bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential Stream Segregation Affects Localisation of Diotic Tones among Tones with Time-Varying Interaural Time Difference
Authors: Kawabe Takahiro
Published: September 2009

In this study, I examined how sequential stream segregation contributes to the detection of diotic tones among tones with time-varying interaural time differences (ITDs). Target (T) and distractor (D) tones, and a silent duration (–) formed a sequence (DTD–) and this sequence was presented repeatedly. A frequency difference was introduced between target and distractor tones. The distractor tones were also given time-varying ITDs to produce a percept of smooth auditory motion along the interaural axis. In half of the trials, the target tones were not given time-varying ITDs, and thus were diotically presented. The task of the listeners was to determine whether the repeated sequences of DTD–had target tones without motion. The sensitivity d′ for the detection of diotic target tones was higher with larger frequency differences. On the other hand, the criterion c was lower with larger frequency differences. In another session, I confirmed that proportions of reports “two streams” was positively and negatively correlated with d′ and c, respectively. The results indicate that the localisation of a sound image could be influenced by sequential stream segregation in complex sound environments.
Outline, Mental States, and Drawings by a Blind Woman
Authors: Kennedy John M
Published: September 2009

Outline pictures depict surface edges, and via extensions from this base they can represent sensory and psychological referents. Outline drawings standing for edges of surfaces are relatively ancient, and lines for actions, sounds, and psychological states quite recent—mostly little more than a century. The novel finding here is that lines for psychological states of several kinds are invented by a blind woman, EW, who began making raised-line drawings as an adult. Notably, she invented novel devices representing thoughts and emotional impressions. If lines depict surface edges literally, they depict motion, sensory effects, impressions, and thoughts metaphorically.
Effect of Photographic Negation on Face Expression Aftereffects
Authors: Benton Christopher P
Published: September 2009

Our visual representation of facial expression is examined in this study: is this representation built from edge information, or does it incorporate surface-based information? To answer this question, photographic negation of grey-scale images is used. Negation preserves edge information whilst disrupting the surface-based information. In two experiments visual aftereffects produced by prolonged viewing of images of facial expressions were measured. This adaptation-based technique allows a behavioural assessment of the characteristics encoded by the neural systems underlying our representation of facial expression. The experiments show that photographic negation of the adapting images results in a profound decrease of expression aftereffect. Our visual representation of facial expression therefore appears to not just be built from edge information, but to also incorporate surface information. The latter allows an appreciation of the 3-D structure of the expressing face that, it is argued, may underpin the subtlety and range of our non-verbal facial communication.
Fabrication of large binary colloidal crystals with a NaCl structure
Authors: Vermolen E. C. M. , Kuijk A. , Filion L. C. , Hermes M. , Thijssen J. H. J. , Dijkstra M. , van Blaaderen A.
Published: September 2009

Binary colloidal crystals offer great potential for tuning material properties for applications in, for example, photonics, semiconductors and spintronics, because they allow the positioning of particles with quite different characteristics on one lattice. For micrometer-sized colloids, it is believed that gravity and slow crystallization rates hinder the formation of high-quality binary crystals. Here, we present methods for growing binary colloidal crystals with a NaCl structure from relatively heavy, hard-sphere-like, micrometer-sized silica particles by exploring the following external fields: electric, gravitational, and dielectrophoretic fields and a structured surface (colloidal epitaxy). Our simulations show that the free-energy difference between the NaCl and NiAs structures, which differ in their stacking of the hexagonal planes of the larger spheres, is very small (≈0.002
k
B
T
). However, we demonstrate that the fcc stacking of the large spheres, which is crucial for obtaining the pure NaCl structure, can be favored by using a combination of the above-mentioned external fields. In this way, we have successfully fabricated large, 3D, oriented single crystals having a NaCl structure without stacking disorder.
Molecular clock is involved in predictive circadian adjustment of renal function
Authors: Zuber Annie Mercier , Centeno Gabriel , Pradervand Sylvain , Nikolaeva Svetlana , Maquelin Lionel , Cardinaux Léonard , Bonny Olivier , Firsov Dmitri
Published: September 2009

Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (
clock
,
bma11
,
npas2
,
per
,
cry
,
nr1d1
) and clock-controlled Par bZip transcriptional factors
dbp
,
hlf
, and
tef
. The
clock
knockout mice or mice devoid of
dbp
/
hlf
/
tef
(triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, αENaC). Functionally, the loss of
clock
leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.
A humanIL10BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome
Authors: Ranatunga Dilini , Hedrich Christian M. , Wang Fengying , McVicar Daniel W. , Nowak Nathan , Joshi Trupti , Feigenbaum Lionel , Grant Lindsay R. , Stäger Simona , Bream Jay H.
Published: September 2009

Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by diverse cell populations. Studies in mice suggest that the cellular source of IL-10 is a key determinant in various disease pathologies, yet little is known regarding the control of tissue-specific human IL-10 expression. To assess cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC) in which theIL10gene is positioned centrally. Since human IL-10 is biologically active in the mouse, we could examine the in vivo capacity of tissue-specific human IL-10 expression to recapitulate IL-10-dependent phenotypes by reconstitutingIl10−/−mice (Il10−/−/hIL10BAC). In response to LPS, Il10−/−/hIL10BAC mice proficiently regulate IL-10-target genes and normalize sensitivity to LPS toxicity via faithful human IL-10 expression from macrophages and dendritic cells. However, in theLeishmania donovanimodel of pathogen persistence, Il10−/−/hIL10BAC mice did not develop the characteristic IL-10+IFN-γ+CD4 T cell subset thought to mediate persistence and, likeIl10−/−mice, cleared the parasites. Furthermore, the IL-10-promoting cytokine IL-27 failed to regulate transgenic human IL-10 production in CD4+T cells in vitro which together suggests that the hIL10BAC encodes for weak T cell-specific IL-10 expression. Thus, the hIL10BAC mouse is a model of human gene structure and function revealing tissue-specific regulatory requirements for IL-10 expression which impacts disease outcomes.
A polycomb repressive complex 2 gene regulates apogamy and gives evolutionary insights into early land plant evolution
Authors: Okano Yosuke , Aono Naoki , Hiwatashi Yuji , Murata Takashi , Nishiyama Tomoaki , Ishikawa Takaaki , Kubo Minoru , Hasebe Mitsuyasu
Published: September 2009

Land plants have distinct developmental programs in haploid (gametophyte) and diploid (sporophyte) generations. Although usually the two programs strictly alternate at fertilization and meiosis, one program can be induced during the other program. In a process called apogamy, cells of the gametophyte other than the egg cell initiate sporophyte development. Here, we report for the moss
Physcomitrella patens
that apogamy resulted from deletion of the gene orthologous to the
Arabidopsis thaliana CURLY LEAF
(
PpCLF
), which encodes a component of polycomb repressive complex 2 (PRC2). In the deletion lines, a gametophytic vegetative cell frequently gave rise to a sporophyte-like body. This body grew indeterminately from an apical cell with the character of a sporophytic pluripotent stem cell but did not form a sporangium. Furthermore, with continued culture, the sporophyte-like body branched. Sporophyte branching is almost unknown among extant bryophytes. When PpCLF was expressed in the deletion lines once the sporophyte-like bodies had formed, pluripotent stem cell activity was arrested and a sporangium-like organ formed. Supported by the observed pattern of PpCLF expression, these results demonstrate that, in the gametophyte, PpCLF represses initiation of a sporophytic pluripotent stem cell and, in the sporophyte, represses that stem cell activity and induces reproductive organ development. In land plants, branching, along with indeterminate apical growth and delayed initiation of spore-bearing reproductive organs, were conspicuous innovations for the evolution of a dominant sporophyte plant body. Our study provides insights into the role of PRC2 gene regulation for sustaining evolutionary innovation in land plants.
Myosin II is required for interkinetic nuclear migration of neural progenitors
Authors: Schenk Judith , Wilsch-Bräuninger Michaela , Calegari Federico , Huttner Wieland B.
Published: September 2009

Interkinetic nuclear migration (INM) is a hallmark of the polarized stem and progenitor cells in the ventricular zone (VZ) of the developing vertebrate CNS. INM is responsible for the pseudostratification of the VZ, a crucial aspect of brain evolution. The nuclear migration toward the apical centrosomes in G2 is thought to be a dynein-microtubule-based process. By contrast, the cytoskeletal machinery involved in the basally directed nuclear translocation away from the centrosome in G1 has been enigmatic. Studying the latter aspect of INM requires manipulation of the cytoskeleton without impairing mitosis and cytokinesis. To this end, we have established a culture system of mouse embryonic telencephalon that reproduces cortical development, and have applied it to explore a role of actomyosin in INM. Using the nonmuscle myosin II inhibitor blebbistatin at a low concentration at which neither cell cycle progression nor cytokinesis is impaired, we show that myosin II is required for the apical-to-basal (ap→bl), ab-centrosomal INM. Myosin II activity is also necessary for the nuclear translocation during delamination of subventricular zone (SVZ) cells, a second, telencephalon-specific type of neural progenitor. Moreover, the inhibition of ab-centrosomal INM changes the balance between VZ and SVZ progenitor cell fate. Our data suggest a unifying concept in which the actomyosin contraction underlying ab-centrosomal INM sets the stage for the evolutionary increase in VZ pseudostratification and for SVZ progenitor delamination, a key process in cortical expansion.
Curriculum as narration: tales from the children of the colonised
Authors: Goodson Ivor , Deakin Crick Ruth
Published: September 2009

This article will explore the centrality of narrative in both the process and the content of enquiry‐based learning, as a formative process which does not predetermine either its starting point or its outcome. Rather, it takes as its starting point the agency and life narrative of the learner and builds from this to a formally assessed outcome. It will argue for the importance of what one of us has coined ‘narrative learning’ (Goodson 2006, 2009). The article will draw upon a research project in New South Wales in which this archaeological pedagogy and curriculum were studied and evaluated with, and by, a cohort of previously disengaged students. These students are from an Indigenous community devastated by dispossession and colonisation. Their stories and those of their mentors will be used to explain, expand and ground our argument. They demonstrate how the curriculum becomes a ‘narratable pathway’ towards the formation of identity and agency when ‘knowing as storying’ is valued, promoted and represented. Narratives provide and create space for ‘pedagogic moments’ in which people can connect with themselves, their own culture and tradition, their hopes and aspirations and ultimately with an intentional, mentored construction of knowledge which serves their personal and public trajectories. The article makes use of Bateson's three levels of learning and builds on concepts of learning how to learn, by linking this with the ‘person’ who is learning, their selfhood and agency, and their need for meaning‐making and purpose as a foundation for engagement.
Assessing enquiry‐based learning: developing objective criteria from personal knowledge
Authors: Small Tim
Published: September 2009

What gives personal knowledge its objectivity, Polanyi maintains, is the free and responsible submission to the claims laid upon the inquirer by the truth he is seeking to discover. (Fitzpatrick 1982, 185)

This article takes as its starting point the idea that policies of ‘personalising learning’ and promoting ‘creativity’ raise issues for assessment which the present framework for assessment and testing in schools in England and Wales does little to address. It explores the notion, also touched on elsewhere in this issue, of a dichotomy that needs resolving between subjective (or ‘personal’) and objective (or ‘public’) concerns in the assessment of learning. Drawing on previous research using Rosenblatt's transactional theory of response to literature, the article proposes a resolution based on the unifying concepts of a continuum between two poles and movement of the selective attention between them. Tracing this movement offers a ‘vantage point’ from which the ‘hidden’ or ‘inner’ values of a creative process can be glimpsed, which is likened to the dynamic self‐assessment of learning power. Relating closely to Polanyi's philosophy of personal or ‘tacit’ knowledge, the article argues that enquiry‐based learning is essentially as creative an activity as composing or responding aesthetically to poetry. After constructing five principles from theoretical observations on the evaluation of creativity, the article goes on to develop a set of criteria and objectives, related to the values already discussed, which are offered as a framework to support self‐assessment and joint assessment of enquiry‐based learning.
Working backwards towards curriculum: on the curricular implications of Quality Teaching
Authors: Ladwig James G.
Published: September 2009

This essay builds from ongoing development and research work on a model of pedagogy, from New South Wales, Australia, known as the Quality Teaching model. Where international calls for the professional development and certification of teachers rely on mechanisms of credentialing, often with scant direct attention to the acts of teaching, the NSW Quality Teaching model was developed specifically to examine classroom practice and assessment with a shared, generic, analytical framework across subject areas in K‐12 settings. The article presents a summary and some elaboration of the Quality Teaching model and then raises the question of just what implications for curriculum lie underneath the push for improving teaching. Using this model, for example, it is clear that many of our long standing curricular debates must be soundly re‐cast if the ideals of Quality Teaching are to be taken seriously. Coming from a context where curriculum is designed and governed centrally, in very conventional terms, the curriculum implications of Quality Teaching raise a big challange for international understandings of just what is included in school curricula.
Revisiting Crohn's disease as a primary immunodeficiency of macrophages
Authors: Casanova Jean-Laurent , Abel Laurent
Published: September 2009

Despite two decades of mouse immunology and human genetics studies, the pathogenesis of Crohn's disease (CD) remains elusive. New clinical investigations suggest that CD may be caused by inborn errors of macrophages. These errors may result in impaired attraction of granulocytes to the gut wall, causing impaired clearance of intruding bacteria, thereby precipitating the formation of granulomas. This theory paves the way for a macrophage-based Mendelian genetic dissection of CD.
Epidemiology of Methicillin-Resistant Staphylococcus aureus in a University Medical Center Day Care Facility
Authors: Hewlett Angela L. , Falk Pamela S. , Hughes Katrina S. , Mayhall C. Glen
Published: September 2009

Objective.

Few data are available on methicillin-resistant Staphylococcus aureus (MRSA) colonization in day care. We performed a study in a medical university child care center to study the epidemiology of MRSA in this population.

Design.

Survey.

Setting.

A child care center on the campus of a university medical center.

Methods.

One hundred four children who attended the child care center and 32 employees gave samples that were cultured for MRSA. Seventeen household members of the children and employee found to be colonized with MRSA also gave samples that were cultured. Parents and employees completed questionnaires about demographic characteristics, medical conditions and treatments, and possible exposure risks outside the child care center. In addition, 195 environmental samples were taken from sites at the childcare center. Isolates were analyzed for relatedness by use of molecular typing, and statistical analysis was performed.

Results.

The prevalence of MRSA in the children was 6.7%. One employee (3.1%) was colonized with MRSA. Cultures of samples given by 6 of 17 (35.3%) family members of these children and the employee yielded MRSA. MRSA was recovered from 4 of 195 environmental samples. Molecular typing revealed that many of the MRSA isolates were indistinguishable, and 18 of the 21 isolates were community-associated MRSA. Multivariable analysis revealed that receipt of macrolide antibiotics (P = .002; odds ratio, 39.6 [95% confidence interval, 3.4—651.4]) and receipt of asthma medications (P = .024; odds ratio, 26.9 [95% confidence interval, 1.5-500.7]) were related to MRSA colonization.

Conclusions.

There was a low prevalence of MRSA colonization in children and employees in the child care center but a higher prevalence of colonization in their families. Molecular typing showed that transmission of MRSA likely occurred in the child care center. The use of macrolide antibiotics and asthma medications may increase the risk of MRSA colonization in this population.
Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients
Authors: Bellissimo-Rodrigues Fernando , Bellissimo-Rodrigues Wanessa Teixeira , Viana Jaciara Machado , Teixeira Gil Cezar Alkmim , Nicolini Edson , Auxiliadora-Martins Maria , Passos Afonso Dinis Costa , Martinez Edson Zangiacomi , Basile-Filho Anibal , Martinez Roberto
Published: September 2009

Objective.

To evaluate the effectiveness of the oral application of a 0.12% solution of Chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients.

Design.

The study design was a double-blind, randomized, placebo-controlled trial.

Setting.

The study was performed in an ICU in a tertiary care hospital at a public university.

Patients.

Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received Chlorhexidine (n = 98) and those who received a placebo (n = 96).

Intervention.

Oral rinses with Chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patient's stay in the ICU. Clinical data were collected prospectively.

Results.

Both groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the Chlorhexidine and placebo groups. However, patients in the Chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]).

Conclusion.

Oral application of a 0.12% solution of Chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.
Special issue: Overview reports from FEC 2008 (Geneva, Switzerland)
Authors: Thomas Paul
Published: September 2009

The full text of this editorial is available in the PDF.
22nd IAEA Fusion Energy Conference: summary of contributions on Fusion Technology and ITER Activities
Authors: Stork D.
Published: September 2009

The contributions to the 22nd IAEA Fusion Energy Conference (FEC) in the categories of Fusion Technology (FT), ITER Activities (IT) and Safety and Economic Studies (SE) are reviewed. In the FT category, 68 papers were submitted, along with 57 papers submitted through the ITER Organisation in the IT category. Finally two papers were submitted in the SE category. The assembled body of work gave a good overview of the worldwide effort in fusion technology and particularly the prolific activity surrounding the ITER Design Review and the major progress with the ITER technology programme.
Overview of physics research on the TCV tokamak
Authors: Fasolifor the TCV Teama A.
Published: September 2009

The Tokamak à Configuration Variable (TCV) tokamak is equipped with high-power (4.5 MW), real-time-controllable EC systems and flexible shaping, and plays an important role in fusion research by broadening the parameter range of reactor relevant regimes, by investigating tokamak physics questions and by developing new control tools. Steady-state discharges are achieved, in which the current is entirely self-generated through the bootstrap mechanism, a fundamental ingredient for ITER steady-state operation. The discharge remains quiescent over several current redistribution times, demonstrating that a self-consistent, ‘bootstrap-aligned’ equilibrium state is possible. Electron internal transport barrier regimes sustained by EC current drive have also been explored. MHD activity is shown to be crucial in scenarios characterized by large and slow oscillations in plasma confinement, which in turn can be modified by small Ohmic current perturbations altering the barrier strength. In studies of the relation between anomalous transport and plasma shape, the observed dependences of the electron thermal diffusivity on triangularity (direct) and collisionality (inverse) are qualitatively reproduced by non-linear gyro-kinetic simulations and shown to be governed by TEM turbulence. Parallel SOL flows are studied for their importance for material migration. Flow profiles are measured using a reciprocating Mach probe by changing from lower to upper single-null diverted equilibria and shifting the plasmas vertically. The dominant, field-direction-dependent Pfirsch–Schlüter component is found to be in good agreement with theoretical predictions. A field-direction-independent component is identified and is consistent with flows generated by transient over-pressure due to ballooning-like interchange turbulence. Initial high-resolution infrared images confirm that ELMs have a filamentary structure, while fast, localized radiation measurements reveal that ELM activity first appears in the X-point region. Real time control techniques are currently being applied to EC multiple independent power supplies and beam launchers, e.g. to control the plasma current in fully non-inductive conditions, and the plasma elongation through current broadening by far-off-axis heating at constant shaping field.
Overview of JT-60U results towards the establishment of advanced tokamak operation
Authors: Oyama N.
Published: September 2009

Recent JT-60U experimental results towards the establishment of advanced tokamak (AT) operation are reviewed. We focused on the further expansion of the operational regime of AT plasmas towards higher βN regime with wall stabilization. After the installation of ferritic steel tiles in 2005, the high power heating in a large plasma cross-section in which the wall stabilization is expected has been possible. In 2007, the modification of power supply of NBIs improved the flexibility of the heating profile in long-pulse plasmas. The investigation of key physics issues for the establishment of steady-state AT operation is also in progress using new diagnostics and improved heating systems. In weak magnetic shear plasma, high βN ∼ 3 exceeding the ideal MHD limit without a conducting wall (
) is sustained for ∼5 s (∼3τR) with RWM stabilization by a toroidal rotation at the q = 2 surface. External current drivers of negative-ion based NB and lower-hybrid waves together with a large bootstrap current fraction (f
BS) of 0.5 can sustain the whole plasma current of 0.8 MA for 2 s (1.5τR). In reversed magnetic shear plasma, high βN ∼ 2.7 (βp ∼ 2.3) exceeding
with q
min ∼ 2.4 (q
95 ∼ 5.3), H
H98(y,2) ∼ 1.7 and f
BS ∼ 0.9 is obtained with wall stabilization. These plasma parameters almost satisfy the requirement of ITER steady-state scenario. In long-pulse plasmas with positive magnetic shear, a high βN
H
H98(y,2) of 2.6 with βN ∼ 2.6 and H
H98(y,2) ∼ 1 is sustained for 25 s, significantly longer than the current diffusion time (∼14τR) without neoclassical tearing modes (NTMs). A high G-factor,
(a major of fusion gain), of 0.54 and a large f
BS > 0.43 are suitable for ITER hybrid operation scenario. Based on the plasma for ITER hybrid operation scenario, the high βN of 2.1 with good thermal plasma confinement of H
H98(y,2) > 0.85 is sustained for longer than 12 s at
and f
rad > 0.79. Physics studies for the development of AT plasmas, physics studies of H-mode, pedestal and ELM characteristics and physics studies on impurity transport, SOL/divertor plasmas and plasma–wall interactions are also in progress. The active NTM stabilization system using modulated ECCD, which is synchronized to rotating island, has been developed and the efficiency of modulated ECCD in m/n = 2/1 NTM stabilization has been demonstrated. The intrinsic toroidal rotation driven by the ion pressure gradient and by the ECH is confirmed. The dedicated H-mode and pedestal experiments indicate two scalings, H-factor evaluated for the core plasma as
and pedestal width scaling of
. New fast diagnostics with high spatial and temporal resolutions reveals the different structures of pedestal pressure between co- and counter-rotating plasma, resulting in different ELM sizes determined by the radial penetration depth of the ELM crash. The tungsten accumulation becomes more significant with increasing toroidal rotation in the counter-direction.
DIII-D research in support of ITER
Authors: Straitfor the DIII-D Team E.J.
Published: September 2009

DIII-D research is providing key information for the design and operation of ITER. Investigations of axisymmetric stability and of edge-localized mode (ELM) suppression with resonant magnetic perturbations have helped provide the physics basis for new axisymmetric and non-axisymmetric control coils in ITER. Discharges that simulate ITER operating scenarios in conventional H-mode, advanced inductive, hybrid and steady state regimes have achieved normalized performance consistent with ITER's goals for fusion performance. Stationary discharges with high βN and 90% non-inductive current that project to Q = 5 in ITER have been sustained for a current relaxation time (∼2.5 s), and high beta wall-stabilized discharges with fully non-inductive current drive have been sustained for more than one second. Detailed issues of plasma control have been addressed, including the development of a new large-bore startup scenario for ITER. DIII-D research also contributes to the basis for reliable operation in ITER, through active control of the chief performance-limiting instabilities. Simultaneous stabilization of neoclassical tearing modes (by localized current drive) and resistive wall modes (by magnetic feedback) has allowed stable operation at high beta and low rotation. In research aimed at improving the lifetime of material surfaces near the plasma, recent experiments have investigated several approaches to mitigation of disruptions, including injection of low-Z gas and low-Z pellets, and have shown the conditions that minimize core impurity accumulation during radiative divertor operation. Investigation of carbon erosion, transport and co-deposition with hydrogenic species, and methods for the removal of co-deposits, will contribute to the physics basis for initial operation of ITER with a carbon divertor. A broad research programme provides the physics basis for predicting the performance of ITER. Recent key results include the discovery that the L–H power threshold is reduced with low neutral beam torque, and the development of a successful model for prediction of the H-mode pedestal height in DIII-D. Research areas with the potential to improve ITER's performance include the demonstration of ELM-free ‘quiescent H-mode’ discharges with both co- and counter-neutral beam injection, and validation of the predicted torque generated by static, non-axisymmetric magnetic fields. New diagnostics provide detailed benchmarking of turbulent transport codes and direct measurements of the anomalous transport of fast ions by Alfvén instabilities. Successful comparison of experiment and modelling for off-axis neutral beam current drive provides the basis for more flexible current profile control in advanced scenarios.
Unbalancing the Phosphatidylinositol-4,5-bisphosphate–Cofilin Interaction Impairs Cell Steering
Authors: Leyman Shirley , Sidani Mazen , Ritsma Laila , Waterschoot Davy , Eddy Robert , Dewitte Daisy , Debeir Olivier , Decaestecker Christine , Vandekerckhove Joël , van Rheenen Jacco , Ampe Christophe , Condeelis John , Van Troys Marleen
Published: September 2009

Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P2and slower release from the plasma membrane to study the role of the PI(4,5)P2–cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P2is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P2regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.
Physical and Functional Interaction of Transmembrane Thioredoxin-related Protein with Major Histocompatibility Complex Class I Heavy Chain: Redox-based Protein Quality Control and Its Potential Relevance to Immune Responses
Authors: Matsuo Yoshiyuki , Masutani Hiroshi , Son Aoi , Kizaka-Kondoh Shinae , Yodoi Junji
Published: September 2009

In the endoplasmic reticulum (ER), a variety of oxidoreductases classified in the thioredoxin superfamily have been found to catalyze the formation and rearrangement of disulfide bonds. However, the precise function and specificity of the individual thioredoxin family proteins remain to be elucidated. Here, we characterize a transmembrane thioredoxin-related protein (TMX), a membrane-bound oxidoreductase in the ER. TMX exists in a predominantly reduced form and associates with the molecular chaperon calnexin, which can mediate substrate binding. To determine the target molecules for TMX, we apply a substrate-trapping approach based on the reaction mechanism of thiol-disulfide exchange, identifying major histocompatibility complex (MHC) class I heavy chain (HC) as a candidate substrate. Unlike the classical ER oxidoreductases such as protein disulfide isomerase and ERp57, TMX seems not to be essential for normal assembly of MHC class I molecules. However, we show that TMX–class I HC interaction is enhanced during tunicamycin-induced ER stress, and TMX prevents the ER-to-cytosol retrotranslocation of misfolded class I HC targeted for proteasomal degradation. These results suggest a specific role for TMX and its mechanism of action in redox-based ER quality control.
3. Sampling, study size, and power
Authors: Cole Tim J.
Published: September 2009

Precise definitions of study populations and samples are key to the interpretation and generalizability of findings. This chapter describes types of sampling, how to deal with non-response, and validity of measures (including problems relating to bias and variance). Details are then given of how sample size relates to the testing of the null hypothesis, and the meaning and definition of significance level and power. This is followed by detailed techniques for the determination of sample size for different types of epidemiological studies (ecological, cross-sectional, case-control studies, cohort studies, and experimental studies). It defines sample size and power in relation to measures of difference between matched and unmatched samples, correlation, odds ratio, and relative risk.
4. Covariate measurement errors in nutritional epidemiology: effects and remedies
Authors: Clayton David , Gill Caroline
Published: September 2009

The key problem in epidemiological studies is the identification of relevant exposures and outcomes, and the relationship (and error modelling) between observed and relevant measures, and between relevant measures and relevant outcomes. Measurement errors and bias undermine the ability to detect diet-disease relationships, and the problem is particularly acute in nutritional epidemiological studies because of the difficulties of measuring relevant dietary exposures accurately, and the particular problem of differential misclassification (i.e., the differences in bias in the measurements between individuals, or between one subset of a sample and another). Correcting for measurement error is a controversial topic, but the chapter provides illustrations of the extent of attenuation or misrepresentation of diet-disease associations.
9. Socio-demographic and psycho-social variables
Authors: Macintyre Sally , Anderson Annie
Published: September 2009

This chapter describes and defines socio-demographic and psycho-social variables, and highlights the importance of attaining accurate measures of socio-demographic and psycho-social variables in the context of nutritional epidemiological studies. The scales of measurement and their determination are set out in detail. Criteria for developing sound and comparable measures are given.
10. Anthropometric measures
Authors: Ulijaszek Stanley J.
Published: September 2009

Anthropometric measures play a dual role in nutritional epidemiology, as measures of exposure and measures of outcome. General problems associated with anthropometric measurement are discussed, including the training of field workers and use of equipment. Anthropometric indices are defined. The treatment of data prior to analysis is described. Appropriate measurements and indices for the assessment of under- and over-nutrition in children and adults are considered. The relative merits of the use of reference data from different sources are reviewed.
11. Gene–nutrient interactions in nutritional epidemiology
Authors: Kohlmeier Lenore , DeMarini David , Piegorsch Walter
Published: September 2009

There is increasing evidence that the ways in which nutrients are handled metabolically is, to a greater or lesser extent, under genetic control. Equally, nutrient (and non-nutrient) intakes affect the expression of genetic predispositions. These complex interactions (nutrient regulation of gene transcription, food-induced DNA damage, phytochemical enhancement or protection of DNA integrity, genetic susceptibility to nutrition-related diseases) increasingly shed light on epidemiological relationships between diet and health and disease. This chapter considers design and analytical implications for understanding gene-nutrient interactions, including specific statistical models. It concludes with a discussion of ethical issues, and an appendix for sample size determination in relation to the determination of genetic characteristics in nutritional epidemiological studies.
12. Ecological studies
Authors: Hiller Janet E. , McMichael Anthony J.
Published: September 2009

Ecological studies examine characteristics of population groups rather than individuals. This chapter provides useful examples of how to develop hypotheses using ecological data (based on the collection of relevant indices of diet and health status), assess geographic differences and time trends, and understand the value of ecological studies especially in international comparisons of diet and disease. The need to collect non-nutritional population data and the limitations of the ecological approach are illustrated, including a discussion of calibration. Sampling is discussed in detail, as are the issues of time-lagging, cohort analysis, and adjusting for confounders. The chapter concludes with a discussion of the criteria for ‘proof’ in ecological studies, their limitations, and a consideration of when ecological studies are the method of choice.
13. Cross-sectional studies
Authors: Cade Janet E.
Published: September 2009

Cross-sectional studies involve identifying a defined population at a given point in time and measuring a range of variables on an individual basis which can include current and past dietary exposures and well as health outcomes and disease status. They are also known as prevalence surveys. They include a type of migrant study. This chapter considers the use and limitations of cross-sectional studies and their value in generating hypotheses. It provides details of their design (including a flow chart and a consideration of the choice of variables) and discusses the approaches to analysis.
14. Cohort studies
Authors: Burr Michael L.
Published: September 2009

Cohort studies follow a group of individuals over time to identify changes in status (such as disease or mortality) and relate these to observations made at baseline. They can also be carried out where observations on a group of individuals have been collected in the past and can be related to their current status. This chapter summarizes the strengths and weaknesses of cohort studies, and looks in detail at some of the practical issues in their implementation. Their implementation is illustrated using studies in both infancy and childhood and in middle-aged adults and the elderly. The issue of confounding is discussed. Details of study design are summarized in a checklist for planning a cohort study, and their statistical analysis considered in detail.
Tests using single markers
Authors: Cuckle Howard S. , Wald Nicholas
Published: September 2009

This chapter describes screening based on the measurement of a single variable. Before considering the screening test in detail, it is necessary to consider the disorder for which screening is being carried out, its definition, its prevalence, its natural history, and the efficacy of its treatment or prevention. Information on the overlap of test values from affected and unaffected individuals is necessary to determine detection rates and false-positive rates, which, together with data on prevalence, permit the estimation of the risk of being affected. This information is also needed for subsequent screening or diagnostic tests.
Neural tube defects
Authors: Wald Nicholas
Published: September 2009

Antenatal screening and diagnosis for neural tube defects involves the application of two methods — maternal serum alphafetoprotein (AFP) followed by amniotic fluid AFP measurement, and ultrasound examination of the fetus. The present challenge in screening is to integrate the two methods into a coherent screening strategy. This chapter quantifies the screening and diagnostic performance of the different methods, and offers a view on how they could be integrated.
Disorders associated with hyperglycaemia in pregnancy
Authors: Jarrett R. J.
Published: September 2009

This chapter considers whether screening in order to identify new cases of diabetes in pregnancy is worthwhile. It focuses on non-insulin-dependent diabetes mellitus (NIDDM) and gestational diabetes mellitus (GDM), and concludes that there is insufficient evidence to justify screening.
Acquired haematological disorders
Authors: Letsky Elizabeth A. , Weatherall Sir David
Published: September 2009

This chapter discusses screening for maternal anaemia and thrombocytopaenia and fetal allo-immune thrombocytopaenia (FAIT) during pregnancy. The use of haemoglobin measurement to detect maternal anaemia is held to be justified, but screening for maternal thrombocytopaenia by measuring platelet count seems to be of no value. The possibility of screening for FAIT by typing pregnant women's platelet antigens is raised.
Genetic haematological disorders
Authors: Weatherall Sir David , Letsky Elizabeth A.
Published: September 2009

This main focus of this chapter is on genetic disorders of the structure or synthesis of haemoglobin — especially sickle cell disease and the thalassaemias, which are common enough in many populations to justify antenatal and neonatal screening. Glucose-6-phosphate dehydrogenase deficiency also merits screening in certain populations where it commonly causes neonatal jaundice and kernicterus; and screening for hereditary bleeding diseases is indicated if there is a history of a previously affected child.
Rhesus and other haemolytic diseases
Authors: Letsky Elizabeth A. , Leck Ian , Bowman John M. , Leek Ian
Published: September 2009

This chapter describes antenatal and neonatal screening for rhesus and other blood group incompatibilities. These incompatibilities can cause maternal antibodies to fetal blood cell antigens to enter the fetal circulation, leading to fetal and neonatal haemolytic disease (generally referred to as haemolytic disease of the newborn, HDN). Without screening and appropriate treatment, HDN would be an important cause of perinatal death and brain damage. With screening and treatment these complications are almost completely prevented.
Cystic fibrosis
Authors: Brock David J. H.
Published: September 2009

This chapter describes screening and diagnosis for cystic fibrosis (CF). CF is the most common life-shortening Mendelian disorder found in children and in young adults of Caucasian descent. It is concluded that antenatal screening for CF is highly effective and justified, but that the case for neonatal screening has not been made.
Phenylketonuria and other inherited metabolic defects
Authors: Cunningham George C.
Published: September 2009

This chapter deals mainly with screening and diagnosis for phenylketonuria (PKU), but comments briefly on other inherited metabolic defects for which screening has been proposed. PKU is a disorder of amino acid metabolism due to failure of phenylalanine hydroxylation, which almost always results in severe mental retardation and retarded growth. Screening followed by treatment is effective in preventing these effects.
Ultrasound as an ancillary investigation in the management of pregnancy
Authors: Levine Amy B. , Lockwood Charles J.
Published: September 2009

This chapter reviews the role of ultrasound as an ancillary technique in the establishment of gestational age; diagnosis of placenta previa; identification of intrauterine growth retardation; and detection and surveillance of multiple gestation. It is concluded that whether ultrasound is of benefit in these conditions is an open question.
Ultrasound scanning for congenital abnormalities
Authors: Wald Nicholas , Kennard Anne , Donnenfeld Alan , Leck Ian
Published: September 2009

This chapter evaluates the value of ultrasound scanning both as a screening and a diagnostic test for fetal abnormalities, considering published evidence of ultrasound scanning performance, natural history, and birth prevalence of the disorders. The chapter includes a list of abnormalities for which ultrasound scanning and subsequent action can lead to a benefit and others for which evidence is lacking.
Amniocentesis and chorionic villus sampling
Authors: Gosden Christine , Tabor Ann , Leck Ian , Grant Adrian , Alfirevic Zarko , Wald Nicholas
Published: September 2009

This chapter reviews amniocentesis and chorionic villus sampling (CVS) to obtain tissue of the same genetic origin as the fetus for diagnostic purposes (most often testing for chromosomal abnormalities) without removing any tissue from the fetus itself. Second-trimester amniocentesis is a very effective test: failure to make a diagnosis is very rare. It involves a small risk of fetal loss, estimated at about 1 in 100 pregnancies. CVS is somewhat less effective, comparably safe if performed transabdominally, but less so if performed transvaginally.
Fetal blood and tissue sampling
Authors: Hurley Pauline A. , Rodeck Charles H.
Published: September 2009

This chapter examines the place of fetal blood and tissue sampling in the diagnosis of fetal disorders. Samples of fetal tissue or body fluids are needed for many of the diagnostic tests that are indicated when antenatal screening tests are positive. Sampling is most often prompted by the results of ultrasound scans. It may also be indicated when a familial or past obstetric history raises the possibility of a genetic disorder.
What needs to be prevented?
Authors: Rose Geoffrey
Published: September 2009

This chapter argues that the clinical or high-risk approach to prevention has tended to concentrate attention on the conspicuous segment of disease and risk, seeking to understand and control it as though it were the whole of the problem and failing to recognize its integral links with the state of the population in general. Conversely, those taking the public health or environmentalist approach have often been suspicious of medicalization and doctors, and this has isolated them from mainstream medicine, from first-hand experience of illness and disease, and from relevant biological insights.