bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear of falling more important than pain and depression for functional recovery after surgery for hip fracture in older people
Authors: OUDE VOSHAAR RICHARD C. , BANERJEE SUBE , HORAN MIKE , BALDWIN ROBERT , PENDLETON NEIL , PROCTOR REBEKAH , TARRIER NICHOLAS , WOODWARD YVONNE , BURNS ALISTAIR
Published: July 2006

Background. Depression and cognitive functioning have a negative impact on functional recovery after hip fracture surgery in older people, and the same has been suggested for pain and fear of falling. These variables, however, have never been studied together, nor has the timing of psychiatric assessment been taken into account.

Method. Two parallel, randomized controlled trials were undertaken aiming to prevent and treat depression after hip fracture surgery in older people. Multiple logistic regression analyses corrected for age and pre-morbid level of functioning were performed to evaluate the effect of depressive symptoms (15-item Geriatric Depression Scale, GDS), pain (Wong–Baker pain scale), cognitive functioning (Mini-mental State Examination, MMSE) and fear of falling (Modified Falls Efficacy Scale, MFES) within 2 weeks after surgery and 6 weeks later on functional recovery at 6 months. Main outcome measures were performance-based measures (up-and-go test, gait test, functional reach) and the self-report Sickness Impact Profile (SIP) questionnaire to assess the impact of the hip fracture on activities of daily living (ADL).

Results. Two hundred and ninety-one patients participated and outcome measures for 187 (64%) patients were available at 6 months. All mental health variables interfered with functional recovery. However, in the final multivariate model, cognitive functioning and fear of falling assessed 6 weeks after surgery consistently predicted functional recovery, whereas pain and depressive symptoms were no longer significant.

Conclusion. Fear of falling and cognitive functioning may be more important than pain and depression to predict functional recovery after hip fracture surgery. Rehabilitation strategies should take this into account.
Without shame or desire: the pronouncements of Jesus on children and the kingdom, and early Syriac attitudes to childhood
Authors: Salvesen Alison
Published: July 2006

This paper demonstrates the techniques used by five Syriac writers of the mid-fourth to early sixth centuries in interpreting the dominical injunction in Matt 18:3 to become like children in order to enter the kingdom of Heaven. Unlike modern critical approaches, early Syriac exegesis of this saying is shaped less by the surrounding context than by association with other scriptural texts, in a manner more reminiscent of Jewish midrashic technique. The writers are Aphrahat, Ephrem, the author of the Book of Steps, Narsai and Jacob of Serugh. This study notes the interaction in some of the sources with their interpretation of Gen 2–3 and demonstrates the influence of the writers' pre-existing protology and eschatology on their exegesis of the New Testament passage. Recurring themes include whether Adam and Eve were believed to be children before the fall; whether the goal of the believer should be a return to a state of prelapsarian innocence; the existence of sexuality before the fall; and how to imitate angels as well as children. Key terms used in the sources are ̆sabrutā ‘infancy’ or ‘naivety’, and gmirutā ‘perfection’ or ‘maturity’, and the rather different concepts they represent in the five writers.
Feedback on second language students' writing
Authors: Hyland Ken , Hyland Fiona
Published: July 2006

Feedback is widely seen as crucial for encouraging and consolidating learning, and this significance has also been recognised by those working in the field of second language (L2) writing. Its importance is acknowledged in process-based classrooms, where it forms a key element of the students' growing control over composing skills, and by genre-oriented teachers employing scaffolded learning techniques. In fact, over the past twenty years, changes in writing pedagogy and research have transformed feedback practices, with teacher written comments often supplemented with peer feedback, writing workshops, conferences, and computer-delivered feedback. But while feedback is a central aspect of ESL/EFL writing programs across the world, the research literature has not been unequivocally positive about its role in writing development, and teachers often have a sense that they are not making use of its full potential. In this paper we examine recent research related to feedback on L2 students' writing, focusing on the role of feedback in writing instruction and discussing current issues relating to teacher written and oral feedback, collaborative peer feedback and computer-mediated feedback.
On matrix differential equations with several unbounded delays
Authors: ĈERMÁK J.
Published: July 2006

The paper focuses on the matrix differential equation \[ \dot y(t)=A(t)y(t)+\sum_{j=1}^{m}B_j(t)y(\tau_j(t))+f(t),\quad t\in I=[t_0,\infty)\vspace*{-3pt} \] with continuous matrices $A$, $B_j$, a continuous vector $f$ and continuous delays $\tau_j$ satisfying $\tau_k\circ\tau_l =\tau_l\circ\tau_k$ on $I$ for any pair $\tau_k,\tau_l$. Assuming that the equation \[ \dot y(t)=A(t)y(t)\] is uniformly exponentially stable, we present some asymptotic bounds of solutions $y$ of the considered delay equation. A system of simultaneous Schröder equations is used to formulate these asymptotic bounds.
ENSO‐controlled rainfall variability records archived in tropical stalagmites from the mid‐ocean island of Niue, South Pacific
Authors: Rasbury Michael , Aharon Paul
Published: July 2006

Niue Island is located in close proximity to the epicenter of the South Pacific Convergence Zone (SPCZ), and its rainfall variability is controlled by changes in the phase of the El Niño–Southern Oscillation (ENSO) phenomenon. Four actively growing stalagmites displaying couplets of light and dark calcite layers were sampled from a flank‐margin cave on Niue Island in order to determine the dominant climate factor controlling lamina thickness and establish the usefulness of the stalagmites as archives of ENSO variability records. Couplets counting, AMS radiocarbon assays, and growth rates analysis (mean growth rate: 0.34 ± 0.04 mm/yr for n = 604) support the premise that these couplets are annually deposited and their stalagmites contain records of up to two centuries long. Comparison of band thickness records with instrumental records of air temperature and rainfall kept on the island since 1930 and 1906, respectively, suggests that rainfall variability is the dominant controlling factor. Coherency between the spectral power of the annual layers unraveling periodicities at 2.4 and 5.4 years and that of annual and monsoon rainfall at 2.4–2.7 and 5.2 years corroborates the rainfall control on the band thickness variability of the Niuean stalagmites. Phase lags and amplitude discrepancies between rainfall and stalagmite records are attributed to the impact of torrential rains accompanying cyclones that occasionally struck the island. The excellent agreement between the periodicities prominent in the Niuean stalagmites and those typical of the ENSO phenomenon (2.4 and 4.3–6.0 years) suggests the latter exerts a dominant control on the stalagmite growth rates via rainfall variability. Interdecadal periodicities at 10, 14, and 30 years contained in the Niuean stalagmites spectral power are tentatively attributed to ENSO phase changes driven by the Inter‐Decadal Pacific Oscillation (IPO). The Niuean stalagmites, exhibiting relative fast growth rates and prominent layered sequences, hold promise to provide continuous century to millennium‐long high‐resolution atmospheric records of ENSO history that will complement and expand the sea surface temperature records archived in tropical Pacific corals.
Ten years of GOME/ERS‐2 total ozone data—The new GOME data processor (GDP) version 4: 1. Algorithm description
Authors: Van Roozendael M. , Loyola D. , Spurr R. , Balis D. , Lambert J.‐C. , Livschitz Y. , Valks P. , Ruppert T. , Kenter P. , Fayt C. , Zehner C.
Published: July 2006

The Global Ozone Monitoring Instrument (GOME) was launched on European Space Agency's ERS‐2 platform in April 1995. The GOME data processor (GDP) operational retrieval algorithm has generated total ozone columns since July 1995. In 2004 the GDP system was given a major upgrade to version 4.0, a new validation was performed, and the 10‐year GOME level 1 data record was reprocessed. In two papers, we describe the GDP 4.0 retrieval algorithm and present an error budget and sensitivity analysis (paper 1) and validation of the GDP total ozone product and the overall accuracy of the entire GOME ozone record (paper 2). GDP 4.0 uses an optimized differential optical absorption spectroscopy (DOAS) algorithm, with air mass factor (AMF) conversions calculated using the radiative transfer code linearized discrete ordinate radiative transfer (LIDORT). AMF computation is based on the TOMS version 8 ozone profile climatology, classified by total column, and AMFs are adjusted iteratively to reflect the DOAS slant column result. GDP 4.0 has improved wavelength calibration and reference spectra and includes a new molecular Ring correction to deal with distortion of ozone absorption features due to inelastic rotational Raman scattering effects. Preprocessing for cloud parameter estimation in GDP 4.0 is done using two new cloud correction algorithms: OCRA and ROCINN. For clear and cloudy scenes the precision of the ozone column product is better than 2.4 and 3.3%, respectively, for solar zenith angles up to 80°. Comparisons with ground‐based data are generally at the 1–1.5% level or better for all regions outside the poles.
Remote sensing of stratocumulus clouds: Uncertainties and biases due to inhomogeneity
Authors: Zinner T. , Mayer B.
Published: July 2006

Standard cloud remote sensing techniques rely on two basic assumptions: First, clouds are assumed to be plane‐parallel and homogeneous within each satellite pixel. Second, pixels are assumed independent and the net horizontal radiative transport between pixels is neglected. These assumptions cause considerable uncertainty and bias in the retrieval of cloud properties, which depend on the sensors spatial resolution as well as the illumination and observation geometry. The errors are quantified for several typical sensor settings. The basis of the investigation is a data set of high‐resolution three‐dimensional cloud property distributions of marine stratocumulus obtained from airborne radiance observations. For this predefined cloud data the sensor signals are simulated using a three‐dimensional Monte Carlo radiative transfer model. Cloud properties (optical thickness, effective radius) are retrieved for the simulated observations using a two‐channel retrieval, which are then compared to the given cloud data. For the retrieval of the optical thickness the main findings are large uncertainty of individual pixel values occurs for a high spatial resolution (e.g., airborne sensors) due to nonnegligible horizontal photon transport at this pixel size. For the typical polar‐orbiting and geostationary sensor settings the neglect of subpixel inhomogeneity takes effect as well. Nonetheless, biases are generally small within ±5%, if pixels are overcast. If this is not guaranteed, the bias grows rapidly, for example, to typical underestimations of 20% and more for a geostationary sensor. For the retrieval of effective radius values are generally found to be about 5% larger than expected for idealized homogeneous plane‐parallel cloud conditions.
Alternatives to stabilization scenarios
Authors: Frame D. J. , Stone D. A. , Stott P. A. , Allen M. R.
Published: July 2006

Studies attempting to constrain climate sensitivity, or equilibrium surface warming in response to a doubling of atmospheric carbon dioxide, by comparing models with observations report a wide range of distributions, particularly regarding the upper bound. There is, by contrast, a considerable consensus surrounding the transient climate response, in large part because it is directly related to observed warming attributable to greenhouse gases. We argue that scenarios which can exploit this consensus may be preferable to stabilization scenarios for practical policy‐making purposes. The difficulty of ruling out a high equilibrium warming response to elevated carbon dioxide levels may provide an opportunity for reassessment of the stabilization scenario as the centerpiece of climate policy in favour of scenarios that are more directly constrained by the transient response.
CO2 in the upper troposphere: Influence of stratosphere‐troposphere exchange
Authors: Shia Run‐Lie , Liang Mao‐Chang , Miller Charles E. , Yung Yuk L.
Published: July 2006

A two‐dimensional transport model constrained to measured surface CO2 concentrations was used to simulate the spatial and temporal variation of CO2 in the atmosphere for the period from 1975 to 2004. We find that the amplitude, phase and shape of the CO2 seasonal cycle vary as a function of both altitude and latitude. Cross tropopause exchanges, especially the downward branch of the Brewer‐Dobson circulation, which brings stratospheric air to the upper troposphere at middle and high latitudes, change the CO2 concentration and seasonal cycle in the extra‐tropics. The model results match recent aircraft measurements of CO2 in the upper troposphere (Matsueda et al., 2002) remarkably well. We conclude that upper tropospheric CO2 volume mixing ratios will provide a valuable tool for validating vertical transport. The implications of the CO2 variation caused by the stratosphere‐troposphere exchange for remote sensing of CO2 are discussed.
Magnetic reconnection induced by weak Kelvin‐Helmholtz instability and the formation of the low‐latitude boundary layer
Authors: Nakamura T. K. M. , Fujimoto M. , Otto A.
Published: July 2006

We have performed two‐dimensional two‐fluid simulations including finite electron inertial effects to investigate the role of Kelvin‐Helmholtz Instability (KHI) on the formation of Low‐Latitude Boundary Layer (LLBL). The results from a case in which the magnetic field components along the k‐vector of the KHI are anti‐parallel across the shear layer indicate that KHI forces magnetic reconnection as its flow compresses the current sheet in its early phase. Reconnection can be triggered even when the Alfven Mach number of the shear (MA) is small (2 < MA < 5: weak KHI). The reconnection process allows the vortex to highly roll‐up and thus to form a large scale mixing region. The results imply that the combination of anti‐parallel geometry and weak‐KHI may play an important role in the formation of the LLBL, which is obtained rather commonly for a realistic LLBL situation under northward IMF.
Magnetic tunnel junctions based on CrO2∕SnO2 epitaxial bilayers
Authors: Miao G. X. , LeClair P. , Gupta A. , Xiao G. , Varela M. , Pennycook S.
Published: July 2006

Magnetic tunnel junctions were fabricated using thin films of the half-metallic ferromagnet CrO2, employing SnO2 tunnel barriers. Heteroepitaxial CrO2∕SnO2 bilayers were grown on (100)-TiO2 substrates via chemical vapor deposition. X-ray diffraction and transmission electron microscopy confirmed heteroepitaxy. A polycrystalline cobalt film forms the top magnetic electrode, yielding CrO2(001)∕SnO2(001)∕Co structures after patterning. Tunneling magnetoresistances (TMR) up to +14% at 10K were observed. The sign of the TMR reverses for barrier thicknesses <1nm, attributed to tunneling being dominated by Co-3d states at low thicknesses and Co-4s states at larger thicknesses.
Ballisticity of nanotube field-effect transistors: Role of phonon energy and gate bias
Authors: Koswatta Siyuranga O. , Hasan Sayed , Lundstrom Mark S. , Anantram M. P. , Nikonov Dmitri E.
Published: July 2006

We investigate the role of electron-phonon scattering and gate bias in degrading the drive current of nanotube field-effect transistors (FETs). Optical phonon scattering significantly decreases the drive current only when gate voltage is higher than a well-defined threshold. For comparable electron-phonon coupling, a lower phonon energy leads to a larger degradation of drive current. Thus in semiconductor nanowire FETs, the drive current will be more sensitive than in carbon nanotube FETs because of the smaller phonon energies in semiconductors. Acoustic phonons and other elastic scattering mechanisms are most detrimental to nanotube FETs irrespective of biasing conditions.
Field emission study of SiC nanowires/nanorods directly grown on SiC ceramic substrate
Authors: Deng S. Z. , Li Z. B. , Wang W. L. , Xu N. S. , Zhou Jun , Zheng X. G. , Xu H. T. , Chen Jun , She J. C.
Published: July 2006

Single crystalline silicon carbide (SiC) nanowires were grown directly on the surface of bulk SiC ceramic substrate in a catalyst-assisted thermal heating process. The morphology of the nanowire film and the diameter of nanowires were found to be sensitive to the thickness of catalyst film and both of them had a strong effect on field emission performance. Very low turn-on and threshold fields for electron emission were observed with SiC nanowires of small diameter. A model is proposed to qualitatively explain the field emission findings, which assumes the occurrence of an insulator-to-metal-like transition in a field emitting nanowire.
Heat conduction in graphite-nanoplatelet-reinforced polymer nanocomposites
Authors: Hung M.-T. , Choi O. , Ju Y. S. , Hahn H. T.
Published: July 2006

Heat transport in polymer nanocomposites reinforced with graphite nanoplatelets (GNPs) is studied using high-precision thermal conductivity measurements. The resistance to heat conduction across interfaces between GNPs and the polymer matrix has a strong effect on energy transport in the nanocomposites. The thermal conductivity is observed to increase when GNPs are pretreated with nitric acid to improve interfacial bonding. The improvement in the thermal conductivity, however, is much smaller than the corresponding improvement in mechanical properties. The thermal interface resistance extracted from the present thermal conductivity data is comparable to that obtained from the previously reported data on carbon nanotube suspensions.
Coarse-grained model for a molecular crystal
Authors: Gee Richard H. , Wu Christine , Maiti Amitesh
Published: July 2006

Using the energetic material pentaerythritol tetranitrate as a specific example of molecular crystal, we describe the development of a simple coarse-graining procedure by grouping several atoms or whole functional groups into single charge-neutral beads. As compared to fully atomistic calculations the coarse-grained model speeds up simulations by more than two orders of magnitude. Yet, by adjusting only two parameters in the coarse-grained interaction, the model accurately predicts the lattice constants, sublimation energy, pressure-volume curve up to P=10GPa, and energetically the most stable facets. Computed surface and desorption energies, bulk modulus, and equilibrium morphology are reported as well.
Experimental studies on intermediate compound of LiBH4
Authors: Orimo Shin-Ichi , Nakamori Yuko , Ohba Nobuko , Miwa Kazutoshi , Aoki Masakazu , Towata Shin-ichi , Züttel Andreas
Published: July 2006

The formation condition of an intermediate compound of LiBH4 during the partial dehydriding reaction and its local atomistic structure have been experimentally investigated. LiBH4 changes into an intermediate compound accompanying the release of approximately 11mass% of hydrogen at 700–730K. The Raman spectra indicate that the B–H bending and stretching modes of the compound appear at lower and higher frequencies, respectively, as compared to those of LiBH4. These features are consistent with the theoretical calculation on the monoclinic Li2B12H12, consisting of Li+ and [B12H12]2− ions, as a possible intermediate compound of LiBH4.
Growth of epitaxial thin films of the ordered double perovskite La2NiMnO6 on different substrates
Authors: Guo H. , Burgess J. , Street S. , Gupta A. , Calvarese T. G. , Subramanian M. A.
Published: July 2006

Epitaxial thin films of La2NiMnO6, a ferromagnetic semiconductor, have been fabricated on different substrates by pulsed laser deposition. The x-ray diffraction and Raman scattering observations reveal that the films are single crystalline and have an orthorhombic structure. The magnetic properties of the films, including the coercive field, remanent magnetization, and Curie temperature, are strongly dependent on the choice of the substrate. The optimized films exhibit a magnetic moment of 4.63μB∕f.u. at 5K, with a Curie temperature close to 280K. The film characteristics are promising for potential device applications in information storage, spintronics, and sensors.
Low-frequency vortex dynamic susceptibility and relaxation in mesoscopic ferromagnetic dots
Authors: Guslienko K. Yu.
Published: July 2006

Vortex dynamics in a restricted geometry is considered for a magnetic system consisting of ferromagnetic cylindrical dots. To describe the vortex dynamic susceptibility and relaxation the equation of motion for the vortex center position is applied. The dependencies of the vortex dynamic susceptibility and resonance linewidth on geometrical parameters are calculated. A method of extracting damping parameter from the vortex low-frequency resonance peaks is proposed and applied for interpretation of resonance data on FeNi circular dots.
Direct observation of DNA rotation during branch migration of Holliday junction DNA by
Escherichia coli
RuvA–RuvB protein complex
Authors: Han Yong-Woon , Tani Tomomi , Hayashi Masahito , Hishida Takashi , Iwasaki Hiroshi , Shinagawa Hideo , Harada Yoshie
Published: July 2006

The
Escherichia coli
RuvA–RuvB complex promotes branch migration of Holliday junction DNA, which is the central intermediate of homologous recombination. Like many DNA motor proteins, it is suggested that RuvA–RuvB promotes branch migration by driving helical rotation of the DNA. To clarify the RuvA–RuvB-mediated branch migration mechanism in more detail, we observed DNA rotation during Holliday junction branch migration by attaching a bead to one end of cruciform DNA that was fixed to a glass surface at the opposite end. Bead rotation was observed when RuvA, RuvB, and ATP were added to the solution. We measured the rotational rates of the beads caused by RuvA–RuvB-mediated branch migration at various ATP concentrations. The data provided a
K
m
value of 65 μM and a
V
max
value of 1.6 revolutions per second, which corresponds to 8.3 bp per second. This real-time observation of the DNA rotation not only allows us to measure the kinetics of the RuvA–RuvB-mediated branch migration, but also opens the possibility of elucidating the branch migration mechanism in detail.
Liprin-α is required for photoreceptor target selection in
Drosophila
Authors: Choe Kwang-Min , Prakash Saurabh , Bright Ali , Clandinin Thomas R.
Published: July 2006

Classical cadherin-mediated interactions between axons and dendrites are critical to target selection and synapse assembly. However, the molecular mechanisms by which these interactions are controlled are incompletely understood. In the
Drosophila
visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection. Here we identify the scaffolding protein Liprin-α as a critical component in this process. We isolated mutations in
Liprin
-α in a genetic screen for mutations affecting the pattern of synaptic connections made by R1–R6 photoreceptors. Using eye-specific mosaics, we demonstrate a previously undescribed, axonal function for
Liprin
-α in target selection: Liprin-α is required to be cell-autonomous in all subtypes of R1–R6 cells for their axons to reach their targets. Because Liprin-α, the receptor tyrosine phosphatase LAR, and N-cadherin share qualitatively similar mutant phenotypes in R1–R6 cells and are coexpressed in R cells and their synaptic targets, we infer that these three genes act at the same step in the targeting process. However, unlike N-cadherin, neither Liprin-α nor LAR is required postsynaptically for R cells to project to their correct targets. Thus, these two proteins, unlike N-cadherin, are functionally asymmetric between axons and dendrites. We propose that the adhesive mechanisms that link pre- and postsynaptic cells before synapse formation may be differentially regulated in these two compartments.
Regulation of T cell activation and tolerance by PDL2
Authors: Zhang Yongliang , Chung Yeonseok , Bishop Caroline , Daugherty Betsy , Chute Hilary , Holst Paige , Kurahara Carole , Lott Fred , Sun Ning , Welcher Andrew A. , Dong Chen
Published: July 2006

T cell activation and tolerance are regulated by costimulatory molecules. Although PD-1 serves as a crucial negative regulator of T cells, the function of its ligands, PDL1 and PDL2, is still controversial. In this study, we created a PDL2-deficient mouse to characterize its function in T cell activation and tolerance. Antigen-presenting cells from PDL2−/− mice were found to be more potent in activation of T cells
in vitro
over the wild-type controls, which depended on PD-1. Upon immunization with chicken ovalbumin, PDL2−/− mice exhibited increased activation of CD4
+
and CD8
+
T cells
in vivo
when compared with WT animals. In addition, T cell tolerance to an oral antigen was abrogated by the lack of PDL2. Our results thus demonstrate that PDL2 negatively regulates T cells in immune responses and plays an essential role in immune tolerance.
Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration
Authors: Muñoz-Pinedo Cristina , Guío-Carrión Ana , Goldstein Joshua C. , Fitzgerald Patrick , Newmeyer Donald D. , Green Douglas R.
Published: July 2006

The release of mitochondrial intermembrane space proteins to the cytosol is a key event during apoptosis. We used
in situ
fluorescent labeling of proteins tagged with a short tetracysteine-containing sequence to follow the release of Smac, Omi, adenylate kinase-2, cytochrome
c
, and apoptosis-inducing factor (AIF) during apoptosis and compared the release with that of cytochrome
c
tagged with GFP in individual cells observed over time. We observed a caspase-independent, simultaneous release of cytochrome
c
, Smac, Omi, and adenylate kinase-2. Although AIF release also was caspase-independent and commenced with that of the other proteins, it proceeded much more slowly and incompletely from mitochondria, perhaps because of a requirement for a secondary event. These results suggest that these proteins are released through the same mitochondrial pore and that apoptosis may not be regulated through a selective release of individual mitochondrial proteins. The timing and extent of AIF release makes it unlikely that it is involved in the induction of apoptosis, either upstream or downstream of mitochondrial outer membrane permeabilization.
Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function
Authors: Wang Chenguang , Li Zhiping , Lu Yinan , Du Runlei , Katiyar Sanjay , Yang Jianguo , Fu Maofu , Leader Jennifer E. , Quong Andrew , Novikoff Phyllis M. , Pestell Richard G.
Published: July 2006

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein,
cyclin D1
deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.
Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy
Authors: Shou Yan , Ma Zhijun , Lu Taihe , Sorrentino Brian P.
Published: July 2006

Although gene therapy can cure patients with severe combined immunodeficiency (SCID) syndromes, the clinical occurrence of T cell malignancies due to insertional mutagenesis has raised concerns about the safety of gene therapy. Several key questions have remained unanswered: (i) are there unique risk factors for X-linked SCID (XSCID) gene therapy that increase the risk of insertional mutagenesis; (ii) what other genetic lesions may contribute to transformation; and (iii) what systems can be used to test different vectors for their relative safety? To address these questions, we have developed an XSCID mouse model in which both theArftumor-suppressor gene and the γcgene were ablated. Gene therapy in this animal model recapitulates the high incidence of integration-dependent, T cell tumors that was seen in the clinical trial. Ligation-mediated PCR analysis showed integration sites near or within established protooncogenes (Chd9,Slamf6,Tde1,Camk2b, andLy6e), demonstrating that T cell transformation was associated with targeting of oncogene loci; however, no integrations within theLmo2locus were identified. The X-SCID background in transplanted cells was required for high rate transformation and was associated with expansion of primitive hematopoietic cells that may serve tumor precursors. This model should be useful for testing safety-modified vectors and for further exploring the risk factors leading to insertional mutagenesis in gene therapy trials.
Noninvasive imaging of islet grafts using positron-emission tomography
Authors: Lu Yuxin , Dang Hoa , Middleton Blake , Zhang Zesong , Washburn Lorraine , Stout David B. , Campbell-Thompson Martha , Atkinson Mark A. , Phelps Michael , Gambhir Sanjiv Sam , Tian Jide , Kaufman Daniel L.
Published: July 2006

Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET.
B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia
Authors: Yan Xiao-jie , Albesiano Emilia , Zanesi Nicola , Yancopoulos Sophia , Sawyer Alan , Romano Egidio , Petlickovski Aleksandar , Efremov Dimitar G. , Croce Carlo M. , Chiorazzi Nicholas
Published: July 2006

B cell chronic lymphocytic leukemia (B-CLL) is a clonal overgrowth of CD5+B lymphocytes. In this disease, the B cell antigen receptor (BCR) is intimately linked to disease severity, because patients with BCRs, comprised of unmutated VHgenes, follow a much more aggressive course. This and related observations suggest that B-CLL derives from a B cell subset comprised of restricted BCR structural diversity and that antigen-selection and drive are major factors promoting the disease. Nevertheless, the initiating event(s) that lead to the development of B-CLL are still unclear, in part because of the lack of an animal model that spontaneously evolves the molecular abnormalities that occur in the human disease. Because overexpression of the TCL1 gene in murine B cells leads to a CD5+B cell lymphoproliferative disorder with many of the features of human B-CLL, we studied leukemias emerging in these mice to examine the extent to which their BCRs resemble those in B-CLL. Our data indicate that the immunoglobulin heavy and light chain rearrangements in TCL1 mice display minimal levels of somatic mutations and exhibit several molecular features found in the human disease. Like human B-CLL, TCL1 leukemic rearrangements from different mice can be very similar structurally and closely resemble autoantibodies and antibodies reactive with microbial antigens. Antigen-binding analyses confirm that selected TCL1 clones react with glycerophospholipid, lipoprotein, and polysaccharides that can be autoantigens and be expressed by microbes. This (auto)antigen-driven mouse model reliably captures the BCR characteristics of aggressive, treatment-resistant human B-CLL.
Liprin-α has LAR-independent functions in R7 photoreceptor axon targeting
Authors: Hofmeyer Kerstin , Maurel-Zaffran Corinne , Sink Helen , Treisman Jessica E.
Published: July 2006

In the
Drosophila
visual system, the color-sensing photoreceptors R7 and R8 project their axons to two distinct layers in the medulla. Loss of the receptor tyrosine phosphatase LAR from R7 photoreceptors causes their axons to terminate prematurely in the R8 layer. Here we identify a null mutation in the
Liprin
-α gene based on a similar R7 projection defect. Liprin-α physically interacts with the inactive D2 phosphatase domain of LAR, and this domain is also essential for R7 targeting. However, another LAR-dependent function, egg elongation, requires neither
Liprin
-α nor the LAR D2 domain. Although human and
Caenorhabditis elegans
Liprin-α proteins have been reported to control the localization of LAR, we find that LAR localizes to focal adhesions in
Drosophila
S2R+ cells and to photoreceptor growth cones
in vivo
independently of Liprin-α. In addition,
Liprin
-α overexpression or loss of function can affect R7 targeting in the complete absence of
LAR
. We conclude that Liprin-α does not simply act by regulating LAR localization but also has LAR-independent functions.
Macromolecular-scale resolution in biological fluorescence microscopy
Authors: Donnert Gerald , Keller Jan , Medda Rebecca , Andrei M. Alexandra , Rizzoli Silvio O. , Lührmann Reinhard , Jahn Reinhard , Eggeling Christian , Hell Stefan W.
Published: July 2006

We demonstrate far-field fluorescence microscopy with a focal-plane resolution of 15–20 nm in biological samples. The 10- to 12-fold multilateral increase in resolution below the diffraction barrier has been enabled by the elimination of molecular triplet state excitation as a major source of photobleaching of a number of dyes in stimulated emission depletion microscopy. Allowing for relaxation of the triplet state between subsequent excitation–depletion cycles yields an up to 30-fold increase in total fluorescence signal as compared with reported stimulated emission depletion illumination schemes. Moreover, it enables the reduction of the effective focal spot area by up to ≈140-fold below that given by diffraction. Triplet-state relaxation can be realized either by reducing the repetition rate of pulsed lasers or by increasing the scanning speed such that the build-up of the triplet state is effectively prevented. This resolution in immunofluorescence imaging is evidenced by revealing nanoscale protein patterns on endosomes, the punctuated structures of intermediate filaments in neurons, and nuclear protein speckles in mammalian cells with conventional optics. The reported performance of diffraction-unlimited fluorescence microscopy opens up a pathway for addressing fundamental problems in the life sciences.
Switching between Methadone and Morphine for Maintenance Treatment of Opioid Dependence: Impact on Pain Sensitivity and Mood Status
Authors: Mitchell Timothy B. , White Jason M. , Somogyi Andrew A. , Bochner Felix
Published: July 2006

Methadone maintenance is associated with hyperalgesia and elevated mood disturbance—effects opposite to those induced by acute opioid administration, which may undermine outcomes during substitution therapy. This study examined the impact of switching between methadone and slow‐release morphine on pain sensitivity and mood status in 14 methadone maintenance patients using an open‐label crossover design. Pain responses were nearly identical for each drug. Patients reporting inadequate withdrawal suppression on methadone showed greater mood stability when transferred to morphine, but overall mood disturbance levels did not differ between drugs. Hyperalgesia and mood disturbance cannot be resolved by changing from methadone to morphine maintenance.
Mannose receptor regulates myoblast motility and muscle growth
Authors: Jansen Katie M. , Pavlath Grace K.
Published: July 2006

Myoblast fusion is critical for the formation, growth, and maintenance of skeletal muscle. The initial formation of nascent myotubes requires myoblast–myoblast fusion, but further growth involves myoblast–myotube fusion. We demonstrate that the mannose receptor (MR), a type I transmembrane protein, is required for myoblast–myotube fusion. Mannose receptor (MR)–null myotubes were small in size and contained a decreased myonuclear number both in vitro and in vivo. We hypothesized that this defect may arise from a possible role of MR in cell migration. Time-lapse microscopy revealed that MR-null myoblasts migrated with decreased velocity during myotube growth and were unable to migrate in a directed manner up a chemoattractant gradient. Furthermore, collagen uptake was impaired in MR-null myoblasts, suggesting a role in extracellular matrix remodeling during cell motility. These data identify a novel function for MR during skeletal muscle growth and suggest that myoblast motility may be a key aspect of regulating myotube growth.
Wavelet packet denoising for online partial discharge detection in cables and its application to experimental field results
Authors: Kyprianou A , Lewin P L , Efthimiou V , Stavrou A , Georghiou G E
Published: July 2006

Partial discharge measurements taken online are severely corrupted by noise due to external disturbances. In this paper a powerful noise reduction technique, based on a wavelet packet denoising algorithm, is employed to isolate the signals from the noise. This methodology enables the denoising of partial discharges that are heavily corrupted by noise without assuming anya prioriknowledge about the partial discharge features. A brief description of the wavelet packet theory as an extension of the multi-resolution analysis is given. Results of the application of this algorithm to simulated data of low signal-to-noise ratio are presented, demonstrating substantial improvement in signal recovery with minimum shape distortion. Finally, the capability of this technique is highlighted by applying it to experimental field data taken from three-phase 11 kV cables.
arrayQCplot: software for checking the quality of microarray data
Authors: Lee Eun-Kyung , Yi Sung-Gon , Park Taesung
Published: July 2006

Summary: arrayQCplot is a software for the exploratory analysis of microarray data. This software focuses on quality control and generates newly developed plots for quality and reproducibility checks. It is developed using R and provides a user-friendly graphical interface for graphics and statistical analysis. Therefore, novice users will find arrayQCplot as an easy-to-use software for checking the quality of their data by a simple mouse click.

Availability: arrayQCplot software is available from Bioconductor at A more detailed manual is available at

Contact:  tspark@stats.snu.ac.kr
Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients
Authors: Egi Moritoki , Bellomo Rinaldo , Stachowski Edward , French Craig J. , Hart Graeme
Published: July 2006

Background

Intensive insulin therapy may reduce mortality and morbidity in selected surgical patients. Intensive insulin therapy also reduced the SD of blood glucose concentration, an accepted measure of variability. There is no information on the possible significance of variability in glucose concentration.

Methods

The methods included extraction of blood glucose values from electronically stored biochemical databases and of data on patient's characteristics, clinical features, and outcome from electronically stored prospectively collected patient databases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statistical assessment of the relation between these variables and intensive care unit mortality.

Results

There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly measurements on average). The mean +/- SD of blood glucose concentration was 1.7 +/- 1.3 mM in survivors and 2.3 +/- 1.6 mM in nonsurvivors (P < 0.001). Using multiple variable logistic regression analysis, both mean and SD of blood glucose were significantly associated with intensive care unit mortality (P < 0.001; odds ratios [per 1 mM] 1.23 and 1.27, respectively) and hospital mortality (P < 0.001 and P = 0.013; odds ratios [per 1 mM] 1.21 and 1.18, respectively).

Conclusions

The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mortality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management.
Human Opioid Receptor A118G Polymorphism Affects Intravenous Patient-controlled Analgesia Morphine Consumption after Total Abdominal Hysterectomy
Authors: Chou Wen-Ying , Wang Cheng-Haung , Liu Ping-Hsin , Liu Chien-Cheng , Tseng Chia-Chih , Jawan Bruno
Published: July 2006

Background

Animal and human studies indicate that genetics may contribute to the variability of morphine efficacy. A recent report suggested that cancer patients homozygous for the 118G allele caused by the single nucleotide polymorphism at nucleotide position 118 in the mu-opioid receptor gene require higher doses of morphine to relieve pain. The purpose of the current study was to investigate whether this polymorphism contributes to the variability of morphine efficacy in women who undergo abdominal total hysterectomy.

Methods

After informed consent was obtained, 80 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective total hysterectomy surgery were enrolled in this study. All patients received general anesthesia and were screened for A118G polymorphism by blood sample. Intravenous morphine patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The authors recorded the morphine consumption doses and demand times. Pain at rest and side effects were measured with rating scales.

Results

Forty-three women were A118 homozygous, 19 were heterozygous, and 18 were G118 homozygous. Patients homozygous for G118 required more morphine doses (33 +/- 10 mg) to achieve adequate pain relief compared with patients homozygous for A118 (27 +/- 10 mg) in the first 24 h (P = 0.02). However, there was no statistically significant difference for morphine consumption at 48 h.

Conclusion

Genetic variation of the mu-opioid receptor may contribute to interindividual differences in postoperative morphine consumption. In the future, identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control.
Effects of Aging on Current Vocalization Threshold in Mice Measured by a Novel Nociception Assay
Authors: Finkel Julia C. , Besch Virginia G. , Hergen Adrienne , Kakareka John , Pohida Thomas , Melzer Jonathan M. , Koziol Deloris , Wesley Robert , Quezado Zenaide M. N.
Published: July 2006

Background

Age-related changes in nociception have been extensively studied in the past decades. However, it remains unclear whether in addition to the increased incidence of chronic illness, age-related changes in nociception contribute to increased prevalence of pain in the elderly. Although a great deal of evidence suggests that nociception thresholds increase with aging, other studies yield disparate results. The aim of this investigation was to longitudinally determine the effect of aging on nociception.

Methods

The authors developed a nociception assay for mice using electrical stimuli at 2,000, 250, and 5 Hz that reportedly stimulate Abeta, Adelta, and C sensory nerve fibers, respectively. A system was designed to automate a method that elicits and detects pain-avoiding behavior in mice. Using a Latin square design, the authors measured current vocalization thresholds serially over the course of mice's life span.

Results

For 2,000-Hz (Abeta), 250-Hz (Adelta), and 5-Hz (C) electrical stimuli, current vocalization thresholds first decreases and then increases with aging following a U-shaped pattern (P < 0.001). In addition, average current vocalization thresholds at youth and senescence are significantly higher than those at middle age for the 250-Hz (Adelta) and 5-Hz (C fiber) electrical stimulus (P < 0.05).

Conclusions

Using a novel and noninjurious nociception assay, the authors showed that over the life span of mice, current vocalization threshold to electrical stimuli changes in a U-shaped pattern. The findings support the notion that age-related changes in nociception are curvilinear, and to properly study and treat pain, the age of subjects should be considered.
Influence of intrapyloric botulinum toxin injection on gastric emptying and meal‐related symptoms in gastroparesis patients
Authors: ARTS J. , VAN GOOL S. , CAENEPEEL P. , VERBEKE K. , JANSSENS J. , TACK J.
Published: July 2006

Background

Recent observations in limited numbers of patients suggest a potential benefit of intrapyloric injection of botulinum toxin in the treatment of gastroparesis.

Aim

To characterize the effect of botulinum toxin on solid and liquid gastric emptying and on meal‐related symptoms.

Methods

In 20 gastroparesis patients (17 women, mean age 37 ± 3 years, three diabetic and 17 idiopathic), gastric emptying for solids and liquids was measured before and one month after intrapyloric botulinum toxin 4 × 25 units. Before the meal and at 15‐min intervals up to 240 min postprandially, the patient graded the intensity of six gastroparesis symptoms, and a meal‐related severity score was obtained by adding all intensities. Data (mean ± S.E.M.) were compared using paired Student's t‐test.

Results

Treatment with botulinum toxin significantly enhanced solid (t1/2 132 ± 16 vs. 204 ± 35 min, P < 0.05) but not liquid (92 ± 10 vs. 104 ± 11 min, N.S.) emptying. This was accompanied by a significant decrease in cumulative meal‐related symptom score (73.5 ± 16.3 vs. 103 ± 17.1 baseline, P = 0.01) as well as individual severity scores for postprandial fullness, bloating, nausea and belching (all P < 0.001, two‐way anova).

Conclusions

Botulinum toxin improves solid but not liquid gastric emptying in gastroparesis, and this is accompanied by significant improvement of several meal‐related symptoms.