial 2 to 3 days after experimental subarachnoid hemorrhage.
Assessment of Functional Outcome in a National Quality Register for Acute Stroke
Authors: Eriksson Marie , Appelros Peter , Norrving Bo , Terént Andreas , Stegmayr Birgitta
Published: February 2007

Background and Purpose—

To enable self-reporting of functional outcome in quality registers, the corresponding questions have to be easy to interpret. In scientific research, the modified Rankin Scale (mRS) is a standard assessment method. Such methods, with an outsider observer, are not feasible to use in quality registers. For several aspects, eg, comparisons between outcome in clinical studies and observational studies, we determined to see whether the functional outcome, as assessed in a quality register, can be transformed into mRS grades.

Methods—

The agreement between self-reported functional outcome (including dependency, living situation, mobility, dressing and toileting) and mRS were analyzed using 555 stroke patients registered in Riks-Stroke, the Swedish quality register for acute stroke, during a 5-month period in 4 hospitals. The self-reported outcome and the mRS grades were concurrently assessed by a telephone interview performed by an experienced nurse 3 months after stroke.

Results—

A translation using 5 of the questions from Riks-Stroke classified 76% of the patients to the correct mRS grade. The correlation between Riks-Stroke and mRS was 0.821 and Cohen’s κ (weighted) was 0.853.

Conclusion—

The study shows that self-reported functional outcome can be transformed into mRS grades with a high precision, making the translation useful for future comparative purposes in stroke outcome studies.