bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of British Commercial and Political Networks in the Straits Settlements 1800 to 1868: The Rise of a Colonial and Regional Economic Identity?
Authors: WEBSTER ANTHONY
Published: November 2010

This paper examines the growth of the British commercial communities in the Straits Settlements in the first half of the nineteenth century. It describes how they emerged as a coherent commercial and political interest group, separate from the Indian empire, with their own network of allies and commercial partners in Britain. As such, the Straits merchants emerged as a significant political lobby in their own right. It contends that in the process, they revived earlier notions of Southeast Asia as a discrete geographical region, in which political and ethnic diversity was bridged by the flourishing of maritime commercial networks.
REFASHIONING PURITAN NEW ENGLAND: THE CHURCH OF ENGLAND IN BRITISH NORTH AMERICA,c. 1680–c. 1770
Authors: Gregory Jeremy
Published: November 2010

The position of the Church of England in colonial New England has usually been seen through the lens of the ‘bishop controversy’ of the 1760s and early 1770s, where Congregational fears of the introduction of a Laudian style bishop to British North America have been viewed as one of the key factors leading to the American Revolution. By contrast, this paper explores some of the successes enjoyed by the Church of England in New England, particularly in the period from the 1730s to the early 1760s, and examines some of the reasons for the Church's growth in these years. It argues that in some respects the Church in New England was in fact becoming rather more popular, more indigenous and more integrated into New England life than both eighteenth-century Congregationalists or modern historians have wanted to believe, and that the Church was making headway both in the Puritan heartlands, and in the newer centres of population growth. Up until the early 1760s, the progress of the Church of England in New England was beginning to look like a success story rather than one with in-built failure.
The Concept of Heaven
Authors: Smart Ninian
Published: November 2010

My title is in a way misleading, for I want to show that there is a number of concepts of heaven. I want to explore these in the first part of this lecture. In the second part I shall comment on most ofthem, to see which, ifany, seem to be viable.
Eternal Life
Authors: Wisdom John
Published: November 2010

I Fear you will be disappointed in what I have to say. For I am going to talk about those who, though they have said ‘There is a way to eternal life’, have then gone on to explain that what they mean does not imply that there is a way to a life that endures for ever or even a life after death. It is plain that those who do this take from the words ‘There is a way to eternal life’ a part of their meaning which has been and still is to very many people of very great importance. Nevertheless between those who when they speak of a way to eternal life are thinking of a life after death which endures for ever, and those who when they speak of eternal life give to their words a meaning which carries no implication as to whether there is a life after death, there is a link, in that both are seeking a remedy against a sort of despair which comes not merely from the thought of death but from a disappointment with life together with the thought that it ends in death.
On Being Obliged to Act
Authors: White Alan R.
Published: November 2010

There are various ways in which a person's freedom of action may be diminished or restricted. Instead of acting, he may be acted upon; or he may be unable to help doing what he does. He may suffer from some disability, have a duty imposed on him or do something because he is obliged to do it. In this essay, I wish to examine the notion of being obliged to do something. I shall investigate the differences between ‘being obliged by A to do X’ and ‘being obliged to A for X’; between ‘being obliged to do X’ and ‘having (or being under) an obligation to do X’; between being physically obliged and being morally, legally and logically obliged; and between saying ‘X is something I am obliged to do’, ‘X is something I choose to do’ and ‘X is something I ought to do’.
Urbanism, Militarism, and Architectural Design: An Analysis of Epidassic sociopolitical structure at Xochicalco
Authors: Hirth Kenneth G.
Published: November 2010

The form and organization of urban architecture is examined at the central Mexico site of Xochicalco to reconstruct aspects of both its internal community structure and regional political organization during the Epiclassic period (A.D. 700-900). Analysis of the site's defensive architecture provides unique information about the city's internal design. Dry moats, walled roads, and steep terrace facades subdivide the community into a series of population segments that on the basis of both size and architecture type resemble ward divisions found in central Mexico cities at the time of Conquest. Furthermore, Xochicalco does not have a single defensive perimeter characteristic of a strongly centralized polity; instead, it possesses a series of defensive precincts located on the hills and ridges adjacent to Cerro Xochicalco that are equivalent in form and redundant in function. The model that best approximates the segmentary nature of this structure is that of a regional confederacy dominated by Xochicalco during the Epiclassic.
‘Where Two are to Become One’: Mysticism and Monism
Authors: Jantzen Grace
Published: November 2010

(1) If you would know God, you must not merely belikethe Son, you mustbethe Son yourself.

With these words Meister Eckhart encapsulates the aim of Christian mysticism as he understood it: to know God, and to know God in such a way that the knower is not merelylikeChrist but actuallybecomesChrist, taken into the Trinity itself. Eckhart speaks frequently of this in his sermons.
Assessing the Accuracy of Landscape‐Scale Phenology Products: An International Workshop on the Validation of Satellite‐Based Phenology Products; Dublin, Ireland, 18 June 2010
Authors: Morisette Jeffrey T. , Nightingale Joanne , Nickeson Jaime
Published: November 2010

A 1‐day international workshop on the accuracy assessment of phenology products derived from satellite observations of the land surface was held at Trinity College Dublin. This was in conjunction with the larger 4‐day Phenology 2010 conference. Phenology is the study of recurring plant and animal life cycle stages (such as leafing and flowering, maturation of agricultural plants, emergence of insects, and migration of birds). The workshop brought together producers of continental‐ to global‐scale phenology products based on satellite data, as well as providers of field observations and tower‐mounted near‐surface imaging sensors whose data are useful for evaluating the satellite products. The meeting was held under the auspices of the Committee on Earth Observing Satellites (CEOS) Land Product Validation (LPV) subgroup. The mission of LPV is to foster quantitative validation of high‐level global land products derived from remotely sensed data and relay results that are relevant to users.
Martin Dodson (1932–2010)
Authors: Cliff Bob , Wilson Marge
Published: November 2010

Martin Dodson, a pioneer of geochronology and thermochronology, died at age 78 on 27 June 2010. Martin read natural sciences at the University of Cambridge, United Kingdom. His main subject was physics, but significantly for his future career, he also studied geology.
New Editors, Editorial Advisory Board for Eos
Authors: Richman Barbara T.
Published: November 2010

Eos has two new editors and, with this issue, a revitalized Editorial Advisory Board.

Christina M. S. Cohen, of the California Institute of Technology, is the new editor for space sciences. She succeeds Manuel Grande, who had served since 2006. Carol A. Stein, of the University of Illinois at Chicago, is the new editor for solid Earth. She succeeds John W. Geissman, who has been solid Earth editor since 2001; he will continue through the end of 2010.
High‐resolution seismic images of potentially seismogenic structures beneath the northwest Canterbury Plains, New Zealand
Authors: Dorn C. , Green A. G. , Jongens R. , Carpentier S. , Kaiser A. E. , Campbell F. , Horstmeyer H. , Campbell J. , Finnemore M. , Pettinga J.
Published: November 2010

The transpressional boundary between the Australian and Pacific plates in the central South Island of New Zealand comprises the Alpine Fault and a broad region of distributed strain concentrated in the Southern Alps but encompassing regions further to the east, including the northwest Canterbury Plains. Low to moderate levels of seismicity (e.g., 2 > M 5 events since 1974 and 2 > M 4.0 in 2009) and Holocene sediments offset or disrupted along rare exposed active fault segments are evidence for ongoing tectonism in the northwest plains, the surface topography of which is remarkably flat and even. Because the geology underlying the late Quaternary alluvial fan deposits that carpet most of the plains is not established, the detailed tectonic evolution of this region and the potential for larger earthquakes is only poorly understood. To address these issues, we have processed and interpreted high‐resolution (2.5 m subsurface sampling interval) seismic data acquired along lines strategically located relative to extensive rock exposures to the north, west, and southwest and rare exposures to the east. Geological information provided by these rock exposures offer important constraints on the interpretation of the seismic data. The processed seismic reflection sections image a variably thick layer of generally undisturbed younger (i.e., < 24 ka) Quaternary alluvial sediments unconformably overlying an older (>59 ka) Quaternary sedimentary sequence that shows evidence of moderate faulting and folding during and subsequent to deposition. These Quaternary units are in unconformable contact with Late Cretaceous–Tertiary interbedded sedimentary and volcanic rocks that are highly faulted, folded, and tilted. The lowest imaged unit is largely reflection‐free Permian ‐ Triassic basement rocks. Quaternary‐age deformation has affected all the rocks underlying the younger alluvial sediments, and there is evidence for ongoing deformation. Eight primary and numerous secondary faults as well as a major anticlinal fold are revealed on the seismic sections. Folded sedimentary and volcanic units are observed in the hanging walls and footwalls of most faults. Five of the primary faults represent plausible extensions of mapped faults, three of which are active. The major anticlinal fold is the probable continuation of known active structure. A magnitude 7.1 earthquake occurred on 4 September 2010 near the southeastern edge of our study area. This predominantly right‐lateral strike‐slip event and numerous aftershocks (ten with magnitudes ≥5 within one week of the main event) highlight the primary message of our paper: that the generally flat and topographically featureless Canterbury Plains is underlain by a network of active faults that have the potential to generate significant earthquakes.
DNA end resection by CtIP and exonuclease 1 prevents genomic instability
Authors: Eid Wassim , Steger Martin , El‐Shemerly Mahmoud , Ferretti Lorenza P , Peña‐Diaz Javier , König Christiane , Valtorta Emanuele , Sartori Alessandro A , Ferrari Stefano
Published: November 2010

End resection of DNA—which is essential for the repair of DNA double‐strand breaks (DSBs) by homologous recombination—relies first on the partnership between MRE11–RAD50–NBS1 (MRN) and CtIP, followed by a processive step involving helicases and exonucleases such as exonuclease 1 (EXO1). In this study, we show that the localization of EXO1 to DSBs depends on both CtIP and MRN. We also establish that CtIP interacts with EXO1 and restrains its exonucleolytic activity in vitro. Finally, we show that on exposure to camptothecin, depletion of EXO1 in CtIP‐deficient cells increases the frequency of DNA–PK‐dependent radial chromosome formation. Thus, our study identifies new functions of CtIP and EXO1 in DNA end resection and provides new information on the regulation of DSB repair pathways, which is a key factor in the maintenance of genome integrity.
Linguistic Complexity, Speech Production, and Comprehension in Parkinson’s Disease: Behavioral and Physiological Indices
Authors: Walsh Bridget , Smith Anne
Published: November 2010

Purpose

To investigate the effects of increased syntactic complexity and utterance length demands on speech production and comprehension in individuals with Parkinson’s disease (PD) using behavioral and physiological measures.

Method

Speech response latency, interarticulatory coordinative consistency, accuracy of speech production, and response latency and accuracy on a receptive language task were analyzed in 16 individuals with PD and 16 matched control participants.

Results

Individuals with PD had higher oral motor coordination variability, took a longer time to initiate speech, and made more errors on the speaking task compared with the control group. They also received lower scores on the 2 complex conditions of the receptive language task. Increased length and syntactic complexity negatively affected performance in both groups of speakers.

Conclusions

These findings provide a novel window into the speech deficits associated with PD by examining performance on longer, sentence-level utterances in contrast to earlier investigations of single-word or nonword productions. Speech motor control processes and language comprehension were adversely affected in the majority of our participants with mild to moderate PD compared to the control group. Finally, increased syntactic complexity and sentence length affected both the healthy aging and PD groups' speech production performance at the behavioral and kinematic levels.
Distribution of alcohol dehydrogenase mRNA in the rat central nervous system.
Authors: Martínez Susana E. , Vaglenova Julia , Sabrià Josefa , Martínez M. Carmen , Farrés Jaume , Parés Xavier
Published: November 2010

The localization of alcohol dehydrogenase (ADH) in brain regions would demonstrate active ethanol metabolism in brain during alcohol consumption, which would be a new basis to explain the effects of ethanol in the central nervous system. Tissue sections from several regions of adult rat brain were examined by in situ hybridization to detect the expression of genes encoding ADH1 and ADH4, enzymes highly active with ethanol and retinol. ADH1 mRNA was found in the granular and Purkinje cell layers of cerebellum, in the pyramidal and granule cells of the hippocampal formation and in some cell types of cerebral cortex. ADH4 expression was detected in the Purkinje cells, in the pyramidal and granule cells of the hippocampal formation and in the pyramidal cells of cerebral cortex. High levels of ADH1 and ADH4 mRNAs were detected in the CNS epithelial and vascular tissues: leptomeninges, choroid plexus, ependymocytes of ventricle walls, and endothelium of brain vessels. Histochemical methods detected ADH activity in rodent cerebellar slices, while Western‐blot analysis showed ADH4 protein in homogenates from several brain regions. In consequence, small but significant levels of ethanol metabolism can take place in distinct areas of the CNS following alcohol consumption, which could be related to brain damage caused by a local accumulation of acetaldehyde. Moreover, the involvement of ADH in the synthesis of retinoic acid suggests a role for the enzyme in the regulation of adult brain functions. The impairment of retinol oxidation by competitive inhibition of ADH in the presence of ethanol may be an additional origin of CNS abnormalities caused by ethanol.
Welfare Effects of National Taxes in an Economy with Regions
Authors: Petchey Jeffrey D. , Levtchenkova Sofia
Published: November 2010

The present paper illustrates that changes in national commodity and income tax rates will affect the location choices of mobile factors of production within an economy with regions as well as the total supply of these factors to the economy. It is also argued that revenue (expenditure) neutral changes in the tax mix, for example, an increase in the commodity tax combined with a decrease in the income tax rate, will affect the domestic distribution of mobile factors, their supply to the economy and social welfare. In other words, revenue neutrality should not be used as a guide to the welfare effects of tax mix changes.
Study of a high-order-mode gyrotron traveling-wave amplifier
Authors: Chiu C. C. , Tsai C. Y. , Kao S. H. , Chu K. R. , Barnett L. R. , Luhmann N. C.
Published: November 2010

Physics and performance issues of a TE01-mode gyrotron traveling-wave amplifier are studied in theory. For a high order mode, absolute instabilities on neighboring modes at the fundamental and higher cyclotron harmonic frequencies impose severe constraints to the device capability. Methods for their stabilization are outlined, on the basis of which the performance characteristics are examined in a multidimensional parameter space under the marginal stability criterion. The results demonstrate the viability of a high-order-mode traveling-wave amplifier and provide a roadmap for design tradeoffs among power, bandwidth, and efficiency. General trends are observed and illustrated with specific examples.
Future climate affects management strategies for maintaining forest restoration treatments
Authors: Diggins Corinne , Fulé Peter Z. , Kaye Jason P. , Covington W. Wallace
Published: November 2010

Forests adapted to frequent-fire regimes are being treated to reduce fuel hazards and restore ecosystem processes. The maintenance of treatment effects under future climates is a critical issue. We modelled forest change under different climate scenarios for 100 years on ponderosa pine landscapes in the south-western USA, comparing management regimes that included prescribed burning, tree cutting, and no-management. We applied the Forest Vegetation Simulator (1) in its standard form, and (2) with modifications of reduced tree growth and increased mortality to simulate the effects of two levels of climate change. Without climate change effects, several management regimes, including the use of frequent burning similar to the historical fire frequency (~5 year), maintained future forest structure within a target range of variability. In contrast, simulations that accounted for climate change effects indicated that burning intervals should be lengthened (~20 year) and future tree thinning should be avoided to minimise forest decline. Although it has been widely predicted that future climate conditions will support more burning (warmer, drier fuels, longer fire season), our modelling suggests that the production of fuels will decline, so there will eventually be a trade-off between increased fire, driven by climate, v. reduced fuel, also driven by climate.
Neural activity associated with monitoring the oscillating threat value of a tarantula
Authors: Mobbs Dean , Yu Rongjun , Rowe James B. , Eich Hannah , FeldmanHall Oriel , Dalgleish Tim
Published: November 2010

Phylogenetic threats such as spiders evoke our deepest primitive fears. When close or looming, such threats engage evolutionarily conserved monitoring systems and defense reactions that promote self-preservation. With the use of a modified behavioral approach task within functional MRI, we show that, as a tarantula was placed closer to a subject's foot, increased experiences of fear coincided with augmented activity in a cascade of fear-related brain networks including the periaqueductal gray, amygdala, and bed nucleus of the stria terminalis. Activity in the amygdala was also associated with underprediction of the tarantula's threat value and, in addition to the bed nucleus of the stria terminalis, with monitoring the tarantula's threat value as indexed by its direction of movement. Conversely, the orbitofrontal cortex was engaged as the tarantula grew more distant, suggesting that this region emits safety signals or expels fear. Our findings fractionate the neurobiological mechanisms associated with basic fear and potentially illuminate the perturbed reactions that characterize clinical phobias.
CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells
Authors: Jähnichen Sven , Blanchetot Christophe , Maussang David , Gonzalez-Pajuelo Maria , Chow Ken Y. , Bosch Leontien , De Vrieze Sindi , Serruys Benedikte , Ulrichts Hans , Vandevelde Wesly , Saunders Michael , De Haard Hans J. , Schols Dominique , Leurs Rob , Vanlandschoot Peter , Verrips Theo , Smit Martine J.
Published: November 2010

The important family of G protein-coupled receptors has so far not been targeted very successfully with conventional monoclonal antibodies. Here we report the isolation and characterization of functional VHH-based immunoglobulin single variable domains (or nanobodies) against the chemokine receptor CXCR4. Two highly selective monovalent nanobodies, 238D2 and 238D4, were obtained using a time-efficient whole cell immunization, phage display, and counterselection method. The highly selective VHH-based immunoglobulin single variable domains competitively inhibited the CXCR4-mediated signaling and antagonized the chemoattractant effect of the CXCR4 ligand CXCL12. Epitope mapping showed that the two nanobodies bind to distinct but partially overlapping sites in the extracellular loops. Short peptide linkage of 238D2 with 238D4 resulted in significantly increased affinity for CXCR4 and picomolar activity in antichemotactic assays. Interestingly, the monovalent nanobodies behaved as neutral antagonists, whereas the biparatopic nanobodies acted as inverse agonists at the constitutively active CXCR4-N3.35A. The CXCR4 nanobodies displayed strong antiretroviral activity against T cell-tropic and dual-tropic HIV-1 strains. Moreover, the biparatopic nanobody effectively mobilized CD34-positive stem cells in cynomolgus monkeys. Thus, the nanobody platform may be highly effective at generating extremely potent and selective G protein-coupled receptor modulators.
Analytical model of a longitudinal hollow cathode discharge
Authors: Hagelaar G J M , Mihailova D B , van Dijk J
Published: November 2010

This paper presents a simple analytical model of a longitudinal hollow cathode discharge used in metal vapour lasers. The model describes the principle relations between the voltage, current, plasma density and axial structure of the discharge. Contrary to standard dc discharges, this discharge does not require electron multiplication in the cathode fall (CF) to produce ions, but rather to satisfy the electron energy balance. A self-sustainment condition is obtained from the energy balance per electron–ion pair. From this, it follows that there is a maximum voltage at which the CF thickness tends to zero and the current density tends asymptotically to infinity. The discharge develops axial non-uniformity and an axial electric field in order to evacuate the created electrons to the anode, such that the characteristic time for transport losses is the same for electrons as for ions. The axial profiles of the current density, plasma density and potential are obtained from the electron continuity equation. It is shown that additional energy absorption from the axial field, similar to electron heating in dc positive columns, modifies the self-sustainment condition and thus leads to a shift in the voltage–current characteristic, depending on the cathode length.
The plant alkaloid piperine as a potential inhibitor of ethidium bromide efflux in Mycobacterium smegmatis
Authors: Jin Jing , Zhang Jiyu , Guo Na , Feng Haihua , Li Lei , Liang Junchao , Sun Kai , Wu Xiuping , Wang Xuelin , Liu Mingyuan , Deng Xuming , Yu Lu
Published: November 2010

Piperine, a major plant alkaloid found in black pepper (Piper nigrum) and long pepper (Piper longum), has shown potential for inhibiting the efflux pump (EP) ofStaphylococcus aureus. In this study, a modulation assay showed that piperine could decrease the MIC of ethidium bromide (EtBr) twofold at 32 μg ml−1and fourfold at 64 μg ml−1againstMycobacterium smegmatismc2155 ATCC 700084. A real-time, 96-well plate fluorometric method was employed to evaluate the EP inhibition ability of piperine inM. smegmatis. Reserpine, chlorpromazine, verapamil and carbonyl cyanidem-chlorophenylhydrazone were used as positive controls. Piperine significantly enhanced accumulation and decreased the efflux of EtBr inM. smegmatis, which suggests that it has the ability to inhibit mycobacterial EPs.
Comparative evaluation of DQ‐2511, a novel gastroprokinetic agent, with cisapride in ameliorative action on experimentally induced delayed gastric emptying
Authors: HATANAKA S. , KAWARABAYASHI K. , ISERI M. , TSUBOKURA K. , FURUHAMA K. , NIJIMA A.
Published: November 2010

We compared the main pharmacological effect of DQ‐2511 (3‐[[[2‐(3,4‐dimethoxyphenyl)‐ethyl]carbamoyl]methyl]amino ‐N‐ methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ‐2511 (3–10 mg kg−1) caused similar significant improvements to delays in gastric emptying of semi‐solid meals evoked by chole‐cystokinin‐octapeptide (CCK8: 5 μ kg−1, i.v.) in monkeys, to that with cisapride (3 mg kg−1). A 2‐week oral treatment of unilaterally vagotomized rats with DQ‐2511 (1–10 mg kg−1) lessened delays in gastric emptying, whereas cisapride (0.3–10 mg kg−1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 μg kg−1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ‐2511 (6–60 μ kg−1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ‐2511 on delayed gastric emptying may differ from that of cisapride.
Prognostic prediction of long‐term clinical courses in individual IgA nephropathy patients
Authors: KOBAYASHI Yutaka , KOKUBO Tohru , HORII Akira , HIKI Yoshiyuki , TATENO Sumio
Published: November 2010

Summary: This study was performed to evaluate predictive factors determining a long‐term prognosis in individual IgA nephropathy patients. One hundred and fifty‐five patients who have been continuously followed up for 10 years or more from the first renal biopsy in our renal unit were the subjects of this study. As predictive factors, initial proteinuria, initial creatinine clearance (Ccr) values, initial hypertension, histological severity (eight parameters and total score), persistence of massive proteinuria (% duration of massive proteinuria; % DP) and persistence of hypertension were evaluated. All 25 of the 155 patients who had either high total score of 17 or more, or less than 60 mL/min in initial Ccr values, went onto haemodialysis (HD). However, all 38 patients who had TS of 4 or less did not. The remaining 95 patients who showed both total score from 5 to16 and Ccr values of 60 mL/min or more were divided into two groups: HD group (32 cases) and non‐HD group (63 cases). All patients but one in the HD group showed 30% or more in %DP, and 50 of 63 patients in the non‐HD group snowed 30% or less (P < 0.001). Multivariate analysis using a logistic model of factors associated with prognosis indicating HD revealed that %DP was the highest relative risk (19.5) compared with interstitial fibrosis (10.2), initial Ccr values (6.8), persistent hypertension (4.2) and initial proteinuria (1.4). These results indicated that the most reliable, independent factor determining a long‐term individual prognosis is persistent massive proteinuria of 1.0 g/day or more.
Heterogeneity of carbohydrate moieties of IgA1 molecules from IgA nephropathy patients and normal individuals
Authors: MESTECKY Jiri , TOMANA Milan , MATOUSOVIC Karel , KONECNY Karel , Radl Jiri , JULIAN Bruce A.
Published: November 2010

Summary: IgA nephropathy (IgAN) is characterized by the deposition of IgA1 in kidney mesangia and the presence of IgA1‐containing immune complexes in the circulation. Structural studies of IgA1 isolated from sera of IgAN patients indicated a statistically significant decrease in the content of galactose (Gal). Using a combination of lectins specific for glycans in O‐ or N‐linked glycan side chains, this Gal deficiency was restricted to O‐linked glycans present in the hinge region of IgA1 molecules. Gal‐deficient IgA1 displayed a significantly higher binding to mesangial cells through a putative non‐internalizing receptor specific for N‐acetyl galactosamine (GalNAc) in O‐linked glycans. These data suggest that Gal deficiency results in diversion of IgA1 molecules from the usual degradative pathway and deposition of altered IgA1 in the mesangium.
Activation of mRNA expression of collagen, collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy
Authors: SAKAI Hideto , JINDE Kiichiro , SAOTOME Noboru , SUNG Wei , YAGAME Mitsunori , NOMOTO Yasuo , MIYAZAKI Masanobu , HARADA Takashi
Published: November 2010

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP‐3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.
Survival after prostate brachytherapy in patients aged 60 years and younger
Authors: Hinnen Karel A. , Roeloffzen Ellen M. A. , Battermann Jan J. , Van Moorselaar R. Jeroen A. , van Roermund Joep G.H. , van Vulpen Marco
Published: November 2010

Study Type – Aetiology (prospective cohort)

Level of Evidence 2B

OBJECTIVE

• To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years.

patientS AND METHODS

• We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I‐125 implantation monotherapy.

• Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease‐specific and overall survival.

• Patients were subdivided into age ≤60 years and age >60 years.

• Cox proportional‐hazards regression analyses were performed to study the independent effect of age on BF and disease‐specific survival.

RESULTS

• The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow‐up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort.

• The 10‐year (95% CI) freedom from BF, disease‐specific survival and overall survival rates were 63% (51–75), 87% (78–96) and 81% (69–89), respectively, for the younger cohort and 46% (39–54), 83% (78–89) and 60% (54–66), respectively, for the older patient cohort.

• Although a trend for better freedom from BF and disease‐specific survival was observed in younger patients, the difference proved not clinically significant.

CONCLUSION

• Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger.
THE CONTENT AND CONTEXT OF ORGANIZATIONAL ETHICS
Authors: VAN DER WAL ZEGER
Published: November 2010

The aim of this paper is to provide an empirical contextual picture of what is truly valued most in different public and private sector organizations. Through a series of qualitative in‐depth interviews (n = 38), that were a follow‐up to an earlier survey study among public and private sector managers (n = 382), a number of crucial organizational values were presented to and discussed with a selection of top managers from a variety of Dutch public and private sector organizations. The decision‐making context from the interviews provides insight into why, when, how and to what extent specific values are important. A number of unexpected differences and similarities between organizations with a different sectoral status emerge from the data, which shed new light on existing predispositions on value preferences in government and business conduct.
Intrathecal orexin A increases sympathetic outflow and respiratory drive, enhances baroreflex sensitivity and blocks the somato‐sympathetic reflex
Authors: Shahid IZ , Rahman AA , Pilowsky PM
Published: November 2010

BACKGROUND Intrathecal (i.t.) injection of orexin A (OX‐A) increases blood pressure and heart rate (HR), but the effects of OX‐A on sympathetic and phrenic, nerve activity, and the baroreflex(es), somato‐sympathetic and hypoxic chemoreflex(es) are unknown.

EXPERIMENTAL APPROACH Urethane‐anaesthetized, vagotomized and artificially ventilated male Sprague‐Dawley rats were examined in this study. The effects of i.t. OX‐A (20 nmol 10 µL−1) on cardiorespiratory parameters, and responses to stimulation of the sciatic nerve (electrical), arterial baroreceptors (phenylephrine hydrochloride, 0.01 mg kg−1 i.v.) and peripheral (hypoxia) chemoreceptors were also investigated.

KEY RESULTS i.t. OX‐A caused a prolonged dose‐dependent sympathoexcitation, pressor response and tachycardia. The peak effect was observed at 20 nmol with increases in mean arterial pressure, HR and splanchnic sympathetic nerve activity (sSNA) of 32 mmHg, 52 beats per minute and 100% from baseline respectively. OX‐A also dose‐dependently increased respiratory drive, as indicated by a rise in phrenic nerve amplitude and a fall in phrenic nerve frequency, an increase in neural minute ventilation, a lengthening of the expiratory period, and a shortening of the inspiratory period. All effects of OX‐A (20 nmol) were attenuated by the orexin receptor 1 antagonist SB 334867. OX‐A significantly reduced both sympathoexcitatory peaks of somato‐sympathetic reflex while increasing baroreflex sensitivity. OX‐A increased the amplitude of the pressor response and markedly amplified the effect of hypoxia on sSNA.

CONCLUSIONS Thus, activation of OX receptors in rat spinal cord alters cardiorespiratory function and differentially modulates sympathetic reflexes.
Semaphorin 3A inhibits growth of adult sympathetic and parasympathetic neurones via distinct cyclic nucleotide signalling pathways
Authors: Nangle MR , Keast JR
Published: November 2010

BACKGROUND AND PURPOSE Semaphorin 3A (Sema3A) is an important secreted repulsive guidance factor for many developing neurones. Sema3A continues to be expressed in adulthood, and expression of its receptor, neuropilin‐1 (Nrp‐1), can be altered by nerve injury. Autonomic neurones innervating the pelvic viscera are particularly susceptible to damage during pelvic surgical procedures, and failure to regenerate or aberrant growth of sympathetic and parasympathetic nerves lead to organ dysfunction. However, it is not known if adult pelvic neurones are potential targets for Sema3A.

EXPERIMENTAL APPROACH The effects of Sema3A and activation or inhibition of cyclic nucleotide signalling were assessed in adult rat pelvic ganglion neurones in culture using a growth cone collapse assay.

KEY RESULTS Sema3A caused growth cone collapse in both parasympathetic and sympathetic neurones expressing Nrp‐1. However, the effect of Sema3A was mediated by distinct cyclic nucleotide signalling pathways in each neurone type. In parasympathetic neurones, cAMP and downstream activation of protein kinase A were required for growth cone collapse. In sympathetic neurones, cGMP was required for Sema3A‐induced collapse; cAMP can also cause collapse but was not required. Sema3A‐mediated, cGMP‐dependent collapse in sympathetic neurones may require activation of cyclic nucleotide‐gated ion channels (CNGCs).

CONCLUSIONS AND IMPLICATIONS We propose that Sema3A is an important guidance factor for adult pelvic autonomic neurones, and that manipulation of their distinct signalling mechanisms could potentially promote functional selective regeneration or attenuate aberrant growth. To our knowledge, this is also the first study to implicate CNGCs in regulating growth cone dynamics of adult neurones.
Pregabalin effect on steady‐state pharmacokinetics of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, and tiagabine
Authors: Bockbrader Howard N. , Burger Paula , Knapp Lloyd
Published: November 2010

By reducing neuronal excitability through selective binding to the α2δ subunit of voltage‐dependent calcium channels, pregabalin effectively treats epilepsy, chronic pain, and anxiety disorders. To evaluate if pregabalin coadministration affects pharmacokinetics of other antiepileptic drugs, population pharmacokinetic analyses using NONMEM software were performed on data from three epilepsy trials involving seven antiepileptic drugs with pregabalin as add‐on therapy. Results demonstrated that pregabalin did not alter the steady‐state plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate. Furthermore, the small percent change in the population estimate of antiepileptic drug plasma clearance values (−2% to +7%) suggests that pregabalin coadministration exerted no significant effect on the pharmacokinetics of these antiepileptic drugs, with the possible exception of tiagabine (+34.9%). These findings are in agreement with those of previously published reports. A further clarification study is necessary for tiagabine. In conclusion, it appears that pregabalin can be coadministered with other antiepileptic drugs without concern for significantly altering their pharmacokinetic profiles.
Effects of Bilateral Arytenoid Cartilage Stenting on Canine Laryngeal ResistanceEx Vivo
Authors: Cabano Nicholas R. , Greenberg Marc J. , Bureau Stephane , Monnet Eric
Published: November 2010

Objective:To evaluate the effect of Nitinol stents for bilateral arytenoid lateralization on canine laryngeal resistance.

Study Design:Ex vivoexperimental study.

Animals:Canine cadaver larynges (n=7).

Methods:Laryngeal resistance was calculated in all specimens with the epiglottis in open and closed positions. Bilateral arytenoid stenting was performed, rima glottidis width measured, and laryngeal resistance calculated. The effects of stenting on laryngeal resistance were evaluated by repeated measures ANOVA.

Results:Calculated laryngeal resistance in the 3 stented groups, 2 cm (0.034±0.059 cmH2O/L/s), 3 cm (0.034±0.059 cmH2O/L/s), and 4 cm (0.034±0.059 cm H2O/L/s), was significantly decreased versus the control (unstented) group (0.947±0.624 cmH2O/L/s;P=.0098) with an epiglottis in the normal position. Calculated laryngeal resistance in the 3 stented groups, 2 cm (43.407±17.348 cm H2O/L/s), 3 cm (70.659±34.705 cmH2O/L/s), and 4 cm (92.637±44.509 cm H2O/L/s), was significantly increased versus the control (unstented) group (29.561±14.499 cm H2O/L/s) (P=.0185) with an epiglottis in the closed position. The width of the rima glottidis correlated with the size of the stent (r=0.95,P<.001).

Conclusions:Bilateral arytenoid stenting significantly reduced calculated laryngeal resistance with an open epiglottis. Stenting resulted in a significant increase in laryngeal resistance versus the control with a closed epiglottis. Use of bilateral arytenoid stenting in clinical cases of laryngeal paralysis may provide an adequate decrease in open‐epiglottis airway resistance to alleviate clinical signs, while increasing closed‐epiglottis airway resistance. This could potentially lead to a decrease in the risk of postoperative aspiration pneumonia.
Agriculture and global climate stabilization: a public good analysis
Authors: Quiggin John
Published: November 2010

The stabilization of global climate presents one of the most complex problems in public good provision the world has faced. Continuation of “business as usual” policies, leading to warming of more than 2 degrees over the next year, will produce significant damage to agricultural systems and catastrophic damage to the natural ecosystems that ultimately support agriculture. The best solution to the public goods problem is a “contract and converge” agreement in which the ultimate outcome is a common global entitlement to CO2 emissions per person.
Identification of telocytes in the lamina propria of rat duodenum: transmission electron microscopy
Authors: Carmona I. Cantarero , Bartolomé M. J. Luesma , Escribano C. Junquera
Published: November 2010

Recently the new term ‘telocytes’ has been proposed for cells formerly known as interstitial Cajal‐like cells. In fact, telocytes are not really Cajal‐like cells, they being different from all other interstitial cells by the presence of telopodes, which are cell‐body prolongations, very thin, extremely long with a moniliform aspect. The identification of these cells is based on ultrastructural criteria. The presence of telocytes in others organs was previously documented. We reported for the first time, an ultrastructural study of telocytes in the lamina propria of rat duodenum. Our findings show that typical telocytes are present in the rat duodenum. Telocytes are located in the lamina propria, immediately below mucosal crypts. Telopodes frequently establish close spatial relationships with immune cells, blood vessels and nerve endings. On the basis of their distribution and morphology, we suggest that these cells may be involved in immune response and in our opinion, it may be possible that different locations of telocytes could be associated with different roles.
Metoprolol Treatment Lowers Thrombospondin‐4 Expression in Rats with Myocardial Infarction and Left Ventricular Hypertrophy
Authors: Mustonen Erja , Leskinen Hanna , Aro Jani , Luodonpää Marja , Vuolteenaho Olli , Ruskoaho Heikki , Rysä Jaana
Published: November 2010

Abstract:  Thrombospondins are matrix proteins linked to extracellular matrix remodelling but their precise role in the heart is not known. In this study, we characterised left ventricular thrombospondin‐1 and ‐4 expression in rats treated with a beta‐blocker metoprolol during the remodelling process in response to pressure overload and acute myocardial infarction. Left ventricular thrombospondin‐1 and thrombospondin‐4 mRNA levels increased 8.4‐fold (p < 0.001) and 7.3‐fold (p < 0.001) post‐infarction, respectively. Metoprolol infusion by osmotic minipumps (1.5 mg/kg/hr) for 2 weeks after myocardial infarction decreased thrombospondin‐1 and thrombospondin‐4 mRNA levels (55% and 50%, respectively), improved left ventricular function, and attenuated left ventricular remodelling with reduction of left ventricular atrial natriuretic peptide and brain natriuretic peptide gene expression. Thrombospondin‐1 and ‐4 mRNA levels correlated positively with echocardiographic parameters of left ventricular remodelling as well as with atrial natriuretic peptide and brain natriuretic peptide gene expression. Moreover, there was a negative correlation between left ventricular ejection fraction and thrombospondin‐1 mRNA levels. In 12‐month‐old spontaneously hypertensive rats with left ventricular hypertrophy, metoprolol decreased left ventricular thrombospondin‐4 levels and attenuated remodelling while thrombospondin‐1, atrial natriuretic peptide and brain natriuretic peptide mRNA levels as well as left ventricular function remained unchanged. In metoprolol‐treated spontaneously hypertensive rats, thrombospondin‐4 gene expression correlated with parameters of left ventricular remodelling, while no correlations between thrombospondins and natriuretic peptides were observed. These results indicate that thrombospondin‐1 expression is linked exclusively to left ventricular remodelling process post‐infarction while thrombospondin‐4 associates with myocardial remodelling both after myocardial infarction and in hypertensive heart disease suggesting that thrombospondins may have unique roles in extracellular matrix remodelling process.
Gender Identity and Sexual Orientation in Women with Borderline Personality Disorder
Authors: Singh Devita , McMain Shelley , Zucker Kenneth J.
Published: November 2010

Introduction

In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR) (and earlier editions), a disturbance in “identity” is one of the defining features of borderline personality disorder (BPD). Gender identity, a person’s sense of self as a male or a female, constitutes an important aspect of identity formation, but this construct has rarely been examined in patients with BPD.

Aims

In the present study, the presence of gender identity disorder or confusion was examined in women diagnosed with BPD.

Main Outcome Measures

We used a validated dimensional measure of gender dysphoria. Recalled gender identity and gender role behavior from childhood was also assessed with a validated dimensional measure, and current sexual orientation was assessed by two self-report measures.

Methods

A consecutive series of 100 clinic-referred women (mean age, 34 years) with BPD participated in the study. The women were diagnosed with BPD using the International Personality Disorder Exam-BPD Section.

Results

None of the women with BPD met the criterion for caseness on the dimensional measure of gender dysphoria. Women who self-reported either a bisexual or a homosexual sexual orientation had a significantly higher score on the dimensional measure of gender dysphoria than the women who self-reported a heterosexual sexual orientation, and they also recalled significantly more cross-gender behavior during childhood. Results were compared with a previous study on a diagnostically heterogeneous group of women with other clinical problems.

Conclusion

The importance of psychosexual assessment in the clinical evaluation of patients with BPD is discussed.