bluuebunny/crossref_metadata_2025 huggingface dataset:
High quality factor Er3+-activated dielectric microcavity fabricated by rf sputtering
Authors: Chiasera A. , Belli R. , Bhaktha S. N. B. , Chiappini A. , Ferrari M. , Jestin Y. , Moser E. , Righini G. C. , Tosello C.
Published: October 2006

The authors report on one-dimensional dielectric photonic crystals activated by Er3+ ion and fabricated by rf-sputtering deposition. The cavity was constituted by an Er3+-doped SiO2 active layer inserted between two Bragg reflectors consisting of six pairs of SiO2∕TiO2 layers. Near infrared transmittance spectra evidence the presence of a stop band from 1350to1850nm and a cavity resonance centered at 1537nm. Intensity enhancement and narrowing of the I13∕24→I15∕24 emission band of Er3+ ion, due to the cavity effect, were observed. A cavity quality factor of 171 was achieved.
Electron spin filter based on Rashba spin-orbit coupling
Authors: Cummings A. W. , Akis R. , Ferry D. K.
Published: October 2006

The authors present an electron spin filter that consists of a branching structure under the influence of Rashba spin-orbit coupling. The magnitude of the spin polarization in this device can be tuned by the strength of the spin-orbit interaction. The authors find that the mechanism for the spin filtering is the spatial modulation of the spin-resolved wave functions due to the influence of the Rashba effect. The authors also find evidence suggesting that the geometry of the branch at the junction point is primarily responsible for the strength of the spin polarization.
Efficient third harmonic generation of microjoule picosecond pulses at 355nm in BiB3O6
Authors: Ghotbi M. , Sun Z. , Majchrowski A. , Michalski E. , Kityk I. V. , Ebrahim-Zadeh M.
Published: October 2006

The authors report efficient third harmonic generation of microjoule picosecond pulses at 355nm in the nonlinear optical material BiB3O6. Using two crystals of BiB3O6 cut for type I (e+e→o) phase matching in optical yz plane for second and third harmonic generation and fundamental pulses from a mode-locked, amplified picosecond Nd:YAG laser at 1.064μm, they have achieved conversion efficiencies of as much as 50% at 355nm. Third harmonic pulse energies of up to 216μJ in 29ps pulses at 25Hz repetition rate have been obtained for 35ps fundamental pulses. They have also determined the magnitude of two-photon absorption coefficient in BiB3O6 at 355nm to be 0.71 and 1.37cm∕GW for ordinary and extraordinary polarizations, respectively.
Micromachined inking chip for scanning probe nanolithography using local thermal vapor inking method
Authors: Li Shifeng , Shaikh Kashan A. , Szegedi Sandra , Goluch Edgar , Liu Chang
Published: October 2006

Here the authors show a method for inking scanning probes based on local thermal evaporative inking transfer. This method results in low loss, rapid, and parallel inking action. Scanning probes are accommodated at openings of ink reservoirs. A resistive heater is used to initiate vaporization of inks to uniformly coat probes. 1mM 16-mercaptohexadecanoic acid in ethanol solution is used to characterize this inking chip. Moreover, an array of scanning probes can be inked simultaneously using an array of inking reservoirs. During the inking process, each probe is tightly sealed inside individual reservoir so cross contamination is limited.
Temperature dependence of photoluminescence from single core-shell GaAs–AlGaAs nanowires
Authors: Titova L. V. , Hoang Thang B. , Jackson H. E. , Smith L. M. , Yarrison-Rice J. M. , Kim Y. , Joyce H. J. , Tan H. H. , Jagadish C.
Published: October 2006

Temperature-dependent polarized microphotoluminescence measurements of single GaAs∕AlGaAs core-shell nanowires are used to probe their electronic states. The low-temperature emission from these wires is strongly enhanced compared with that observed in bare GaAs nanowires and is strongly polarized, reflecting the dielectric mismatch between the nanowire and the surrounding air. The temperature-dependent band gap of the nanowires is seen to be somewhat different from that observed in bulk GaAs, and the PL rapidly quenches above 120K, with an activation energy of 17meV reflecting the presence of nonradiative defects.
Oxygen vacancy ordering in heavily rare-earth-doped ceria
Authors: Ou Ding Rong , Mori Toshiyuki , Ye Fei , Kobayashi Tomoaki , Zou Jin , Auchterlonie Graeme , Drennan John
Published: October 2006

25 at. % Rare-earth (RE)-doped ceria samples (RE=Sm, Dy, Y, and Yb) were examined using transmission electron microscopy and electron energy loss spectroscopy, from which the oxygen vacancy ordering in nanosized domains was confirmed. The relationships of the dopant type, oxygen vacancy ordering, and ionic conductivity of doped ceria were established. It is found that the ordering of oxygen vacancies depends strongly on the dopant type, and the development of nanosized domains with a higher degree of ordering can lead to a more dramatic decrease of ionic conductivity in doped ceria.
Remotely coupled surface plasmons in a two-colored plasmonic thermal emitter
Authors: Chuang Tzu-Hung , Tsai Ming-Wei , Chang Yi-Tsung , Lee Si-Chen
Published: October 2006

A two-colored plasmonic thermal emitter is fabricated with a multilayer structure, in which the dielectric layers are sandwiched between two Ag films. The top Ag film is perforated periodically with holes in a squared array. The thermal radiation of the dielectric layer resonates between two metal films, and surface plasmon polaritons are induced on the top Ag film and then converted to light radiation. Furthermore, if the single dielectric layer is replaced with double layers, then an emission peak that corresponds to the remotely coupled surface plasmon is found in the plasmonic thermal emitter, and the coupling length is less than 500nm.
Photosensitivity of Ge-doped phosphate glass to 244nm irradiation
Authors: Suzuki S. , Schülzgen A. , Sabet S. , Moloney J. V. , Peyghambarian N.
Published: October 2006

UV photosensitivity of Ge-doped phosphate glasses is examined by writing photoinduced gratings in bulk glass samples. Radiation-induced index changes up to ∼3.5×10−5 were obtained by diffraction efficiency measurements of UV written gratings. In contrast to phosphate glasses without intentional doping, no significant photodarkening at visible wavelength was observed in Ge-doped phosphate glasses after UV exposure. The measured index changes demonstrate the potential of Ge-doped phosphate glasses for the fabrication of a fiber Bragg grating, a key component for phosphate-glass-based photonic devices.
Origins of optical anisotropy in artificial atoms
Authors: Sheng Weidong
Published: October 2006

The author report on a theoretical study of optical anisotropy in quantum dots. The mechanisms how shape anisotropy and strain field lead to optical anisotropy are identified by an empirical tight-binding approach. The anisotropic structure of quantum dots is shown to impose stronger confinement for the localized p orbitals aligning along the short axis. In self-assembled quantum dots, these orbitals are also seen in a higher potential produced by the strain field. As a result, the valence-band electrons prefer to occupy the orbitals aligning along the long axis, which leads to stronger optical emission polarized along that direction.
Fitzroy River, Queensland, Australia. II. Identification of Sources of Estuary Bottom Sediments
Authors: Douglas G. B. , Ford P. W. , Palmer M. , Noble R. M. , Packett R.
Published: October 2006

Environmental Context. The Fitzroy River Basin constitutes a major source of suspended sediment and nutrient fluxes to the southern Great Barrier Reef. Improved land management practices to ameliorate these catchment loads require an understanding of the sediment sources and dynamics. This multidisciplinary geochemical and modelling study provides for the first time a quantitative estimate of sediment sources delivered to, and their degree of retention in, the Fitzroy River Estuary.
Abstract. Sources of sediment deposited in the Fitzroy River Estuary (FRE) have been identified and quantified using an integrated geochemical, modelling and reconnaissance soil sampling approach. A companion paper (this volume) identifies the major sources of sediments in impoundments on the major river systems and sediment sampled from flood events in the Fitzroy River Basin (FRB). Sediment within the FRE may display distinct longitudinal variation with little basaltic material retained. Sediments derived from the Bowen Basin, which occupies the greatest portion of the FRB, and from the Surat Basin display the greatest longitudinal variation. All FRB soils have a similar total phosphorus (P) concentration. Thus, in considering P export from the catchment it is the total sediment flux which is of major importance, rather than the relative proportions of individual catchment soils. This research provides crucial new regional scale information on the sediment sources deposited within the FRE.
Mechanisms of Boron Removal with Electrocoagulation
Authors: Jiang Jia-Qian , Xu Y. , Quill K. , Simon J. , Shettle K.
Published: October 2006

Environmental Context. Various environmental regulation organizations have set up standards or guidelines to regulate the boron concentration in drinking water, as a result of concern for human and animal health. In 2004, the World Health Organization Guidelines for Drinking Water Quality recommended boron values of no more than 0.5 mg L–1 in drinking water. Preliminary studies on boron removal with electrocoagulation have been carried out. However, in order to enhance boron removal using this method, and to meet the stringent guidelines set in place by the World Health Organization, there is a need to obtain a better understanding of how boron is removed from water by electrocoagulation.
Abstract. This study aims to explore the mechanisms of boron removal by electrocoagulation (EC). The results demonstrate that adsorption and precipitation of boron by Al flocs are dominant mechanisms in boron removal using EC. The Al flocs that result from the EC process are found to be mainly composed of polymeric Al13 polymers (43%) and to have a long-lasting positive charge. These characteristics of the flocs contribute to the high levels of boron removal observed using EC. The maximum boron adsorption of the Al flocs is 200 mg g–1 and the solubility product constant (Ksp), which represents the boron precipitate Al(OH)2BO2·nH2O, is 2.6 × 10−40 (at 20°C).
Iodine Excretion and Accumulation in Seaweed-Eating Sheep from Orkney, Scotland
Authors: Lu Ying , Suliman Sazia , Hansen Helle R. , Feldmann Jörg
Published: October 2006

Environmental Context. Iodine is an essential element of mammals and iodine deficiency of mammals has been recorded in more than 100 countries worldwide. Additionally, radioactive iodine is a major threat from nuclear fallout and so-called ‘dirty bombs’. Iodine supplementation is able to counteract deficiency and to reduce the potential for uptake of radioactive iodine. Seaweed, one of the best natural sources of iodine, has often been advocated for use as feed for livestock in order to increase the iodine concentration of our diets. The danger of excess iodine, however, has not been studied extensively. Here we investigate the bioavailability of iodine from brown kelps (Laminaria digitata and Laminaria hyperborea) and the adaptation of sheep to excess iodine intake.
Abstract. Iodine concentrations in tissue and urine samples of 11 seaweed-eating sheep from North Ronaldsay in Orkney, Scotland, were measured during a feeding experiment. Two groups of six sheep (control was kept on grass five months before experiment, while the trial group were caught at the beach) each ate 0.5 ± 0.1 kg dry mass of seaweed (Laminaria digitata and Laminaria hyperborea) each day in an 11-day feeding trial and had a body burden of around 2300 mg iodine daily, almost entirely as iodide. This iodine intake of 124 mg I kg bodyweight–1 is more than 60 000 times higher than the recommended daily intake for humans. The iodine concentration in the urine within 4 h after the seaweed meal was 1295 ± 369 mg I kg–1. Thus, more than 66% of the total iodine ingested by the sheep was excreted within 24 h. The iodine excretion of the control group was slightly slower (T1/2 = 15.9 ± 7.2 h) than that of the trial group (T1/2 = 9.1 ± 1.6 h). In the same experiment, the excretion of iodine was faster than that of arsenic (T1/2 = 24.3 h). Tissue samples from feral North Ronaldsay sheep taken directly from the beach showed elevated iodine levels (liver: 2710 ± 505 μg I kg–1 > kidney: 1827 ± 618 μg I kg–1 > neck muscles: 404 ± 117 μg I kg–1 based on fresh weight), pointing to insufficient homeostatic control of iodine uptake, so that iodine concentrations were 17 times higher than those of non-exposed sheep. A trend of continuous accumulation of iodine in the liver and kidney throughout the life of the sheep was observed. In contrast to arsenic, iodine was higher in the liver and kidney than in the muscle.
Cognitive enhancement with central thalamic electrical stimulation
Authors: Shirvalkar Prasad , Seth Malika , Schiff Nicholas D. , Herrera Daniel G.
Published: October 2006

Central thalamic electrical stimulation has been proposed as a method for remediation of acquired cognitive disability. Long-standing experimental and clinical observations indicate a key role for neurons within the central thalamus in maintaining the alert waking state and facilitating attended behaviors. Here, we show that continuous high frequency (100 Hz) electrical stimulation of the central thalamus generates widespread cortical activation of
c-fos
across all cortical layers and a selective pattern of regulation of
zif268
within the supragranular, granular, and infragranular cortical laminae. Significant elevation of both immediate early genes also is seen in the dentate gyrus of the hippocampus. Use of the same stimulation parameters is shown to facilitate untrained goal-directed seeking behavior and object recognition memory in rodents. An overall increase of exploratory motor behaviors and grooming activity also is observed, consistent with a global increase in arousal. Taken together, these studies indicate that electrical stimulation of the central thalamus may enhance cognitive performance through neocortical and hippocampal neuronal activation and specific regulation of gene expression.
Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland
Authors: Mussi Paola , Liao Lan , Park Seong-Eun , Ciana Paolo , Maggi Adriana , Katzenellenbogen Benita S. , Xu Jianming , O'Malley Bert W.
Published: October 2006

Estrogen receptor (ER)-mediated gene expression plays an essential role in mammary gland morphogenesis, function, and carcinogenesis. The repressor of ER activity (REA) is an ER-interactive protein that counterbalances estrogen-induced ER transcriptional activity. Our previous study showed that genetic deletion of both REA alleles resulted in embryonic lethality. This study demonstrates that REA and ERα are coexpressed in mammary epithelial cells. REA heterozygous (REA
+/−
) mutant mice exhibit faster mammary ductal elongation in virgin animals, increased lobuloalveolar development during pregnancy, and delayed mammary gland involution after weaning. These morphological phenotypes of REA
+/−
mice are associated with significantly increased cell proliferation and ER transcriptional activities, as indicated by the estrogen response element (ERE)-luciferase reporter in the WT/ERE-Luc and REA
+/−
/ERE-Luc bigenic mice and by the higher expression levels of estrogen-responsive genes such as progesterone receptor and cyclin D1 in the mammary gland. Our analysis also revealed that REA is an important repressor of ER transcriptional activity in the mammary gland under natural, as well as ovariectomized and estrogen-replaced, hormonal conditions. Our results indicate that REA is a physiological modulator of ER function in the mammary gland and that its correct gene dosage is required for maintenance of normal ER activity and normal mammary gland development. Consequently, a reduction or loss of REA function may cause overactivation of ER and increase breast cancer risk in humans.
Confirmation of Romer's Gap as a low oxygen interval constraining the timing of initial arthropod and vertebrate terrestrialization
Authors: Ward Peter , Labandeira Conrad , Laurin Michel , Berner Robert A.
Published: October 2006

The first terrestrialization of species that evolved from previously aquatic taxa was a seminal event in evolutionary history. For vertebrates, one of the most important terrestrialized groups, this event was interrupted by a time interval known as Romer's Gap, for which, until recently, few fossils were known. Here, we argue that geochronologic range data of terrestrial arthropods show a pattern similar to that of vertebrates. Thus, Romer's Gap is real, occupied an interval from 360 million years before present (MYBP) to 345 MYBP, and occurred when environmental conditions were unfavorable for air-breathing, terrestrial animals. These model results suggest that atmospheric oxygen levels were the major driver of successful terrestrialization, and a low-oxygen interval accounts for Romer's Gap. Results also show that terrestrialization among members of arthropod and vertebrate clades occurred in two distinct phases. The first phase was a 65-million-year (My) interval from 425 to 360 MYBP, representing an earlier, prolonged event of complete arthropod terrestrialization of smaller-sized forms (425–385 MYBP) and a subsequent, modest, and briefer event of incipient terrestrialization of larger-sized, aquatic vertebrates (385–360 MYBP). The second phase began at 345 MYBP, characterized by numerous new terrestrial species emerging in both major clades. The first and second terrestrialization phases bracket Romer's Gap, which represents a depauperate spectrum of major arthropod and vertebrate taxa before a major Late Paleozoic colonization of terrestrial habitats.
Increased melanizing activity in
Anopheles gambiae
does not affect development of
Plasmodium falciparum
Authors: Michel Kristin , Suwanchaichinda Chansak , Morlais Isabelle , Lambrechts Louis , Cohuet Anna , Awono-Ambene Parfait H. , Simard Frederic , Fontenille Didier , Kanost Michael R. , Kafatos Fotis C.
Published: October 2006

Serpins are central to the modulation of various innate immune responses in insects and are suspected to influence the outcome of malaria parasite infection in mosquito vectors. Three
Anopheles gambiae
serpins (SRPN1, -2, and -3) were tested for their ability to inhibit the prophenoloxidase cascade, a key regulatory process in the melanization response. Recombinant SRPN1 and -2 can bind and inhibit a heterologous phenoloxidase-activating protease and inhibit phenoloxidase activation
in vitro
. Using a reverse genetics approach, we studied the effect of SRPN2 on melanization in
An. gambiae
adult females
in vivo
. Depletion of SRPN2 from the mosquito hemolymph increases melanin deposition on foreign surfaces such as negatively charged Sephadex beads. As reported, the knockdown of SRPN2 adversely affects the ability of the rodent malaria parasite
Plasmodium berghei
to invade the midgut epithelium and develop into oocysts. Importantly, we tested whether the absence of SRPN2 from the hemolymph influences
Plasmodium falciparum
development. RNAi silencing of
SRPN2
in an
An. gambiae
strain originally established from local populations in Yaoundé, Cameroon, did not influence the development of autochthonous field isolates of
P. falciparum
. This study suggests immune evasion strategies of the human malaria parasite and emphasizes the need to study mosquito innate immune responses toward the pathogens they transmit in natural vector–parasite combinations.
Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells
Authors: Kamada Kazuya , Igarashi Tatsuhiko , Martin Malcolm A. , Khamsri Boonruang , Hatcho Kazuki , Yamashita Tomoki , Fujita Mikako , Uchiyama Tsuneo , Adachi Akio
Published: October 2006

The narrow host range of human immunodeficiency virus type 1 (HIV-1) is caused in part by innate cellular factors such as apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) and TRIM5α, which restrict virus replication in monkey cells. Variant HIV-1 molecular clones containing both a 21-nucleotide simian immunodeficiency virus (SIV) Gag CA element, corresponding to the HIV-1 cyclophilin A-binding site, and the entire SIV
vif
gene were constructed. Long-term passage in a cynomolgus monkey lymphoid cell line resulted in the acquisition of two nonsynonymous changes in
env
, which conferred improved replication properties. A proviral molecular clone, derived from infected cells and designated NL-DT5R, was used to generate virus stocks capable of establishing spreading infections in the cynomolgus monkey T cell line and CD8-depleted peripheral blood mononuclear cells from five of five pig-tailed macaques and one of three rhesus monkeys. NL-DT5R, which genetically is >93% HIV-1, provides the opportunity, not possible with currently available SIV/HIV chimeric viruses, to analyze the function of multiple HIV-1 genes in a broad range of nonhuman primate species.
The Cytoplasmic Hsp70 Chaperone Machinery Subjects Misfolded and Endoplasmic Reticulum Import-incompetent Proteins to Degradation via the Ubiquitin–Proteasome System
Authors: Park Sae-Hun , Bolender Natalia , Eisele Frederik , Kostova Zlatka , Takeuchi Junko , Coffino Philip , Wolf Dieter H.
Published: October 2006

The mechanism of protein quality control and elimination of misfolded proteins in the cytoplasm is poorly understood. We studied the involvement of cytoplasmic factors required for degradation of two endoplasmic reticulum (ER)-import–defective mutated derivatives of carboxypeptidase yscY (ΔssCPY* and ΔssCPY*-GFP) and also examined the requirements for degradation of the corresponding wild-type enzyme made ER-import incompetent by removal of its signal sequence (ΔssCPY). All these protein species are rapidly degraded via the ubiquitin–proteasome system. Degradation requires the ubiquitin-conjugating enzymes Ubc4p and Ubc5p, the cytoplasmic Hsp70 Ssa chaperone machinery, and the Hsp70 cochaperone Ydj1p. Neither the Hsp90 chaperones nor Hsp104 or the small heat-shock proteins Hsp26 and Hsp42 are involved in the degradation process. Elimination of a GFP fusion (GFP-cODC), containing the C-terminal 37 amino acids of ornithine decarboxylase (cODC) directing this enzyme to the proteasome, is independent of Ssa1p function. Fusion of ΔssCPY* to GFP-cODC to form ΔssCPY*-GFP-cODC reimposes a dependency on the Ssa1p chaperone for degradation. Evidently, the misfolded protein domain dictates the route of protein elimination. These data and our further results give evidence that the Ssa1p-Ydj1p machinery recognizes misfolded protein domains, keeps misfolded proteins soluble, solubilizes precipitated protein material, and escorts and delivers misfolded proteins in the ubiquitinated state to the proteasome for degradation.
Essential Role of Chromatin Assembly Factor-1–mediated Rapid Nucleosome Assembly for DNA Replication and Cell Division in Vertebrate Cells
Authors: Takami Yasunari , Ono Tatsuya , Fukagawa Tatsuo , Shibahara Kei-ichi , Nakayama Tatsuo
Published: October 2006

Chromatin assembly factor-1 (CAF-1), a complex consisting of p150, p60, and p48 subunits, is highly conserved from yeast to humans and facilitates nucleosome assembly of newly replicated DNA in vitro. To investigate roles of CAF-1 in vertebrates, we generated two conditional DT40 mutants, respectively, devoid of CAF-1p150 and p60. Depletion of each of these CAF-1 subunits led to delayed S-phase progression concomitant with slow DNA synthesis, followed by accumulation in late S/G2 phase and aberrant mitosis associated with extra centrosomes, and then the final consequence was cell death. We demonstrated that CAF-1 is necessary for rapid nucleosome formation during DNA replication in vivo as well as in vitro. Loss of CAF-1 was not associated with the apparent induction of phosphorylations of S-checkpoint kinases Chk1 and Chk2. To elucidate the precise role of domain(s) in CAF-1p150, functional dissection analyses including rescue assays were preformed. Results showed that the binding abilities of CAF-1p150 with CAF-1p60 and DNA polymerase sliding clamp proliferating cell nuclear antigen (PCNA) but not with heterochromatin protein HP1-γ are required for cell viability. These observations highlighted the essential role of CAF-1–dependent nucleosome assembly in DNA replication and cell proliferation through its interaction with PCNA.
NPFXD-mediated Endocytosis Is Required for Polarity and Function of a Yeast Cell Wall Stress Sensor
Authors: Piao Hai Lan , Machado Iara M.P. , Payne Gregory S.
Published: October 2006

The actin-associated protein Sla1p, through its SHD1 domain, acts as an adaptor for the NPFX(1,2)D endocytic targeting signal in yeast. Here we report that Wsc1p, a cell wall stress sensor, depends on this signal-adaptor pair for endocytosis. Mutation of NPFDD in Wsc1p or expression of Sla1p lacking SHD1 blocked Wsc1p internalization. By live cell imaging, endocytically defective Wsc1p was not concentrated at sites of endocytosis. Polarized distribution of Wsc1p to regions of cell growth was lost in the absence of endocytosis. Mutations in genes necessary for endosome to Golgi traffic caused redistribution of Wsc1p from the cell surface to internal compartments, indicative of recycling. Inhibition of Wsc1p endocytosis caused defects in polarized deposition of the cell wall and increased sensitivity to perturbation of cell wall synthesis. Our results reveal that the NPFX(1,2)D-Sla1p system is responsible for directing Wsc1p into an endocytosis and recycling pathway necessary to maintain yeast cell wall polarity. The dynamic localization of Wsc1p, a sensor of the extracellular wall in yeast, resembles polarized distribution of certain extracellular matrix-sensing integrins through endocytic recycling.
The NHR1 Domain of Neuralized Binds Delta and Mediates Delta Trafficking and Notch Signaling
Authors: Commisso Cosimo , Boulianne Gabrielle L.
Published: October 2006

Notch signaling, which is crucial to metazoan development, requires endocytosis of Notch ligands, such as Delta and Serrate. Neuralized is a plasma membrane-associated ubiquitin ligase that is required for neural development and Delta internalization. Neuralized is comprised of three domains that include a C-terminal RING domain and two neuralized homology repeat (NHR) domains. All three domains are conserved between organisms, suggesting that these regions of Neuralized are functionally important. Although the Neuralized RING domain has been shown to be required for Delta ubiquitination, the function of the NHR domains remains elusive. Here we show that neuralized1, a well-characterized neurogenic allele, exhibits a mutation in a conserved residue of the NHR1 domain that results in mislocalization of Neuralized and defects in Delta binding and internalization. Furthermore, we describe a novel isoform of Neuralized and show that it is recruited to the plasma membrane by Delta and that this is mediated by the NHR1 domain. Finally, we show that the NHR1 domain of Neuralized is both necessary and sufficient to bind Delta. Altogether, our data demonstrate that NHR domains can function in facilitating protein–protein interactions and in the case of Neuralized, mediate binding to its ubiquitination target, Delta.
Endobrevin/VAMP-8 Is the Primary v-SNARE for the Platelet Release Reaction
Authors: Ren Qiansheng , Barber Holly Kalani , Crawford Garland L. , Karim Zubair A. , Zhao Chunxia , Choi Wangsun , Wang Cheng-Chun , Hong Wanjin , Whiteheart Sidney W.
Published: October 2006

Platelet secretion is critical to hemostasis. Release of granular cargo is mediated by soluble NSF attachment protein receptors (SNAREs), but despite consensus on t-SNAREs usage, it is unclear which Vesicle Associated Membrane Protein (VAMPs: synaptobrevin/VAMP-2, cellubrevin/VAMP-3, TI-VAMP/VAMP-7, and endobrevin/VAMP-8) is required. We demonstrate that VAMP-8 is required for release from dense core granules, alpha granules, and lysosomes. Platelets from VAMP-8−/−mice have a significant defect in agonist-induced secretion, though signaling, morphology, and cargo levels appear normal. In contrast, VAMP-2+/−, VAMP-3−/−, and VAMP-2+/−/VAMP-3−/−platelets showed no defect. Consistently, tetanus toxin had no effect on secretion from permeabilized mouse VAMP-3−/−platelets or human platelets, despite cleavage of VAMP-2 and/or -3. Tetanus toxin does block the residual release from permeabilized VAMP-8−/−platelets, suggesting a secondary role for VAMP-2 and/or -3. These data imply a ranked redundancy of v-SNARE usage in platelets and suggest that VAMP-8−/−mice will be a useful in vivo model to study platelet exocytosis in hemostasis and vascular inflammation.
Hypothesis testing approaches to the exon prediction problem
Authors: Vilardell Mireia , Sánchez-Pla Alex
Published: October 2006

Motivation: Many gene identification methods assign scores to gene elements prior to their assembly into predicted genes. The scoring system is often based on log-likelihood ratios. These methods usually perform well but it is difficult to interpret how significant a score is.

Results: We have developed several tests of significance for the scores: (1) a sum-of-scores test (SST), (2) an intersection-union test (IUT), based on a multiple hypothesis testing interpretation of an exon's score and (3) a meta-analytical approach (MA), which combines several P-values, corresponding to the exon's parts, to yield a global P-value. We performed simulation studies, which show that the MA has better sensitivity and specificity than other methods and is easier to interpret by non-expert users. This is an improvement over other methods and is especially relevant for users who would like to predict incomplete gene sequences.

Contact:  asanchez@ub.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Kalman filtering for disease-state estimation from microarray data
Authors: Kelemen János Z. , Kertész-Farkas Attila , Kocsor András , Puskás László G.
Published: October 2006

Motivation: In this paper, we propose using the Kalman filter (KF) as a pre-processing step in microarray-based molecular diagnosis. Incorporating the expression covariance between genes is important in such classification problems, since this represents the functional relationships that govern tissue state. Failing to fulfil such requirements may result in biologically implausible class prediction models. Here, we show that employing the KF to remove noise (while retaining meaningful covariance and thus being able to estimate the underlying biological state from microarray measurements) yields linearly separable data suitable for most classification algorithms.

Results: We demonstrate the utility and performance of the KF as a robust disease-state estimator on publicly available binary and multi-class microarray datasets in combination with the most widely used classification methods to date. Moreover, using popular graphical representation schemes we show that our filtered datasets also have an improved visualization capability.

Contact:  kelli@nucleus.szbk.u-szeged.hu.

Supplementary information:
The nicotinic acetylcholine receptor gene family of the honey bee, Apis mellifera
Authors: Jones Andrew K. , Raymond-Delpech Valerie , Thany Steeve H. , Gauthier Monique , Sattelle David B.
Published: October 2006

Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission and play roles in many cognitive processes. They are under intense research as potential targets of drugs used to treat neurodegenerative diseases and neurological disorders such as Alzheimer's disease and schizophrenia. Invertebrate nAChRs are targets of anthelmintics as well as a major group of insecticides, the neonicotinoids. The honey bee, Apis mellifera, is one of the most beneficial insects worldwide, playing an important role in crop pollination, and is also a valuable model system for studies on social interaction, sensory processing, learning, and memory. We have used the A. mellifera genome information to characterize the complete honey bee nAChR gene family. Comparison with the fruit fly Drosophila melanogaster and the malaria mosquito Anopheles gambiae shows that the honey bee possesses the largest family of insect nAChR subunits to date (11 members). As with Drosophila and Anopheles, alternative splicing of conserved exons increases receptor diversity. Also, we show that in one honey bee nAChR subunit, six adenosine residues are targeted for RNA A-to-I editing, two of which are evolutionarily conserved in Drosophila melanogaster and Heliothis virescens orthologs, and that the extent of editing increases as the honey bee lifecycle progresses, serving to maximize receptor diversity at the adult stage. These findings on Apis mellifera enhance our understanding of nAChR functional genomics and provide a useful basis for the development of improved insecticides that spare a major beneficial insect species.
Canonical TTAGG-repeat telomeres and telomerase in the honey bee, Apis mellifera
Authors: Robertson Hugh M. , Gordon Karl H.J.
Published: October 2006

The draft assembly of the honey bee Apis mellifera genome sequence reveals that the 17 centromeric-distal telomeres are of a simple, shared, and canonical structure, with 3–4 kb of a unique subtelomeric sequence, followed by several kilobases of TTAGG or variant telomeric repeats. This simple subtelomeric structure differs from the centromeric-proximal telomeres on the short arms of the 15 acrocentric chromosomes, which are apparently composed primarily of the 176-bp AluI tandem repeat. This dichotomy between the distal and proximal telomeres may involve differential participation of the telomeres of the 15 acrocentric chromosomes in the Rabl configuration after mitosis and the chromosome bouquet in meiotic prophase I. As expected from the presence of canonical TTAGG telomeric repeats, we identified a candidate telomerase gene in the bee, as well as the silkmoth Bombyx mori and the flour beetle Tribolium castaneum.
Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock
Authors: Rubin Elad B. , Shemesh Yair , Cohen Mira , Elgavish Sharona , Robertson Hugh M. , Bloch Guy
Published: October 2006

The circadian clock of the honey bee is implicated in ecologically relevant complex behaviors. These include time sensing, time-compensated sun-compass navigation, and social behaviors such as coordination of activity, dance language communication, and division of labor. The molecular underpinnings of the bee circadian clock are largely unknown. We show that clock gene structure and expression pattern in the honey bee are more similar to the mouse than to Drosophila. The honey bee genome does not encode an ortholog of Drosophila Timeless (Tim1), has only the mammalian type Cryptochrome (Cry-m), and has a single ortholog for each of the other canonical “clock genes.” In foragers that typically have strong circadian rhythms, brain mRNA levels of amCry, but not amTim as in Drosophila, consistently oscillate with strong amplitude and a phase similar to amPeriod (amPer) under both light-dark and constant darkness illumination regimes. In contrast to Drosophila, the honey bee amCYC protein contains a transactivation domain and its brain transcript levels oscillate at virtually an anti-phase to amPer, as it does in the mouse. Phylogenetic analyses indicate that the basal insect lineage had both the mammalian and Drosophila types of Cry and Tim. Our results suggest that during evolution, Drosophila diverged from the ancestral insect clock and specialized in using a set of clock gene orthologs that was lost by both mammals and bees, which in turn converged and specialized in the other set. These findings illustrate a previously unappreciated diversity of insect clockwork and raise critical questions concerning the evolution and functional significance of species-specific variation in molecular clockwork.
Assessing families and other client systems in community‐based programmes: development of the CALF
Authors: Leon Ana M. , Armantrout Elizabeth Marie
Published: October 2006

Programmes providing services to children and families often face the challenge of assessing not only the child referred, but also the child’s family system and its individual members. Recognizing that household/family members can cause, contribute to or affect a child’s problems requires that human service agencies utilize assessment tools capable of assessing family members across the lifespan. The literature references many assessment tools used by clinical programmes in mental‐health settings that are not well suited to use in social service agencies with multidisciplinary staff at different skill levels. As a response to this dilemma, the authors have developed the Collaborative Assessment of Life Functioning (CALF), a user‐friendly tool that assesses various areas of life functioning. Based on Maslow’s motivation theory, person‐in‐environment and systems theories, the CALF can be used with various client systems. This paper describes the development of the tool, its purpose and use, the importance of assessment tools in the helping process and considerations for agencies wishing to use an assessment tool like the CALF. The authors also discuss the applicability of the CALF in human services and social service agency settings and with diverse client populations.
Young people’s satisfaction of transitional care in adolescent rheumatology in the UK
Authors: Shaw K. L. , Southwood T. R. , McDonagh J. E. ,   the British Society of Paediatric and Adolescent Rheumatology
Published: October 2006

Background To examine the quality of transitional health care from the perspectives of young people with juvenile idiopathic arthritis (JIA) and their parents.

Methods Adolescents with JIA and their parents were recruited from 10 major UK rheumatology centres. Satisfaction with health‐care delivery was measured prior to, and 12 months after, the implementation of a structured and co‐ordinated programme of transitional care using self‐completed questionnaires designed for this study.

Results Of 359 families invited to participate, 308 (86%) adolescents with JIA and 303 (84%) parents/guardians accepted. A fifth of adolescents had persistent oligoarthritis. Median age was 14.2 (11–18) years with median disease duration of 5.7 (0–16) years. Young people and their parents rated provider characteristics more important than aspects of the physical environment or process issues. Staff honesty and knowledge were rated as the most essential aspects of best practice. Prior to implementing the programme of transitional care, parents rated service delivery for all items significantly worse than best practice. Overall satisfaction improved 12 months after entering the programme. However, while parent satisfaction improved for 70.4% of items, significant improvements were only observed for three (13.6%) items rated by adolescents.

Conclusion The perceived quality of health care for young people with JIA and their parents was significantly lower than what they would like. Satisfaction with many aspects of care during transition from paediatric to adult services can be improved through the implementation of a structured, co‐ordinated programme of transitional care.
Development and preliminary validation of the ‘Mind the Gap’ scale to assess satisfaction with transitional health care among adolescents with juvenile idiopathic arthritis
Authors: Shaw K. L. , Southwood T. R. , McDonagh J. E. ,   the British Society of Paediatric and Adolescent Rheumatology
Published: October 2006

Background  To develop a scale to assess satisfaction with transitional health care among adolescents with a chronic illness and their parents.

Methods  The ‘Mind the Gap’ scale was developed using evidence from a previous needs assessment, in three stages: (1) definition of the construct; (2) design of the scale items, response options and instructions; (3) full administration of the scale, item analysis and dimensionality analysis. The scale was administered to 308 adolescents with juvenile idiopathic arthritis (JIA) and 303 parents/guardians, prior to and 12 months after the implementation of an evaluation of a structured and co‐ordinated programme of transitional care. The patient population involved adolescents with JIA and their parents recruited from 10 major UK rheumatology centres.

Results  A total of 301 (97.7%) adolescents and 286 (95.0%) parents chose to complete the questionnaire, with median item completion rates of 100.0% (0–100%) for both adolescents and parents thus confirming feasibility. Face and content validity were confirmed. Factor analyses revealed a three‐factor structure which explained 49.5% and 56.1% of the variation in adolescent and parent scores respectively. The internal consistency of each subscale (‘management of environment’, ‘provider characteristics’ and ‘process issues’) was indicated by Cronbach’s alphas of 0.71, 0.89 and 0.89 for adolescents, respectively, and 0.83, 0.91 and 0.92 for parents respectively. Cronbach’s alphas for the entire scales were 0.91 and 0.94 for the adolescent and parent forms respectively.

Conclusion  These preliminary results report the potential of the ‘Mind the Gap’ scale in evaluating transitional care for adolescents with JIA. In view of the generic nature of transitional care reflected in the scale, this scale has wider potential for use with adolescents with other chronic illness in view of the generic nature of transition. This development is particularly timely in the context of transitional care developments in the UK and further validation of the scale is in progress.
Coping styles, psychological functioning and quality of life in children with asthma
Authors: Marsac M. L. , Funk J. B. , Nelson L.
Published: October 2006

Background  Previous research suggests that children dealing with the asthma are at a greater risk for experiencing psychological maladjustment than children without asthma. Research also suggests that coping is a factor in psychological adaptation to chronic stressors such as physical illnesses. The question as to how coping relates to psychological functioning and quality of life in the paediatric asthma population has not yet been answered. The objective of the current study was to examine the relationships among coping, psychological functioning and quality of life in children diagnosed with asthma and to investigate the relationship that mothers’ quality of life has with these variables.

Methods  Forty‐seven youths (aged 8–15 years) diagnosed with asthma completed measures of coping with asthma and quality of life. Each youth’s mother completed measures of her child’s coping, psychological functioning and her own quality of life.

Results  Mothers and children with asthma both reported that children used significantly more approach coping than avoidant coping when dealing with asthma. Three regression analyses indicated that avoidant coping negatively predicted psychological functioning, child’s quality of life and mother’s quality of life. Bivariate analyses also indicated a positive relationship between child’s quality of life and mother’s quality of life.

Conclusions  Results indicate that, in children with asthma, coping style plays an important role in the child’s psychological functioning and quality of life and mother’s quality of life. Therefore, it is recommended that type of coping be assessed when developing comprehensive treatment plans for children with asthma. Further research is needed to determine the efficacy of focused coping interventions in improving quality of life and psychological functioning in children with asthma.
Stability and change in children with Developmental Coordination Disorder
Authors: Sugden D. A. , Chambers M. E.
Published: October 2006

Background  Children with Developmental Coordination Disorder (DCD) are a heterogeneous group who have a marked impairment in the performance of functional motor skills. Provision for these children is usually made via a paediatrician through occupational or physiotherapy; though with a prevalence rate of 5%, regular provision is rarely possible because of limited professional resources.

Methods  This study covers a period of nearly 4 years and initially examined a group of 31 children first identified as having DCD at 7–9 years of age. The children were observed and assessed before, during and after a total of 16 weeks of intervention carried out by parents and teachers. This was followed by a period of monitoring of performance for 26 of the children in the motor domain plus other abilities such as educational progress and self‐concept. Individual children were tracked using a variety of qualitative and quantitative approaches, building up longitudinal whole child profiles.

Results  Following intervention, 14 of the 26 children have shown improvement and stability in all areas and no longer display DCD symptoms. Eight children have profiles which have shown variability, with the children moving in and out of the DCD classification, while the remaining four children have consistently scored poorly in their movement skills and in addition received ongoing support in school for academic subjects.

Conclusions  The study has confirmed that children with DCD show varying profiles over a period of time and that the profiles have distinct characteristics related to events in the child’s life. This approach to examining stability and change in the progressions of children’s difficulties is in keeping with an ecological approach to explaining development with its multilayered influences creating changes.
Histopathological features of breast cancer in carriers of ATM gene variants
Authors: Balleine R L , Murali R , Bilous A M , Farshid G , Waring P , Provan P , Byth K , Thorne H ,   kConFab Investigators, Kirk J A
Published: October 2006

Aims:  Germline variants in the ataxia telangiectasia mutated (ATM) gene have been implicated in increased breast cancer risk. The aim of this study was to determine whether the histopathology of breast cancers occurring in ATM variant carriers is distinctive or resembles the described BRCA1 mutation‐associated phenotype.

Methods:  The histopathological features of breast cancers occurring in ATM variant carriers from multiple‐case breast cancer families were compared with matched controls. The test group included 21 cases of in situ and/or invasive cancer from carriers of either the IVS10‐6T→G, 2424V→G or 1420L→F ATM variants in the absence of BRCA1 or BRCA2 mutations. An additional four invasive cancers from carriers of a pathogenic BRCA1 mutation in the context of a familial ATM variant were also examined.

Results:  The histopathology of breast cancers in ATM variant‐only carriers was not significantly different from controls and known features of BRCA1 mutation‐associated cancer were rarely seen. In contrast, these features were prominent in the small group of cases with a pathogenic BRCA1 mutation.

Conclusions:  Breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features and does not resemble the tumour phenotype commonly observed in BRCA1 mutation carriers.