bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroid Resection Improves Perception of Swallowing Function in Patients with Thyroid Disease
Authors: Greenblatt David Yü , Sippel Rebecca , Leverson Glen , Frydman James , Schaefer Sarah , Chen Herbert
Published: November 2008

Background

Patients with thyroid disease frequently complain of dysphagia. To date, there have been no prospective studies evaluating swallowing function before and after thyroid surgery. We used the swallowing quality of life (SWAL‐QOL) validated outcomes assessment tool to measure changes in swallowing‐related QOL in patients undergoing thyroid surgery.

Methods

Patients undergoing thyroid surgery from May 2002 to December 2004 completed the SWAL‐QOL questionnaire before and one year after surgery. Data were collected on demographic and clinicopathologic variables, and comparisons were made to determine the effect of surgery on patients’ perceptions of swallowing function.

Results

Of 146 eligible patients, 116 (79%) completed the study. The mean patient age was 49 years, and 81% were female. Sixty‐four patients (55%) underwent total thyroidectomy and the remainder received thyroid lobectomy. Thirty patients (26%) had thyroid cancer. The most frequent benign thyroid conditions were multinodular goiter (28%) and Hashimoto’s thyroiditis (27%). Mean preoperative SWAL‐QOL scores were below 90 for nine of the eleven domains, indicating the perception of impaired swallowing and imperfect QOL. After surgery, significant improvements were seen in eight SWAL‐QOL domains. Recurrent laryngeal nerve injury was associated with dramatic score decreases in multiple domains.

Conclusions

In patients with thyroid disease, uncomplicated thyroidectomy leads to significant improvements in many aspects of patient‐reported swallowing‐related QOL measured by the SWAL‐QOL instrument.
A Systemic Evaluation of the State of Affairs Following the Negative Outcome of the Referendum in Cyprus Using the Structured Dialogic Design Process
Authors: Laouris Yiannis , Michaelides Marios , Damdelen Mustafa , Laouri Romina , Beyatli Derya , Christakis Aleco
Published: November 2008

This paper reports the results of the first of a series of co-laboratories organized by Cypriot peace pioneers 30 months after the negative outcome of the referendum concerning UN General Secretary’s plan for reunification of the island. The purpose of this co-laboratory was to support a diverse group of disengaged and disappointed peace pioneers and activists representing Turkish and Greek communities of Cyprus develop a shared understanding of factors contributing to the perceived widening of the gap between the two divided communities in Cyprus. The co-laboratory was organized using the structured dialogic design process (SDDP) approach within the context of a rich web-based communication environment. The root causes contributing to the widening of the gap are discussed and are also compared with those identified during a similar co-laboratory employing the Interactive Management methodology 12 years earlier.
Photodegradation of Pollutants in Air: Enhanced Properties of Nano-TiO2Prepared by Ultrasound
Authors: Cappelletti Giuseppe , Ardizzone Silvia , Bianchi Claudia L , Gialanella Stefano , Naldoni Alberto , Pirola Carlo , Ragaini Vittorio
Published: November 2008

Nanocrystalline TiO2samples were prepared by promoting the growth of a sol–gel precursor, in the presence of water, under continuous (CW), or pulsed (PW) ultrasound. All the samples turned out to be made of both anatase and brookite polymorphs. Pulsed US treatments determine an increase in the sample surface area and a decrease of the crystallite size, that is also accompanied by a more ordered crystalline structure and the samples appear to be more regular and can be considered to contain a relatively low concentration of lattice defects. These features result in a lower recombination rate between electrons and holes and, therefore, in a good photocatalytic performance toward the degradation of NOxin air. The continuous mode induces, instead, the formation of surface defects (two components are present in XPS Ti 2p3/2region) and consequently yields the best photocatalyst. The analysis of all the characterization data seems to suggest that the relevant parameter imposing the final features of the oxides is the ultrasound total energypervolume (Etot/V) and not the acoustic intensity or the pulsed/continuous mode.
Theoretical Simulation on the Assembly of Carbon Nanotubes Between Electrodes by AC Dielectrophoresis
Authors: Lu Yang , Chen Changxin , Yang Liu , Zhang Yafei
Published: November 2008

The assembly of single-walled carbon nanotubes (SWCNTs) using the AC dielectrophoresis technique is studied theoretically. It is found that the comb electrode bears better position control of SWCNTs compared to the parallel electrode. In the assembly, when some SWCNTs bridge the electrode first, they can greatly alter the local electrical field so as to “screen off” later coming SWCNTs, which contributes to the formation of dispersed SWCNT array. The screening distance scales with the gap width of electrodes and the length of SWCNTs, which provides a way to estimate the assembled density of SWCNTs. The influence of thermal noise on SWCNTs alignment is also analyzed in the simulation. It is shown that the status of the array distribution for SWCNTs is decided by the competition between the thermal noise and the AC electric-field strength. This influence of the thermal noise can be suppressed by using higher AC voltage to assemble the SWCNTs.
Habituation and short‐term repeatability of thermal testing in healthy human subjects and patients with chronic non‐neuropathic pain
Authors: Agostinho Claudia Maria Santos , Scherens Andrea , Richter Helmut , Schaub Claudia , Rolke Roman , Treede Rolf‐Detlef , Maier Christoph
Published: November 2008

We investigated habituation effects during thermal quantitative sensory testing (tQST) using 8 repetitive measurements for thermal detection and pain thresholds. The same measurements were repeated two days later. 39 healthy subjects and 36 patients with chronic non‐neuropathic pain syndromes (migraine, tension‐type headache, non‐radicular back pain) were enrolled. The pain intensity was assessed using an 11‐point (0–10) numerical rating scale.

Measurements correlated significantly over the two days in both groups (r=0.41…0.62). Warm detection (WDT) and heat pain threshold (HPT) revealed no significant differences over these days. Cold detection (CDT) and pain thresholds (CPT) showed significant differences but these were small compared to the range of normal variability (CDTΔ −0.28°C; CPTΔ 1.51°C). On both days, WDT showed no habituation during measurements. Although there was a small difference in CDT and CPT between first and second measurement, there was no habituation beyond the second stimuli. In contrast, HPT significantly increased between first and sixth stimuli, indicating pronounced habituation. Average HPT of first to third measurement was significantly lower than HPT of the fourth to sixth assessment (45.9°C; 47.7°C) with a good day‐to‐day repeatability. Repeatability and habituation was identical in both groups. Ongoing pain intensity in the patient groups correlated significantly with CDT/WDT but not with CPT, HPT, indicating that ongoing pain might suppress the sensitivity to non‐painful stimuli. In summary, tQST proved a reliable diagnostic tool for clinical practice. Day‐to‐day differences were small but without clinical relevance. Habituation was most pronounced for HPT, probably due to peripheral fatigue of the receptors.
The Stanford Automated Mounter: Enabling High-Throughput Protein Crystal Screening at SSRL
Authors: Smith Clyde A. , Cohen Aina E.
Published: November 2008

The macromolecular crystallography experiment lends itself perfectly to high-throughput technologies. The initial steps including the expression, purification, and crystallization of protein crystals, along with some of the later steps involving data processing and structure determination have all been automated to the point where some of the last remaining bottlenecks in the process have been crystal mounting, crystal screening, and data collection. At the Stanford Synchrotron Radiation Laboratory, a National User Facility that provides extremely brilliant X-ray photon beams for use in materials science, environmental science, and structural biology research, the incorporation of advanced robotics has enabled crystals to be screened in a true high-throughput fashion, thus dramatically accelerating the final steps. Up to 288 frozen crystals can be mounted by the beamline robot (the Stanford Auto-Mounting System) and screened for diffraction quality in a matter of hours without intervention. The best quality crystals can then be remounted for the collection of complete X-ray diffraction data sets. Furthermore, the entire screening and data collection experiment can be controlled from the experimenter's home laboratory by means of advanced software tools that enable network-based control of the highly automated beamlines.
Advancing Gender Reform in Large-scale Organisations: A New Approach for Practitioners and Researchers
Authors: Connell Raewyn
Published: November 2008

Gender is now understood as an inbuilt feature of organisations, and gender equity strategies need to consider organisational processes as a key issue. Researchers lack, however, an effective common framework for understanding them. An approach is suggested, used in a recent study of gender patterns in a group of Australian public sector organisations. This study was based on a multi-dimensional theory of gender relations. The concept of an organisational gender regime is defined, and a four-dimensional model for analysing gender regimes is outlined. Details of the research are given, including a method for documenting and describing the gender regimes of particular worksites, and a strategy of careful and collaborative analysis. Practical suggestions are made for organisations undertaking their own gender research, emphasising a conceptual and collaborative approach to organisational gender research.
Foreign Direct Investment in the PRC: Preferences, Policies and Performance
Authors: Breslin Shaun
Published: November 2008

In establishing an investment policy in post-Mao China, policy was designed to gain the benefits of foreign direct investment (capital inflow, job creation, export growth, and the upgrading of technology and skills) without suffering any of the perceived negative consequences. As a result policy makers attempted to segregate the investment regime, restricting or prohibiting investment where domestic Chinese producers might be vulnerable to international competition, whilst encouraging investment to produce exports and where there was little or no domestic capacity. In the process, considerable autonomy over investment policy was devolved to local governments, which in turn were heavily influenced by the interests of foreign investors in shaping local investment strategies. From the mid-1990s, the policy of shielding domestic producers from competition was challenged from both external actors seeking the creation of a level playing field, and internal actors who questioned the logic of the status quo. But whilst there has been considerable liberalisation, including the extension of forms of investment and ownership (not least as a result of Chinas WTO entry criteria) conceptions of social stability, the potential impact of investment on such social stability, still remain crucial determinants of investment policy.
Shape and stability of axisymmetric levitated viscous drops
Authors: LISTER JOHN R. , THOMPSON ALICE B. , PERRIOT ANTOINE , DUCHEMIN LAURENT
Published: November 2008

We consider levitation of an axisymmetric drop of molten glass above a spherical porous mould through which air is injected at a constant velocity. Owing to the viscosity contrast, the float height for a given shape is established on a much shorter time scale than the subsequent deformation of the drop under gravity, surface tension and the underlying lubrication pressure. Equilibrium shapes, in which an internal hydrostatic pressure is coupled to the external lubrication pressure through the total curvature and the Young–Laplace equation, are determined using a numerical continuation scheme. The set of solution branches is surprisingly complicated and shows a rich bifurcation structure in the parameter space (Bo=ρgV2/3/γ, Ca=μav/γ), where Bo is bond number and Ca is capillary number, ρ and V are the drop density and volume, γ the surface tension, μa the air viscosity and v the injection velocity. The linear stability of equilibria is determined using a boundary-integral representation for drop deformation that factors out the rapid vertical adjustment of the float height. The results give good agreement with time-dependent simulations. For sufficiently large Ca there are intervals of Bo for which there are no stable solutions and, as Ca increases, these intervals grow and merge. The region of stability decreases as the mould radius aM increases with an approximate scaling Ca~aM−5, which imposes practical limitations on the use of this geometry for the manufacture of lenses.
Kelvin waves in the nonlinear shallow water equations on the sphere: nonlinear travelling waves and the corner wave bifurcation
Authors: BOYD JOHN P. , ZHOU CHENG
Published: November 2008

The Kelvin wave is the lowest eigenmode of Laplace's tidal equation and is widely observed in both the ocean and the atmosphere. In this work, we neglect mean currents and instead include the full effects of the Earth's sphericity and the wave dispersion it induces. Through a mix of perturbation theory and numerical computations using a Fourier/Newton iteration/continuation method, we show that for sufficiently small amplitude, there are Kelvin travelling waves (cnoidal waves). As the amplitude increases, the branch of travelling waves terminates in a so-called corner wave with a discontinuous first derivative. All waves larger than the corner wave evolve to fronts and break. The singularity is a point singularity in which only the longitudinal derivative is discontinuous. As we solve the nonlinear shallow water equations on the sphere, with increasing ε (‘Lamb's parameter’), dispersion weakens, the amplitude of the corner wave decreases rapidly, and the longitudinal profile of the corner wave narrows dramatically.
Structural analysis of fertilization in the fish Brycon orbignyanus
Authors: Ganeco Luciana Nakaghi , Franceschini-Vicentini Irene Bastos , Nakaghi Laura Satiko Okada
Published: November 2008

In the present work, we analyzed the structure of oocytes and fertilized eggs of the piracanjuba fish (Brycon orbignyanus) under light and scanning electron microscopy. After inducing spawning, samples were collected at the moment of oocyte extrusion, when oocytes and semen were mixed (time 0), as well as at 10, 20 and 30 s after mixing, every minute up to 10 min, and then at 15 and 20 min. The oocytes are spherical, translucent and greenish with a mean diameter of 1.3 ± 0.11 mm. During the extrusion, cytoplasmic movement was observed in eggs towards the micropyle, characterizing the animal pole. At the moment of fertilization, the cortical cytoplasm showed a higher concentration of cortical alveoli at the animal pole than at the vegetal pole. The cortical alveoli breakdown promoted the elevation of the chorion with a consequent increase in egg diameter (1.95 ± 0.08 mm). The penetration of the spermatozoon promotes the formation of a fertilization cone of spherical external structure, which obstructs the opening of the micropyle. This structure acts as a main mechanism to avoid polyspermy, intercepting the access of supernumerary spermatozoa. Such studies about the reproductive biology of fish are important to species survival and conservation programmes.
Climatological features of global multiple tropopause events
Authors: Añel Juan A. , Antuña Juan C. , de la Torre Laura , Castanheira José M. , Gimeno Luis
Published: November 2008

This study examines various climatological features related to multiple tropopause events (MT events). The analysis is based on the lapse rate definition of the tropopause and is performed on a radiosonde data subset taken from the Integrated Global Radiosonde Archive database. The global statistics of MT events are analyzed, taking into consideration both their seasonal and geographical variations. Our results are in moderate qualitative agreement with those of earlier studies. They reinforce the analytical findings of other researchers, but at the same time highlight important differences in both the number and position of the maximum occurrence of MT events. We found a latitudinal band of multiple tropopause occurrence in the Northern Hemisphere and three centers in the Southern Hemisphere, which coincided with identified zones of maximum cyclogenesis. The climatological features of pressure, temperature, and vertical separation of MT events revealed the complexity of these phenomena, which behave very differently according to latitude and season.
Annular mode time scales in the Intergovernmental Panel on Climate Change Fourth Assessment Report models
Authors: Gerber E. P. , Polvani L. M. , Ancukiewicz D.
Published: November 2008

The ability of climate models in the Intergovernmental Panel on Climate Change Fourth Assessment Report to capture the temporal structure of the annular modes is evaluated. The vertical structure and annual cycle of the variability is quantified by the e‐folding time scale of the annular mode autocorrelation function. Models vaguely capture the qualitative features of the Northern and Southern Annular Modes: Northern Hemisphere time scales are shorter than those of the Southern Hemisphere and peak in boreal winter, while Southern Hemisphere time scales peak in austral spring and summer. Models, however, systematically overestimate the time scales, particularly in the Southern Hemisphere summer, where the multimodel ensemble average is twice that of reanalyses. Fluctuation‐dissipation theory suggests that long time scales in models could be associated with increased sensitivity to anthropogenic forcing. Comparison of model pairs with similar forcings but different annular mode time scales provides a hint of a fluctuation‐dissipation relationship.
COSMIC/FORMOSAT‐3 tomography of SEP ionization in the polar cap
Authors: Dmitriev A. V. , Tsai L.‐C. , Yeh H.‐C. , Chang C.‐C.
Published: November 2008

We studied ionization effects produced by solar energetic particles (SEP) in the northern polar ionosphere and atmosphere during December 2006 (local night). Height profiles of specific ionization produced by the SEP in the polar cap were calculated using POES data on energetic particles. The SEP ionization dynamics reveals three intensifications at heights from 50 to 100 km in 7 to 8, 13 and 14 December. At the same time a 3‐D tomography of electron content (EC) in the ionosphere and upper atmosphere was performed on the base of COSMIC/FORMOSAT‐3 sounding data. We found pretty close temporal and spatial patterns for the EC enhancements and for the SEP ionization. The discrepancies might be attributed to three effects: unaccounted contribution of low‐energy electrons to the ionization of lower ionosphere, fast growth of electron losses with the depth in atmosphere, and strong contribution from storm‐time ionospheric disturbances.
Contributions of isoprene, monoterpenes,β‐caryophyllene, and toluene to secondary organic aerosols in Hong Kong during the summer of 2006
Authors: Hu Di , Bian Qijing , Li Teresa W. Y. , Lau Alexis K. H. , Yu Jian Zhen
Published: November 2008

Isoprene, monoterpenes,β‐caryophyllene, and toluene are known to be important secondary organic aerosol (SOA) precursors. In this study, characteristic SOA tracers of these precursors were quantified in ambient samples of PM2.5taken in Hong Kong and their contributions to SOA were estimated using a tracer‐based method. Samples were collected every other day from four sampling sites during a field measurement campaign in the summer of 2006. Fourteen SOA tracers, along with 24 other polar oxygenated compounds, were identified and quantified using gas chromatography/ion trap mass spectrometry with prior trimethylsilylation. Concentrations of the individual tracers ranged from a few tenths to a few hundreds ng m−3. The tracer concentrations were found to be 1 order of magnitude higher on days under regional transport influences due to elevated oxidant levels than on days under mainly local emissions influences. Using the measured SOA tracer concentrations in the ambient aerosols and laboratory‐derived tracer mass fractions reported by Kleindienst et al. (2007), we estimated that the average SOA attributable to isoprene, monoterpenes,β‐caryophyllene, and toluene was 8.83μg m−3on days under regional transport influences versus 0.99μg m−3on days under mainly local emissions influences, accounting for approximately 49% and 21%, respectively, of the ambient OC concentrations. The tracer‐based estimates indicate that monoterpenes andβ‐caryophyllene are significant contributors to ambient PM2.5in the summer, which may be due to the high emissions of these biogenic hydrocarbons in Hong Kong.
Physical-Chemical Property Data for Dibenzo-p-dioxin (DD), Dibenzofuran (DF), and Chlorinated DD/Fs: A Critical Review and Recommended Values
Authors: Åberg Annika , MacLeod Matthew , Wiberg Karin
Published: November 2008

Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are of global concern due to their persistence, their tendency to bioaccumulate, and their extremely high toxicity. The fate of the PCDD/Fs in the environment is largely determined by their physical-chemical properties, such as solubility in water (SW, molm−3), solubility in octanol (SO, molm−3), and vapor pressure (P, Pa). It is not unusual that the range of reported values for a given property varies over several orders of magnitude, especially for the highly chlorinated congeners, and consequently, it is a challenge to select physical-chemical property data from the literature for use in chemical fate and risk assessments. In the current study, physical-chemical property data [P, SW, SO, Henry’s law constant (H), partitioning coefficients between octanol-water (KOW) and octanol-air (KOA)] for 15 DDs and 17 DFs at 293–299K are compiled from the literature and evaluated to select literature derived values that are then adjusted to conform to thermodynamic constraints using a least-squares adjustment procedure. We also present an analysis of available data on internal energies of phase change (ΔUA, ΔUW, ΔUO, ΔUOW, ΔUAW, ΔUOA) at 298K, which describe the temperature dependence of the partitioning properties. The final adjusted values (FAVs) derived from this study are recommended as physical-chemical property data for PCDD/Fs for use in environmental fate modeling. The FAVs for internal energies of phase change can be used as a first approximation for estimating properties at temperatures other than 298K.
In vitro unfolding of yeast multicopper oxidase Fet3p variants reveals unique role of each metal site
Authors: Sedlák Erik , Ziegler Lynn , Kosman Daniel J. , Wittung-Stafshede Pernilla
Published: November 2008

Fet3p from
Saccharomyces cerevisiae
is a multicopper oxidase (MCO) that contains 3 cupredoxin-like β-barrel domains and 4 copper ions located in 3 distinct metal sites (T1 in domain 3, T2, and the binuclear T3 at the interface between domains 1 and 3). To better understand how protein structure and stability is defined by cofactor coordination in MCO proteins, we assessed thermal unfolding of apo and metallated forms of Fet3p by using spectroscopic and calorimetric methods in vitro (pH 7). We find that unfolding reactions of apo and different holo forms of Fet3p are irreversible reactions that depend on the scan rate. The domains in apo-Fet3p unfold sequentially [thermal midpoint (
T
m
) of 45 °C, 62 °C, and 72 °C; 1 K/min]. Addition of T3 imposes strain in the apo structure that results in coupled domain unfolding and low stability (
T
m
of 50 °C; 1 K/min). Further inclusion of T2 (i.e., only T1 absent) increases overall stability by ≈5 °C but unfolding remains coupled in 1 step. Introduction of T1, producing fully-loaded holo-Fet3p (or in the absence of T2), results in stabilization of domain 3, which uncouples unfolding of the domains; unfolding of domain 2 occurs first along with Cu-site perturbations (
T
m
50–55 °C; 1 K/min), followed by unfolding of domains 1 and 3 (≈65–70 °C; 1 K/min). Our results suggest that there is a metal-induced tradeoff between overall protein stability and metal coordination in members of the MCO family.
A highly prevalent and genetically diversified
Picornaviridae
genus in South Asian children
Authors: Kapoor Amit , Victoria Joseph , Simmonds Peter , Slikas Elizabeth , Chieochansin Thaweesak , Naeem Asif , Shaukat Shahzad , Sharif Salmaan , Alam Muhammad Masroor , Angez Mehar , Wang Chunlin , Shafer Robert W. , Zaidi Sohail , Delwart Eric
Published: November 2008

Viral metagenomics focused on particle-protected nucleic acids was used on the stools of South Asian children with nonpolio acute flaccid paralysis (AFP). We identified sequences distantly related to Seneca Valley virus and cardioviruses that were then used as genetic footholds to characterize multiple viral species within a previously unreported genus of the
Picornaviridae
family. The picornaviruses were detected in the stools of >40% of AFP and healthy Pakistani children. A genetically diverse and highly prevalent enteric viral infection, characteristics similar to the
Enterovirus
genus, was therefore identified substantially expanding the genetic diversity of the RNA viral flora commonly found in children.
The hormonal action of IGF1 in postnatal mouse growth
Authors: Stratikopoulos Elias , Szabolcs Matthias , Dragatsis Ioannis , Klinakis Apostolos , Efstratiadis Argiris
Published: November 2008

The mammalian insulin-like growth factor 1 (IGF1), which is a member of a major growth-promoting signaling system, is produced by many tissues and functions throughout embryonic and postnatal development in an autocrine/paracrine fashion. In addition to this local action, IGF1 secreted by the liver and circulating in the plasma presumably acts systemically as a classical hormone. However, an endocrine role of IGF1 in growth control was disputed on the basis of the results of a conditional, liver-specific
Igf1
gene knockout in mice, which reduced significantly the level of serum IGF1, but did not affect average body weight. Because alternate interpretations of these negative data were tenable, we addressed genetically the question of hormonal IGF1 action by using a positive experimental strategy based on the features of the
cre
/
loxP
recombination system. Thus, we generated bitransgenic mice carrying in an
Igf1
null background a dormant
Igf1
cDNA placed downstream of a transcriptional “stop” DNA sequence flanked by
loxP
sites (floxed) and also a
cre
transgene driven by a liver-specific promoter. The
Igf1
cDNA, which was inserted by knock-in into the mutated and inactive
Igf1
locus itself to ensure proper transcriptional regulation, was conditionally expressed from cognate promoters exclusively in the liver after Cre-mediated excision of the floxed block. Our genetic study demonstrated that the endocrine IGF1 plays a very significant role in mouse growth, as its action contributes approximately30% of the adult body size and sustains postnatal development, including the reproductive functions of both mouse sexes.
Comparing face patch systems in macaques and humans
Authors: Tsao Doris Y. , Moeller Sebastian , Freiwald Winrich A.
Published: November 2008

Face recognition is of central importance for primate social behavior. In both humans and macaques, the visual analysis of faces is supported by a set of specialized face areas. The precise organization of these areas and the correspondence between individual macaque and human face-selective areas are debated. Here, we examined the organization of face-selective regions across the temporal lobe in a large number of macaque and human subjects. Macaques showed 6 regions of face-selective cortex arranged in a stereotypical pattern along the temporal lobe. Human subjects showed, in addition to 3 reported face areas (the occipital, fusiform, and superior temporal sulcus face areas), a face-selective area located anterior to the fusiform face area, in the anterior collateral sulcus. These results suggest a closer anatomical correspondence between macaque and human face-processing systems than previously realized.
Extinction and resurrection in gene networks
Authors: Schultz Daniel , Walczak Aleksandra M. , Onuchic José N. , Wolynes Peter G.
Published: November 2008

When gene regulatory networks operate in regimes where the number of protein molecules is so small that the molecular species are on the verge of extinction, the death and resurrection of the species greatly modifies the attractor landscape. Deterministic models and the diffusion approximation to the master equation break down at the limits of protein populations in a way very analogous to the breakdown of geometrical optics that occurs at distances <1 wavelength of light from edges. Stable stochastic attractors arise from extinction and resurrection events that are not predicted by the deterministic description. With this view, we explore the attractors of the regular toggle switch and the exclusive switch, focusing on the effects of cooperative binding and the production of protein in bursts. Our arguments suggest that the stability of lysogeny in the λ-phage may be influenced by such extinction phenomena.
Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence
Authors: Suh Jesse J. , Pettinati Helen M. , Kampman Kyle M. , O'Brien Charles P.
Published: November 2008

Recently, we reported that naltrexone at 150 mg/day significantly decreased cocaine and alcohol use for men but not women with co‐occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender responses to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre‐treatment psychiatric problems or nausea while in treatment. Further research on the impact of pre‐treatment and in‐treatment gender differences with naltrexone is warranted.
Form Perception of Partly Occluded Shapes in 4‐Month‐Old Infants
Authors: de Wit Tessa C. J. , Vrins Sven , Dejonckheere Peter J. N. , van Lier Rob
Published: November 2008

Two habituation experiments were conducted to investigate how 4‐month‐old infants perceive partly occluded shapes. In the first experiment, we presented a simple, partly occluded shape to the infants until habituation was reached. Then we showed either a probable completion (one that would be predicted on the basis of both local and global cues) or an improbable completion. Longer looking times were found for the improbably completed shape (compared to probable and control conditions), suggesting that the probable shape was perceived during partial occlusion. In the second experiment, infants were habituated to more ambiguous partly occluded shapes, where local and global cues would result in different completions. For adults, the percept of these shapes is usually dominated by global influences. However, after habituation the infants looked longer at the globally completed shapes. These results suggest that by the age of 4 months, infants are able to infer the perceptual completion of partly occluded shapes, but for more ambiguous shapes, this completion seems to be dominated by local influences.
Development of Visual Selection in 3‐ to 9‐Month‐Olds: Evidence From Saccades to Previously Ignored Locations
Authors: Amso Dima , Johnson Scott P.
Published: November 2008

We examined changes in the efficiency of visual selection over the first postnatal year with an adapted version of a spatial negative priming paradigm. In this task, when a previously ignored location becomes the target to be selected, responses to it are impaired, providing a measure of visual selection. Oculomotor latencies to target selection were the dependent measure. Each trial consisted of a prime and a probe presentation, separated by a 67‐, 200‐, or 550‐msec interstimulus interval (ISI), to test the efficiency of selection as a function of processing time. In the prime, the target was accompanied by a distractor item. In the probe, the target appeared either in the location formerly occupied by the distractor (repeated distractor trials) or in one of the other two locations (control trials). We tested 41 infants in each of 3 age groups (3, 6, and 9 months) on the three different ISIs. Nine‐month‐old infants' saccade latencies were slowed on repeated distractors relative to control trials, given sufficiently long ISIs. Saccade latencies in the youngest two age groups showed only facilitation on repeated distractor trials at short ISIs. These results suggest that visual selection efficiency is a function of the interaction of the processing limitations of a system with environmental conditions, in this case the time allotted for the selection process.
KEPE—a motif frequently superimposed on sumoylation sites in metazoan chromatin proteins and transcription factors
Authors: Diella Francesca , Chabanis Sophie , Luck Katja , Chica Claudia , Ramu Chenna , Nerlov Claus , Gibson Toby J.
Published: November 2008

Motivation: We noted that the sumoylation site in C/EBP homologues is conserved beyond the canonical consensus sequence for sumoylation. Therefore, we investigated whether this pattern might define a more general protein motif.

Results: We undertook a survey of the human proteome using a regular expression based on the C/EBP motif. This revealed significant enrichment of the motif using different Gene Ontology terms (e.g. ‘transcription’) that pertain to the nucleus. When considering requirements for the motif to be functional (evolutionary conservation, structural accessibility of the motif and proper cell localization of the protein), more than 130 human proteins were retrieved from the UniProt/Swiss-Prot database. These candidates were particularly enriched in transcription factors, including FOS, JUN, Hif-1α, MLL2 and members of the KLF, MAF and NFATC families; chromatin modifiers like CHD-8, HDAC4 and DNA Top1; and the transcriptional regulatory kinases HIPK1 and HIPK2. The KEPEmotif appears to be restricted to the metazoan lineage and has three length variants—short, medium and long—which do not appear to interchange.

Contact:  toby.gibson@embl.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Moderation of pathogen-induced mortality: the role of density in
Bacillus thuringiensis
virulence
Authors: Raymond Ben , Ellis Richard J , Bonsall Michael B
Published: November 2008

Virulence in pathogens may be increased or decreased in order to maximize reproduction and transmission. We investigated how reproduction and virulence in the entomopathogen
Bacillus thuringiensis
(
Bt
) changed with bacterial density. We predicted that virulence would be moderated at high pathogen densities because extended time to death allows more growth in hosts. We found that pathogen reproduction (spores produced per cadaver) peaked at an intermediate time to death and was lowest in hosts that die early. Manipulating spore density (spores per unit area of leaf) by combining pathogenic
Bt
spores with a non-pathogenic mutant confirmed our prediction: larval 5-day mortality was reduced at higher pathogen densities. Pathogen reproduction increased with the density of pathogenic
Bt
. We hypothesize that more effective reproduction at high density is a consequence rather than a cause of density-dependent virulence.
ArabidopsisPhosphatidylinositol-4-Monophosphate 5-Kinase 4 Regulates Pollen Tube Growth and Polarity by Modulating Membrane Recycling
Authors: Sousa Eva , Kost Benedikt , Malhó Rui
Published: November 2008

Phosphatidylinositol-4-monophosphate 5-kinases produce phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] and have been implicated in vesicle trafficking and cytoskeletal rearrangements. Here, we adopted a reverse genetics approach to investigate the function of the Arabidopsis thaliana pollen-expressed gene encoding phosphatidylinositol-4-monophosphate 5-kinase 4 (PIP5K4). Pollen germination, tube growth, and polarity were significantly impaired in homozygous mutant plants lacking PIP5K4 transcript. In vitro, supplementation with PtdIns(4,5)P2 rescued these phenotypes. In vivo, mutant pollen fertilized ovules, leading to normal seed set and silique length. However, fertilization took longer than in wild-type plants, and the pip5k4 null mutant allele was transmitted through the pollen at a reduced frequency. Analysis of endocytic events using FM1-43 (or FM4-64) suggested a reduction in endocytosis and membrane recycling in pip5k4 null mutant pollen tubes. Imaging of elongating tobacco (Nicotiana tabacum) pollen tubes transiently transformed with a PIP5K4-green fluorescent protein fusion construct revealed that the protein localized to the plasma membrane, particularly in the subapical region. Overexpression of PIP5K4-GFP delocalized the protein to the apical region of the plasma membrane, perturbed pollen tube growth, and caused apical cell wall thickening. Thus, PIP5K4 plays a crucial role in regulating the polarity of pollen tubes. This study supports a model for membrane secretion and recycling where the apical and subapical regions appear to contain the components required to promote and sustain growth.
The heat shock protein 90 inhibitor IPI‐504 induces apoptosis of AKT‐dependent diffuse large B‐cell lymphomas
Authors: Abramson Jeremy S. , Chen Wen , Juszczynski Przemyslaw , Takahashi Hidenobu , Neuberg Donna , Kutok Jeffery L. , Takeyama Kunihiko , Shipp Margaret A.
Published: November 2008

Heat shock protein 90 (HSP90) is a molecular chaperone that stabilizes critical client proteins in multiple cancers. Gene expression profiling was utilized to characterize HSP90 isoform expression in primary human diffuse large B‐cell lymphomas (DLBCLs). HSP90 α and β isoforms were differentially expressed in subsets of tumours defined by their transcriptional profiles. Thereafter, we assessed the activity of the HSP90 inhibitor, IPI‐504, in an extensive panel of DLBCL cell lines. IPI‐504, which interacts with the conserved ATP‐binding site in both HSP90 isoforms, inhibited proliferation and induced apoptosis in the majority of DLBCL cell lines at low micromolar concentrations. IPI‐504‐sensitive cell lines expressed high levels of the HSP90 client protein, pAKT, and exhibited dose‐dependent decreases in pAKT levels following IPI‐504 treatment and significantly reduced proliferation following AKT RNAi. Furthermore, the combination of low‐dose (<1 μmol/l) IPI‐504 and the AKT/Pi3K pathway inhibitor, LY24009, was synergistic in IPI‐504‐sensitive DLBCL cell lines. Low‐dose IPI‐504 was also synergistic with the chemotherapeutic agent, doxorubicin. The HSP90 inhibitor IPI‐504 warrants further investigation in DLBCL alone and in combination with identified client protein inhibitors and active chemotherapeutic agents.
Regulation of Down Syndrome Critical Region 1 expression by Nuclear Factor of Activated T cells in megakaryocytes
Authors: Kyttälä Satu , Habermann Ivonne , Minami Takashi , Ehninger Gerhard , Kiani Alexander
Published: November 2008

As precursors of platelets, megakaryocytes must fulfil the complex tasks of protein synthesis and platelet assembly. Megakaryocytic dysfunction can lead to neoplastic disorders, such as acute megakaryoblastic leukaemia, an entity with a 500‐fold increased incidence in children with Down syndrome (DS). Down Syndrome Critical Region 1 (DSCR1), a member of the calcipressin family of calcineurin inhibitors, is overexpressed in DS, and destabilization of the calcineurin/Nuclear Factor of Activated T cells (NFAT) pathway by overexpression of DSCR1 has been implicated in some of the pathophysiological features of the disease. The roles of NFAT and DSCR1 in megakaryocyte signalling and gene expression, however, are unknown. In this study, we show that calcineurin and NFAT are components of a calcium‐induced signalling cascade in megakaryocytes. NFAT activation in megakaryocytes was induced by fibrillar collagen type I and was completely sensitive to the calcineurin inhibitor cyclosporin A. We established DSCR1 as a calcium‐induced NFAT target gene in these cells and show that overexpression of DSCR1 in megakaryocytes strongly inhibits NFAT activation as well as NFAT‐dependent expression of the Fas ligand gene (FASLG). These results suggest that DSCR1 acts as an endogenous feedback inhibitor of NFAT signalling in megakaryocytes, and may have implications for megakaryocytic gene expression in DS.
Interleukin (IL)‐3/granulocyte macrophage‐colony stimulating factor/IL‐5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS‐related tyrosine kinase 3 receptor
Authors: Riccioni Roberta , Diverio Daniela , Riti Viviana , Buffolino Sonia , Mariani Gualtiero , Boe Alessandra , Cedrone Michele , Ottone Tiziana , Foà Robin , Testa Ugo
Published: November 2008

The common beta chain subunit (βc), also known as CDw131, shared by the interleukin‐3 (IL‐3), granulocytic macrophage colony‐stimulating factor (GM‐CSF) and IL‐5 receptors, is required for high‐affinity ligand binding and signal transduction. The present study explored the expression of CDw131 in 105 de novo cases of acute myeloid leukaemia (AML). The levels of CDw131 expression were used to identify two AML subgroups characterized by low (75/105) and high (30/105) expression of this receptor chain. It was observed that (i) the level of CDw131 expression strictly correlated with the level of CD116 (GM‐CSFα receptor chain) and CD123 (IL‐3Rα chain); (ii) AMLs with high CDw131 expression were characterized by low CD34 expression and usually high CD11b, CD14 expression; (iii) AMLs with high CDw131 expression frequently co‐expressed receptors for angiogenic growth factors (vascular endothelial growth factor R2, Tie‐2); (iv) AMLs with high CDw131 expression were more cycling than those with low CDw131 expression; (v) AMLs with high CDw131 frequently displayed Feline Murine Sarcoma (FMS‐related) tyrosine kinase 3 (FLT3) internal tandem duplication and constitutively activated Signal Transducer and Activator of Transcription‐5 (STAT5). In conclusion, the analysis of the level of CDw131 expression enabled the identification of a subset of AMLs characterized by a high cycling status, the expression of myelo‐monocytic markers, mutated FLT3 and the co‐expression of receptors for angiogenic growth factors. These findings are of value for the development of new therapeutic strategies for the treatment of these AMLs.
The relevance of the bleeding severity in the treatment of acquired haemophilia – an update of a single‐centre experience with 67 patients
Authors: ZEITLER H. , ULRICH‐MERZENICH G. , GOLDMANN G. , VIDOVIC N. , BRACKMANN H. H. , OLDENBURG J.
Published: November 2008

Summary.  Acquired haemophilia (AH), an autoimmune disorder with clinical features ranging from harmless haematomas to life‐threatening bleedings, still has a mortality rate of up to 25%. Owing to its low frequency (1–4 × 106), standardized treatment protocols for its variable manifestations are not available. In case of prominent severe bleedings, the treatment should aim at rapid elimination of the antibody to protect patients from bleedings and on reinduction of long‐term immune tolerance. Clinical data, short‐ and long‐term treatment results of 67 patients diagnosed by our centre are presented. Patients were treated depending on their bleeding severity either by an immunosuppressive treatment alone, or in case of life‐threatening bleedings, by a combined protocol (modified Bonn–Malmö protocol, MBMP) consisting of antibody depletion through immunoadsorption, intravenous immunoglobulin treatment, immunosuppression and high‐dose factor VIII (FVIII) substitution. Mild bleedings occurred in two patients who were treated successfully alone by immunosuppression. Complete remission (CR) was achieved in 90% of the patients treated with MBMP (60). Of the six patients (10%) who achieved a partial remission (PR), four suffered from cancer. Mortality under MBMP was not seen. In contrast, five patients, in whom diagnosis of AH was delayed, experienced fatal outcome during surgical interventions before initiation of MBMP treatment. Prognosis in AH depends mainly on its prompt diagnosis. Treatment procedures should be adapted to bleeding severity and inhibitor titres. Under these conditions, AH is a potentially curable autoimmune disorder with an excellent prognosis.
Botany without borders: barcoding in focus
Authors: KANE NOLAN C. , CRONK QUENTIN
Published: November 2008

This recent meeting, held on the campus of the University of British Columbia, attracted 1200 delegates and a vast array of talks, but was notable for a remarkable showing of talks and posters on DNA barcoding in plants, spread through many sessions. The Canadian Centre for DNA Barcoding defines barcoding as ‘species identification and discovery through the analysis of short, standardized gene regions known as DNA barcodes’. This approach is somewhat controversial in animals (Rubinoff et al., 2006), although it has been shown to be useful and reliable in many metazoan taxa (Meyer & Paulay 2005; Hajibabaei et al., 2007), in which the mitochondrial cytochrome oxidase I (COI) gene is used. However, in land plants, COI evolves far too slowly to be useful, and there is no obvious single universal alternative (Fazekas et al., 2008). Genes that work well in one taxon may perform poorly in other taxa. Additionally, some perfectly good plant species, reproductively isolated and morphologically and ecologically distinct, are too young to show much sequence divergence at most loci. Nevertheless, as we saw at this conference, progress has been made towards identifying genes that serve many of the functions of DNA barcodes, at least in some plant taxa.
Comparative phylogeography of two seastars and their ectosymbionts within the Coral Triangle
Authors: CRANDALL ERIC D. , JONES M. ELIZABETH , MUÑOZ MARTHA M. , AKINRONBI BOLANLE , ERDMANN MARK V. , BARBER PAUL H.
Published: November 2008

Repeated exposure and flooding of the Sunda and Sahul shelves during Pleistocene sea‐level fluctuations is thought to have contributed to the isolation and diversification of sea‐basin populations within the Coral Triangle. This hypothesis has been tested in numerous phylogeographical studies, recovering an assortment of genetic patterns that the authors have generally attributed to differences in larval dispersal capability or adult habitat specificity. This study compares phylogeographical patterns from mitochondrial COI sequences among two co‐distributed seastars that differ in their adult habitat and dispersal ability, and two seastar ectosymbionts that differ in their degree of host specificity. Of these, only the seastar Linckia laevigata displayed a classical pattern of Indian‐Pacific divergence, but with only moderate genetic structure (ΦCT = 0.067). In contrast, the seastar Protoreaster nodosus exhibited strong structure (ΦCT = 0.23) between Teluk Cenderawasih and the remainder of Indonesia, a pattern of regional structure that was echoed in L. laevigata (ΦCT = 0.03) as well as its obligate gastropod parasite Thyca crystallina (ΦCT = 0.04). The generalist commensal shrimp, Periclimenes soror showed little genetic structuring across the Coral Triangle. Despite species‐specific phylogeographical patterns, all four species showed departures from neutrality that are consistent with massive range expansions onto the continental shelves as the sea levels rose, and that date within the Pleistocene epoch. Our results suggest that habitat differences may affect the manner in which species responded to Pleistocene sea‐level fluctuations, shaping contemporary patterns of genetic structure and diversity.