bluuebunny/crossref_metadata_2025 huggingface dataset:
Symposium 4: Dynamics of the Neuronal Cytoskeleton. Actin‐based vesicle transport in nerve cell extracts: implications for neurodegenerative diseases
Authors: Langford G. M. , Brown J. R. , Simonetta K. R. , Stafford P.
Published: July 2010

Neurodegenerative diseases may result in part from defects in motor‐driven vesicle transport in neuronal cells. Myosin‐V, an actin‐based motor that is highly enriched in the brain, mediates the movement of vesicles on cortical actin filaments. Recent evidence suggests that the globular tail of myosin‐V interacts with the microtubule‐based motor, kinesin, to form a ‘hetero‐motor’ complex on vesicles. The complex of these two motors, one microtubule‐based and the other actin‐based, facilitates the movement of vesicles from microtubules to actin filaments. Based on our studies of vesicle transport by these two motors in extracts of squid neurons, we hypothesize that one of the functions of the tail–tail interaction is to provide feedback between the two proteins to allow seamless transition of vesicles from microtubules to actin filaments. To study the interactions of the globular tail domain of myosin‐V to kinesin and to neuronal vesicles, we used a GST‐tagged globular tail fragment in motility assays. The MyoV tail fragment inhibited vesicle transport by 81–91% and thereby exhibited a dominant negative effect. These data show that the recombinant protein blocked the activity of native myosin‐V presumably by binding to vesicles and competing away the native myosin‐V motors. The GST‐MyoV‐tail fragment pulled down kinesin by immunoprecipitation from squid brain homogenates and therefore it exhibited binding properties of native myosin‐V. These data show that the headless myosin‐V fragment is an effective inhibitor of vesicle transport in cell extracts. These studies support the hypothesis that tail–tail interactions may be a mechanism for feedback between myosin‐V and kinesin to allow transition of vesicles from microtubules to actin filaments. Acknowledgements: Supported by NSF grant MCB9974709.
Life without gangliosides
Authors: Proia R. L.
Published: July 2010

Gangliosides are sialic acid containing glycosphingolipids that are present on all plasma cell membranes. Although they represent the major sialoconjugates in the central nervous system, their precise functions remain obscure. We have generated a series of knockout mice with gene disruptions in the ganglioside biosynthetic pathway. Individually these mice lack subsets of gangliosides allowing investigations into their specific functions. By breeding mice to contain multiple mutations in the biosynthetic pathway we have now produced mice without neuronal gangliosides. These mice display an extremely severe phenotype and neuronal pathology highlighting the essential function of gangliosides in the central nervous system.
Apolipoprotein E modulates the CNS response to injury
Authors: Laskowitz D. T. , Lynch J. R. , Warner D. S. , Pineda J.
Published: July 2010

Apolipoprotein E (apoE) plays an important role in recovery from acute brain injury. One potential mechanism for this is that apoE down‐regulates glial activation and subsequent secretion of inflammatory mediators. Following a pneumatic impact to the closed skull of anesthetized apoE deficient and wildtype mice, MRI was performed to quantify the effacement of the lateral ventricles as a radiographic surrogate for cerebral edema. At 24 hours following injury, apoE deficient animals had a greater degree of cerebral edema as compared to matched controls. This increase in edema was associated with enhanced up‐regulation of TNFα, a pro‐inflammatory cytokine believed to play an important role in mediating blood–brain barrier breakdown and the development of cerebral edema. We have previously demonstrated that a peptide derived from the receptor binding region of apoE retained the anti‐inflammatory activities of the holoprotein in vitro, and we next investigated whether a single intravenous administration of this apoE‐mimetic peptide could exert neuroprotective effects. Thirty minutes after closed head injury, mice were randomized to receive low dose peptide (203 mg/kg); high dose peptide (406 mg/kg), or vehicle. At 24 h post injury, the saline injected animals had a profound deficit in rotorod testing which was associated with weight loss. A single intravenous injection of apoE‐mimetic peptide 30 min following closed head injury protected against motor deficit, weight loss, and neurocognitive deficit in a dose dependent fashion. This suggests that apoE may modify prognosis in brain injury by down‐regulating the CNS inflammatory response, and that mimicking the biological activity of apoE may lead to novel therapeutic strategies in the setting.
Four level, atomic Cs laser at 852.1 nm with a quantum efficiency above 98%: Observation of three body photoassociation
Authors: Readle J. D. , Eden J. G. , Verdeyen J. T. , Carroll D. L.
Published: July 2010

Lasing on the D2 (6p P23/2→6s S21/2) transition of atomic Cs at 852.1 nm has been observed with a four level system in which the Cs 6p P23/2 state is pumped by the photoassociation and subsequent dissociation of Cs-rare gas collision pairs. Characterized by a quantum efficiency >98%, this laser requires no atomic precursor to the upper laser level and provides oscillation on an alkali transition inaccessible to three level, photopumped alkali laser systems. Measurements of photoabsorption and pump energy threshold in Cs–Ar–Kr mixtures reveal the influence of three body photoassociation.
A new accurate and full dimensional potential energy surface of H5+ based on a triatomics-in-molecules analytic functional form
Authors: Aguado A. , Barragán P. , Prosmiti R. , Delgado-Barrio G. , Villarreal P. , Roncero O.
Published: July 2010

In this work a reliable full nine-dimensional potential energy surface for studying the dynamics of H5+ is constructed, which is completely symmetric under any permutation of the nuclei. For this purpose, we develop a triatoms-in-molecules method as an extension of the more common diatoms-in-molecules one, which allows a very accurate description of the asymptotic regions by including correctly the charge-induced dipole and quadrupole interactions. Moreover, this treatment provides a semiquantitative description of all the topological features of the global potential compared with coupled cluster results. In particular, the hop of the proton between two H2 fragments produces a double well in the potential. This resonant structure involving the five atoms produces a stabilization, lowering the barrier, and the triatoms-in-molecules yields to a barrier significantly higher than the ab initio results. Therefore, to improve the triatomics-in-molecules potential surface, two five-body terms are added, which are fitted to more than 110 000 coupled-cluster ab initio points. The global potential energy surface thus obtained in this work has an overall root mean square error of 0.079 kcal/mol for energies below 27 kcal/mol above the global well. The features of the potential are described and compared with previous available surfaces.
Stoichiometric analysis of compositionally graded combinatorial amorphous thin film oxides using laser-induced breakdown spectroscopy
Authors: Widjonarko N. Edwin , Perkins John D. , Leisch Jennifer E. , Parilla Philip A. , Curtis Calvin J. , Ginley David S. , Berry Joseph J.
Published: July 2010

Laser-induced breakdown spectroscopy (LIBS) is a recently developed locally destructive elemental analysis technique that can be used to analyze solid, liquid, and gaseous samples. In the system explored here, a neodymium-doped yttrium aluminum garnet laser ablates a small amount of the sample and spectral emission from the plume is analyzed using a set of synchronized spectrometers. We explore the use of LIBS to map the stoichiometry of compositionally graded amorphous indium zinc oxide thin-film libraries. After optimization of the experimental parameters (distance between lens and samples, spot size on the samples, etc.), the LIBS system was calibrated against inductively coupled plasma atomic emission spectroscopy which resulted in a very consistent LIBS-based elemental analysis. Various parameters that need to be watched closely in order to produce consistent results are discussed. We also compare LIBS and x-ray fluorescence as techniques for the compositional mapping of libraries.
Generation, propagation, and breaking of an internal wave beam
Authors: Clark Heather A. , Sutherland Bruce R.
Published: July 2010

We report upon an experimental study of internal gravity waves generated by the large-amplitude vertical oscillations of a circular cylinder in uniformly stratified fluid. Quantitative measurements are performed using a modified synthetic schlieren technique for strongly stratified solutions of NaCl or NaI. The oscillatory forcing leads to the development of turbulence in the region bounding the cylinder. This turbulence is found to be the primary source of the observed quasimonochromatic wave beams, whose characteristics at early times differ from theoretical predictions and experimental investigations of waves generated by small-amplitude cylinder oscillations. In particular, their wavelength is set by the Ozmidov scale rather than the size of the cylinder. The wave frequency is set by the buoyancy frequency N if the cylinder frequency is larger or much less than N. Otherwise it is set by the cylinder oscillation frequency. Over long times the finite-amplitude waves that have propagated away from their source are observed to break down and the process is examined quantitatively through conductivity probe measurements and qualitatively through unprocessed synthetic schlieren images. From an analysis of the location of wave breakdown we determine that the likely mechanism for breakdown is through parametric subharmonic instability. This conclusion is supported by fully nonlinear numerical simulations of the evolution of a temporally, although not spatially, monochromatic internal wave beam.
Interaction of a large amplitude interfacial solitary wave of depression with a bottom step
Authors: Maderich Vladimir , Talipova Tatiana , Grimshaw Roger , Terletska Katherina , Brovchenko Igor , Pelinovsky Efim , Choi Byung Ho
Published: July 2010

This paper is devoted to the study of the transformation of a finite-amplitude interfacial solitary wave of depression at a bottom step. The parameter range studied goes outside the range of weakly nonlinear theory (the extended Korteweg–de Vries or Gardner equation), and we describe various scenarios of this transformation in terms of the incident wave amplitude and the step height. The dynamics and energy balance of the transformation are described. Several numerical simulations are carried out using the nonhydrostatic model based on the fully nonlinear Navier–Stokes equations in the Boussinesq approximation. Three distinct runs are discussed in detail. The first simulation is done when the ratio of the step height to the lower layer thickness after the step is about 0.4 and the incident wave amplitude is less than the limiting value estimated for a Gardner solitary wave. It shows the applicability of the weakly nonlinear model to describe the transformation of a strongly nonlinear wave in this case. In the second simulation, the ratio of the step height to the lower layer thickness is the same as that in the first run but the incident wave amplitude is increased and then its shape is described by the Miyata–Choi–Camassa solitary wave solution. In this case, the process of wave transformation is accompanied by shear instability and the billows that result in a thickening of the interface layer. In the third simulation, the ratio of the step height to the thickness of the lower layer after the step is 1.33, and then the same Miyata–Choi–Camassa solitary wave passes over the step, it undergoes stronger reflection and mixing between the layers although Kelvin–Helmholtz instability is absent. The energy budget of the wave transformation is calculated. It is shown that the energy loss in the vicinity of the step grows with an increase of the ratio of the incident wave amplitude to the thickness of the lower layer over the step.
Communication: Energetics of reaction pathways for reactions of ethenol with the hydroxyl radical: The importance of internal hydrogen bonding at the transition state
Authors: Tishchenko Oksana , Ilieva Sonia , Truhlar Donald G.
Published: July 2010

We find high multireference character for abstraction of H from the OH group of ethenol (also called vinyl alcohol); therefore we adopt a multireference approach to calculate barrier heights for the various possible reaction channels of OH+C2H3OH. The relative barrier heights of ten possible saddle points for reaction of OH with ethenol are predicted by multireference Møller–Plesset perturbation theory with active spaces based on correlated participating orbitals (CPOs) and CPO plus a correlated π orbital (CPO+π). Six barrier heights for abstracting H from a CH bond range from 3.1 to 7.7 kcal/mol, two barrier heights for abstracting H from an OH bond are both 6.0 kcal/mol, and two barrier heights for OH addition to the double bond are −1.8 and −2.8 kcal/mol. Thus we expect abstraction at high-temperature and addition at low temperature. The factor that determines which H is most favorable to abstract is an internal hydrogen bond that constitutes part of a six-membered ring at one of the abstraction saddle points; the hydrogen bond contributes about 3 kcal/mol stabilization.
A scanning microcavity for in situ control of single-molecule emission
Authors: Toninelli C. , Delley Y. , Stöferle T. , Renn A. , Götzinger S. , Sandoghdar V.
Published: July 2010

We report on the fabrication and characterization of a scannable Fabry–Perot microcavity, consisting of a curved micromirror at the end of an optical fiber and a planar distributed Bragg reflector. Furthermore, we demonstrate the coupling of single organic molecules embedded in a thin film to well-defined resonator modes. We discuss the choice of cavity parameters that will allow sufficiently high Purcell factors for enhancing the zero-phonon transition between the vibrational ground levels of the electronic excited and ground states.
A simple, compact, and efficient diode-side-pumped linear intracavity frequency doubled Nd:YAG rod laser with 50 ns pulse width and 124 W green output power
Authors: Sharma Sunil K. , Mukhopadhyay Pranab K. , Singh Amarjeet , Kandasamy Ranganathan , Oak Shrikant M.
Published: July 2010

We have developed an efficient and high power repetitively Q-switched diode-pumped intracavity frequency doubled Nd:YAG/LiB3O5 based green laser capable of generating 124 W of average green power with 50 ns pulse duration in a highly compact and robust linear cavity configuration. The pump to green beam conversion efficiency is 16.8% and the overall wall-plug efficiency is 8.3%. The long term power stability is excellent with ±0.4 W variation at the maximum output power and ±2% amplitude fluctuation with ±2.9 ns timing jitter. The M2 parameter of the green beam was measured to be ∼27. This, combined with the short pulse duration and the high average power, makes this laser ideal for pumping ultrafast Ti:sapphire laser amplifier systems and for micromachining applications.
Toward the origin of exciton electronic structure in phycobiliproteins
Authors: Womick Jordan M. , Miller Stephen A. , Moran Andrew M.
Published: July 2010

Femtosecond laser spectroscopies are used to examine the electronic structures of two proteins found in the phycobilisome antenna of cyanobacteria, allophycocyanin (APC) and C-phycocyanin (CPC). The wave function composition involving the pairs of phycocyanobilin pigments (i.e., dimers) found in both proteins is the primary focus of this investigation. Despite their similar geometries, earlier experimental studies conducted in our laboratory and elsewhere observe clear signatures of exciton electronic structure in APC but not CPC. This issue is further investigated here using new experiments. Transient grating (TG) experiments employing broadband quasicontinuum probe pulses find a redshift in the signal spectrum of APC, which is almost twice that of CPC. Dynamics in the TG signal spectra suggest that the sub-100 fs dynamics in APC and CPC are respectively dominated by internal conversion and nuclear relaxation. A specialized technique, intraband electronic coherence spectroscopy (IECS), photoexcites electronic and nuclear coherences with nearly full suppression of signals corresponding to electronic populations. The main conclusion drawn by IECS is that dephasing of intraband electronic coherences in APC occurs in less than 25 fs. This result rules out correlated pigment fluctuations as the mechanism enabling exciton formation in APC and leads us to propose that the large Franck–Condon factors of APC promote wave function delocalization in the vibronic basis. For illustration, we compute the Hamiltonian matrix elements involving the electronic origin of the α84 pigment and the first excited vibronic level of the β84 pigment associated with a hydrogen out-of-plane wagging mode at 800 cm−1. For this pair of vibronic states, the −51 cm−1 coupling is larger than the 40 cm−1 energy gap, thereby making wave function delocalization a feasible prospect. By contrast, CPC possesses no pair of vibronic levels for which the intermolecular coupling is larger than the energy gap between vibronic states. This study of APC and CPC may be important for understanding the photophysics of other phycobiliproteins, which generally possess large vibronic couplings.
Digitally tunable, wide-band amplitude, phase, and frequency detection for atomic-resolution scanning force microscopy
Authors: Khan Z. , Leung C. , Tahir B. A. , Hoogenboom B. W.
Published: July 2010

Frequency-modulation atomic force microscopy (FM-AFM) relies on an accurate tracking of the resonance frequency of a scanning probe. It is now used in environments ranging from ultrahigh vacuum to aqueous solutions, for slow and for fast imaging, with probes resonating from a few kilohertz up to several megahertz. Here we present a versatile experimental setup that detects amplitude, phase, and frequency of AFM probes for resonance frequencies up to 15 MHz and with >70 kHz maximum bandwidth for amplitude/phase detection. We provide generic parameter settings for variable-bandwidth frequency detection and test these using our setup. The signal-to-noise ratio of the frequency detector is sufficiently high to record atomic-resolution images of mica by FM-AFM in aqueous solution.
Complete spectral gap in coupled dielectric waveguides embedded into metal
Authors: Liu Wei , Sukhorukov Andrey A. , Miroshnichenko Andrey E. , Poulton Chris G. , Xu Zhiyong , Neshev Dragomir N. , Kivshar Yuri S.
Published: July 2010

We study a plasmonic coupler involving backward (TM01) and forward (HE11) modes of dielectric waveguides embedded into an infinite metallic background. The simultaneously achievable contradirectional energy flows and codirectional phase velocities in different channels lead to a spectral gap, despite the absence of periodic structures along the waveguide. We demonstrate that a complete spectral gap can be achieved in a symmetric structure composed of four coupled waveguides.
DNA sensing using split-ring resonator alone at microwave regime
Authors: Lee Hee-Jo , Lee Hyun-Seok , Yoo Kyung-Hwa , Yook Jong-Gwan
Published: July 2010

In this paper, the feasibility of utilization of a single element double split-ring resonator as a biosensing device has been demonstrated. The compact resonator has been excited by time-varying magnetic fields generated from the 50 Ω microstrip transmission line. In this work, DNA hybridization is recognized with shift in S21 resonant frequency. When thiol-linked single stranded-DNA is immobilized onto a gold (Au) surface and is then coupled with complementary-DNA, the frequency changes by Δfss-DNA=20 MHz and Δfhybridization=60 MHz, respectively. Thus, it is clear that the resonator can be utilized as a DNA sensing element in the microwave regime.
Magnetic force microscopy measurements in external magnetic fields—comparison between coated probes and an iron filled carbon nanotube probe
Authors: Wolny F. , Mühl T. , Weissker U. , Leonhardt A. , Wolff U. , Givord D. , Büchner B.
Published: July 2010

We performed magnetic force microscopy (MFM) measurements in external magnetic fields parallel to the sample plane to qualitatively study their effect on the magnetization of different kinds of MFM probes. As a test structure we used an array of rectangular ferromagnetic thin film elements aligned with the external magnetic field direction. MFM images were taken while the field was increased stepwise to monitor the onset of a tilt in the MFM probe magnetization. Three different probes were investigated: a conventional pyramidal probe coated with 40 nm of CoCrTa, a coated high aspect ratio MFM probe, and a MFM probe based on an iron filled carbon nanotube (FeCNT). The results show that the magnetization of the pyramidal probe is only stable in in-plane fields of up to ∼60 mT, in larger fields a considerable in-plane component of the tip magnetization is observed. This makes it difficult to distinguish the effect of the external field on the sample from those on the MFM probe. The coated high aspect ratio probe is at first stable up to ∼200 mT and then shows a history dependent behavior, in the second sweep the onset of the magnetization tilt is already visible at ∼100 mT. With the FeCNT probe, no tilt of the probe magnetization could be observed in in-plane fields up to the experimental limit of 230 mT. Due to the large shape anisotropy of the enclosed iron nanowire its direction of magnetization stays mainly oriented along the long axis even in moderate fields that deviate from this easy axis. Consequently, this probe is best suited for MFM measurements in external fields.
Induction of apoptosis in human breast cancer cells by a pulsed atmospheric pressure plasma jet
Authors: Kim Sun Ja , Chung T. H. , Bae S. H. , Leem S. H.
Published: July 2010

By using an atmospheric pressure plasma jet driven by pulsed dc voltage with repetition rate of several tens of kilohertz, we were able to induce apoptosis in cultured human breast cancer cells (MCF-7). The apoptotic changes in cells with plasma treatment were detected by flow cytometry and fluorescence staining assay. A significant portion of these cells was observed to exhibit the apoptotic fragmentation. Helium plasma with additive O2 gas was found to be effective in the induction of apoptosis. This plasma jet provides an effective mode of human breast cancer cell therapy.
Probing valence band structure in wurtzite InP nanowires using excitation spectroscopy
Authors: Perera S. , Pemasiri K. , Fickenscher M. A. , Jackson H. E. , Smith L. M. , Yarrison-Rice J. , Paiman S. , Gao Q. , Tan H. H. , Jagadish C.
Published: July 2010

We use time-resolved photoluminescence spectroscopy and photoluminescence excitation spectroscopy to measure the valence band parameters of hexagonal wurtzite InP nanowires. The A exciton emission and excitation energy is observed at 1.504 eV as expected. Excitation spectra show that the B and C hole bands are 30 and 161 meV above the A hole band. From these measurements, we obtain the crystal field and spin-orbit energies of 52 meV and 139 meV, respectively.
Revision of Pycnandra subgenus Achradotypus (Sapotaceae), with five new species from New Caledonia
Authors: Swenson Ulf , Munzinger Jérôme
Published: July 2010

Pycnandra is a genus of Sapotaceae (Chrysophylloideae), restricted to New Caledonia, and includes ~60 species. The genus is a member of the monophyletic Niemeyera complex of Australia and New Caledonia and it is characterised by the lack of staminodes and a fruit containing a single seed, plano-convex cotyledons and absence of endosperm. In New Caledonia, several segregate genera have been recognised, but weak cladistic support for these groups and homoplasious morphology renders a narrow generic concept untenable. Instead, a broad generic circumscription of Pycnandra with an infrageneric classification recognising the subgenera Achradotypus, Leptostylis, Pycnandra, Sebertia and Trouettia results in a stable nomenclature. Here we revise Pycnandra subg. Achradotypus that includes 14 species, of which five (P. belepensis, P. blaffartii, P. bracteolata, P. glabella, and P. ouaiemensis) are described as new. Members of subg. Achradotypus are distinguished from other subgenera on the basis of a character combination of two stamens opposite each corolla lobe (except P. litseiflora), glabrous leaves (except P. belepensis and P. decandra), a distinctive reticulate tertiary leaf venation (except P. comptonii), and sepal-like bracts that often are borne along the pedicel. All species are restricted to Grande Terre except for P. decandra, whose distribution also extends to nearby Art Island (Belep Islands), and P. belepensis, which is endemic to that same island. The members grow in a wide range of vegetation types from dry maquis to humid forest, from sea level to the highest mountain massif, and on ultramafic soils to schist and greywacke (not limestone). Because of past and present threats such as mining, logging and fire, preliminary IUCN Red List assessments are provided for all species. Five taxa (P. chartacea, P. decandra subsp. decandra, P. glabella, P. litseiflora, and P. neocaledonica) are proposed the IUCN status Endangered, and P. belepensis and P. ouaiemensis are proposed to be Critically Endangered. We suggest that some locations where these species occur should be given protection in the form of nature reserves.
Unique precursors for the mesenchymal cells involved in injury response and fibrosis
Authors: Walker Janice L. , Zhai Ni , Zhang Liping , Bleaken Brigid M. , Wolff Iris , Gerhart Jacquelyn , George-Weinstein Mindy , Menko A. Sue
Published: July 2010

We investigated an alternative pathway for emergence of the mesenchymal cells involved in epithelial sheet wound healing and a source of myofibroblasts that cause fibrosis. Using a mock cataract surgery model, we discovered a unique subpopulation of polyploid mesenchymal progenitors nestled in small niches among lens epithelial cells that expressed the surface antigen G8 and mRNA for the myogenic transcription factor MyoD. These cells rapidly responded to wounding of the lens epithelium with population expansion, acquisition of a mesenchymal phenotype, and migration to the wound edges where they regulate the wound response of the epithelium. These mesenchymal cells also were a principal source of myofibroblasts that emerged following lens injury and were responsible for fibrotic disease of the lens that occurs following cataract surgery. These studies provide insight into the mechanisms of wound-healing and fibrosis.
The face-to-face light detection paradigm
Authors: Thompson Laura A. , Malloy Daniel M. , Cone John M. , Hendrickson David L.
Published: July 2010

We introduce a novel paradigm for studying the cognitive processes used by listeners within interactive settings. This paradigm places the talker and the listener in the same physical space, creating opportunities for investigations of attention and comprehension processes taking place during interactive discourse situations. An experiment was conducted to compare results from previous research using videotaped stimuli to those obtained within the live face-to-face task paradigm. A headworn apparatus is used to briefly display LEDs on the talker’s face in four locations as the talker communicates with the participant. In addition to the primary task of comprehending speeches, participants make a secondary task light detection response. In the present experiment, the talker gave non-emotionally-expressive speeches that were used in past research with videotaped stimuli. Signal detection analysis was employed to determine which areas of the face received the greatest focus of attention. Results replicate previous findings using videotaped methods.
Broadband three-dimensional diamond-shaped invisible cloaks composed of tetrahedral homogeneous blocks
Authors: Wang Xinhua , Qu Shaobo , Wu Xiang , Wang Jiafu , Xu Zhuo , Ma Hua
Published: July 2010

By means of embedded optical transformation, three-dimensional diamond-shaped invisible cloaks composed of tetrahedral homogeneous blocks have been designed in this paper. The constitutive parameters of the invisible cloaks can be obtained based on the form invariance of Maxwell's equations in coordinate transformation. Numerical methods using the finite element method verified the diamond-shaped cloaks. The invisible properties of the designed cloaks are nearly perfect when the original line section is sufficiently short compared with its counterpart in the after-transformed space. The designed cloaks can operate in a wide bandwidth due to the line transformation in the coordinate transformation process.
Inflammatory Bowel Disease Developing in Paediatric and Adult Age
Authors: Guariso Graziella , Gasparetto Marco , Visonà Dalla Pozza Laura , D'Incà Renata , Zancan Lucia , Sturniolo Giancarlo , Brotto Francesca , Facchin Paola
Published: July 2010

Background and Objective:

In recent decades, there has been a significant increase in the incidence of inflammatory bowel disease (IBD). It has yet to be established whether the manifestations of IBD are similar in paediatric and adult ages. The objective of this study was to compare the phenotypic expression of the disease between patients with childhood‐onset IBD and adulthood‐onset cases, all afferent to the same clinical centre.

Patients and Methods:

Descriptive and multivariate analyses were completed on retrospective and prospective data of paediatric‐onset and adult‐onset consecutive cases who were diagnosed and followed at the same tertiary referral hospital of the University of Padua, Italy, during a period of 14 years (1994–2008). Paediatric‐onset patients were further divided into age brackets (0–5, 6–12, and 13–17 year‐olds). Analyses were conducted using the SAS package, version 9.1 (SAS Institute Inc, Cary, NC).

Results:

Three hundred twelve patients were analysed. At disease onset, the manifestations which were more frequent among the 133 paediatric patients (50.4% with diagnosis of Crohn disease [CD], 43.6% with ulcerative colitis, and 6% with unclassified IBD) with respect to the adult‐onset patients were perianal disease (12.8%) (P < 0.0001) and extraintestinal manifestations (14.3%) (P = 0.043). Among the 179 adult patients (55.3% with diagnosis of ulcerative colitis, 36.3% with CD, and 8.3% with unclassified IBD) instead, severe abdominal pain (P = 0.008), diarrhoea (P = 0.005), and anorexia (P < 0.0001) were more frequently observed. During the follow‐up, the presence of extraintestinal manifestations (50.4%) (P = 0.005) and perianal disease (44.8% of the patients with childhood‐onset CD) (P = 0.006) was observed more often in the paediatric‐onset group.

Conclusions:

In our cases, the phenotypic expression of IBD developing in paediatric age differs from that seen in adults.
Comparative genomics of the genus Bifidobacterium
Authors: Bottacini Francesca , Medini Duccio , Pavesi Angelo , Turroni Francesca , Foroni Elena , Riley David , Giubellini Vanessa , Tettelin Hervé , van Sinderen Douwe , Ventura Marco
Published: July 2010

Whole-genome sequencing efforts have revolutionized the study of bifidobacterial genetics and physiology. Unfortunately, the sequence of a single genome does not provide information on bifidobacterial genetic diversity and on how genetic variability supports improved adaptation of these bacteria to the environment of the human gastrointestinal tract (GIT). Analysis of nine genomes from bifidobacterial species showed that such genomes display an open pan-genome structure. Mathematical extrapolation of the data indicates that the genome reservoir available to the bifidobacterial pan-genome consists of more than 5000 genes, many of which are uncharacterized, but which are probably important to provide adaptive abilities pertinent to the human GIT. We also define a core bifidobacterial gene set which will undoubtedly provide a new baseline from which one can examine the evolution of bifidobacteria. Phylogenetic investigation performed on a total of 506 orthologues that are common to nine complete bifidobacterial genomes allowed the construction of aBifidobacteriumsupertree which is largely concordant with the phylogenetic tree obtained using 16S rRNA genes. Moreover, this supertree provided a more robust phylogenetic resolution than the 16S rRNA gene-based analysis. This comparative study of the genusBifidobacteriumthus presents a foundation for future functional analyses of this important group of GIT bacteria.
Bisulfite Patch PCR enables multiplexed sequencing of promoter methylation across cancer samples
Authors: Varley Katherine Elena , Mitra Robi David
Published: July 2010

Aberrant DNA methylation frequently occurs at gene promoters during cancer progression. It is important to identify these loci because they are often misregulated and drive tumorigenesis. Bisulfite sequencing is the most direct and highest resolution assay for identifying aberrant promoter methylation. Recently, genomic capture methods have been combined with next-generation sequencing to enable genome-scale surveys of methylation in individual samples. However, it is challenging to validate candidate loci identified by these approaches because an efficient method to bisulfite sequence more than 50 differentially methylated loci across a large number of samples does not exist. To address this problem, we developed Bisulfite Patch PCR, which enables highly multiplexed bisulfite PCR and sequencing across many samples. Using this method, we successfully amplified 100% of 94 targeted gene promoters simultaneously in the same reaction. By incorporating sample-specific DNA barcodes into the amplicons, we analyzed 48 samples in a single run of the 454 Life Sciences (Roche) FLX sequencer. The method requires small amounts of starting DNA (250 ng) and does not require a shotgun library construction. The method was highly specific; 90% of sequencing reads aligned to targeted loci. The targeted promoters were from genes that are frequently mutated in breast and colon cancer, and the samples included breast and colon tumor and adjacent normal tissue. This approach allowed us to identify nine gene promoters that exhibit tumor-specific DNA methylation defects that occur frequently in colon and breast cancer. We also analyzed single nucleotide polymorphisms to observe DNA methylation that accumulated on specific alleles during tumor development. This method is broadly applicable for studying DNA methylation across large numbers of patient samples using next-generation sequencing.
An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer
Authors: Wasserman Nora F. , Aneas Ivy , Nobrega Marcelo A.
Published: July 2010

Genome-wide association studies (GWAS) routinely identify risk variants in noncoding DNA, as exemplified by reports of multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer in five independent regions in a gene desert on 8q24. Two of these regions also have been associated with breast and colorectal cancer. These findings implicate functional variation within long-range cis-regulatory elements in disease etiology. We used an in vivo bacterial artificial chromosome (BAC) enhancer-trapping strategy in mice to scan a half-megabase of the 8q24 gene desert encompassing the prostate cancer-associated regions for long-range cis-regulatory elements. These BAC assays identified both prostate and mammary gland enhancer activities within the region. We demonstrate that the 8q24 cancer-associated variant rs6983267 lies within an in vivo prostate enhancer whose expression mimics that of the nearby MYC proto-oncogene. Additionally, we show that the cancer risk allele increases prostate enhancer activity in vivo relative to the non-risk allele. This allele-specific enhancer activity is detectable during early prostate development and throughout prostate maturation, raising the possibility that this SNP could assert its influence on prostate cancer risk before tumorigenesis occurs. Our study represents an efficient strategy to build experimentally on GWAS findings with an in vivo method for rapidly scanning large regions of noncoding DNA for functional cis-regulatory sequences harboring variation implicated in complex diseases.
Pilot study: rapamycin in advanced hepatocellular carcinoma
Authors: Schöniger‐Hekele M. , Müller C.
Published: July 2010

Background  The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant.

Aim  To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC).

Methods  Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study.

Results  Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver‐Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months.

Conclusion  Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.
short report: Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders
Authors: Lasne Dominique , Baujat Geneviève , Mirault Tristan , Lunardi Joël , Grelac Françoise , Egot Marion , Salomon Rémi , Bachelot‐Loza Christilla
Published: July 2010

Lowe syndrome (LS) is a rare X‐linked disorder caused by mutations in the oculocerebrorenal gene (OCRL), encoding OCRL, a phosphatidylinositol 5–phosphatase with a RhoGAP domain. An abnormal rate of haemorrhagic events was found in a retrospective clinical survey. Herein, we report the results of exploration of haemostasis in six LS patients. All patients had normal coagulation tests but prolonged closure times (CTs) in the PFA–100 system. Healthy donors’ blood samples incubated with a RhoA kinase inhibitor had prolonged CTs. This suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in LS.
Preventing obesity at weaning: parental views about the EMPOWER programme
Authors: Barlow J. , Whitlock S. , Hanson S. , Davis H. , Hunt C. , Kirkpatrick S. , Rudolf M.
Published: July 2010

Background  Infant growth and lifestyle are now recognized as being critical determinants of later obesity. EMPOWER (Empowering Parents to Prevent Obesity at Weaning: Exploratory Research) was developed as an intervention for parents whose babies are at high risk. Delivered by specially trained health visitors, it is underpinned by the Family Partnership Model and uses a strengths‐based, solution‐focused way of working with families.

Methods  Mothers of babies participating in the pilot of EMPOWER in Leeds were recruited to take part in a study to examine perceptions about the programme's acceptability and usefulness. Interviews were taped and transcribed, and thematic analysis undertaken.

Results  Families talked positively about the approach of the EMPOWER health visitor with her emphasis on listening, partnership working and shared problem‐solving. Parents particularly valued the use of a non‐judgemental approach, which they felt had helped them to discuss openly, sensitive issues such as weight and diet. They identified a number of important benefits ranging from increased knowledge about the most appropriate types and amount of food to feed their toddler, to more far‐reaching changes within the family as a whole, including modifications to their own diet and lifestyle. Programmes of this nature were perceived as more valuable than the standard help that is currently available.

Conclusion  The EMPOWER programme appears to be both acceptable and valued by targeted parents and a potentially effective means of supporting high‐risk families to prevent their children from developing obesity. An exploratory randomized controlled trial is now underway to ascertain the feasibility of conducting a definitive phase 3 trial.
An epidemiologic study of irritable bowel syndrome in adolescents and children in South China: a school‐based study
Authors: Zhou H. , Li D. , Cheng G. , Fan J. , Lu H.
Published: July 2010

Background  To explore the prevalence of irritable bowel syndrome (IBS) among school‐aged children in South China, and identify distribution characteristics and contributing factors.

Methods  Primary, middle and high school students (n= 2013) were recruited from schools in Shanghai. Students completed two questionnaires, one for IBS in adolescents and children and the Screen for Child Anxiety Related Emotional Disorders (SCARED).

Results  (1) The prevalence of IBS among students was 20.72% and the incidence increased with age. (2) Several physical factors and overuse of analgesics were significantly associated with IBS. (3) The prevalence of anxiety disorder was higher in older students, and in females vs. males. Students with IBS tended towards anxiety‐related emotional disorders (38.14% vs. 18.96%). (4) IBS students scored higher in all SCARED categories. Within IBS students, those who frequently sought medical care reported higher scores in the somatization/panic category.

Conclusion  (1) Irritable bowel syndrome is a common disorder among adolescents in South China and prevalence increases with age. (2) Gastrointestinal infection, abuse of analgesics and psychological factors might be related to the incidence of IBS. (3) The tendency towards anxiety‐related emotional disorders also increases with age, suggesting a possible correlation with IBS and underlining the importance of positive family and school environments. Although the prevalence of anxiety‐related emotional disorders was higher in females than males, this trend was not correlated with the occurrence of IBS.
Intestinal parasites, nutritional status and physchomotor development delay in migratory farm worker's children
Authors: Koruk I. , Simsek Z. , Tekin Koruk S. , Doni N. , Gürses G.
Published: July 2010

Objective  The aim of this study was to investigate the prevalence of intestinal parasites, nutritional status and physchomotor developmental delay and anaemia in children of migratory seasonal farm worker families.

Material and methods  In this cross‐sectional study, 168 children aged between 6 and 59 months selected through probability sampling method were contacted in the Sanliurfa district of south‐eastern Anatolia of Turkey. The data were collected using a structured questionnaire, anthropometry and Ankara Developmental Screening Inventory to measure physchomotor development. In order to evaluate the anaemia, finger‐prick blood samples were used and laboratory analyses of faecal samples were conducted.

Results  55.4% of children were infected by intestinal parasites. The most common infections involved the protozoan parasite Giardia intestinalis (37.2%). Of the children 17.8% had general psychomotor development delay. Regarding the nutritional status of the 168 children who participated, 38.1% were stunted, 20.8% were underweight, and 5.4% were wasted. Of these children, 16.6% were anaemic.

Conclusion  The findings demonstrated that the children of migratory seasonal farm workers were defined as a high‐risk group in terms of nutritional status, intestinal parasites and physchomotor development delay. Therefore, the effective delivery of mobile environmental and individual primary healthcare services to the farm workers' children must be ensured both while residing in the agricultural zone and in their permanent addresses.
Depletion of CD4+CD25+ T cells switches the whey‐allergic response from immunoglobulin E‐ to immunoglobulin free light chain‐dependent
Authors: Van Esch B. C. A. M. , Schouten B. , Blokhuis B. R. J. , Hofman G. A. , Boon L. , Garssen J. , Knippels L. M. J. , Willemsen L. E. M. , Redegeld F. A.
Published: July 2010

Background
Symptoms of allergy are largely attributed to an IgE‐mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig‐free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4+CD25+ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens.

Objective
To examine the contribution of CD4+CD25+ T cells and IgLC towards the whey‐allergic response.

Methods
Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25+ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey‐specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4+CD25+ T cells was confirmed in the spleen.

Results
Anti‐CD25 treatment strongly reduced whey‐specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3+ regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25‐depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti‐CD25‐treated mice, indicating that these responses were mainly IgLC dependent.

Conclusions
Depletion of CD4+CD25+ T cells resulted in a switch from an IgE‐ to an IgLC‐dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25+ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE‐independent responses and both mechanisms might play a role in allergic responses to the same allergen.

Cite this as: B. C. A. M. van Esch, B. Schouten, B. R. J. Blokhuis, G. A. Hofman, L. Boon, J. Garssen L. M. J. Knippels, L. E. M. Willemsen and F. A. Redegeld, Clinical & Experimental Allergy, 2010 (40) 1414–1421.