bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690
Authors: Zhou Xiao-Long , Tan Min , Wang Meng , Chen Xin , Wang En-Duo
Published: June 2010

Some aaRSs (aminoacyl-tRNA synthetases) develop editing mechanisms to correct mis-charged tRNA. The CP1 (connective peptide 1) domain of LeuRS (leucyl-tRNA synthetase) contains the editing active site, which is the proven target for the broad-spectrum drug AN2690 (5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole). The ESI (eukarya-specific insertion 1) in the CP1 domain of GlLeuRS (Giardia lamblia LeuRS) has been identified. Similar substitution with the ESI from HsLeuRS (Homo sapiens LeuRS) impeded the leucine activation, aminoacylation and post-transfer editing of the enzyme, but had no effect on the editing specificity toward non-specific amino acids. Thr341 in GlLeuRS served as a specificity discriminator, as found in other LeuRS systems, although its substitution with an alanine residue did not destroy Leu-tRNALeu synthesis in vitro and in vivo. The Arg338 was crucial for tRNALeu charging and the Asp440 was crucial for leucine activation and aminoacylation. The post-transfer editing required the CTD (C-terminal domain), Arg338 and Asp440 of GlLeuRS. Interestingly, GlLeuRS was completely resistant to the AN2690, which is an inhibitor of various LeuRSs. The universally conserved aspartate residue in the LeuRS CP1 domains was responsible for the resistance of GlLeuRS and another recently reported AN2690-resistant AaLeuRS (Aquifex aeolicus LeuRS). Our results indicate the functional divergence of some absolutely conserved sites, improve the understanding of the editing function of eukaryotic/archaeal LeuRSs and shed light on the development of a GlLeuRS-specific inhibitor for the treatment of giardiasis.
Endocytosis of hyaluronidase-1 by the liver
Authors: Gasingirwa Marie-Christine , Thirion Jacqueline , Mertens-Strijthagen Jeannine , Wattiaux-De Coninck Simone , Flamion Bruno , Wattiaux Robert , Jadot Michel
Published: June 2010

It has been suggested that intracellular Hyal-1 (hyaluronidase-1), which is considered a lysosomal enzyme, originates via endocytosis of the serum enzyme. To test this proposal we have investigated the uptake and intracellular distribution of rhHyal-1 (recombinant human Hyal-1) by mouse liver, making use of centrifugation methods. Experiments were performed on wild-type mice injected with 125I-labelled rhHyal-1 and on Hyal-1−/− mice injected with the unlabelled enzyme, which were killed at various times after injection. Activity of the unlabelled enzyme was determined by zymography. Intracellular distribution of Hyal-1 was investigated by differential and isopycnic centrifugation. The results of the study indicated that rhHyal-1 is endocytosed by the liver, mainly by sinusoidal cells, and follows the intracellular pathway described for many endocytosed proteins that are eventually located in lysosomes. However, Hyal-1 endocytosis has some particular features. First, endocytosed rhHyal-1 is quickly degraded. Secondly, its distribution, as analysed by differential centrifugation, differs from the distribution of β-galactosidase, taken as the reference lysosomal enzyme. Further analysis by isopycnic centrifugation in a sucrose gradient shows endocytosed rhHyal-1 behaves like β-galactosidase shortly after injection. However the Hyal-1 distribution is markedly less affected than β-galactosidase, following a prior injection of Triton WR-1339, which is a specific density perturbant of lysosomes. The behaviour in centrifugation of endogenous liver Hyal-1, identified by hyaluronan zymography, exhibits some similarity with the behaviour of the endocytosed enzyme, suggesting that it could originate from endocytosis of the serum enzyme. Overall, these results can be explained by supposing that active endocytosed Hyal-1 is mainly present in early lysosomes. Although its degradation half-time is short, Hyal-1 could exert its activity due to a constant supply of active molecules from the blood.
Conviviality of Internet Social Networks: An Exploratory Study of Internet Campaigns in Iran
Authors: Ameripour Aghil , Nicholson Brian , Newman Michael
Published: June 2010

In this study, we focus on the relationship between Internet social networks and societal change by examining case studies of the impact of Internet-based campaigns in Iran. Ivan Illich's theory of ‘Conviviality of Tools’ enables an analysis of the conviviality of the Internet. Subsequently, this conceptual lens is used to examine empirical data from two Internet-based campaigns. The paper contributes theoretical and practical Implications regarding conviviality of Internet social networks and the accomplishment of conviviality in society. Our findings show that Internet conviviality cannot be treated as an independent variable with deterministic outcomes on society, but as a technology that is shaped by ongoing economic and political forces. The Iranian Internet social networks are not universally accessible, frequently induce fragmented, nonsensical, and enraged discussion and its potential as a tool of liberation is tempered by the Iranian government adaption of systems of surveillance and censorship. We argue that the findings of this study have some general implications of value to researchers studying computerisation movements and Internet social networks in other countries.
Surface properties of the (001) surface of cubic BaMnO3: A density functional theory study
Authors: Li N. , Yao K. L. , Gao G. Y. , Zhu L. , Wu Y. Y.
Published: June 2010

We have theoretically investigated surface properties of the (001) surface in cubic barium manganese (BaMnO3) by the full-potential linear augmented plane wave methods within the local spin-density approximation. We present and discuss the electronic properties of the (001) surface of cubic BaMnO3 with BaO- and MnO2-terminations. Surface structure, Mulliken effective atomic charges, surface energies and stability, band structure, and partial density of states have been obtained. For the BaO-terminated surface, we find that all layer atoms relax inward (toward the central layer), while for the MnO2-terminated surface all layer atoms relax outward (toward the vacuum). The largest relaxations emerge on the first-layer atoms on the two terminations. The surface rumpling of the BaO-terminated is much larger than that of the MnO2-terminated surface. Based on the results of the calculated surface energies and stability, we obtain that only the BaO-terminated surface can exist in the (001) surface of cubic BaMnO3. From the analysis of their band structure, we can see that the BaO-terminated surface has obvious half-metallic character, compared with the bulk materials and the MnO2-terminated surface.
Mechanism, dynamics, and biological existence of multistability in a large class of bursting neurons
Authors: Newman Jonathan P. , Butera Robert J.
Published: June 2010

Multistability, the coexistence of multiple attractors in a dynamical system, is explored in bursting nerve cells. A modeling study is performed to show that a large class of bursting systems, as defined by a shared topology when represented as dynamical systems, is inherently suited to support multistability. We derive the bifurcation structure and parametric trends leading to multistability in these systems. Evidence for the existence of multirhythmic behavior in neurons of the aquatic mollusc Aplysia californica that is consistent with our proposed mechanism is presented. Although these experimental results are preliminary, they indicate that single neurons may be capable of dynamically storing information for longer time scales than typically attributed to nonsynaptic mechanisms.
Fabrication and subband gap optical properties of silicon supersaturated with chalcogens by ion implantation and pulsed laser melting
Authors: Bob Brion P. , Kohno Atsushi , Charnvanichborikarn Supakit , Warrender Jeffrey M. , Umezu Ikurou , Tabbal Malek , Williams James S. , Aziz Michael J.
Published: June 2010

Topographically flat, single crystal silicon supersaturated with the chalcogens S, Se, and Te was prepared by ion implantation followed by pulsed laser melting and rapid solidification. The influences of the number of laser shots on the atomic and carrier concentration-depth profiles were measured with secondary ion mass spectrometry and spreading resistance profiling, respectively. We found good agreement between the atomic concentration-depth profiles obtained from experiments and a one-dimensional model for plane-front melting, solidification, liquid-phase diffusion, with kinetic solute trapping, and surface evaporation. Broadband subband gap absorption is exhibited by all dopants over a wavelength range from 1 to 2.5 microns. The absorption did not change appreciably with increasing number of laser shots, despite a measurable loss of chalcogen and of electronic carriers after each shot.
Common multifractality in the heart rate variability and brain activity of healthy humans
Authors: Lin D. C. , Sharif A.
Published: June 2010

The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems.
Morphology-dependent optical absorption and conduction properties of photoelectrochemical photocatalysts for H2 production: A case study
Authors: Huda Muhammad N. , Turner John A.
Published: June 2010

Efficient photoelectrochemical H2 production by solar irradiation depends not only on the photocatalyst’s band gap and its band-edge positions but also on the detailed electronic nature of the bands, such as the localization or delocalization of the band edges and their orbital characteristics. These determine the carrier transport properties, reactivity, light absorption strength, etc. and significantly impact the material’s efficiency as a photoconverter. The localization or delocalization of the band edges may arise either due to the orbital nature of the bands or the structural morphology of the material. A recent experimental report on a photocatalyst based on s/p orbitals showed very poor performance for H2 production despite the delocalized nature of the s/p bands as compared to the d-bands of transition metal oxides. It is then important to examine whether this poor performance is inherent to these materials or rather arises from some experimental limitations. A theoretical analysis by first-principle methods is well suited to shed light on this question.
Geometry influence on the transmission spectra of dielectric single layers of spheres with different compactness
Authors: Andueza A. , Echeverría R. , Morales P. , Sevilla J.
Published: June 2010

The transmission of spectra of different dielectric spheres single layer arrangements has been measured. High dielectric permittivity (ε=7) spheres of several millimeters of diameter were used to build the samples whose transmission was measured in the microwave range. The behavior of lattices arranged in square and triangular geometries have been compared in a number of different compactness cases. The same patterns measured have also been calculated by finite-difference time-domain (FDTD) method. Spectra from different geometrical arrangements of the same compactness (measured with the same filling fraction value) are very similar in some cases. Based on the level of similarity we propose three compactness regions. The high compactness region, where the structure effect is important, presents spectra clearly different for the two geometries. In a medium compactness region spectra are almost identical, suggesting a dominant effect of single sphere effects. Finally, in the low compactness region, the spectra from the two geometrical configurations diverge again as the Bragg diffraction values are approached.
Persistence of In/Ga intermixing beyond the emission energy blueshift saturation of proton-implanted InAs/GaAs quantum dots
Authors: Zaâboub Z. , Ilahi B. , Salem B. , Aimez V. , Morris D. , Sfaxi L. , Maaref H.
Published: June 2010

Low temperature photoluminescence (PL) measurements are carried out to investigate the influence of the high extent of intermixing induced by proton implantation and subsequent annealing on the optical and electronic properties of the InAs/GaAs quantum dots (QDs). Several QDs structures were proton implanted at various doses (5×1011–1×1015 ions cm−2) with an acceleration energy of 18 keV and then annealed at 700 °C for 30 s. A saturation of the emission energy blueshift is found to occur for implantation doses higher than 5×1013 ions cm−2 accompanied with a continual decrease in the intersublevel spacing energy suggesting that the intermixing process persists beyond the emission energy blueshift saturation. An additional emission peak was found to appear in PL spectra for proton doses higher than 1×1014 ions cm−2 and attributed to the coalescence of closely spaced QDs. Strain assisted predominant lateral intermixing is proposed as the main factor responsible for the observed behavior.
Effects of heavy phosphorus-doping on mechanical properties of Czochralski silicon
Authors: Zeng Zhidan , Ma Xiangyang , Chen Jiahe , Zeng Yuheng , Yang Deren , Liu Yonggang
Published: June 2010

The mechanical properties including hardness, Young’s modulus, and fracture toughness of heavily phosphorus (P)-doped Czochralski (Cz) silicon have been investigated by means of nanoindentation and microindentation. In view of the results of nanoindentation characterization, it is derived that the hardness of heavily P-doped Cz silicon is essentially the same as that of lightly P-doped Cz silicon. While, the Young’s modulus of Cz silicon is to a certain extent decreased by the heavy P-doping. With the same microindentation load, the lengths of the radial and lateral cracks in the heavily P-doped silicon are shorter than those in the lightly P-doped silicon, indicating that the heavily P-doped Cz silicon possesses a higher indentation fracture toughness.
Magnetotransport properties of high quality Co:ZnO and Mn:ZnO single crystal pulsed laser deposition films: Pitfalls associated with magnetotransport on high resistivity materials
Authors: McCloy John S. , Ryan Joseph V. , Droubay Timothy , Kaspar Tiffany C. , Chambers Scott , Look David C.
Published: June 2010

The electrical resistivity values for a series of pure and doped (Co, Mn, Al) ZnO epitaxial films grown by pulsed laser deposition were measured with equipment designed for determining the direct current resistivity of high resistance samples. Room-temperature resistances ranging from 7×101 to 4×108 Ω/sq were measured on vacuum-reduced cobalt-doped ZnO, (Al,Co) co-doped ZnO, pure cobalt-doped ZnO, Mn-doped ZnO, and undoped ZnO. Using a four-point collinear geometry with gold spring-loaded contacts, resistivities were measured from 295 to 5 K for resistances of <∼1012 Ω/sq. In addition, magnetoresistance and Hall effect were measured as a function of temperature for select samples. Throughout the investigation, samples were also measured on commercially available instrumentation with good agreement. The challenges of transport measurements on high resistivity samples are discussed, along with some offered solutions to those challenges.
Generation of tunable narrow bandwidth nanosecond pulses in the deep ultraviolet for efficient optical pumping and high resolution spectroscopy
Authors: Velarde Luis , Engelhart Daniel P. , Matsiev Daniel , LaRue Jerry , Auerbach Daniel J. , Wodtke Alec M.
Published: June 2010

Nanosecond optical pulses with high power and spectral brightness in the deep ultraviolet (UV) region have been produced by sum frequency mixing of nearly transform-limited-bandwidth IR light originating from a home-built injection-seeded ring cavity KTiOPO4 optical parametric oscillator (OPO) and the fourth harmonic beam of an injection-seeded Nd:YAG laser used simultaneously to pump the OPO with the second harmonic. We demonstrate UV output, tunable from 204 to 207 nm, which exhibits pulse energies up to 5 mJ with a bandwidth better than 0.01 cm−1. We describe how the approach shown in this paper can be extended to wavelengths shorter than 185 nm. The injection-seeded OPO provides high conversion efficiency (>40% overall energy conversion) and superior beam quality required for highly efficient downstream mixing where sum frequencies are generated in the UV. The frequency stability of the system is excellent, making it highly suitable for optical pumping. We demonstrate high resolution spectroscopy as well as optical pumping using laser-induced fluorescence and stimulated emission pumping, respectively, in supersonic pulsed molecular beams of nitric oxide.
Atmospheric pressure plasma jet in Ar and Ar/H2O mixtures: Optical emission spectroscopy and temperature measurements
Authors: Sarani Abdollah , Nikiforov Anton Yu. , Leys Christophe
Published: June 2010

An atmospheric pressure plasma jet generated in Ar/water vapor mixtures has been investigated and the effect of water content on plasma properties has been studied. Plasma generated in Ar/water (0.05%) mixture shows higher intensity of OH radicals in emission spectra than pure argon alone. Plasma density has been estimated from current measurement and is in order of 1.5×1013 cm−3. Electron temperature has been estimated as 0.97 eV in pure Ar and it decreases with an increase in water content in plasma. The gas temperature has been determined by fitting of the experimental spectra and using the Boltzmann plot method. The gas temperature increases with the addition of water to feed gas from 620 K in pure Ar up to 1130 K for 0.76% H2O.
Absolute detection efficiencies of a microchannel plate detector for 0.5–5 keV neutrals
Authors: Hosokawa S. , Takahashi N. , Saito M. , Haruyama Y.
Published: June 2010

The absolute detection efficiencies of a microchannel plate detector for neutral atoms were measured using the coincidence method for neutralized incident ions and ionized target atoms in electron capture collisions. This method does not require knowledge of the absolute electron-capture rates for determination of the detection efficiencies. Results for Ne, Ar, and Kr atoms at energies of 0.5–5 keV are reported. The detection efficiencies for all atomic species increase concomitantly with increasing impact energy and plateau at the efficiency of about 50%. For low impact energies, the efficiency decreases with increasing mass of the impact atom at a given energy.
Modeling diffusion in restricted systems using the heat kernel expansion
Authors: Ghadirian Bahman , Stait-Gardner Tim , Castillo Reynaldo , Price William S.
Published: June 2010

The averaged return-to-origin probability of finding a diffusing particle within a volume or in the neighborhood of the surface of a bounded region can be separated into a volume and a surface integral of the corresponding probability densities. However with the usual treatments (e.g., the commonly encountered diffusion propagator approach) there is no clear method to separate the integration of the diffusion propagators in each domain. Here we propose a general procedure based on applying the heat kernel expansion in restricted diffusion problems for the Green’s function of the diffusion equation on an arbitrary region with an arbitrary boundary condition. We apply this method to the treatment of surface reaction rate in a sphere subject to the reflecting boundary condition. We determine that the rate of diffusion of a particle from the interior to the surface of the sphere changes by the square root of time plus some extra correction terms. Further, we are able to relate the diffusion propagator to the invariant properties of the region. Also in this approach we investigate how the heat kernel expansion can be applied to the problem of determining the return-to-origin probability, where we obtain a more precise result for the expansion of this probability in the case of a sphere. The advantage of this method lies in its generality and applicability to any geometrical boundary configuration and any kind of boundary condition.
Achieving anisotropy in metamaterials made of dielectric cylindrical rods
Authors: Peng L. , Ran Lixin , Mortensen N. A.
Published: June 2010

We show that anisotropic negative effective dispersion relation can be achieved in pure dielectric rod-type metamaterials by turning from the symmetry of a square lattice to that of a rectangular one. Theoretical predictions and conclusions are verified by both numerical calculations and computer based simulations. The proposed anisotropic metamaterial, is used to construct a refocusing slab lens and a subdiffraction hyperlens. The all-dielectric origin makes it more straightforward to address loss and scaling, thus facilitating future applications in both the terahertz and optical range.
Poly(3-hexylthiophene) crystalline nanoribbon network for organic field effect transistors
Authors: Arif M. , Liu Jianhua , Zhai Lei , Khondaker Saiful I.
Published: June 2010

We report on the fabrication of crystalline nanoribbon network field effect transistors (FETs) using low molecular weight (MW) poly(3-hexylthiophene) (P3HT) with different surface treatments and compare with thin film FETs cast from the same MW regioregular P3HT. Nanoribbon FET shows improved performance with a maximum mobility of 0.012 cm2/V s and current on/off ratios of 6.5×104 due to unique crystalline structure and morphology. With various surface treatments, the nanoribbon FETs show less variation in device mobilities, while thin film FETs show more than ten times variation in device mobilities and up to 100 times change in current on/off ratios.
Monitoring advanced oxidation of Suwannee River fulvic acid
Authors: Camp Janey V. , George Dennis B. , Wells Martha J. M. , Arce Pedro E.
Published: June 2010

Environmental context.Potentially toxic disinfection by-products form when water containing humic and fulvic acids is chlorinated to destroy pathogenic microorganisms. A pulsed electrical discharge was examined for its ability to destroy an aquatic fulvic acid by oxidation. Spectroscopically, changes in the organic structures were observed, but carbon content and disinfection by-products were not reduced.
Abstract.A pilot-scale pulsed electrical discharge (PED) system was used to treat Suwannee River fulvic acid (SRFA) as a representative precursor material for the formation of disinfection by-products (DBPs), specifically trihalomethane compounds. Ultraviolet-visible and fluorescence spectroscopy, dissolved organic carbon (DOC), and the trihalomethane formation potential (THMFP) were used as analytical parameters to monitor the effects of treatment on the substrate. The potential for SRFA degradation (5 mg L–1 DOC) was examined over 60 min at each of four operational configurations, varying pulse energy and frequency (0.15 J and 60 Hz, 0.15 J and 120 Hz, 0.4 J and 60 Hz, and 0.4 J and 120 Hz) in a factorial design. Statistically significant changes occurred for UV254, EX254EM460, and EX328EM460 under selected conditions; however, concomitant changes in DOC and THMFP were not observed. The composition of SRFA changed, but organic carbon was not mineralised to carbon dioxide. In addition to showing degradation by PED, the significance of the preliminary findings of this research was to demonstrate that spectroscopic monitoring of precursor degradation alone can be misleading, and that whereas ultraviolet-visible and fluorescence spectroscopy indicated degradation of precursor compounds, DOC and THMFP measurements were unchanged and did not support the occurrence of mineralisation in this system.
Palladium(II) sequestration by phytate in aqueous solution - speciation analysis and ionic medium effects
Authors: Gianguzza Antonio , Milea Demetrio , Pettignano Alberto , Sammartano Silvio
Published: June 2010

Environmental context.In the last 20 years, the demand for palladium and other platinum-group elements has intensified, causing a significant increase in their concentration in the environment, with particular accumulation in urban areas. Knowledge about Pd2+ speciation in aqueous media is fundamental for the understanding of its biological and environmental activity in contaminated areas. Phytic acid appears to be a good sequestering agent towards Pd2+ under various conditions, indicating its potential use in the remediation of contaminated sites.
Abstract. Palladium(II) speciation in the presence of phytate (Phy12–) was studied by H+ ion selective electrode (ISE) potentiometry at 25°C in NaNO3(aq) and in NaCl(aq) at ionic strength I = 0.1 mol L–1, in order to evaluate the effect of the ionic medium on the sequestering ability of phytate towards palladium(II). Owing to the discrepancies found in the literature on both the nature and the stability of hydrolytic species formed by this cation, Pd2+ hydrolysis was studied under the same experimental conditions as phytate/PdII measurements. As palladium(II) forms stable complex species with the chloride ion, the stability constants of various Pd2+–Cl– species were also calculated, as well as those of weak species formed with nitrate. The stability constants of six palladium(II)–phytate species, namely PdPhyOH11–, PdPhy10–, PdPhyH9–, PdPhyH28–, PdPhyH37– and PdPhyH46–, were determined. The sequestering ability of this ligand towards Pd2+ was evaluated by the calculation of various pL50 values (total ligand concentrations, as antilogarithm, necessary to bind the 50% of the metal ion as a trace present in the solution) under different conditions. Phytate sequestering ability towards palladium(II) was then compared with that towards other divalent cations under various conditions. Finally, the dependence of pL50 on pH was modelled by a simple empirical relationship.
Inducible Foxp3
+
regulatory T-cell development by a commensal bacterium of the intestinal microbiota
Authors: Round June L. , Mazmanian Sarkis K.
Published: June 2010

To maintain intestinal health, the immune system must faithfully respond to antigens from pathogenic microbes while limiting reactions to self-molecules. The gastrointestinal tract represents a unique challenge to the immune system, as it is permanently colonized by a diverse amalgam of bacterial phylotypes producing multitudes of foreign microbial products. Evidence from human and animal studies indicates that inflammatory bowel disease results from uncontrolled inflammation to the intestinal microbiota. However, molecular mechanisms that actively promote mucosal tolerance to the microbiota remain unknown. We report herein that a prominent human commensal,
Bacteroides fragilis
, directs the development of Foxp3
+
regulatory T cells (Tregs) with a unique “inducible” genetic signature. Monocolonization of germ-free animals with
B. fragilis
increases the suppressive capacity of Tregs and induces anti-inflammatory cytokine production exclusively from Foxp3
+
T cells in the gut. We show that the immunomodulatory molecule, polysaccharide A (PSA), of
B. fragilis
mediates the conversion of CD4
+
T cells into Foxp3
+
Treg cells that produce IL-10 during commensal colonization. Functional Foxp3
+
Treg cells are also produced by PSA during intestinal inflammation, and Toll-like receptor 2 signaling is required for both Treg induction and IL-10 expression. Most significantly, we show that PSA is not only able to prevent, but also cure experimental colitis in animals. Our results therefore demonstrate that
B. fragilis
co-opts the Treg lineage differentiation pathway in the gut to actively induce mucosal tolerance.
Kinesin-associated protein 3 (KIFAP3) has no effect on survival in a population-based cohort of ALS patients
Authors: Traynor Bryan J. , Nalls Michael , Lai Shiao-Lin , Gibbs Raphael J. , Schymick Jennifer C. , Arepalli Sampath , Hernandez Dena , van der Brug Marcel P. , Johnson Janel O. , Dillman Allissa , Cookson Mark , Moglia Cristina , Calvo Andrea , Restagno Gabriella , Mora Gabriele , Chiò Adriano
Published: June 2010

It was recently reported that rs1541160 on chromosome 1q24.2 has a marked effect on survival of amyotrophic lateral sclerosis (ALS) patients by influencing
KIFAP3
expression. The cohorts used in that study were collected from ALS specialty clinics. We attempted to replicate these findings in a population-based cohort of 504 Italian ALS patients. None of 140 SNPs genotyped within the
KIFAP3
locus (including rs1541160) had an effect on survival (log-rank
P
value for rs1541160 = 0.47) or on gene expression in that region. These data illustrate the complexities associated with analyzing ALS phenotypes for association.
Dissecting the THz spectrum of liquid water from first principles via correlations in time and space
Authors: Heyden Matthias , Sun Jian , Funkner Stefan , Mathias Gerald , Forbert Harald , Havenith Martina , Marx Dominik
Published: June 2010

Solvation of molecules in water is at the heart of a myriad of molecular phenomena and of crucial importance to understanding such diverse issues as chemical reactivity or biomolecular function. Complementing well-established approaches, it has been shown that laser spectroscopy in the THz frequency domain offers new insights into hydration from small solutes to proteins. Upon introducing spatially-resolved analyses of the absorption cross section by simulations, the sensitivity of THz spectroscopy is traced back to characteristic distance-dependent modulations of absorption intensities for bulk water. The prominent peak at ≈200 cm
-1
is dominated by first-shell dynamics, whereas a concerted motion involving the second solvation shell contributes most significantly to the absorption at about 80 cm
-1
≈2.4 THz. The latter can be understood in terms of an umbrella-like motion of two hydrogen-bonded tetrahedra along the connecting hydrogen bond axis. Thus, a modification of the hydrogen bond network, e.g., due to the presence of a solute, is expected to affect vibrational motion and THz absorption intensity at least on a length scale that corresponds to two layers of solvating water molecules. This result provides a molecular mechanism explaining the experimentally determined sensitivity of absorption changes in the THz domain in terms of distinct, solute-induced dynamical properties in solvation shells of (bio)molecules—even in the absence of well-defined resonances.
Localization-dependent activity of the Kv2.1 delayed-rectifier K
+
channel
Authors: O'Connell Kristen M. S. , Loftus Robert , Tamkun Michael M.
Published: June 2010

The Kv2.1 K
+
channel is highly expressed throughout the brain, where it regulates excitability during periods of high-frequency stimulation. Kv2.1 is unique among Kv channels in that it targets to large surface clusters on the neuronal soma and proximal dendrites. These clusters also form in transfected HEK cells. Following excessive excitatory stimulation, Kv2.1 declusters with an accompanying 20- to 30-mV hyperpolarizing shift in the activation threshold. Although most Kv2.1 channels are clustered, there is a pool of Kv2.1 resident outside of these domains. Using the cell-attached patch clamp technique, we investigated the hypothesis that Kv2.1 activity varies as a function of cell surface location. We found that clustered Kv2.1 channels do not efficiently conduct K
+
, whereas the nonclustered channels are responsible for the high threshold delayed rectifier K
+
current typical of Kv2.1. Comparison of gating and ionic currents indicates only 2% of the surface channels conduct, suggesting that the clustered channels still respond to membrane potential changes. Declustering induced via either actin depolymerization or alkaline phosphatase treatment did not increase whole-cell currents. Dephosphorylation resulted in a 25-mV hyperpolarizing shift, whereas actin depolymerization did not alter the activation midpoint. Taken together, these data demonstrate that clusters do not contain high threshold Kv2.1 channels whose voltage sensitivity shifts upon declustering; nor are they a reservoir of nonconducting channels that are activated upon release. On the basis of these findings, we propose unique roles for the clustered Kv2.1 that are independent of K
+
conductance.
Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner
Authors: Taubenfeld Stephen M. , Muravieva Elizaveta V. , Garcia-Osta Ana , Alberini Cristina M.
Published: June 2010

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.
Global fishery development patterns are driven by profit but not trophic level
Authors: Sethi Suresh A. , Branch Trevor A. , Watson Reg
Published: June 2010

Successful ocean management needs to consider not only fishing impacts but drivers of harvest. Consolidating post-1950 global catch and economic data, we assess which attributes of fisheries are good indicators for fishery development. Surprisingly, year of development and economic value are not correlated with fishery trophic levels. Instead, patterns emerge of profit-driven fishing for attributes related to costs and revenues. Post-1950 fisheries initially developed on shallow ranging species with large catch, high price, and big body size, and then expanded to less desirable species. Revenues expected from developed fisheries declined 95% from 1951 to 1999, and few high catch or valuable fishing opportunities remain. These results highlight the importance of economic attributes of species as leading indicators for harvest-related impacts in ocean ecosystems.
Retroviral Rem protein requires processing by signal peptidase and retrotranslocation for nuclear function
Authors: Byun Hyewon , Halani Nimita , Mertz Jennifer A. , Ali Almas F. , Lozano Mary M. , Dudley Jaquelin P.
Published: June 2010

Mouse mammary tumor virus (MMTV) is a complex murine retrovirus that encodes an HIV Rev-like export protein, Rem, from a doubly spliced version of envelope (Env) mRNA. Previously, the N-terminal 98-amino acid sequence of Rem, which is identical to Env signal peptide (SP), and full-length Rem were shown to be functional in a reporter assay that measures a postexport function. Here we show that MMTV-infected cells or cells transfected with
rem
or
env
cDNAs express SP, which is the active component in the reporter assay. Uncleaved Rem was partially glycosylated, but mutations in both glycosylation sites within the C terminus prevented Rem function. Mutations that reduced Rem or Env cleavage by signal peptidase greatly reduced SP levels and functional activity in the reporter assay and allowed accumulation of the uncleaved protein. Fluorescence microscopy revealed that GFP-tagged cleavage-site mutants are unstable and lack fluorescence compared with wild-type Rem, suggesting improper folding. Proteasome inhibitors allowed accumulation of uncleaved Rem relative to SP and increased reporter activity, consistent with SP retrotranslocation and proteasome escape before nuclear entry. Expression of a dominant-negative p97 ATPase did not alter levels of unprocessed Rem and SP but decreased reporter activity, suggesting p97-facilitated retrotranslocation of SP. Our results provide an example of a SP that is processed by signal peptidase and retrotranslocated to allow nuclear localization and function.
miR-33 links SREBP-2 induction to repression of sterol transporters
Authors: Marquart Tyler J. , Allen Ryan M. , Ory Daniel S. , Baldán Ángel
Published: June 2010

The sterol regulatory element binding protein 2 (SREBP-2) and the liver X receptor (LXR) control antagonistic transcriptional programs that stimulate cellular cholesterol uptake and synthesis, and cholesterol efflux, respectively. The clinical importance of SREBP-2 is revealed in patients with hypercholesterolemia treated with statins, which reduce low-density lipoprotein (LDL) cholesterol levels by increasing hepatic expression of SREBP-2 and its target, the LDL receptor. Here we show that miR-33 is encoded within SREBP-2 and that both mRNAs are coexpressed. We also identify sequences in the 3′ UTR of ABCA1 and ABCG1, sterol transporter genes both previously shown to be regulated by LXR, as targets for miR-33–mediated silencing. Our data show that LXR-dependent cholesterol efflux to both ApoAI and serum is ameliorated by miR-33 overexpression and, conversely, stimulated by miR-33 silencing. Finally, we show that ABCA1 mRNA and protein and plasma HDL levels decline after hepatic overexpression of miR-33, whereas they increase after hepatic miR-33 silencing. These results suggest novel ways to manage hypercholesterolemic patients.
NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection
Authors: Volakakis Nikolaos , Kadkhodaei Banafsheh , Joodmardi Eliza , Wallis Karin , Panman Lia , Silvaggi Jessica , Spiegelman Bruce M. , Perlmann Thomas
Published: June 2010

Induced expression of neuroprotective genes is essential for maintaining neuronal integrity after stressful insults to the brain. Here we show that NR4A nuclear orphan receptors are induced after excitotoxic and oxidative stress in neurons, up-regulate neuroprotective genes, and increase neuronal survival. Moreover, we show that NR4A proteins are induced by cAMP response element binding protein (CREB) in neurons exposed to stressful insults and that they function as mediators of CREB-induced neuronal survival. Animals with null mutations in three of sixNR4Aalleles show increased oxidative damage, blunted induction of neuroprotective genes, and increased vulnerability in the hippocampus after treatment with kainic acid. We also demonstrate that NR4A and the transcriptional coactivator PGC-1α independently regulate distinct CREB-dependent neuroprotective gene programs. These data identify NR4A nuclear orphan receptors as essential mediators of neuroprotection after exposure to neuropathological stress.
Does it Matter? Primary Teacher Trainees' Subject Knowledge in Mathematics
Authors: Goulding Maria , Rowland Tim , Barber Patti
Published: June 2010

The mathematical subject knowledge of primary teacher trainees in England and Wales now has to be audited in line with government requirements for initial teacher training. This article examines how this knowledge has been conceptualised and presents the results of research in two institutions into the audited subject knowledge of primary teacher trainees and its relationship with classroom teaching. The research identified weaknesses in understanding, particularly in the syntactic elements of mathematics, and a link between insecure subject knowledge and poor planning and teaching. The dilemmas and policy issues which this focus on subject knowledge presents are discussed.
Identifying the Probable Timing and Setting of Respiratory Virus Infections
Authors: Lessler Justin , Brookmeyer Ron , Reich Nicholas G. , Nelson Kenrad E. , Cummings Derek A. T. , Perl Trish M.
Published: June 2010

Objective.

Show how detailed incubation period estimates can be used to identify and investigate potential healthcare-associated infections and dangerous diseases.

Methods.

We used the incubation period of 9 respiratory viruses to derive decision rules for distinguishing between community- and hospital-acquired infection. We developed a method, implemented in a simple spreadsheet, that can be used to investigate the exposure history of an individual patient and more specifically to identify the probable time and location of infection. Illustrative examples are used to explain and evaluate this technique.

Results.

If the risks of hospital and community infection are equal, 95% of patients who develop symptoms of adenovirus infection within 5 days of hospital admission will have been infected in the community, as will 95% of patients who develop symptoms within 3 days for human-coronavirus infection, 2.5 days for severe acute respiratory syndrome, 1 day for influenza A, 0.5 day for influenza B, 12 days for measles, 2 days for parainfluenza, 4 days for respiratory syncytial virus infection, and 1.5 days for rhinovirus infection. Sources of infection suggested by analysis of the symptom onset times of individual patients are consistent with those from detailed investigations.

Conclusions.

This work shows how a detailed understanding of the incubation period can be an effective tool for identifying the source of infection, ultimately ensuring patient safety.
Integral models for Shimura varieties of abelian type
Authors: Kisin Mark
Published: June 2010

We construct smooth integral models of Shimura varieties of abelian type at primes where the level structure is hyperspecial.
Management of Pruritus
Authors: Uddin Ferhat
Published: June 2010

Pruritus, or itch, is a common sensation that causes a person to want to scratch. It is a complex process that commonly occurs with skin disorders such as xerotic eczema, atopic dermatitis and urticaria. It may also be related to an underlying disease process such as cholestasis or hyperthyroidism or simply be caused by dry skin, especially in the cold. Effective treatment of pruritus can prevent scratch-induced complications such as lichen simplex chronicus and impetigo. Therapy is often aimed at eliminating the underlying cause first, followed by the management of the itchy sensation.
Changing Indications for Upper Endoscopy in Children During a 20‐year Period
Authors: Franciosi James P , Fiorino Kristin , Ruchelli Eduardo , Shults Justine , Spergel Jonathan , Liacouras Chris A , Leonard Mary
Published: June 2010

Objectives:

In parallel with the increase in pediatric esophagogastroduodenoscopy (EGD) procedures since the 1970s, the incidence of disorders that require EGD for diagnosis in children has increased. The aim of this study was to identify changes in subject characteristics and endoscopic procedures during a 20‐year interval in children undergoing EGD at a single center.

Patients and Methods:

All of the children undergoing first EGD with biopsy in 1985, 1995, or 2005 were identified. Details of the clinical presentation and EGD were abstracted from medical records in a random sample of subjects within each time point.

Results:

The number of first‐time EGDs rose dramatically from 107 in 1985 to 1294 in 2005. The proportion of subjects that were younger than 1 year of age varied significantly from 13% in 1985 to 23% in 1995 and 8% in 2005 (P < 0.001). The proportion of subjects with gastrointestinal (GI) bleeding declined from 34% to 5% during the 20‐year interval (P < 0.001), whereas the proportion with abdominal pain increased from 23% to 43% (P < 0.01). During the same interval, the proportion of subjects with complete EGD (biopsies from the esophagus, stomach, and duodenum) increased from 18% of EGDs in 1985 to 95% in 2005 (P < 0.001).

Conclusions:

This study of children undergoing first‐time EGDs with biopsy during a 20‐year interval demonstrated significant differences in subject characteristics and endoscopy practices. The inclusion of children with less severe clinical presentation and the collection of greater numbers of biopsies per procedure may contribute to the rising incidence rates of pediatric GI disorders.
Role of Small Bowel Follow‐through in Diagnosing Inflammation of the Terminal Ileum in Pediatric Patients
Authors: Stenerson Matthew , Vittinghoff Eric , Heyman Melvin B , Kim Grace E , Gupta Neera
Published: June 2010

Background:

The small bowel follow‐through (SBFT) is a noninvasive imaging modality for evaluating terminal ileum (TI) inflammation. The accuracy of this modality in pediatric patients is not well established.

Patients and Methods:

We retrospectively determined the sensitivity and specificity of SBFT for detecting TI inflammation diagnosed on histology in 93 pediatric patients studied in a single institution.

Results:

The mean age at the first study was 12.9 years (range 1.1–20.9 years). Forty‐five percent were girls. Twenty‐five patients (27%) had abnormal TIs on SBFT. Seventeen patients (18%) had TI inflammation diagnosed by biopsy. The sensitivity of SBFT was 59% and the specificity was 80% for detecting TI inflammation diagnosed on histology. Sensitivity and specificity did not change by demographic factors, final diagnoses, presenting symptoms, or laboratory parameters, reflecting the presence of intestinal inflammation.

Conclusions:

The sensitivity and specificity of SBFT in pediatric patients were poor and did not vary with demographic factors, final diagnoses, presenting symptoms, or laboratory parameters. Prospective longitudinal studies comparing various imaging modalities (SBFT, magnetic resonance enterography, and capsule endoscopy) are required to determine which is the most effective tool for evaluating pediatric patients for TI inflammation.
Anastomotic Strictures Following Esophageal Atresia Repair: A 20‐year Experience With Endoscopic Balloon Dilatation
Authors: Antoniou Dimitris , Soutis Michael , Christopoulos‐Geroulanos George
Published: June 2010

Objectives:

The aim of the study was to evaluate the safety, effectiveness, and long‐term results of endoscopic balloon dilatation in children with anastomotic strictures following esophageal atresia (EA) repair.

Patients and Methods:

From January 1988 to January 2008, 59 patients were treated with balloon dilatation for anastomotic stricture following EA repair. Indication for dilatation was dysphagia of varying degree. Outcome parameters included the number of dilatations, response to dilatation, effectiveness, and complications. Response to dilatation was considered excellent when there was no need for any additional dilatation for recurrent dysphagia, satisfactory when up to 5 dilatations were required, and fair when >5 sessions were required. The treatment was considered effective when dysphagia was grade 0 or 1 for >12 months after the last dilatation session.

Results:

A total of 165 balloon dilatations were undertaken, with an average of 279 per patient (range 1–9). Age range at diagnosis was 1 to 36 months (mean 10.5). Response to dilatation was excellent in 21 cases (35.6%), satisfactory in 26 (44.1%), and fair in 12 (20.3%). The treatment was effective in 47 patients (79.7%) and ineffective in 12 (20.3%). The median follow‐up period was 19.5 months. Four patients underwent surgery; in 1 patient a retrievable stent was placed. No perforation occurred.

Conclusions:

Endoscopic balloon dilatation can be accomplished safely and effectively as a first‐line therapy for the management of anastomotic strictures following EA repair.