bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Distribution Volume Estimates Affect The Kinetic Model and Targeted Infusions
Authors: Avram Michael J. , Krejcie Tom C.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P85–P85; doi:
Life‐Threatening Bradycardia: The Clinical Relevance of Propoxyphene Inhibition of CYP2D6
Authors: Marraffa J. , Ong G. , Lehmann D. F.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P85–P85; doi:
When Should Dose Be Adjusted To Body Size? A Population Pharmacokinetc (PPK) Simulation
Authors: Lu J. , Gourlay S. , Bruno R.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P86–P86; doi:
Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti‐CD11a Antibody) Following Weekly Dosing in Psoriasis Patients
Authors: Sun Y. , Lu J. , Amita J. , Compton P. , Bruno R. A.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P86–P86; doi:
Population PK/PD Modeling of Testosterone (T), LH and Dihydrotestosterone (DHT) Response to Single SC Degarelix in Male Volunteers
Authors: Svensson U.S.H. , Senderovitz T. , Karlsson M.O.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P87–P87; doi:
A Novel Method For Deriving Intersubject Variability For Baseline Hazard Rates and Relative Risks For Secondary Vascular Events
Authors: Lee H. , Tannenbaum S. , Peck C. C.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P88–P88; doi:
Soluble Vascular Cell Adhesion Molecule‐1 (SVCAM‐1) Levels are Suppressed By Estrogens in Women on Oral Contraceptives Compared to Normally Menstruating Women
Authors: Janzen C. , Souter I. , Martinez‐Maza O. , Stanczyk F. , Chaudhuri G. , Nathan L.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P90–P90; doi:
Increased α1 Adrenergic Vascular Sensitivity in The Dorsal Hand Vein in African‐Americans
Authors: Sofowora G. , Muszkat M. , Disby V. , Prasad H.C. , Wood A.J.J. , Stein C.M.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P90–P90; doi:
Three Day 12‐Hour Cocaine Infusion Produces Tolerance in Cardiovascular and Subjective Effects, But Does Not Alter Cocaine Self‐Administration Behavior in Humans
Authors: Uemura N. , Manari A. , Nath R. P. , Harris D. S. , Jones R. T. , Mendelson J. E.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P91–P91; doi:
The Placebo Effect: Adverse Events Commonly Seen in Healthy Volunteer Phase I Drug Trials ‐ An Observation on Findings, Comparing Active With Placebo Treatment
Authors: Bradford D. A. , Mant T. G. , Amin D. A. , Angell M. P.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P92–P92; doi:
Establishment of a clinical pharmacology curriculum in a community‐based medical school
Authors: Naritoku D. K. , Faingold C. L.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P95–P95; doi:
Teaching pharmacokinetic logic through example: Application of modeling to observations from three perplexing overdoses
Authors: Pollak P. , Shafer S. L.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P95–P95; doi:
Variability in thiopurine methyltransferase (TPMT) and outcome in pediatric renal transplant patients
Authors: Lowry J. A. , Gaedigk A. , Reed L. , Leeder J. S. , Blowey D.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P97–P97; doi:
Pharmacogenetic determinant of cyclophosphamide therapy in patients with lupus nephritis
Authors: Arefayene M. , Desta Z. , Takada K. , Yarboro C. , Carrero H. , Illei G. , Flockhart D. A.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P97–P97; doi:
Endothelial nitric oxide synthase GLU298ASP polymorphism and blood pressure responses to salt
Authors: Sofowora G. , Muszkat M. , Dishy V. , Xie H‐G. , Prasad H. C. , Wood A. J. J. , Stein C. M.
Published: February 2005

Clinical Pharmacology & Therapeutics (2003) 73, P98–P98; doi:
Winning the war, but losing the peace? The dilemma of SPLM/A civil administration and the tasks ahead
Authors: Branch Adam , Cherian Mampilly Zachariah
Published: February 2005

The debate over peace in Sudan has centred on the ongoing talks in Naivasha, Kenya. This paper argues, however, that sustainable peace is not simply a function of the implementation of an agreement between the SPLA and Khartoum, but that other fracture lines will run through post-conflict Sudan. Here we draw attention to the rupture between the Dinka, dominant within the SPLA, and the Equatorian peoples of the far south, hundreds of thousands of whom were driven from their homes or faced with economic and political oppression under SPLA occupation. As these refugees return, it will be through local government structures that Equatorians will or will not be integrated into the SPLA political project for Southern Sudan. Thus, local government figures prominently in the possibility for sustainable peace. We describe the origins and structure of local government in Southern Sudan, situating it in the history of political tension between Dinka and Equatorians. We then describe the challenge of equitably distributing land and foreign aid to returnees in the context of ethnic politics and a massive NGO presence.
Cause and consequence in law and development
Authors: Manji Ambreena
Published: February 2005

Patrick McAuslan, Bringing the Law Back In: essays in land, law and development (Aldershot: Ashgate. 2003)

The title of the book sums up my overall stance: there is an important role for law in development generally and in land reform in particular and it is, in my view, wholly beneficial that after almost three decades of virtually ignoring the role of law in development … international financial institutions, aid agencies and scholars in the West are beginning to appreciate and reaffirm both its centrality to development in practice and its centrality to understanding the process of development and change in societies in developing countries. (McAuslan 2003: vii)

He who is able to translate others' interests into his own language carries the day. (Latour 1983: 144)
Mammal assemblage structure in Amazonian flooded and unflooded forests
Authors: Haugaasen Torbjørn , Peres Carlos A.
Published: February 2005

Few studies have contrasted faunal communities between flooded and unflooded tropical forests, and such attempts have largely been restricted to a few taxonomic groups. We present the first comparison of the composition and structure of an entire assemblage of mid-sized to large-bodied mammals in adjacent unflooded (terra firme) and flooded (várzea) forests of central-western Amazonia. We extend this comparison to 13 other terra firme and várzea forest sites in order to examine the fundamental dichotomy between mammal communities in these Amazonian environments. We found a consistently impoverished fauna in várzea environments both in terms of primates and other non-volant mammals, although primate density and biomass was substantially higher in várzea than in terra firme. The average Bray–Curtis mammal community dissimilarity between terra firme and várzea forests was 74%, whereas mean dissimilarity within várzea and terra firme samples was 40% and 39%, respectively. The results seem to be largely a function of high habitat heterogeneity and floristic diversity in terra firme and the physical connectivity and proximity of várzeas to adjacent terra firme forests. We suggest that inundated forests should be set aside as a crucial complement to Amazonian reserves dominated by terra firme forests in future biodiversity conservation planning.
Herbivory in epiphytic bromeliads, orchids and ferns in a Mexican montane forest
Authors: Winkler Manuela , Hülber Karl , Mehltreter Klaus , Franco José García , Hietz Peter
Published: February 2005

Herbivory is important in tropical woody plants, but the few data available suggest that rates of herbivory are mostly low in epiphytes. We quantified herbivory at the community level in five bromeliad, three orchid and five fern species of a Mexican humid montane forest. Leaf area loss was <1.5% in bromeliads and orchids, but much higher (7–20%) in ferns. Damage was positively correlated with leaf nitrogen content but not with leaf life span. In contrast to low leaf damage, many bromeliads were infested by curculionid larvae feeding on the meristematic tissue at the ramet base, and we estimate that this accounts for 18 and 31% of ramet and shoot death of large individuals of Tillandsia punctulata and T. deppeana, respectively. Herbivory in flowers, capsules or inflorescence stalks reduced fecundity by c. 14–18% in three of the five bromeliads and by 90% in the orchid Lycaste aromatica, but had little effect on the other species. These data show that even if the leaf area consumed is indeed low in epiphytic orchids and bromeliads, the less conspicuous damage done to reproductive organs and meristematic tissue can have a strong effect on fecundity and survival.
Low fruit set in a dioecious tree: pollination ecology of Commiphora harveyi in South Africa
Authors: Voigt Friederike A. , Jung Stefanie , Farwig Nina , Böhning-Gaese Katrin
Published: February 2005

Dioecious plant species differ in floral morphology and rewards between females and males. Pistillate flowers on female plants often lack pollen and can be less attractive to pollinators, which can have consequences for the visitation rates of the sexes. We studied the pollination ecology of the dioecious tree Commiphora harveyi in a coastal scarp forest in eastern South Africa. Floral display, visiting insect species, visitation rate and natural fruit set were recorded. Additionally, we pollinated flowers by hand to determine experimental fruit set. We found that male trees had more and larger flowers per inflorescence than female trees. Both sexes produced nectar in low amounts. During 203.5 h of observation we recorded 28 insect species visiting the flowers. No difference in mean visitation rate (0.20 visits per flower h−1) was recorded between the sexes. The daily and seasonal pattern was similar between the sexes. The natural fruit set was low (3.8%) and increased significantly with hand-pollination (45.5%), an indication of pollen limitation. We compared our results with the pollination ecology of C. guillauminii in Madagascar, a dioecious tree species on an island with a depauperate pollinator fauna. This comparison revealed a similar pattern with low visitation rates, low insect diversity and low fruit set, suggesting that this pattern may be more common in dioecious tree species than previously reported in the literature.
Seasonal variation in population and community structure of shrews in a tropical forest of Gabon
Authors: Nicolas Violaine , Barrière Patrick , Colyn Marc
Published: February 2005

The composition, structure and reproductive phenology of a shrew community were investigated for 1 y at two neighbouring sites in an undisturbed African forest of south-western Gabon. We captured 717 shrews, belonging to four genera and 10 species. The data were analysed to answer three main questions: (1) to what extent does the shrew abundance vary seasonally? (2) is there a shift in species dominance over time? and (3) does the intensity of breeding activity vary seasonally? The number of species captured varied seasonally and tended to be least during the period of minimal trap success. Trap success for the four most abundant species (Sylvisorex johnstoni, Crocidura batesi, Paracrocidura schoutedeni and Sylvisorex ollula) varied seasonally with a minimum around the long dry season. Sylvisorex johnstoni remained the dominant species throughout the year. Seasonal variation in trap success of shrews might be related, at least partly, to their reproductive characteristics. Litter size, based on embryo counts, ranged from 1–4 among the species. Breeding occurred throughout the year, but its intensity was lower during the long dry season corresponding with the period of higher ecological constraints for shrews.
Fractal reconnection structures on the magnetopause
Authors: Coleman Iain J. , Freeman Mervyn P.
Published: February 2005

Simple laminar flow models of the magnetosheath plasma lead to predictions of large‐scale reconnection structures on the dayside magnetopause. There is observational evidence from the ionosphere that such structures exist. However, in situ observations of the magnetosheath plasma near the magnetopause indicate that the fluid is highly disordered, with the magnetic field orientation in particular being extremely noisy. This raises the question of how coherent large‐scale reconnection structures can be created and persist. This paper shows that, if the apparent noise in the magnetosheath field has the characteristics of fractal turbulence, large‐scale structures can persist even when the apparent noise levels in the draped magnetic field are very large. Furthermore, the common observation of reconnection transients is naturally explained by this model.
Air quality impacts of the October 2003 Southern California wildfires
Authors: Phuleria Harish C. , Fine Philip M. , Zhu Yifang , Sioutas Constantinos
Published: February 2005

In Southern California, dry summers followed by hot and dry westerly wind conditions contribute to the region's autumn fire season. In late October 2003, 13 large Southern California wildfires burned more than 750,000 acres of land, destroyed over 3500 structures, and displaced approximately 100,000 people. The fire episode was declared the deadliest and most devastating in more than a decade, and local media advised individuals to stay indoors to avoid exposure to excessive levels of PM, CO, VOCs, and ozone caused by the wildfires. This study examines the actual impact of these wildfires on air quality in urban Los Angeles (LA) using “opportunistic” data from other air pollution studies being conducted at the time of the fires. Measurements of pollutant gases (CO, NOx, and ozone), particulate matter (PM), particle number (PN) concentrations, and particle size distributions at several sampling locations in the LA basin before, during, and after the fire episode are presented. In general, the wildfires caused the greatest increases in PM10 levels (a factor of 3–4) and lesser increases in CO, NO, and PN (a factor of up to 2). NO2 levels remained essentially unchanged, and ozone concentrations dropped during the fire episode. Particle size distributions of air sampled downwind of the fires showed number modes at diameters between 100 and 200 nm, significantly larger than that of typical urban air. The particles in this size range were shown to effectively penetrate indoors, raising questions about the effectiveness of staying indoors to avoid exposure to wildfire emissions.
Modification of secondary craters on the Martian South Polar Layered Deposits
Authors: Schaller E. L. , Murray B. , Pathare A. V. , Rasmussen J. , Byrne S.
Published: February 2005

Secondary crater fields are important stratigraphic markers that can shed light on resurfacing processes that have occurred since their formation. We examine the morphologies of secondary craters formed from the ejection of material from two large impacts on the Martian South Polar Layered Deposits (SPLD): McMurdo crater at 84.5°S, 0°W, and an unnamed impact at 80.8°S, 284°W. The morphologies of these secondary craters allow us to impose constraints on the modification history of the SPLD. We have quantified crater morphologies using data sets from the Mars Global Surveyor and Mars Odyssey missions. We find a complete lack of secondary craters smaller than 300 m in diameter in both crater fields, which implies that at least the upper 30 m of the deposits have been resurfaced since the time of these impacts. Secondary crater depth‐to‐diameter ratios are low (average of 0.016), indicating that significant degradation has occurred since their emplacement. We find that vertical resurfacing alone is not enough to explain the observed depth‐to‐diameter distribution and suggest that viscous relaxation of craters coupled with a small amount of vertical resurfacing best fits the data. In the McMurdo field, high depth‐to‐diameter craters are found preferentially on steeper terrain associated with scarps cutting through the secondary field. This observation suggests that crater modification exhibits a dependence on slope. We comment on possible mechanisms that may explain this observation. The morphologies of secondary craters on the SPLD point to modification processes without lunar parallel and not yet fully modeled for Mars.
Inhibition of endogenous nitric oxide in the heart enhances matrix metalloproteinase‐2 release
Authors: Wang Wenjie , Viappiani Serena , Sawicka Jolanta , Schulz Richard
Published: February 2005

Matrix metalloproteinase (MMP) activity is upregulated in pathologies such as atherosclerosis during which endogenous nitric oxide (NO) biosynthesis is reduced. Diminished levels of NO, an antioxidant species, may result in higher oxidative stress. Oxidants are capable of activating MMPs from their zymogen forms. We examined whether basal biosynthesis of NO in the coronary circulation regulates MMP‐2 activity.

In isolated rat hearts perfused with Krebs–Henseleit buffer at a constant flow of 10 ml min−1, we measured the release of MMP‐2 into the coronary effluent by gelatin zymography. The main gelatinolytic activity of 72‐kDa corresponds to MMP‐2. Infusion of the NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) concentration dependently increased coronary perfusion pressure (CPP) (by 48±11 mmHg with 100 μM) and enhanced the release of the 72‐kDa MMP‐2 in the effluent. Coinfusion of the NO donor S‐nitroso‐N‐acetyl‐D,L‐penicillamine (SNAP, 1 μM) with L‐NAME abolished both the increase in CPP and the enhanced MMP‐2 release.

The thromboxane A2 mimetic U46619 increased CPP to the same extent as L‐NAME without increasing 72‐kDa activity in the effluent, suggesting that MMP‐2 release is not caused simply by enhanced perfusion pressure.

Infusion of either L‐NAME or U46619 did not significantly enhance LDH release.

L‐NAME infusion concentration dependently increased the level of lipid hydroperoxides in homogenates prepared from the perfused hearts. Coinfusion of SNAP prevented this increase.

These data reveal another cytoprotective mechanism of endogenous NO biosynthesis in the heart, the inhibition of MMP‐2 release.

British Journal of Pharmacology (2005) 145, 43–49. doi:10.1038/sj.bjp.0706144
Effects of diadenosine polyphosphates on glomerular volume
Authors: Szczepańska‐Konkel Miroslawa , Jankowski Maciej , Stiepanow‐Trzeciak Anna , Angielski Stefan
Published: February 2005

Diadenosine polyphosphates (P1,P3‐diadenosine triphosphate, Ap3A; P1,P4‐diadenosine tetraphosphate, Ap4A; and P1,P5‐diadenosine pentaphosphate, Ap5A) are vasoactive molecules. The experimental model of isolated rat renal glomeruli was used to investigate their effects on glomerular vasculature. We measured the changes of glomerular inulin space (GIS) as a marker of glomeruli contractility.

Ap4A and Ap5A induced concentration‐ and time‐dependent reduction of GIS whereas Ap3A had no effect. The effects of Ap4A and Ap5A (both at 1 μM) were prevented by a nonselective P2 receptor antagonist, that is, suramin (10 μM) and P2Y receptor antagonist – reactive blue 2 (50 μM). However, the antagonist of P1 receptor, that is, theophylline (1 μM) and A1 receptor 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 10 μM) did not affect the responses of glomeruli to Ap4A or Ap5A.

Ap3A, in contrast to Ap4A and Ap5A, prevented angiotensin II‐induced reduction of GIS in a concentration‐ and time‐dependent manner. This effect was partially prevented by suramin and markedly reduced by reactive blue 2 and the specific antagonist of P2Y1 receptor – MRS 2179 (10 μM). However, theophylline and the specific antagonist of A2 receptor – 3,7‐dimethyl‐1‐propargylxanthine (DMPX; 10 μM) – did not affect Ap3A action.

We indicate that diadenosine polyphosphates changed the glomerular volume via activation of P2 receptors. We suggest that extracellular Ap4A and Ap5A via P2X and P2Y receptors may decrease and Ap3A via, at least in part, P2Y1 receptors may increase filtration surface, which in turn may modify glomerular filtration rate.

British Journal of Pharmacology (2005) 144, 1109–1117. doi:10.1038/sj.bjp.0706149
Transient Changes in Cortical Glucose and Lactate Levels Associated with Peri-Infarct Depolarisations, Studied with Rapid-Sampling Microdialysis
Authors: Hopwood Sarah E , Parkin Mark C , Bezzina Elizabeth L , Boutelle Martyn G , Strong Anthony J
Published: February 2005

Peri-infarct depolarisations (PIDs) contribute to infarct expansion in experimental focal ischaemia; furthermore, depolarisations propagate in the injured human brain. Glucose utilisation is increased under both conditions, and depletion of brain glucose carries a poor prognosis. We studied dynamics of cerebral glucose and lactate in relation to PID patterns in experimental stroke. The middle cerebral artery was occluded for 3 h in 23 cats under terminal chloralose anaesthesia. We used fluorescence imaging to detect occurrence of PIDs, and rapid-sampling online microdialysis (rsMD), coupled to a flow-injection assay, to examine changes in cerebral cortical extracellular glucose and lactate at intervals of 30 sec each. After 30 min' ischaemia, lactate had increased by 43.6±s.d. 45.9 μmol/L, and stabilised in that range for 3 h. In contrast, glucose fell only slightly initially (11.9±9.7 μmol/L), but progressively decreased to a reduction of 56.7±47.2 μmol/L at 3 h, with no evidence of stabilisation. There was a highly significant inverse relationship of frequency of PIDs with plasma glucose ( P<0.001). The results also characterise a metabolic signature for PIDs for possible application in clinical work, and emphasise potential risks in the use of insulin to control plasma glucose in patients with brain injury.
Quantitative Evaluation of BBB Permeability after Embolic Stroke in Rat Using MRI
Authors: Jiang Quan , Ewing James R , Ding Guang Liang , Zhang Li , Zhang Zheng Gang , Li Lian , Whitton Polly , Lu Mei , Hu Jiani , Li Qing Jiang , Knight Robert A , Chopp Michael
Published: February 2005

We sought to identify magnetic resonance imaging (MRI) parameters that can identify as well as predict disruption of the blood–brain barrier (BBB) after embolic stroke in the rat. Rats subjected to embolic stroke with ( n=13) and without ( n=13) rt-PA treatment were followed with MRI using quantitative permeability-related parameters, consisting of: transfer constant ( K i) of Gd- DTPA, the distribution volume ( Vp) of the mobile protons, and the inverse of the apparent forward transfer rate for magnetization transfer ( kinv), as well as the apparent diffusion coefficient of water ( ADCw), T2, and cerebral cerebral blood flow (CBF). Tissue progressing to fibrin leakage resulting from BBB disruption and adjacent tissue were then analyzed to identify MRI markers that characterize BBB disruption. Animals were killed after final MRI measurements at 24 h after induction of embolic stroke and cerebral tissues were perfused and stained to detect fibrin leakage. K i, Vp, and kinv were the most sensitive early (2 to 3 h) indices of the cerebral tissue that progresses to fibrin leakage. Cerebral blood flow was not significantly different between ischemic tissue with a compromised and an intact BBB. Our data indicate that compromise of the BBB can be sensitively predicted using a select set of MR parameters.
Neuroprotection against Focal Ischemic Brain Injury by Inhibition of c-Jun N-Terminal Kinase and Attenuation of the Mitochondrial Apoptosis-Signaling Pathway
Authors: Gao Yanqin , Signore Armando P. , Yin Wei , Cao Guodong , Yin Xiao-Ming , Sun Fengyan , Luo Yumin , Graham Steven H. , Chen Jun
Published: February 2005

c-Jun N-terminal kinase (JNK) is an important stress-responsive kinase that is activated by various forms of brain insults. In this study, we have examined the role of JNK activation in neuronal cell death in a murine model of focal ischemia and reperfusion; furthermore, we investigated the mechanism of JNK in apoptosis signaling, focusing on the mitochondrial-signaling pathway. We show here that JNK activity was induced in the brain 0.5 to 24 h after ischemia. Systemic administration of SP600125, a small molecule JNK-specific inhibitor, diminished JNK activity after ischemia and dose-dependently reduced infarct volume. c-Jun N-terminal kinase inhibition also attenuated ischemia-induced expression of Bim, Hrk/DP5, and Fas, but not the expression of Bcl-2 or FasL. In strong support of a role for JNK in promoting the mitochondrial apoptosis-signaling pathway, JNK inhibition prevented ischemia-induced mitochondrial translocation of Bax and Bim, release of cytochrome c and Smac, and activation of caspase-9 and caspase-3. The potential mechanism by which JNK promoted Bax translocation after ischemia was further studied using coimmunoprecipitation, and the results revealed that JNK activation caused serine phosphorylation of 14-3-3, a cytoplasmic sequestration protein of Bax, leading to Bax disassociation from 14-3-3 and subsequent translocation to mitochondria. These results confirm the role of JNK as a critical cell death mediator in ischemic brain injury, and suggest that one of the mechanisms by which JNK triggers the mitochondrial apoptosis-signaling pathway is via promoting Bax and Bim translocation.
Protective Effects of Statins Involving Both eNOS and tPA in Focal Cerebral Ischemia
Authors: Asahi Minoru , Huang Zhihong , Thomas Sunu , Yoshimura Shin-ichi , Sumii Toshihisa , Mori Tatsuro , Qiu Jianhua , Amin-Hanjani Sepideh , Huang Paul L. , Liao James K. , Lo Eng H. , Moskowitz Michael A.
Published: February 2005

Previous studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) protect the brain against ischemic injury by upregulating endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that statins provide additional beneficial effects by also upregulating endogenous tissue plasminogen activator (tPA) and enhancing clot lysis in a mouse model of embolic focal ischemia. Heterologous blood clots (0.2 mm) were injected into the distal internal carotid artery to occlude blood flow in the middle cerebral artery territory after long-term (14 days) simvastatin, atorvastatin or vehicle treatment. Ischemic lesion volume, neurologic deficits, as well as residual blood clots were measured at 22 h. Reverse transcription-polymerase chain reaction assessed mRNA levels of eNOS, tPA, and the endogenous plasminogen activator inhibitor PAI-1. Ischemic lesion volumes and neurologic deficits were significantly reduced in wild-type mice by both simvastatin and atorvastatin. Statins increased eNOS and tPA mRNA levels but did not change mRNA levels of PAI-1. In eNOS knockout mice, atorvastatin reduced the volume of ischemic tissue and improved neurologic outcomes after arterial occlusion by blood clot emboli. In contrast, statins did not have protective effects in tPA knockout mice after embolic focal ischemia, but only in a filament model where focal ischemia was achieved via mechanical occlusion. These results suggest that statins protect against stroke by multiple mechanisms involving both eNOS and tPA. The involvement of each pathway may be revealed depending on the choice of experimental stroke model.
Does colonization contribute to spatial patterns of common invertebrates in coralline algal turf?
Authors: Kelaher Brendan P.
Published: February 2005

Abstract  The potential of colonization to contribute to the spatial patterns of six common invertebrates in coralline algal turf was investigated on a rocky shore near Sydney, Australia. The species, which included two amphipods (Elasmopus warra, Hyale spp.), a small bivalve (Lasaea australis), a fly larva (Limonia marina), and two microgastropods (Amphithalamus incidata and Eatoniella atropurpurea), had a range of dispersal modes (larval dispersal, crawling, swimming, rafting, and passive transport). Field sampling between May 1997 and November 1999 demonstrated that the amphipods were more abundant in low‐shore areas, the fly larvae and bivalves were more abundant in mid‐shore areas, and the abundances of gastropods did not vary with tidal height. Furthermore, abundances of all species varied among patches separated by tens of metres at one time or another. To test whether rates of colonization could contribute to established patterns of abundance, habitat mimics were deployed for 2‐week periods. The supply of new individuals matched long‐term patterns of abundance at different tidal heights for E. warra and L. marina. Colonization rates also differed among patches separated by tens of metres for three of the six species. Overall, there was little evidence to suggest that common species in coralline turf are limited by colonization on local scales, regardless of their major mode of dispersal. However, the potential for colonization to determine patterns of abundance varied from species to species.
A long‐term record of Nothofagus dominance in the southern Andes, Chile
Authors: Pollmann William
Published: February 2005

Abstract  The general model of regeneration dynamics in Nothofagus forests of southern South America could have value in community ecology if predictive relationships between disturbance history, functional traits and site attributes could be identified. Examined here is the proposal that on favourable sites shade‐intolerant Nothofagus are likely not to survive in competition with shade‐tolerant, broad‐leaved evergreen taxa of temperate rain forests, and persistence, thus, is dependent on periodic coarse‐scale disturbance. Comparison of stand dynamics of three old‐growth Nothofagus forests at different elevations in the southern Andes, Chile where deciduous Nothofagus alpina dominates the upper canopy, and examination of the life history trade‐offs of this variation were made. Stem density of all stems ≥5.0 cm d.b.h. was 233–303 stems per hectare, and basal area was 123.9–171.0 m2ha−1. Maximum lifespan of N. alpina was found to be greater than ca 640 years, exceeding all previously reported ages for this species in the region. Forests had a stable canopy composition for this long‐term, but some appeared to lack effective regeneration of N. alpina in recent years. Regeneration of N. alpina was generally greater in disturbed stands and higher elevation than in undisturbed stands and at lower elevation. Recruitment emerged to be strongly affected by competitive over‐ and understorey associates. There was a gradient of increasing dependence of N. alpina on disturbance towards the more productive end of the environment gradients, and hence less dependence of N. alpina on disturbance for its regeneration towards higher elevation. The study confirms that changes in forest composition may be explained by processes occurring in accordance with the predictions of the existing model of Nothofagus regeneration dynamics, providing stronger evidence specifically directed at mid‐tolerant N. alpina, and by factoring out regeneration dynamics on favourable sites. Thus, for N. alpina, trait differences probably contribute to the competitive advantage over its associates in productive habitats, and may be linked to small‐to‐intermediate‐sized disturbances which inevitably occur as older trees die, enabling N. alpina to persist in forests and therefore maintain species coexistence for the long‐term.
Electrophysiological and Histopathological Characteristics of Progressive Atrioventricular Block Accompanied by Familial Dilated Cardiomyopathy Caused by a Novel Mutation of Lamin A/C Gene
Authors: OTOMO JUN , KURE SHIGEO , SHIBA TOMOKO , KARIBE AKIHIKO , SHINOZAKI TSUYOSHI , YAGI TETSUO , NAGANUMA HIROSHI , TEZUKA FUMIAKI , MIURA MASAETSU , ITO MEIICHI , WATANABE JUN , MATSUBARA YOICHI , SHIRATO KUNIO
Published: February 2005

Introduction: Mutations of lamin A/C gene (LMNA) cause dilated cardiomyopathy (DCM) with atrioventricular (AV) conduction defect, although the electrophysiological and histological profiles are not fully understood.

Methods and Results: We analyzed a large Japanese family (21 affected and 203 unaffected members) of DCM with AV block. The responsible LMNA mutation of IVS3–10A>G was novel and caused an aberrant splicing. The first clinical manifestation was low‐grade AV block or atrial fibrillation (AF), which developed in affected members aged ≥30 years. We observed that the AV block progressed to third‐degree within several years. The electrophysiological study of the four affected members revealed an impairment of intra‐AV nodal conduction. Because of advanced AV block, pacemakers were implanted in 14 out of 21 affected members at the mean age of 44 years. Three affected members died suddenly and two affected members died of heart failure and/or ventricular tachycardia (VT) even after the pacemaker implantation. Postmortem examination showed conspicuous fibrofatty degeneration of the AV node. Endomyocardial biopsies showed remarkably deformed nuclei and substantial glycogen deposits in the subsarcolemma.

Conclusion: The clinical phenotype in this family was characterized by (1) the first manifestation of the prolonged PQ interval or AF in adolescence, (2) progressive intra‐AV nodal block to the third degree in several years, and (3) progressive heart failure after pacemaker implantation. Histological study revealed preferential degeneration at the AV node area and novel cellular damages in the working myocardium.
Numerical Simulation of Paced Electrogram Fractionation: Relating Clinical Observations to Changes in Fibrosis and Action Potential Duration
Authors: TURNER IAN , L.‐H. HUANG CHRISTOPHER , SAUMAREZ RICHARD C
Published: February 2005

Introduction: Paced electrogram fractionation analysis (PEFA) may identify a re‐entrant substrate in patients at risk of ventricular fibrillation (VF) by detecting prolonged, fractionated ventricular electrograms (“fractionation”) in response to premature extrastimuli. Numerical simulations of action potential (AP) propagation through human myocardium following such premature stimulation were performed to study the relationship between electrogram fractionation, fibrosis, and changes in AP currents.

Methods and Results: Activation in a resistive monodomain 2 cm2 sheet of myocardium containing nonconducting fibrous tissue was modeled using standard numerical methods for solutions of partial differential equations using the Priebe–Beukelmann (PB) AP equations. Myocardial fibrosis significantly influenced electrogram morphology. High densities of closely spaced fibrous septa caused functional block and altered propagation paths at short coupling intervals, and produced large increases in electrogram duration similar to those associated with increased risk of VF in clinical studies. Prolongation of the cardiac AP using the heart failure variant of the PB model further increased the amount of fractionation and thereby replicated clinical recordings more closely than did fibrosis alone. Increasing AP dispersion by a variable reduction in the potassium current IKr simulated results seen in patients with the long QT syndrome with an abrupt increase in electrogram duration, while a uniform reduction in IKr alone did not result in fractionated electrograms. In contrast, increases in cytosolic Ca2+ and Ca2+ buffering by troponin to simulate HCM had little effect on fractionation.

Conclusions: These results relate the effects of fibrosis, AP abnormalities, and dispersion of AP duration to the characteristic electrograms recorded in patients at risk of sudden death.
Characterization of Right Atrial Substrate in Patients with Supraventricular Tachyarrhythmias
Authors: LIN YENN‐JIANG , TAI CHING‐TAI , HUANG JIN‐LONG , LEE KUN‐TAI , LEE PI‐CHANG , HSIEH MING‐HSIUNG , LEE SHIH‐HUANG , HIGA SATOSHI , YUNIADI YOGA , LIU TU‐YING , CHEN SHIH‐ANN
Published: February 2005

Background: Voltage mapping has been used to detect diseased myocardium. However, accurate determination of the local atrial voltage at the same site, and simultaneous recordings from multiple mapping sites were limited. The purpose of this study was to investigate the right atrial (RA) substrate properties in patients with supraventricular tachyarrhythmias (SVT).

Methods and Results: Forty patients (aged 55 ± 20 years) undergoing noncontact mapping and ablation of SVT constituted the study population. There were eight patients with atrioventricular node reentrant tachycardia (AVNRT), eight patients with focal atrial tachycardia (AT), 14 patients with atrial flutter (AFL), and 10 patients with atrial fibrillation (AF). The mean peak negative voltage (PNV) was analyzed in virtual unipolar electrograms, which were obtained from 256 equally distributed RA endocardial sites during sinus rhythm (SR), atrial pacing, and tachycardia. The mean PNV of global RA during SR (−1.34 ± 0.22 vs. −0.90 ± 0.40 vs. −1.00 ± 0.36 vs. −0.85 ± 0.35 mV, P = 0.04), atrial pacing at cycle lengths of 500 ms (−1.30 ± 0.29 vs. −0.70 ± 0.35 vs. −0.76 ± 0.25 vs. −0.64 ± 0.26 mV, P = 0.02), and 300 ms (−1.54 ± 0.47 vs. −0.94 ± 0.21 vs. −0.75 ± 0.27 vs. −0.57 ± 0.22 mV, P < 0.01) were significantly greater in patients with AVNRT compared to AT, AFL, and AF. Furthermore, the mean PNV decreased during atrial pacing with shorter pacing cycle length was demonstrated only in patients with AFL and AF.

Conclusion: Negative unipolar voltage analysis of global RA showed different RA substrate characteristics during various SVT. The substrate property of activation and cycle length‐dependent voltage reduction may be related to the development of AFL and AF.
The High Frequency Magnetic Field of a Flat Spiral Coil
Authors: Githens Sherwood , Stuhlman Otto
Published: February 2005

The high frequency magnetic field of a flat spiral coil, with an inner opening about one-fourth the diameter of the coil, was excited by single-tube tuned plate-tuned grid and push-pull oscillators. Frequency range 1500 to 6000 kc/sec. The magnetic fields thus excited were compared with the fields produced by a direct current. The results when a push-pull oscillator was used to excite the high frequency field showed no apparent difference, except near the far edges lying about 25 cm from the center of the coil, and were independent of frequency.

Unbalanced high frequency excitation showed magnetic field crowded toward the normal axis when filament lead was connected to inner turn of spiral. Field strength across inner diameter was found to be non-uniform when field was excited by a balanced push-pull oscillator. Field strength along normal axis of coil diminished more rapidly for a balanced than for unbalanced excitation, independent of method of lead connections and was much smaller for the case of filament lead connected to outer end of spiral.
Improved Design of the Mechanical Interval Sorter and Its Application to the Analysis of Complex Spectra
Authors: Harrison George R.
Published: February 2005

The spectrum interval sorter recently described by the writer has been considerably modified to increase its accuracy and convenience. Probability considerations of the relative numbers of real and accidental interval coincidences to be expected in typical complex spectra indicate the desirability of applying the combination principle to selected groups of lines, each group to contain not more than a limited number of lines given by their frequency density and by the accuracy with which their frequencies are known. The modified machine greatly facilitates the use of such groups of lines. Sprocket driven perforated paper tape replaces the plain tape previously used, which introduced errors due to mechanical stretching when intervals were recorded which involved a loop of tape greater than four meters in length. With the device in its present form intervals up to 10,000 wave numbers can be recorded with accuracy to ±0.02 wave number. A new system of tape calibration has been introduced, in which a separate punch produces small round holes in the tape at regular intervals, which combine with one another to produce fiducial marks, but do not interfere with the holes representing the spectrum lines. In this way errors due to tape stretch introduced by any cause whatever are apparent at a glance. Electric drive and mercury arc illumination have been provided so that the recording speed has been greatly increased, and the instrument will record when the tape is sent in either direction, thus eliminating rewinding. Separate motors are used for tape drive, record drive, and tape winding, giving great flexibility in the choice of scales for the coordinates wave number and wave-number interval. Applications of the instrument to the spectra of osmium, iridium, and cerium have been made and have already given results which indicate its value. Its use makes very evident the fact that improved wave-length measurements are greatly needed for further analyses of the spectra of the rare earths.
On Balanced d.c. Amplifying Circuits
Authors: Turner Louis A.
Published: February 2005

Three different circuits for use with a single vacuum tube in order to balance out effects of fluctuations of the e.m.f. of the plate battery are described. The theory of the circuits is worked out and the expressions for the galvanometer current given. The circuit in which the stability of balance depends upon the constancy of the amplification factor, μ, is found to be the most stable. A modified two tube circuit operating on this principle is suggested.
Lacquer-Coated Resistors
Authors: Curtiss L. F.
Published: February 2005

A compact form of resistor of high resistance, consisting of graphite on Pyrex, sealed in glyptal lacquer, which has been found very satisfactory is described. Resistors of this type with a resistance of 108 to 1012 ohms may be made with comparative ease. They are not appreciably affected by changes of temperature or of humidity. Their small size renders them useful where economy of space is essential.
On the Quantitative Theory of the Wimshurst Static Machine. I
Authors: Simon A. W.
Published: February 2005

Following the general method of previous papers on the theory of static machines the quantitative theory of an eight carrier (per disk), birotational Wimshurst static machine is developed in detail. From the equations connecting the charges on the elements of the machine after any number of eighth turns, the equations connecting the corresponding voltages are deduced, and from these finally the general formulas for the potentials after any number of eighth turns. Provided the original potentials are in proper relation, the voltages increase by a constant factor (per eighth turn), and this factor is the same for all of the conductors of the machine. If the original potentials are not regularly distributed, the machine tends continually toward a state in which they are, and the corresponding formulae contain transient terms. The theory is extended to polysymmetric static machines of the same general type. A trisymmetric Wimshurst machine is treated in detail. It is shown that in general Wimshurst machines with an even number of symmetries are direct-current machines, while those with an odd number are electrostatic alternators.
A High Potential Porcelain X-Ray Tube
Authors: Crane Richard , Lauritsen Charles C.
Published: February 2005

An x-ray tube which operates successfully up to 650,000 volts has been constructed from a conical porcelain transformer bushing, rated at 750,000 volts external flashover. Although the bushing had previously been filled with transformer oil, no difficulties were encountered in outgassing the inner surface. With a pumping system of about 300 liters per second capacity, a vacuum of 10−5 mm can be maintained, and this does not change appreciably during operation. Cold emission from the anode, rather than gas current or breakdown of the porcelain, limits the voltage which can be applied. Filament emission currents up to 4 milliamperes can be employed without undue heating of the target. For a given voltage, a porcelain tube of this type is much more compact than a glass tube, the strength of its walls against puncture makes elaborate internal shielding unnecessary, and there is no more difficulty in maintaining a good vacuum than in a glass tube of comparable volume. The source of high potential is the 1,000,000 volt transformer set in the High Tension Laboratory.
Technique for the Determination of the Radioactive Content of Liquids
Authors: Evans Robley D.
Published: February 2005

For the removal of radon from liquids, simplified apparatus, including a special reflux condenser, free from carry-over difficulties, is described. For the measurement of small quantities of radon or thoron, cylindrical ionization chambers, with moisture proof insulation, together with a removable head, evacuated, bifilar electrometer are described. The importance of constancy of the background ionization due to cosmic and local radiation is emphasized, and precautions are described which insure a highly constant background in the present type of apparatus.
Radioactive Contamination of Ionization Chamber Materials
Authors: Bearden J. A.
Published: February 2005

A determination of the number of α-particles emitted per unit areas per unit time by materials usually used in the construction of ionization chambers has been made. The radioactive contamination of a few gases was examined and methods of removing radioactive material from surfaces were investigated. A FP54 vacuum tube, operated at about one-tenth of the maximum sensitivity, was used with a photographic recorder for detecting the α-particles. With this sensitivity α-particles of a range in air of 2 mm or more could be detected. Cold rolled steel which emitted about 3 α-particles per 100 cm2 per hour was the freest from contamination of any material examined. Brass and copper were the next best materials. Careful sandpapering of a surface was very effective in removing radioactive material. It was also found that a clean surface when exposed to air became contaminated. This made it necessary to keep such surfaces in an atmosphere of nitrogen or some gas which was free from radioactive contamination. Celluloid which was cleaned with alcohol and painted with good drawing ink made a satisfactory material for ionization chamber windows. Amber emitted no more α-particles than steel but Pyrex glass emitted about 5 times as many α-particles as steel. Methyl bromide, good quality carbon dioxide, and nitrogen were found to be suitable gases for filling ionization chambers.
An Amplifying Lever for the Measurement of Small Displacements
Authors: Fink George A. , Fox Gerald W.
Published: February 2005

An amplifying lever system used for measuring piezoelectric deformations of quartz and tourmaline plates is described. Interference fringes are formed between a semi-transparent coating of silver on glass and a mirror on the long end of a lever. With an arm ratio of 1864 to 1 the sensitivity of the lever is such that a displacement of a knife edge on the short end of about 0.15A can be detected. The chief difficulty in its use was found to be disturbance from vibrations. Sources of error, possible improvements, and possibilities for other uses are discussed.
An Improved Cosmic-Ray Meter
Authors: Compton A. H. , Hopfield J. J.
Published: February 2005

An improved cosmic-ray meter is described in detail. Directions for its use in the measurement of cosmic rays are given; and various errors and ways of minimizing them are discussed.
A Combined Tesla Coil and Vacuum Tube
Authors: Lauritsen Charles C. , Crane Richard
Published: February 2005

An oil emersed high frequency resonance coil has been constructed and combined with a vacuum tube in such a way that none of the high voltage parts are exposed to the air. This makes a very compact apparatus, and it is not subject to corona losses. Potentials up to 750,000 volts have been produced on the inner electrode, by exciting the primary circuit with a condenser discharge. An improvement in the design is proposed, which makes use of a system of concentric shields around the inner electrode, for the purpose of distributing the potential drop in a more advantageous manner, and making it possible to go to higher voltages before cold emission occurs. Excitation of the apparatus by means of a continuous wave oscillator, and its use as a high voltage x-ray outfit for practical purposes is discussed.