bluuebunny/crossref_metadata_2025 huggingface dataset:
Gain saturation and high-power pulsed operation of GaSb-based tapered diode lasers with separately contacted ridge and tapered section
Authors: Pfahler C. , Eichhorn M. , Kelemen M. T. , Kaufel G. , Mikulla M. , Schmitz J. , Wagner J.
Published: July 2006

(AlGaIn)(AsSb) ridge-waveguide tapered diode lasers with separately contacted ridge and tapered sections, emitting at 1.93μm, have been analyzed in pulsed mode with respect to their high-power capability and wavelength tunability. Operating the ridge section above saturation, a variation of the current through this section resulted in a change in lasing wavelength, while changing the current injected into the tapered section at a constant ridge current allowed to vary the output power at constant lasing wavelength. Furthermore, the optical power required to saturate the tapered amplifier section has been derived from a comparison of the experimental characteristics with beam propagation method calculations.
Error signal artifact in apertureless scanning near-field optical microscopy
Authors: Billot L. , Lamy de la Chapelle M. , Barchiesi D. , Chang S.-H. , Gray S. K. , Rogers J. A. , Bouhelier A. , Adam P.-M. , Bijeon J.-L. , Wiederrecht G. P. , Bachelot R. , Royer P.
Published: July 2006

Apertureless scanning near-field optical microscopy is a method for obtaining subwavelength optical images of nanostructures. However, great care must be taken to avoid artifactual images. We report on one artifact related to the error signal in cantilever vibration amplitude when operating in tapping mode atomic force microscopy. The artifact is described experimentally and modeled by electromagnetic calculations based on the finite element method. We report specific steps to identify and avoid this artifact with experimental results on gold nanostructures. It is suggested that future apertureless scanning near-field optical microscopy studies verify that optical image does not correlate with error signal.
Ion cascade acceleration from the interaction of a relativistic femtosecond laser pulse with a narrow thin target
Authors: He Feng , Xu Han , Tian Youwei , Yu Wei , Lu Peixiang , Li Ruxin
Published: July 2006

Particle-in-cell simulations are performed to study the acceleration of ions due to the interaction of a relativistic femtosecond laser pulse with a narrow thin target. The numerical results show that ions can be accelerated in a cascade by two electrostatic fields if the width of the target is smaller than the laser beam waist. The first field is formed in front of the target by the central part of the laser beam, which pushes the electron layer inward. The major part of the abaxial laser energy propagates along the edges to the rear side of the target and pulls out some hot electrons from the edges of the target, which form another electrostatic field at the rear side of the target. The ions from the front surface are accelerated stepwise by these two electrostatic fields to high energies at the rear side of the target. The simulations show that the largest ion energy gain for a narrow target is about four times higher than in the case of a wide target.
A self-similar magnetohydrodynamic model for ball lightnings
Authors: Tsui K. H.
Published: July 2006

Ball lightning is modeled by magnetohydrodynamic (MHD) equations in two-dimensional spherical geometry with azimuthal symmetry. Dynamic evolutions in the radial direction are described by the self-similar evolution function y(t). The plasma pressure, mass density, and magnetic fields are solved in terms of the radial label η. This model gives spherical MHD plasmoids with axisymmetric force-free magnetic field, and spherically symmetric plasma pressure and mass density, which self-consistently determine the polytropic index γ. The spatially oscillating nature of the radial and meridional field structures indicate embedded regions of closed field lines. These regions are named secondary plasmoids, whereas the overall self-similar spherical structure is named the primary plasmoid. According to this model, the time evolution function allows the primary plasmoid expand outward in two modes. The corresponding ejection of the embedded secondary plasmoids results in ball lightning offering an answer as how they come into being. The first is an accelerated expanding mode. This mode appears to fit plasmoids ejected from thundercloud tops with acceleration to ionosphere seen in high altitude atmospheric observations of sprites and blue jets. It also appears to account for midair high-speed ball lightning overtaking airplanes, and ground level high-speed energetic ball lightning. The second is a decelerated expanding mode, and it appears to be compatible to slowly moving ball lightning seen near ground level. The inverse of this second mode corresponds to an accelerated inward collapse, which could bring ball lightning to an end sometimes with a cracking sound.
A specific property of electromagnetic waves interacting with dust-laden plasma
Authors: Tsintsadze N. L. , Ehsan Z. , Shah H. A. , Murtaza G.
Published: July 2006

The propagation pattern of electromagnetic waves (EMWs) in dusty plasmas is quite different from that in electron-ion plasmas. For instance, here the ponderomotive force acts on dust grains as a negative pressure, and a nonlinear Schrödinger equation with an additional nonlinear term is obtained. Based on this equation, the modulation instability is examined and it is shown that the growth rate becomes maximum when that additional term compensates the diffraction term. The main part of this work is devoted to the localization of the grains by the EMW. Considering both subsonic and supersonic regimes, it has been shown that under certain conditions the grains are localized and the ions circumnavigate the grains, whereas the electrons escape from the region of localization. Further, the localization of grains by the EMW is found to be shape-dependent of the pulse. Comparing pancake and light bullet shaped pulses in the supersonic regime, and it is shown that only the light bullet shape leads to the compression of grains. Finally, investigating nonstationary solution, it is shown that for some parameters, the nonlinear wave breaking and the formation of a shock wave can take place.
Nonvolatile memory cell effect in multilayered Ni1−xFex self-assembled nanoparticle arrays in polyimide
Authors: Jung Jae Hun , Kim Jae Ho , Kim Tae Whan , Yoon Chong Seung , Kim Young-Ho , Jin Sungho
Published: July 2006

Transmission electron microscopy images showed that self-assembled Ni1−xFex nanoparticle arrays were periodically inserted in the polyimide (PI) layers. Capacitance-voltage (C-V) measurements on Al/PI/multiple-stacked Ni1−xFex nanoparticle arrays/PI/p-Si (100) structures at 300K showed a metal-insulator-semiconductor capacitor behavior with different flatband voltage shifts, which depended on the value of the sweep voltage, due to the variations of the charged electron density in the multiple-stacked Ni1−xFex nanoparticle arrays. Conductance-voltage (G-V) measurements showed that the conductance peak related to the interface trap disappeared, and that the positions of the C-V and the G-V hystereses at the sweep voltage were different.
Frequency tunability of the terahertz silicon laser by a magnetic field
Authors: Pavlov S. G. , Hübers H.-W. , Kimmitt M. F. , Riemann H. , Shastin V. N.
Published: July 2006

By applying a magnetic field to the terahertz intracenter silicon laser the degeneracy of the donor states is lifted. In the case of a bismuth doped silicon laser operating at 6THz it is demonstrated that this effect can be used to tune the emission frequency. The frequency change depends on the relative orientation of the magnetic field and the crystallographic axis of the laser. The tuning rate is 40–60GHz∕T. The frequency tunability is explained by the linear Zeeman effect which splits the 2p± donor state acting as the upper laser level in the Si:Bi laser.
Tuning the optical absorption properties of Ag nanorods by their topologic shapes: A discrete dipole approximation calculation
Authors: Zhang Z.-Y. , Zhao Y.-P.
Published: July 2006

The optical extinction spectra of four topologically different Ag nanorod structures, needle, periodic, L, and Y shapes, have been calculated by the discrete dipole approximation. Both the needle and periodic shaped nanorods can be used to effectively tune plasmon resonant peaks, while the L- and Y-shaped nanorods influence the shape of the extinction spectra. This study shows that the topologic defects of nanorods have significant effects on the optical properties, and provides an alternative way to tune the plasmonic characteristics of metallic nanorods.
Charge transport in disordered films of non-redox proteins
Authors: Pompa P. P. , Della Torre A. , del Mercato L. L. , Chiuri R. , Bramanti A. , Calabi F. , Maruccio G. , Cingolani R. , Rinaldi R.
Published: July 2006

Electrical conduction in solid state disordered multilayers of non-redox proteins is demonstrated by two-terminal transport experiments at the nanoscale and by scanning tunneling microscopy (STM/STS experiments). We also show that the conduction of the biomolecular films can be modulated by means of a gate field. These results may lead to the implementation of protein-based three-terminal nanodevices and open important new perspectives for a wide range of bioelectronic/biosensing applications.
Design of infrared laser pulses for the deexcitation of highly excited homonuclear diatomic molecules
Authors: Ren Qinghua , Balint-Kurti Gabriel G. , Manby Frederick R. , Artamonov Maxim , Ho Tak-San , Rabitz Herschel
Published: July 2006

We explore the possibility of using shaped infrared laser pulses to deexcite a homonuclear diatomic molecule from its highest vibrational state down to its ground vibrational state. The motivation for this study arises from the need to deexcite alkali metal dimers in a similar way so as to stabilize molecular Bose–Einstein condensates. We demonstrate that for the case of the H2 molecule, where it is possible to evaluate all the necessary high accuracy ab initio data on the interaction of the molecule with an electric field, we are able to successfully design a sequence of infrared laser pulses to accomplish the desired deexcitation process in a highly efficient manner.
Environmental Governance in the Information Age: The Emergence of Informational Governance
Authors: Mol Arthur P J
Published: July 2006

Castells's influential work on the Information Age has hardly impacted on the environmental social sciences; and where it has, it has been mainly in terms of intrusions of global flows and networks in fragile environments. This paper explores to what extent and how environmental governance is changing under the conditions of the Information Age. On the waves of information and communication technologies and globalisation processes, a new informational mode of environmental governance—or informational governance—is emerging, in which environmental information gains transformative powers. Information generation, processing, transmission, and use become fundamental (re)sources of power and transformation in environmental reform. As illustrated by several examples, the conventional powers of (state) authority in environmental protection are partly replaced by informational resources, flows, and processes in new governance arrangements and networks. These new modes of informational governance not only point at innovative means of environmental reform, but also pose a series of more critical questions related to new power constellations, (information) access and democracy, and structural uncertainties following multiple knowledges. Hence, a new research agenda emerges for the environmental social sciences.
Evaluating Land-Use Restrictions concerning the Floor Area Ratio of Lots
Authors: Gao Xiaolu , Asami Yasushi , Katsumata Wataru
Published: July 2006

In Japanese city planning, the effective floor area ratio (FAR) of land lots, or housing density, is delimited by zoning and restrictions on the form of buildings (shape controls). To evaluate this system comprehensively, the authors analyze how the maximum allowable FAR (effective FAR) of residential lots affects land prices with a hedonic approach. Based on data on Tokyo, the analysis reveals that lots with an effective FAR of less than 110%, or between 170% and 210%, were significantly cheaper than those with an effective FAR of between 110% and 160%. The result for the low effective FAR group was explained by restrictions on floor space, and the result for the 170% to 210% group applied to areas with relatively unattractive landscape. Further examination showed that the FAR currently specified by zoning is more often effective when it is low, and that restrictions in the form of shape controls are more often effective when the effective FAR is high. These analyses provided criteria for evaluating the current land use control system. Based on the results, concrete proposals are made for improving the regulation system.
Monitoring Spatial Strategies: The Case of Local Development Documents in England
Authors: Wong Cecilia , Baker Mark , Kidd Sue
Published: July 2006

Since its recent overhaul, the British planning system has placed a strong emphasis on the development of ‘spatial’ rather than purely ‘land-use’ plans, and on the importance of adopting a systematic approach towards strategy monitoring. Such an evidence-based approach to spatial planning is already in use at the pan-European level and in Northern America. The authors aim to discuss the latest methodological developments in the monitoring of complex spatial strategies by examining the monitoring framework for local development documents in England. They examine the concept of spatial planning, issues and challenges surrounding spatial policy monitoring, and some emerging views over policy monitoring and evaluation. They then discuss the relevance of these latest ideas and different design principles of indicator frameworks to underpin the development of a monitoring framework for local development documents. Six core design components are discussed: the structure – performance model; the objectives – targets – indicators approach; a nested hierarchy of indicators; a framework of indicators; the use of analytical indicator bundles; and analytical principles. The authors identify the gaps and challenges in the developing monitoring framework for spatial planning in England and the wider, transferable, lessons to be learnt for complex policy monitoring.
Disintegrated Transport Policy: The Multimodal Studies Process in England
Authors: Shaw Jon , Hunter Colin , Gray David
Published: July 2006

As part of a broader effort to promote more sustainable or ‘integrated’ transport, the United Kingdom Labour government commissioned a series of multimodal studies designed to seek genuinely multimodal solutions to traffic congestion problems in England. Consultants undertaking the studies were instructed to presume against new roads unless all other options were clearly impractical. We build upon previous work to assess the extent to which the outcome of the multi-modal study process is consistent with the government's original intentions, as specified in relevant policy documentation. Our findings are that, although the process led to substantial achievements in some areas, its main outcome has been the approval of a host of new road schemes and—apart from some potentially significant public transport investment in the West Midlands—very little else. Viewed in the context of other developments since Labour came to power in 1997, such an outcome would appear to indicate the further disintegration of the party's much-vaunted ‘integrated’ transport policy.
The Planning — Policy Connection in US and Canadian Economic Development
Authors: Reese Laura A
Published: July 2006

The evidence regarding the extent of planning for local economic development decisions is mixed, and there is a general dearth of studies that examine whether rational planning is tied to policy choices in any systematic way. The research reported here rests on two premises. The first is the simple assumption that for planning to play an integral part in the economic development policy process there should be some empirical connection between local economic development goals—what officials want to achieve—and the economic development strategies they pursue. The second premise, based on extant literature, is that Canadian cities have different and more institutionally integrated planning traditions and practices than those in the USA, and hence should evidence a closer link between development goals and policies. Based on a survey of all of the municipalities in the USA and Canada with populations over 10 000, it is concluded that for US cities goals do not appear to correlate with discrimination among economic development policies; that is, planning is not related to the selection of activities. On the other hand, in Canada, cities' goals are related to specific policies in a more logical or rational fashion. In short, it appears that economic development planning is tied to the selection of policies to a greater extent in Canadian cities than in the USA.
Reshaping Spaces of Local Governance? Community Strategies and the Modernisation of Local Government in England
Authors: Raco Mike , Parker Gavin , Doak Joe
Published: July 2006

The preparation of Community Strategies (CS) has been required of Local Strategic Partnerships and local authorities in England since the passing of the Local Government Act 2000. The authors examine the process and content of two CSs in southern England as part of an ongoing project to understand their impact and explore ways in which CSs may be prepared in a meaningful and effective manner. They critically evaluate a number of dimensions of CS formulation, including: the important role of local political and cultural context; the extent to which they reflect and reproduce a shift from representational to participatory forms of democracy; the impact of national policy agendas; the role of place identity; the relative influence of local government officers and members; and the dynamics and implications of particular forms of conflict mediation and consensus building. They conclude that the process of CS formation studied illustrates the tensions and opportunities contained within the Labour government's modernisation agenda. Governmentalities of active citizenship and participatory democracy mingle with more representational and managerial modes of local governance, creating hybrid structures, processes, and outcomes that shape the process of strategy formulation. All this is set within a context of a dynamic and variable set of place identities and pervasive resource (inter)dependencies which both close down and open up the range of issues and interests that are drawn into the process of CS formulation.
Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells
Authors: Miao Robert Qing , Gao Yuan , Harrison Kenneth D. , Prendergast Jay , Acevedo Lisette M. , Yu Jun , Hu Fenghua , Strittmatter Stephen M. , Sessa William C.
Published: July 2006

Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates vascular function is unknown. Here, we identify a previously uncharacterized Nogo-B receptor specific for the amino terminus of Nogo-B and show that Nogo-B receptor localizes with the ligand Nogo-B during VEGF and wound healing angiogenesis
in vivo
, mediates chemotaxis in a heterologous expression system and chemotaxis, and 3D tube formation in native endothelial cells. Thus, identification of this receptor may lead to the discovery of agonists or antagonists of this pathway to regulate vascular remodeling and angiogenesis.
Small-molecule modulators of p53 family signaling and antitumor effects in p53-deficient human colon tumor xenografts
Authors: Wang Wenge , Kim Seok-Hyun , El-Deiry Wafik S.
Published: July 2006

p53 deficiency is common in almost all human tumors and contributes to an aggressive chemo- or radiotherapy-resistant phenotype, therefore providing a target for drug development. Molecular targeting to restore wild-type p53 activity has been attempted in drug development and has led to the identification of CP-31398, PRIMA1, and the Nutlins. However, strategies targeting p53-activated transcriptional responses or p53 family member expression in p53-deficient tumors have yet to be explored. Here we demonstrate the use of noninvasive bioluminescence imaging in a high-throughput cell-based screen of small molecules that activate p53 responses and cell death in human tumor cells carrying a mutant p53. We isolated a number of small molecules that activate p53 reporter activity, increase expression of p53 target genes such as p21(WAF1) or death receptor 5 (KILLER/DR5) of TNF-related apoptosis-inducing ligand (TRAIL), and induce apoptosis in p53-deficient cells. Some of the compounds activate a p53 response by increasing p73 expression, and knockdown of transactivating isoforms of p73 by small interfering RNA reduces their induction of p53-responsive transcriptional activity. Some compounds do not induce significant p73 expression but induce a high p53-responsive transcriptional activity in the absence of p53.
In vivo
experiments demonstrate potent antitumor effects of selected compounds, using either HCT116/p53(−/−) or DLD1 human colon tumor xenografts. The results establish the feasibility of a cell-based drug screening strategy targeting the p53 transcription factor family of importance in human cancer and provide lead compounds for further development in cancer therapy.
Time, Space and Gender: Understanding ‘Problem’ Behaviour in Young Children
Authors: Brown Jane
Published: July 2006

The following article reports on a small‐scale, exploratory study of aggressive and ‘problem’ behaviour in pre‐school children. This project was conceived in the wider context of anxieties about childhood and New Labour’s policy focus on ‘anti‐social’ behaviour in children. Based on interviews with nursery staff and parents in addition to participant observation undertaken in nursery playrooms, this article examines the relevance of time, space and gender for understanding problem behaviour in young children. Taking a social constructionist perspective and drawing on Foucault's ideas in particular, it examines the social processes which regulate and normalise behaviour in young children. © 2006 The Author(s) Journal compilation © 2006 National Children's Bureau.
Alcohol dependence in relation to burnout among the Finnish working population
Authors: Ahola Kirsi , Honkonen Teija , Pirkola Sami , Isometsä Erkki , Kalimo Raija , Nykyri Erkki , Aromaa Arpo , Lönnqvist Jouko
Published: July 2006

Aims  To investigate the relationship of burnout to alcohol dependence and high alcohol consumption.

Design  A cross‐sectional population‐based multi‐disciplinary ‘Health 2000 Study’. The analyses were performed separately for the women and the men and adjusted for socio‐demographic factors.

Setting and participants  In Finland, 3276 active employees (1637 women and 1639 men), aged 30–64 years, from a representative population sample.

Measurements  The diagnosis of Diagnostic and Statistical Manual of Mental Disorders version IV (DSM‐IV) alcohol dependence was based on the standardized Munich Composite International Diagnostic Interview (M‐CIDI). The assessment of high alcohol consumption was based on self‐reported alcohol use. Burnout was assessed with the Maslach Burnout Inventory—General Survey (MBI‐GS).

Findings  The 12‐month prevalence of alcohol dependence was associated with burnout among both men and women. Each one‐point increase in burnout score was associated with an 80% increase in the incidence for alcohol dependence among women and a 51% increase among men. These associations persisted when socio‐demographic factors were adjusted. The associations between burnout and high alcohol consumption were not statistically significant.

Conclusions  There is an association between burnout and alcohol dependence among both genders. Among both women and men, attention to alcohol‐related behaviour is warranted in the clinical context when burnout and other problems related to work are encountered. Interventions which include assessment of work conditions and management of work‐related stress should be targeted at employees with alcohol dependence in addition to traditional treatment.
Smoking reduction and biomarkers in two longitudinal studies
Authors: Godtfredsen Nina S. , Prescott Eva , Vestbo Jørgen , Osler Merete
Published: July 2006

Aims  To measure reduction in exposure to smoke in two population‐based studies of self‐reported smoking reduction not using nicotine replacement.

Design  Cross‐sectional analyses of biomarkers and smoking.

Setting  Data from two time‐points in the Copenhagen City Heart Study (CCHS), 1981/83 and 1991/94, and the Copenhagen Male Study (CMS) in 1976 and 1985/86, respectively.

Participants  There were 3026 adults who were smokers at both time‐points in the CCHS and 1319 men smoking at both time‐points in the CMS.

Measurements  Smoking status and tobacco consumption were assessed by self‐completion questionnaire. Measurements of biomarkers of smoke intake were taken at the second time‐point in the two studies: expired‐air carbon monoxide (CO) in the CCHS and serum cotinine in the CMS. Biomarker levels in medium (15–29 g tobacco/day) and heavy (> 30 g/day) smokers at the first time‐point who later reported a reduction in cigarettes per day of 50% or more without quitting were compared with continuing medium, heavy and light smokers (1–14 g/day) using linear regression. Sex (CCHS only), age, self‐reported inhalation of smoke, duration of smoking, type of tobacco and amount smoked were included as covariates in multivariate models.

Findings  Heavy smokers who reduced did not show lower levels of biomarkers at follow‐up. Medium smokers who reduced showed a reduction in cotinine but not CO. The reduction in cotinine was not commensurate with the reported reduction in consumption.

Conclusions  Long‐term reductions in self‐reported tobacco smoking are probably associated with, at best, modest reductions in smoke exposure.
Incidence and risk factors for hepatitis C seroconversion in injecting drug users in Australia
Authors: Maher Lisa , Jalaludin Bin , Chant Kerry G. , Jayasuriya Rohan , Sladden Tim , Kaldor John M. , Sargent Penny L.
Published: July 2006

Aims To determine the incidence of hepatitis C virus (HCV) infection and identify risk factors for seroconversion.

Design Prospective cohort study. Participants were recruited through direct approaches, street‐based outreach, methadone and sexual health clinics and needle and syringe programmes.

Setting Urban, regional and rural settings in New South Wales, Australia.

Participants Injecting drug users (IDUs) (n = 584) were screened and tested for exposure to HCV. Between 1999 and 2002 antibody HCV negative IDUs (n = 368) were enrolled and followed‐up every 3–6 months until seroconversion or study completion.

Measurements Interviewer‐administered baseline and follow‐up questionnaires consisted of 131 items and included demographics, drug use and risk behaviour. Approximately 10 cc of whole blood was drawn at each visit. Specimens were stored at −70C and serology performed using one or two third‐generation enzyme‐linked immunosorbent assays and polymerase chain reaction testing.

Findings Sixty‐eight seroconversions were observed and incidence was 30.8 per 100 person‐years, with incidence in IDUs injecting < 1 year, 133 per 100 person‐years. Independent predictors of seroconversion were female gender, duration of injecting, injecting cocaine, shared use of filters and recruitment strategy.

Conclusions Women, new initiates and IDUs recruited via outreach appear to be at increased risk of infection. Results confirm the significance of cocaine injection as a risk factor and provide the first evidence outside North America of the link between shared use of drug preparation equipment and incident HCV infection. Prevention efforts should attempt to raise awareness of the risks associated with drug sharing and, in particular, the role of potentially contaminated syringes in HCV infection.
Long‐term reversal of hypocholesterolaemia in patients with chronic hepatitis C is related to sustained viral response and viral genotype
Authors: FERNÁNDEZ‐RODRÍGUEZ C. M. , LÓPEZ‐SERRANO P. , ALONSO S. , GUTIÉRREZ M. L. , LLEDÓ J. L. , PÉREZ‐CALLE J. L. , TEMIÑO R. , CACHO G. , NEVADO M. , CASAS M. L. , GASALLA J. M. , BONET B.
Published: July 2006

Background

Genotype‐3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis.

Aim

To characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients.

Methods

Patients (n = 215) with chronic hepatitis C (157 with genotype‐1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, β‐hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)‐infected subjects.

Results

Genotype‐3 of HCV patients had age‐adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype‐3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120–151) to 180 mg/dL (95% CI: 171–199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype‐3 of HCV non‐responders and in patients with genotype‐1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in β‐hydroxybutyrate.

Conclusions

Besides causing hepatic steatosis, genotype‐3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.
Review article: management of hepatic disease following haematopoietic cell transplant
Authors: McDONALD G. B.
Published: July 2006

Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft‐versus‐host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug‐induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant.

Pre‐transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes.

This review covers pre‐transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long‐term survivors.
Meta‐analysis: intradermal vs. intramuscular vaccination against hepatitis B virus in patients with chronic kidney disease
Authors: FABRIZI F. , DIXIT V. , MAGNINI M. , ELLI A. , MARTIN P.
Published: July 2006

Background

Dialysis patients have suboptimal response towards hepatitis B virus (HBV) vaccine and intradermal hepatitis B virus vaccination has been used to improve the response rate; however, its efficacy remains unclear.

Design

Meta‐analysis of controlled trials comparing intradermal vs. intramuscular vaccine against HBV among chronic kidney disease patients.

Identification

Twelve studies involving 640 unique patients were included if they had controlled design, intervention and control group patients received intradermal or intramuscular vaccine against HBV, respectively. Patients were followed for a minimum of 7 months after the first vaccine dose.

Main outcome measures

The odds ratio of failure to respond to HBV vaccine among patients who received vaccine by intradermal vs. intramuscular route was the end point of interest. It was calculated at completion of HBV vaccination and over follow‐up.

Results

Pooling of study results demonstrated a decreased risk of failure to respond to HBV vaccine among patients who were vaccinated by intradermal vs. intramuscular route (pooled odds ratio at completion of vaccine protocol: 0.36; 95% CI: 0.21–0.62; test of study heterogeneity, P =0.089). This difference did not occur over follow‐up (6–60 months after completing vaccine schedule; pooled odds ratio: 1.1; 95% CI: 0.47–2.5).

Conclusions

Dialysis patients show higher seroprotection after intradermal than intramuscular vaccination schedules; this was not apparent over follow‐up. Further studies are warranted to assess if the higher seroprotection rates obtained by intradermal route translates into reduced incidence of de novo HBV virus among chronic kidney disease patients.
Relationship of glutathione S‐transferase genotypes with side‐effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus
Authors: Zhong Shilong , Huang Min , Yang Xiuyan , Liang Liuqin , Wang Yixi , Romkes Marjorie , Duan Wei , Chan Eli , Zhou Shu‐Feng
Published: July 2006

Aims

Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S‐transferases (GSTs). However, data are lacking on the relationship between the short‐term side‐effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.

Methods

DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)‐multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile→Val) was analyzed by a PCR‐restriction fragment length polymorphism (RFLP) assay.

Results

Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*‐105I/V (heterozygote) and GSTP1*‐105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high‐dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high‐dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short‐term side‐effects of pulsed high‐dose CTX therapy in SLE patients.

Conclusions

The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short‐term side‐effects of pulsed high‐dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high‐dose CTX therapy in SLE patients.
Pharmacokinetics of ribavirin in patients with hepatitis C virus
Authors: Wade Janet R. , Snoeck Eric , Duff Frank , Lamb Matthew , Jorga Karin
Published: July 2006

Aim

A population pharmacokinetic analysis was performed using plasma concentration data (n = 7025) from 380 patients to examine the relationship between ribavirin dose and its pharmacokinetics.

Methods

Ribavirin pharmacokinetics were described by a three‐compartment model with sequential zero‐order and a first‐order absorption processes. Interoccasion variability and food effects were included.

Results

Lean body weight (range 41–91 kg) was the only covariate with a clinically significant influence on ribavirin pharmacokinetics, affecting clearance (15.3–23.9 l h−1) and the volume of the larger peripheral compartment.

Conclusion

The model provided a good description of the available data, confirmed by accurate estimates of parameter values and low residual variability (17%).
Ultraviolet-A (UVA-1) radiation suppresses immunoglobulin production of activated B lymphocytesin vitro
Authors: Polderman M C A , Van Kooten C , Smit N P M , Kamerling S W A , Pavel S
Published: July 2006

Previous studies have shown that low-dose ultraviolet-A (UVA-1) total body irradiations were capable of improving disease activity in patients with systemic lupus erythematosus (SLE). We hypothesized that UVA-1-induced suppression of immunoglobulin production by activated B cells in the dermal capillaries could be (partly) responsible for this effect. Our experiments with donor skin demonstrated that approximately 40% of UVA-1 could penetrate through the epidermis. Irradiation of peripheral blood mononuclear cells (PBMCs) with 2 J/cm2 of UVA-1 resulted in 20% cell death. This toxic effect could be prevented totally by preincubation of the cell cultures with catalase. This indicates that the generation of hydrogen peroxide plays a role in UVA-1 cytotoxicity. T cells and B cells appeared to be less susceptible to UVA-1 cytotoxicity than monocytes. With the use of a CD40–CD40L B cell activation method we measured immunoglobulin production after various doses of UVA-1 irradiation (0–2 J/cm2). The doses of 2 J/cm2 caused a significant decrease of IgM, IgG, IgA and IgE production under the conditions of interleukin (IL)-10 or IL-4 (IgE) stimulation. Although UVA-1 can cause apoptosis of B lymphocytes, we show that relatively low doses of UVA-1 radiation also affect the function of these cells. Both effects may be responsible for the observed improvement of disease activity in SLE patients.
A potential role for interleukin-18 in inhibition of the development ofCryptosporidium parvum
Authors: McDonald V , Pollok R C G , Dhaliwal W , Naik S , Farthing M J G , Bajaj-Elliott M
Published: July 2006

Accumulating evidence suggests that intestinal epithelial cells (IECs) constitutively express the immunoregulatory cytokine interleukin (IL)-18. IECs also serve as the host cell for the intracellular parasitic protozoan Cryptosporidium parvum. In the present study, C. parvum infection of a human enterocyte cell-line HCT-8 resulted in increased expression of IL-18 mRNA as measured by quantitative reverse transcription–polymerase chain reaction (RT-PCR). IL-18 protein was detected in control uninfected cells and following infection there was increased expression as measured by enzyme-linked immunosorbent assay (ELISA). Gene expression revealed the presence of the IL-18 receptor subunits not only in cell-lines but also in freshly isolated IECs, suggesting that IL-18-mediated signalling events may contribute to epithelial host defence during infection. Recombinant IL-18 inhibited intracellular development of the parasite in HCT-8 and HT-29 cells. Increased expression of bactericidal antibiotic peptides LL-37 and α-defensin 2 by IL-18 in HCT-8 and HT-29 cells may represent one mode of action by which this pluripotent cytokine aids in limiting the development of intracellular pathogens such as C. parvum in the gastrointestinal tract.
Emerging role of a phosphatonin in mineral homeostasis and its derangements
Authors: Bielesz B.
Published: July 2006

Background  The study of a distinct group of renal phosphate wasting disorders with bone disease which comprise X‐linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR) and tumour‐induced osteomalacia (TIO) gave rise to the identification of different hormone‐like peptides, also known as phosphatonins. These factors are responsible for the major disease features that characterize XLH, ADHR and TIO. Recent reports on one of these phosphatonins, fibroblast growth factor‐23 (FGF‐23), point to a general role of this factor in mineral ion metabolism.

Objectives  The main focus regards recent evidence implicating FGF‐23 in normal and disordered mineral homeostasis with special emphasis on chronic kidney disease. The interactions of FGF‐23 with phosphate, parathyroid hormone and vitamin D are discussed in detail.

Summary  The FGF‐23 has been shown to increase urinary phosphate excretion, inhibit bone mineralization and suppress 1,25‐dihydroxy vitamin D3[1,25(OH)2D3], the main characteristics that XLH, ADHR and TIO have in common. Apart from its role in these phosphate wasting disorders serum FGF‐23 is elevated in hypoparathyroidism and humoral hypercalcaemia of malignancy and responds to altered dietary phosphate and calcium supply in healthy subjects. The FGF‐23 is also variably elevated in chronic kidney disease and associated secondary hyperparathyroidism where it correlates positively with serum phosphate and parathyroid hormone and negatively with 1,25(OH)2D3. Such relationships, along with data from experimental studies, raise the question of whether FGF‐23 contributes to the pathophysiology of chronic kidney disease.
Development of renal bone disease
Authors: Ferreira A.
Published: July 2006

Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of ‘mixed bone disease’ and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients.

In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia.

Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed.
Diagnosis of renal osteodystrophy
Authors: Schwarz C. , Sulzbacher I. , Oberbauer R.
Published: July 2006

The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different.

Bone histology remains the gold standard for the exact classification of ROD. Serological markers of bone metabolism are not suited for the accurate nomenclature of ROD but are useful for the sequential follow up of ROD after a clear diagnosis has been made. Similarly, radiological diagnosis of ROD using dual energy X‐ray absorptiometry (DEXA) or quantitative computer tomography scan (q‐CT) is inaccurate and thus more suited for the routine follow up of established disease.

Besides mineralization, bone strength and the rate of fractures are strongly determined by the architecture of the bone matrix. This information, however, is also only available on bone biopsy sections and cannot be estimated by non‐invasive diagnostic methods.

In summary, bone biopsy should be used more liberally for correct classification of bone disease. The sequential follow up and guidance of therapy success can be performed by non‐invasive procedures such as biochemical bone marker determination in blood. X‐ray imaging and densitometry is suitable only for sequential evaluation of osteoporosis.
Expression of CD8α identifies a distinct subset of effector memory CD4+ T lymphocytes
Authors: Macchia Iole , Gauduin Marie‐Claire , Kaur Amitinder , Johnson R. Paul
Published: July 2006

Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8αα homodimer, while the minor population was CD4lo CD8hi and expressed the CD8αβ heterodimer. The majority of CD4hi CD8αlo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7– CD28– HLA‐DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus‐specific T cells was enriched five‐fold in CD4hi CD8αlo T cells compared to single‐positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)‐specific T cells. Cross‐sectional studies of SIV‐infected animals demonstrated that the frequency of CD4hi CD8αlo T cells was lower in wild‐type SIV‐infected animals compared to uninfected controls, although prospective studies of SIV‐infected animals demonstrated depletion of CD4hi CD8αlo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8α represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection.
Base‐pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq
Authors: Kawamoto Hiroshi , Koide Yukari , Morita Teppei , Aiba Hiroji
Published: July 2006

SgrS is an Hfq‐binding small antisense RNA that is induced upon phosphosugar stress. It forms a ribonucleoprotein complex with RNase E through Hfq to mediate silencing of the target ptsG mRNA encoding the membrane component of the glucose‐specific phosphoenolpyruvate phosphotransferase system. Although SgrS is believed to act on ptsG mRNA through base pairing between complementary regions, this was not previously tested experimentally. We addressed the question of whether SgrS indeed forms an RNA–RNA duplex with ptsG mRNA to exert its regulatory function. Specific single nucleotide substitutions around the Shine–Dalgarno (SD) sequence of ptsG completely eliminated SgrS action while compensatory mutations in SgrS restored it. A systematic mutational analysis of both ptsG and SgrS RNAs revealed that six base pairs around SD sequence of ptsG are particularly important for SgrS action. We also showed in vitro that SgrS forms a stable duplex with the ptsG mRNA, and that Hfq markedly facilitates the rate of duplex formation.