bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high‐risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor
Authors: Sung Ki Woong , Yoo Keon Hee , Cho Eun Joo , Koo Hong Hoe , Lim Do Hoon , Shin Hyung Jin , Ahn Seung Do , Ra Young Shin , Choi Eun Seok , Ghim Thad T.
Published: October 2006

Background

Single or tandem double high‐dose chemotherapy (HDCT) was used to treat children with newly diagnosed high‐risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor (MB/sPNET) in order to defer or avoid radiotherapy in young children.

Procedure

Thirty‐seven HDCTs were given to 25 children with newly diagnosed high‐risk or relapsed MB/sPNET. Tandem double HDCT was used for 12 of 15 patients initially intended to receive double HDCT.

Results

Three‐year EFS (±SE) in 6 newly diagnosed high‐risk (>3 years old), 8 newly diagnosed (<3 years old), and 11 relapsed MB/sPNET was 83.3 ± 15.2%, 62.5 ± 20.5%, and 29.1 ± 15.7%, respectively. Three‐year EFS for patients in CR or PR and in less than PR at first HDCT was 67.4 ± 11.0% and 16.7 ± 15.2%, respectively (P = 0.001). Three‐year EFS in patients initially intended to receive double HDCT and single HDCT was 66.0 ± 12.4% and 40.0 ± 15.5%, respectively. For 19 patients in CR or PR at first HDCT, 3‐year EFS was 88.9 ± 10.5% in tandem double HDCT group, and 44.4 ± 16.6% in single HDCT group, respectively (P = 0.037). Although four treatment‐related mortalities (TRMs) occurred during 25 first HDCTs, no TRM occurred during 12 second HDCTs. In four of eight young children, craniospinal radiotherapy was successfully withheld without subsequent relapse.

Conclusions

High‐dose chemotherapy may improve the survival of children with newly diagnosed high‐risk MB/sPNET, and, to some extent, the survival of those with relapsed MB/sPNET. Further study is necessary to elucidate the efficacy of tandem double HDCT. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Hepatitic pattern of graft versus host disease in children
Authors: Melín‐Aldana Héctor , Thormann Kimberly , Duerst Reggie , Kletzel Morris , Jacobsohn David A.
Published: October 2006

Background

Liver involvement by graft‐versus‐host disease (GVHD) is characterized histologically by bile duct damage, which may be severe. A different pattern, “hepatitic GVHD,” has been described in adult patients. This pattern also shows marked lobular hepatitis and hepatocellular damage. We report the development of hepatitic GVHD in six pediatric patients.

Procedure

Clinical information and histologic features of liver biopsy samples were retrospectively reviewed.

Results

Patients' ages ranged from 3 to 11 years. Underlying diagnosis, pre‐transplant conditioning and GVHD prophylaxis varied. Peripheral blood stem cells were the source of the allograft in four patients, matched sibling in one, and matched‐unrelated donor in one. Hepatic GVHD was detected between 149 and 310 days post‐transplant. Prior acute GVHD had developed in two patients, and involved the skin and/or gastrointestinal tract. No patients had significant ductopenia. Only one patient had significant lymphocytic infiltration of bile ducts (ductitis). Bile duct epithelial damage and significant portal/periportal inflammation were present in all patients. Lobular necro‐inflammation was present in five patients. Five patients improved with immunosuppression and one died with progressive GVHD.

Conclusions

This series focuses on hepatitic GVHD in pediatric patients. Clinical and histologic patterns are similar to what has been described in adults. Specific etiology and pathogenesis of this entity remain unclear. Pediatr Blood Cancer 2007;49:727–730. © 2006 Wiley‐Liss, Inc.
Impact of telemedicine on pediatric neuro‐oncology in a developing country: The Jordanian‐Canadian experience
Authors: Qaddoumi Ibrahim , Mansour Asem , Musharbash Awni , Drake James , Swaidan Maisa , Tihan Tarik , Bouffet Eric
Published: October 2006

Background

Telemedicine is widely used in industrialized countries for educational purposes. Twinning experiences using telemedicine between institutions in industrialized and developing countries (DC) have been limited. Pediatric neuro‐oncology is a complex multidisciplinary discipline that is underserved in most of DC and provides a model to test the feasibility of such tool for twinning purposes.

Methods

A computer, an EMLO visual presenter HV‐7600SX document camera, and a TANDBERG 6000 model videoconference unit were used to present data. For connectivity, we used a six‐channel ISDN telephone line. Each channel is 64 megabytes/sec.

Results

Between December 2004 and May 2006, 20 sessions of videoconference were held between King Hussein Cancer Center and the Hospital for Sick Children to discuss 72 cases of 64 patients with various brain tumors (5 patients were discussed twice and 1 patient four times). In 23 patients (36%), major changes from original plan were recommended on different aspects of the care. In 21 patients (91%), those recommendations were followed, with potentially significant positive impact on patients' care.

Conclusions

Videoconferencing is a feasible and practical twinning tool in pediatric neuro‐oncology with a potentially major impact on patient care. Pediatr Blood Cancer 2007;48:39–43. © 2006 Wiley‐Liss, Inc.
Phase transitions in anisotropic two‐dimensional quantum antiferromagnets
Authors: Roscilde T. , Cuccoli A. , Verrucchi P.
Published: October 2006

We study the thermodynamic properties of anisotropic two‐dimensional quantum antiferromagnets, with both easy‐plane and easy‐axis anisotropy. We make use of the Quantum Monte Carlo (QMC) method based on the continuous‐time loop algorithm. For S = 1/2 and very small anisotropies our QMC data reveal that both the Ising and Berezinskii–Kosterlitz–Thouless universality class (for the easy‐axis and easy‐plane models, respectively) are well observed and that the critical temperature remains finite even for anisotropies as small as 10–3, i.e. comparable to the anisotropies measured in real layered compounds; this result rules out the possibility of quantum fluctuations to destroy the finite‐temperature transition before the isotropic limit is reached. The phase diagram of the S = 1/2 2d‐XXZ antiferromagnet in the region of small anisotropies is then presented.
Atomic determinants of state‐dependent block of sodium channels by charged local anesthetics and benzocaine
Authors: Tikhonov Denis B. , Bruhova Iva , Zhorov Boris S.
Published: October 2006

Molecular modeling predicts that a local anesthetic (LA) lidocaine binds to the resting and open Nav1.5 in different modes, interacting with LA‐sensing residues known from experiments. Besides the major pathway via the open activation gate, LAs can reach the inner pore via a “sidewalk” between D3S6, D4S6, and D3P. The ammonium group of a cationic LA binds in the focus of the pore‐helices macrodipoles, which also stabilize a Na+ ion chelated by two benzocaine molecules. The LA's cationic group and a Na+ ion in the selectivity filter repel each other suggesting that the Na+ depletion upon slow inactivation would stabilize a LA, while a LA would stabilize slow‐inactivated states.
Thy Word In Me: On the Prayer of Union in St. Teresa of Avila's Interior Castle
Authors: Anderson Mary Margaret
Published: October 2006

But I know that it can only be gained by abandoning everything.—St. Teresa of Avila
SPIRITUAL GENEALOGY: SUFISM AND SAINTLY PLACES IN THE NILE DELTA
Authors: el-Aswad el-Sayed
Published: October 2006

Although spiritual realities do not find a place in the explanatory scheme of modern science, they nevertheless play a significant role in the everyday life of people. This article discusses the interrelationship between blood and spiritual genealogies among Sufi orders in the Muslim world in general and in the Nile Delta of Egypt in particular. Contrary to theories of geographic reductionism that highlight the geographical features of the Delta, this research sheds light on the impact of cultural and religious factors, such as regional Sufi orders and related saint cults, on the inhabitation and perpetuation of the local landscape. Moreover, compared with the rich scholarship of the grand Sufi orders and saints, studies that deal with local branches of dominant Sufi orders are sparse. The relationship between Sufi beliefs and practices in local contexts and in broader national or global (Muslim) worldviews is also considered.
CONTEMPORARY LEBANESE FICTION: MODERNIZATION WITHOUT MODERNITY
Authors: Aghacy Samira
Published: October 2006

This study focuses on the nature of the Lebanese encounter with modernity in Lebanese fiction over the past forty years or so, a time of great ideological, political, and cultural upheavals. The first part traces the effect of modernity on works by Lebanese writers since the 1950s, a period of “revolutionary political and social change,” and of learning and cultural and social ferment. The second part of the study focuses on Rashid al-Daif's novel עAzizi al-Sayyed Kawabata. My choice of this particular novel is related to the fact that it is a representative work that underlines the impact of modernity on Lebanese individuals and society during and in the wake of the civil war. The novel raises questions about rationality, ideology, the individual self, and the relevance of these Western constructs to the local situation in Lebanon. The structure of the novel itself and the use of the epistolary and autobiographical modes of writing underscore the novel's obsession with modernity. Within this context, one could say that al-Daif's novel can be viewed as a complex work of fiction that encompasses different forms of modernity, the tensions between these modernities, and between modernity and authenticity.
Application of holmium yttrium aluminium garnet (YAG) laser in treatment of acquired posterior choanal atresia following radiotherapy for nasopharyngeal carcinoma
Authors: Ku Peter K M , Tong Michael C F , van Hasselt Andrew
Published: October 2006

Aims: To report on the use of holmium yttrium aluminium garnet (YAG) laser in the treatment of acquired posterior choanal atresia following radiotherapy in patients with nasopharyngeal carcinoma.

Materials and methods: Five patients with acquired bilateral choanal atresia and two with unilateral choanal atresia in the posterior choanae were identified following treatment of nasopharyngeal carcinoma by external radiotherapy, from July 1998 to April 1999. The mean age was 44.6 years (range, 22–65 years). Two patients had stage two and five had stage three disease according to Ho's classification. All patients received 66 Gy of external irradiation delivered to the nasopharynx and a mean dose of 61 Gy (39.8–72 Gy) to the neck. Five patients received an additional external boost of 20 Gy and two received 14 Gy delivered to the parapharyngeal region. Two other patients also received intracavitatory brachytherapy of 18 Gy delivered to the nasopharynx. One patient had concurrent chemotherapy by cisplatinum during external radiotherapy. The mean onset of nasal symptoms was 17 months (range, 2–38 months) following irradiation. All patients were treated by transnasal endoscopic holmium YAG laser resection. Merocel® epistaxis packing and a modified nasopharyngeal tube were used to stent the nasal airway for two weeks post-operatively.

Results: The mean follow up was 26.8 months (range, 20–32 months) after surgery. All patients were symptom free on follow up. Five patients (71 per cent) retained full patency in the posterior choanae. Two patients (28 per cent) had bilateral mild restenosis in the postnasal space, not requiring revision surgery. The surgical fields were almost bloodless. No adverse post-operative complications occurred, except for delayed nasal septal perforation in one patient and unilateral exposure of the septal cartilage in another; no further treatment was required in either patient.

Conclusion: Acquired posterior choanal atresia is an unusual complication following radiotherapy, and it can occur early after treatment. It can be successfully treated by transnasal endoscopic holmium YAG laser resection of the scar tissue, with minimal bleeding. A two week period of Merocel® nasal packing and nasopharyngeal tube stenting was sufficient to prevent severe restenosis in the posterior choanae; nasal breathing through the tube lumen was possible during this time.
Information technology in ENT: are we ready to be ‘Connected For Health’?
Authors: Clamp P J , Virdi P , Vats A , Pothier D D
Published: October 2006

The NHS Connecting for Health agency continues to implement the national programme for information technology within the National Health Service (NHS). In preparation, NHS employees are being encouraged to develop their information technology skills via the European computer driving licence training course.

A postal survey of British Association of Otorhinolaryngologists members was undertaken to evaluate their levels of information technology training, competency and knowledge. Three hundred and thirty-six surgeons responded.

Most respondents had received no formal information technology training. Only 3.9 per cent had taken the European computer driving licence course.

Most surgeons felt comfortable using word processing and presentation software but were less comfortable with other applications. Junior surgeons were more confident in all areas of information technology application than senior surgeons.

Seventy-two per cent of surgeons wanted more information technology training. Most felt that such training should be routine at undergraduate and postgraduate level.

With the national programme committed to improving information technology infrastructure within the NHS, more formal training should be provided to ensure a basic standard of information technology competency amongst ENT surgeons.
Enhancing meaning in palliative care practice: A meaning-centered intervention to promote job satisfaction
Authors: FILLION LISE , DUPUIS RÉJEANNE , TREMBLAY ISABELLE , DE GRÂCE GASTON-RENÉ , BREITBART WILLIAM
Published: October 2006

Objectives:This article introduces a new meaning-centered psycho-educational group intervention, calledEnhancing meaning in palliative care nursing, designed to support nurses providing palliative care. This intervention aims at increasing job satisfaction and quality of life, as well as preventing burnout in this particular population.

Theoretical frameworks:Its format and content are founded on the meaning-centered psychotherapy approach developed for terminally ill cancer patients (Breitbart, 2001; Greenstein & Breitbart, 2000). Frankl's existential therapeutic approach, calledlogotherapy, serves as the underlying theoretical framework to this intervention.

Development:Following the presentation of the context and the development of the intervention, its content is described.

Conclusion:A brief description of the ongoing randomized controlled trial testing the intervention is then provided. Finally, the way in which this intervention could contribute to nurses' quality of life and suggestions for future developments are briefly discussed.
The relation between the experience of time and psychological distress in patients with hematological malignancies
Authors: WITTMANN MARC , VOLLMER TANJA , SCHWEIGER CLAUDIA , HIDDEMANN WOLFGANG
Published: October 2006

Objective:The experience of time is strongly related to our momentary mood states. Patients with a life-threatening illness experience an extreme change in mood and suffer from psychological distress that can develop into clinically relevant psychiatric disorders, like anxiety and depression. The aim of this study was to investigate the associations among the subjective perception of time, psychological distress, and quality of life in patients with hematological malignancies.

Methods:Eighty-eight inpatients with hematological malignancies rated how fast time passes subjectively on a visual analog scale and prospectively estimated a time span of 13 min. The Hospital Anxiety and Depression Scale (HADS) self-report measures of health-related quality of life (FACT-G) and spiritual well-being (FACIT-Sp) were employed to assess psychological distress and quality of life.

Results:Those patients who reported a lower quality of life, less spiritual well-being, and more anxiety experienced a slower passage of subjective time and overestimated the 13-min time interval.

Significance of results:Our interpretation of the results is that patients with a life-threatening illness who show symptoms of psychological distress draw attention away from meaningful thoughts and actions and, thus, experience time as passing more slowly. An altered sense of time can be a sign of mental suffering, which should be addressed within psycho-oncological interventions. As this is the first study to demonstrate this relation in cancer patients, further research is needed to investigate the experience of time and its relation to meaning as an issue in clinical diagnostics.
PSALM
Authors: SHERMAN RITA
Published: October 2006

Psalm.
Effect of Glucose or Glycerol as the Sole Carbon Source on Gene Expression from the Salmonella prpBCDE Promoter in Escherichia coli
Authors: Lee Sung Kuk , Keasling Jay D.
Published: October 2006

We have developed an expression system (Salmonella‐based pPro system) containing the Salmonella enterica prpBCDE promoter (PprpB) and prpR encoding the positive transcriptional regulator of this promoter. In this study, the transcriptional efficiency of the pPro expression system was measured by placing the gene encoding the green fluorescent protein (gfp) under the control of PprpB and growing cells containing this construct in minimal medium supplemented with glucose or glycerol as a sole carbon source. In wild‐type Escherichia coli (E. coli) BL21, the system exhibited high induced expression as well as high background expression; however, in E. coli JSB, a sbm‐ygfDGHI deletion mutant of E. coli BL21(DE3), the system showed low background expression and high induced expression. The system exhibited homogeneous expression at the single‐cell level, highly regulatable expression over a wide range of propionate concentrations, and fully induced expression at a low propionate concentration relative to that needed to induce the system in rich, undefined medium. The expression system is comparable to the widely used T7 promoter‐driven expression systems in glucose or glycerol minimal medium.
Success rate of predicting the heliospheric magnetic field polarity with Michelson Doppler Imager (MDI) synoptic charts
Authors: Zhao X. P. , Hoeksema J. T. , Liu Y. , Scherrer P. H.
Published: October 2006

The photospheric and heliospheric magnetic fields have been continuously observed at the L1 point by the Michelson Doppler Imager (MDI) on the Solar and Heliospheric Observatory (SOHO) and Wind and the Advanced Composition Explorer (ACE) spacecraft since 1996. The combined observations of the photospheric and heliospheric magnetic fields make it possible to more reliably predict the heliospheric magnetic field and more accurately estimate the success rate of the prediction. On the basis of the latitude dependence of the zonal polar field inferred from high‐resolution MDI synoptic charts between 1996 and 2003 we fill in the polar data gaps in the MDI synoptic charts. To assess the influence of synoptic charts from different data sources on the prediction of the coronal and heliospheric magnetic fields, we compare the success rate of the heliospheric magnetic field (HMF) polarity predicted over 107 Carrington rotations from June 1996 to June 2004. We used the potential field source surface model and the synoptic charts from the Kitt Peak National Observatory, MDI, and the Wilcox Solar Observatory. The mean success rate of the HMF polarity predicted using MDI synoptic charts over 8 years is 0.862 ± 0.101, the best among the three photospheric data sources, although the difference among the three sources is small. This result validates the MDI synoptic charts in modeling coronal and heliospheric magnetic fields.
Constraining seismic velocity and density for the mantle transition zone with reflected and transmitted waveforms
Authors: Lawrence Jesse F. , Shearer Peter M.
Published: October 2006

We examine stacks of several seismic phases having different sensitivities to mantle transition zone structure. When analyzed separately, underside P and S reflections (PdP and SdS) are suggestive of very different structures despite similar raypaths and data coverage. By stacking the radial component of PdP rather than the vertical PdP, we show that this difference does not result from interference from other more steeply inclined phases such as PKP and Ppdpdiff. In general, stacks of P‐to‐S converted phases (Pds) appear to lack evidence of a 520‐km discontinuity when examined without other phases. When these phases and stacked topside P reflections (Ppdp) are analyzed jointly using a nonlinear inversion method, consistent but nonunique, seismological models emerge. These models show that a discontinuity at ∼653 km depth has smaller contrasts in density and velocity than found in most previous studies. A sub‐660 gradient can account for the majority of this difference. A 1.6 ± 0.5% P‐velocity contrast and a 2.2 ± 0.3% density contrast at ∼518 km depth without a S‐velocity contrast can explain the lack of a P520s, together with robust Pp520p and S520S phases. For models parameterized with a finite thickness for each discontinuity, the 410‐km discontinuity is consistently ∼3 times thicker than the 660‐km discontinuity.
A simulation of a lake effect snowstorm with a cloud resolving numerical model
Authors: Maesaka Takeshi , Moore G. W. K. , Liu Q. , Tsuboki K.
Published: October 2006

Lake‐effect snowstorms (LES), linearly organized bands of convective clouds, are a major source of snowfall and severe weather in the North American Great Lakes region. LES develop as cold and dry air flows over the warm lake surfaces triggering convection that is often organized into quasi‐linear structures known as band clouds. The small horizontal width of these bands, often less than 5 km, combined with their regional‐scale evolution that is impacted by the distribution of open water, lake‐ice and land makes the forecasting of LES particularly challenging. Here, we describe the simulation of an observed LES event using a cloud resolving numerical model in a domain that includes much of the Great Lakes region. The model was able to successfully capture many of the characteristics associated with the event. This simulation suggests that it soon may be possible to forecast the development of this class of convective weather systems.
Influence of low‐level wind speed on droplet spectra near cloud base in trade wind cumulus
Authors: Colón‐Robles Marilé , Rauber Robert M. , Jensen Jørgen B.
Published: October 2006

Data collected during the Rain In Cumulus over the Ocean (RICO) campaign demonstrate a relationship between the low‐level wind speed, droplet concentrations and the presence of large cloud droplets near cloud base in trade wind clouds in a clean marine background atmosphere. Weak winds were associated with fewer activated cloud droplets, larger mean droplet sizes, and more large cloud droplets, even though the concentration of giant/ultragiant sea‐salt aerosol increased with increasing near‐surface wind speed. The data suggest that in unpolluted trade wind cumuli: (1) the production of large cloud droplets near cloud base is controlled primarily by the intensity of the cloud base updraft rather than the concentration of giant/ultragiant sea‐salt particles; (2) higher droplet concentrations are more likely under conditions of stronger low‐level wind speeds, primarily because stronger low‐level wind speeds are associated with more intense cloud base updrafts.
Rapid fluctuations of stratospheric electric field following a solar energetic particle event
Authors: Kokorowski M. , Sample J. G. , Holzworth R. H. , Bering E. A. , Bale S. D. , Blake J. B. , Collier A. B. , Hughes A. R. W. , Lay E. , Lin R. P. , McCarthy M. P. , Millan R. M. , Moraal H. , O'Brien T. P. , Parks G. K. , Pulupa M. , Reddell B. D. , Smith D. M. , Stoker P. H. , Woodger L.
Published: October 2006

During January, 2005, there were several large X‐class solar flares and associated solar energetic particle (SEP) events. Coincidentally, the MINIS balloon campaign had multiple payloads aloft in the stratosphere above Antarctica measuring dc electric fields, conductivity and x‐ray flux. One‐to‐one increases in the electrical conductivity and decreases to near zero of both the vertical and horizontal electric field components were observed in conjunction with an increase in particle flux at SEP onset. Combined with an atmospheric electric field mapping model, these data are consistent with a shorting out of the global electric circuit and point toward substantial ionospheric convection modifications. Additionally, two subsequent, rapid changes were detected in the vertical electric field component several hours after SEP onset. These changes result in similar fluctuations in the calculated vertical current density. We will describe how rigidity cut‐off dynamics may be crucial in understanding these sudden jumps in the vertical electric field.
Crustal earthquake bursts in California and Japan: Their patterns and relation to volcanoes
Authors: Vidale John E. , Boyle Katie L. , Shearer Peter M.
Published: October 2006

We analyze 153 bursts of earthquakes in southern California and Japan. The burst patterns are similar in southern California and Japan; they fill a spectrum between “swarm‐like” sequences without obvious mainshocks and mainshocks with Omori‐law‐abiding aftershocks. In agreement with our previous work, the “swarm‐like” sequences in Japan have more events, are more voluminous, and tend to expand with time, when compared to “mainshock‐aftershock” type sequences. In both regions, we find that the sequences starting with their largest events tend to be much shorter in duration. Bursts within 50 km of volcanoes are similar in character to those elsewhere except they tend to have longer duration. We hypothesize that swarminess is a proxy for fluid pressure redistribution and/or aseismic slip driving the seismicity bursts, and conversely, the mainshock‐aftershock‐style sequences have end‐member behavior that results solely from a cascade of elastic failures. The complexity of the spatial seismicity distribution does not correlate with the style of swarm observed, indicating that fluid conditions and composition are likely more influential than geometry in determining the patterns we observe.
Kinetic simulations of ring current evolution during the Geospace Environment Modeling challenge events
Authors: Jordanova V. K. , Miyoshi Y. S. , Zaharia S. , Thomsen M. F. , Reeves G. D. , Evans D. S. , Mouikis C. G. , Fennell J. F.
Published: October 2006

We investigate the temporal and spatial evolution of the ring current during two storms selected for study by the Geospace Environment Modeling (GEM) program using our kinetic drift‐loss model coupled with a time‐dependent plasmasphere model. We use geosynchronous data from LANL satellites to model the inflow of plasma from the magnetotail. We compare results from simulations using either Volland‐Stern (VS) or Weimer (W01) model of the convection electric field and investigate the relative effect of magnetospheric convection and radial diffusion on the storm‐time injection and trapping of energetic particles and ring current asymmetry. Model comparisons with in situ Cluster, NOAA, and Polar energetic particle observations show overall better agreement with W01 than with VS model. On the other hand, VS model reproduced better the evolution of the plasmapause as observed by IMAGE. Additional ring current ion injections caused by radial diffusion near Dst minima improved the agreement with observations. Radial diffusion did not affect much ring current buildup during the main phase of the storms and the ring current fluxes remained asymmetric, in good agreement with NOAA data. We calculated the excitation of electromagnetic ion cyclotron (EMIC) waves self‐consistently with the evolving plasma populations, and the resulting precipitating fluxes of resonant protons. These fluxes increased significantly within regions of enhanced plasma wave excitation near the plasmapause or inside plasmaspheric plumes and reduced the total H+ energy by ∼10% during the storm recovery phase. Initial results from self‐consistent magnetic field calculations are presented as well. We found that while the magnitude of the ring current fluxes was reduced when adiabatic drifts in a self‐consistent magnetic field were calculated, their morphology was not affected significantly and the local time of the equatorial flux peaks remained almost unchanged.
Bounce‐averaged diffusion coefficients for field‐aligned chorus waves
Authors: Shprits Yuri Y. , Thorne Richard M. , Horne Richard B. , Summers Danny
Published: October 2006

Whistler mode chorus emissions in the Earth's magnetosphere extend from the plasmapause to the boundary of trapping. Knowledge of the pitch angle and energy scattering rates is essential for accurate radiation belt modeling. Scattering rates, which are used as an input for radiation belt codes, should be evaluated dynamically and should account for the changes in plasma density, latitudinal and MLT distribution of waves, and wave spectral properties. Bounce‐averaged diffusion coefficients computed with the assumption of parallel wave propagation are compared to the results of the PADIE diffusion code, which takes into account the oblique propagation of waves and higher‐order resonances. The inaccuracies associated with the neglect of higher‐order resonances are compared to potential errors introduced by inaccuracies in determining plasma density and the latitudinal distribution of waves. Numerical sensitivity tests show that the errors associated with the neglect of the high‐order scattering are smaller than inaccuracies associated with the uncertainties in the parameters of the codes.
Power spectrum of small‐scale turbulent velocity fluctuations in the solar wind
Authors: Podesta J. J. , Roberts D. A. , Goldstein M. L.
Published: October 2006

It is well known that the power spectrum of magnetic field fluctuations in the solar wind exhibits a Kolmogorov spectrum f−α in the inertial range of the turbulence with a power law exponent α near 5/3. The power spectrum of velocity fluctuations has not been as well studied, partly because of the lack of high time resolution measurements needed to resolve a significant fraction of the inertial range. In situ measurements in the ecliptic plane at 1 AU acquired by the 3DP instrument on board the Wind spacecraft near solar minimum in 1995 are used to determine power spectra of the proton bulk velocity fluctuations between 10−5 and 10−1 Hz. The spectrum for the proton kinetic energy (the sum of the spectra for the individual components Vx, Vy, and Vz) obtained using 3‐s velocity data is found to possess the spectral exponent α = 1.50 in the inertial range of the turbulence. A similar calculation of the magnetic energy spectrum yields the exponent α = 1.67. The Alfvén ratio, the ratio of the kinetic to magnetic energy spectrum, is a slowly increasing function of frequency throughout the inertial range increasing from approximately 0.5 to 1 in the frequency interval from 10−4 to 10−2 Hz. This indicates that the partition of energy between small‐scale velocity and magnetic field fluctuations is frequency‐dependent, contrary to some theories. The total energy spectrum (kinetic plus magnetic) has the power law exponent 3/2. A brief investigation of high‐ and low‐speed solar wind streams is also performed, which shows that different spectral exponents for velocity and magnetic field fluctuations are observed in both high‐ and low‐speed wind.
Nitric acid phase partitioning and cycling in the New England coastal atmosphere
Authors: Fischer E. , Pszenny A. , Keene W. , Maben J. , Smith A. , Stohl A. , Talbot R.
Published: October 2006

During summer 2004, HNO3 and size‐resolved aerosols were measured in parallel, and corresponding dry‐deposition fluxes were modeled at Appledore Island, Maine, as part of the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) field program. HNO3 concentrations varied widely on the timescale of hours; however, all days were characterized by a minimum near sunrise. Mixing ratios normally peaked in the early afternoon; maximum and median concentrations of HNO3 during the campaign were 337 and 22.8 nmol m−3, respectively. Aerosol NO3− exhibited a bimodal size distribution with a primary peak associated with sea salt at ∼4 μm and a secondary sub‐μm peak. The median NO3− concentrations in sub‐ and super‐μm diameter size fractions were 3.3 and 7.7 nmol m−3, respectively. Peak HNO3 and super‐μm NO3− concentrations were associated with westerly and southwesterly flow regimes respectively. The multiphase cycling of HNO3 was evaluated as a function of transport sector. Although median total nitrate (HNO3 + NO3−) concentrations were higher under westerly flow, higher median dry‐deposition rates of total nitrate were associated with southwesterly flow. Sea‐salt concentrations were ∼3 times greater during southwesterly flow, which shifted the phase partitioning toward particulate NO3−. Consequently, under westerly flow, HNO3 deposited more quickly than aerosol NO3−, while for southwesterly flow, the fluxes from the two phases were comparable. On the basis of all data, the median dry‐deposition fluxes for HNO3 and aerosol NO3− were 8.2 and 5.6 μmol m−2 d−1; super‐μm size fractions dominated the NO3− flux.
A Direct Method for Measuring Mouse Capillary Cortical Blood Volume Using Multiphoton Laser Scanning Microscopy
Authors: Vérant Pascale , Serduc Raphaël , Van Der Sanden Boudewijn , Rémy Chantal , Vial Jean-Claude
Published: October 2006

Knowledge of the blood volume per unit volume of brain tissue is important for understanding brain function in health and disease. We describe a direct method using two-photon laser scanning microscopy to obtain in vivo the local capillary blood volume in the cortex of anesthetized mouse. We infused fluorescent dyes in the circulating blood and imaged the blood vessels, including the capillaries, to a depth of 600 μm below the dura at the brain surface. Capillary cortical blood volume ( CCBV) was calculated without any form recognition and segmentation, by normalizing the total fluorescence measured at each depth and integrating the collected intensities all over the stack. Theoretical justifications are presented and numerical simulations were performed to validate this method which was weakly sensitive to background noise. Then, CCBV had been estimated on seven healthy mice between 2% ± 0.3% and 2.4% ± 0.4%. We showed that this measure of CCBV is reproductible and that this method is highly sensitive to the explored zones in the cortex (vessel density and size). This method, which dispenses with form recognition, is rapid and would allow to study in vivo temporal and highly resolute spatial variations of CCBV under different conditions or stimulations.
The mystery of intracellular developmental programmes and timers
Authors: Raff M.
Published: October 2006

There has been a revolution in understanding animal development in the last 25 years or so, but there is at least one area of development that has been relatively neglected and therefore remains largely mysterious. This is the intracellular programmes and timers that run in developing precursor cells and change the cells over time. The molecular mechanisms underlying these programmes are largely unknown. My colleagues and I have studied such programmes in two types of rodent neural precursor cells: those that give rise to oligodendrocytes, which make myelin in the CNS (central nervous system), and those that give rise to the various cell types in the retina.
Rapid three-dimensional imaging of individual insulin release events by Nipkow disc confocal microscopy
Authors: Rutter G.A. , Loder M.K. , Ravier M.A.
Published: October 2006

Minute-to-minute control of the release of insulin by pancreatic β-cells in response to glucose or other stimuli requires the precise delivery of large dense-core vesicles to the plasma membrane and regulated exocytosis. At present, the precise spatial organization at the cell surface and the nature of these events (‘transient’ versus ‘full fusion’) are debated. In order to monitor secretory events simultaneously over most of the surface of clusters of single MIN6 β-cells, we have expressed recombinant neuropeptide Y-Venus (an enhanced and vesicle-targeted form of yellow fluorescent protein) as an insulin surrogate. Individual exocytotic events were monitored using Nipkow spinning disc confocal microscopy, with acquisition of a three-dimensional complete image (eight to twelve confocal slices) in <1 s, in response to cell depolarization. Corroborating earlier studies using TIRF (total internal reflection fluorescence) microscopy, this approach indicates that events occur with roughly equal probability over the entire cell surface, with only minimal clustering in individual areas, and provides no evidence for multiple events at the same site. Nipkow disc confocal imaging may thus provide a useful tool to determine whether event types occur at different sites at the cell surface and to explore the role of endocytic proteins including dynamin-1 and -2 in terminating individual exocytotic events.
Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis
Authors: Novick P. , Medkova M. , Dong G. , Hutagalung A. , Reinisch K. , Grosshans B.
Published: October 2006

Sec2p is the exchange factor that activates Sec4p, the Rab GTPase controlling the final stage of the yeast exocytic pathway. Sec2p is recruited to secretory vesicles by Ypt32-GTP, a Rab controlling exit from the Golgi. Sec15p, a subunit of the octameric exocyst tethering complex and an effector of Sec4p, binds to Sec2p on secretory vesicles, displacing Ypt32p. Sec2p mutants defective in the region 450–508 amino acids bind to Sec15p more tightly. In these mutants, Sec2p accumulates in the cytosol in a complex with the exocyst and is not recruited to vesicles by Ypt32p. Thus the region 450–508 amino acids negatively regulates the association of Sec2p with the exocyst, allowing it to recycle on to new vesicles. The structures of one nearly full-length exocyst subunit and three partial subunits have been determined and, despite very low sequence identity, all form rod-like structures built of helical bundles stacked end to end. These rods may bind to each other along their sides to form the assembled complex. While Sec15p binds Sec4-GTP on the vesicle, other subunits bind Rho GTPases on the plasma membrane, thus tethering vesicles to exocytic sites. Sec4-GTP also binds Sro7p, a yeast homologue of the Drosophila lgl (lethal giant larvae) tumour suppressor. Sro7 also binds to Sec9p, a SNAP25 (25 kDa synaptosome-associated protein)-like t-SNARE [target-membrane-associated SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor)], and can form a Sec4p–Sro7p–Sec9p ternary complex. Overexpression of Sec4p, Sro7p or Sec1p (another SNARE regulator) can bypass deletions of three different exocyst subunits. Thus promoting SNARE function can compensate for tethering defects.
Ran at kinetochores
Authors: Dasso M.
Published: October 2006

The Ran GTPase controls many cellular functions, including nucleocytoplasmic trafficking, spindle assembly, nuclear assembly and cell-cycle progression. Considerable evidence suggests that diffusible Ran-GTP near mitotic chromatin facilitates the release of critical factors from nuclear transport receptors, thereby promoting organization of mitotic spindles with respect to chromosomes. In addition to this role of soluble Ran-GTP, Ran has two important but less understood roles at mitotic kinetochores. Namely, it is essential for regulation of the spindle assembly checkpoint and for assembly of microtubule fibres that attach kinetochores to spindle poles. Here, I will briefly summarize evidence for these kinetochore-associated functions and mention some of the issues that remain to be addressed regarding them.
Phosphoinositide 3-kinase signalling and FoxO transcription factors in rheumatoid arthritis
Authors: Reedquist K.A. , Ludikhuize J. , Tak P.P.
Published: October 2006

Although the mechanisms leading to the induction of RA (rheumatoid arthritis) are poorly understood, improper activation, proliferation, survival and retention of neutrophils, macrophages, lymphocytes and other leucocytes contribute to perpetuation of inflammation and eventual joint destruction through activation of stromal fibroblast-like synoviocytes. Fundamental studies in developmental biology, cellular biology and immunology have established critical roles for PI3K (phosphoinositide 3-kinase) signal transduction pathways in cellular chemotactic responses, proliferation, apoptosis and survival. Despite profound alteration of these cellular processes in RA, involvement of PI3K signalling pathways in this chronic inflammatory disease, and their assessment as potential therapeutic targets, has until recently received scant attention. This review highlights recent advances in our understanding of PI3K signalling pathways, in particular regulation of FoxO (forkhead box O) transcription factors, and their relevance to RA.
FOXOs in the maintenance of vascular homoeostasis
Authors: Paik J.-H.
Published: October 2006

The mammalian FoxO (forkhead box O) transcription factors FoxO1, FoxO3 and FoxO4 represent one of several effector arms of the PI3K (phosphoinositide 3-kinase)–Akt signalling network that has been linked to cancer, metabolism and aging. Specific roles of the FoxOs in the vascular cell types have been investigated to reveal that they play redundant yet critical roles in the proliferation and survival of ECs (endothelial cells). Somatic deletions of all FoxOs engendered progressive, widespread and highly penetrant haemangiomas associated with altered proliferative/survival dynamics of ECs in our genetic model. Related work by Akt–FoxO manipulation reported differentially regulated genes in ECs that may represent novel FoxO targets, controlling EC growth and morphogenesis and mediating many of the consequences of FoxO inactivation in the endothelium. Further studies on the action of these surrogate genes may provide important new insights into how the PI3K–Akt–FoxO pathway could be exploited clinically to treat vascular diseases and lead to the invention of novel therapeutic approaches. Here recent studies elucidating the role of FoxOs in the maintenance of vascular homoeostasis and supporting that the mammalian FoxO family serves essential roles in the maintenance of vascular stability and the suppression of aberrant vascular outgrowth are discussed.
Molecular misreading: the occurrence of frameshift proteins in different diseases
Authors: van Leeuwen F.W. , Kros J.M. , Kamphorst W. , van Schravendijk C. , de Vos R.A.I.
Published: October 2006

Neuronal homoeostasis requires a constant balance between biosynthetic and catabolic processes. Eukaryotic cells primarily use two distinct mechanisms for degradation: the proteasome and autophagy of aggregates by the lysosomes. We focused on the UPS (ubiquitin–proteasome system). As a result of molecular misreading, misframed UBB (ubiquitin B) (UBB+1) is generated. UBB+1 accumulates in the neuritic plaques and neurofibrillary tangles in all patients with AD (Alzheimer's disease) and in the neuronal and glial hallmarks of other tauopathies and in polyglutamine diseases such as Huntington's disease. UBB+1 is not present in synucleinopathies such as Parkinson's disease. We showed that UBB+1 causes UPS dysfunction, aggregation and apoptotic cell death. UBB+1 is also present in non-neurological cells, hepatocytes of the diseased liver and in muscles during inclusion body myositis. Other frequently occurring (age-related) diseases such as Type 2 (non-insulin-dependent) diabetes mellitus are currently under investigation. These findings point to the importance of the UPS in diseases and open new avenues for target identification of the main players of the UPS. Treatment of these diseases with tools (e.g. viral RNA interference constructs) to intervene with specific targets is the next step.
Gankyrin, the 26 S proteasome, the cell cycle and cancer
Authors: Mayer R.J. , Fujita J.
Published: October 2006

The known molecular players in cell-cycle control are much studied, not only to learn more about this intricate system, but also to understand the molecular features of oncogenic transformation. Infrequently, new players are discovered that change the interpretation of cell-cycle control. Gankyrin is one such player and was discovered in yeast two-hybrid screens as a new proteasomal subunit that interacts specifically with the S6b (rpt3) AAA (ATPase associated with various cellular activities) ATPase, which, with five other AAAs, are present in the so-called base of the 19 S regulator of the 26 S proteasome. Gankyrin is also the first liver oncogene. Gankyrin is found in other complexes that contain Rb (retinoblastoma protein) and the ubiquitin protein ligase Mdm2 (murine double minute 2). Gankyrin increases the hyperphosphorylation of Rb and therefore activates E2F-dependent transcription of DNA synthesis genes. Additionally, gankyrin, by binding to Mdm2, increases the ubiquitylation and degradation of p53 and prevents apoptosis. Gankyrin controls the functions of two major tumour suppressors and, when overexpressed, causes hepatocellular carcinoma.
Maternal nutrition during pregnancy and health of the offspring
Authors: Martin-Gronert M.S. , Ozanne S.E.
Published: October 2006

The ability of mother to provide nutrients and oxygen for her baby is a critical factor for fetal health and its survival. Failure in supplying the adequate amount of nutrients to meet fetal demand can lead to fetal malnutrition. The fetus responds and adapts to undernutrition but by doing so it permanently alters the structure and function of the body. Maternal overnutrition also has long-lasting and detrimental effects on the health of the offspring. There is growing evidence that maternal nutrition can induce epigenetic modifications of the fetal genome. Only relatively recently has evidence from epidemiological and animal studies emerged suggesting that fetal responses to the intrauterine environment may underlie the prevalence of many chronic diseases of adulthood including Type 2 (non-insulin-dependent) diabetes. It is now of crucial importance to gain the understanding of the molecular mechanisms underlying the relationship between fetal alterations to the intra-uterine environment and their long-term effects on the health of an individual.
Regulation of purine nucleotide biosynthesis: in yeast and beyond
Authors: Rolfes R.J.
Published: October 2006

Purine nucleotides are critically important for the normal functioning of cells due to their myriad of activities. It is important for cells to maintain a balance in the pool sizes of the adenine-containing and guanine-containing nucleotides, which occurs by a combination of de novo synthesis and salvage pathways that interconvert the purine nucleotides. This review describes the mechanism for regulation of the biosynthetic genes in the yeast Saccharomyces cerevisiae and compares this mechanism with that described in several microbial species.