bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Rydberg states in photoionization of NO2 and (NO+, O−) ion pair formation induced by one VUV photon
Authors: Marggi Poullain S. , Veyrinas K. , Billaud P. , Lebech M. , Picard Y. J. , Lucchese R. R. , Dowek D.
Published: July 2013

We report a combined experimental and theoretical study of photoionization (PI) of the NO2 molecule into the NO2+ (X 1Σg+) ground state and the photodissociation of NO2 into the NO+(1Σ+) + O−(2P) ion pair. These processes were induced by 10.9 eV–13 eV synchrotron radiation and the products were detected using electron-ion or O−–NO+ coincident momentum spectroscopy. The results demonstrate the strong influence of [R*(4b2)−1, nlαi, $v_2^\prime $v2′] Rydberg states vibrationally resolved in the $v_2^\prime $v2′ bending modes for both processes. In particular, we emphasize two regions around 11.5 eV and 12.5 eV that were studied in more detail for their relevance to 400 nm multiphoton ionization induced by femtosecond pulses. The photoelectron energy spectra and asymmetry parameters support the existence of two PI mechanisms, as probed with the help of fixed-nuclei frozen-core Hartree-Fock calculations. We found significant deviations from Franck-Condon ionization predictions which may be assigned to vibronic coupling of NO2* states such as that induced by a conical intersection. The limited agreement between theory and experiment, even for the non-resonant processes, indicates the need for calculations that go beyond the approximations used in the current study. Ion pair formation leads to strong vibrational and rotational excitation of the NO+(1Σ+,v) product, with an ion fragment angular anisotropy depending on both the $v_2^\prime $v2′ bending quantum number of the excited parent molecule and the v vibrational level of the fragment.
A dynamic regularized gradient model of the subgrid-scale scalar flux for large eddy simulations
Authors: Balarac G. , Le Sommer J. , Meunier X. , Vollant A.
Published: July 2013

Accurate predictions of scalar fields advected by a turbulent flow is needed for various industrial and geophysical applications. In the framework of large-eddy simulation (LES), a subgrid-scale (SGS) model for the subgrid-scale scalar flux has to be used. The gradient model (GM), which is derived from a Taylor series expansions of the filtering operation, is a well-known approach to model SGS scalar fluxes. This model is known to lead to high correlation level with the SGS scalar flux. However, this type of model cannot be used in practical LES because it does not lead to enough global scalar variance transfer from the large to the small scales. In this work, a regularization of the GM is proposed based on a physical interpretation of this model. The impact of the resolved velocity field on the resolved scalar gradient is decomposed into compressional, stretching, and rotational effects. It is shown that rotational effect is not associated with transfers of variance across scales. Conversely, the compressional effect is shown to lead to forward transfer, whereas the stretching effect leads to back-scatter of scalar variance. The proposed regularization is to neglect the stretching effect in the model formulation. The accuracy of this regularized gradient model (RGM) is tested in comparison with direct numerical simulations and compared with other classic SGS models. The accuracy of the RGM is evaluated in term of structural and functional performances, i.e., the model ability to locally approximate the SGS unknown term and to reproduce its global effect on tracer variance, respectively. It is found that the RGM associated with a dynamic procedure exhibits good performances in comparison with the standard dynamic eddy diffusivity model and the standard gradient model. In particular, the dynamic regularized gradient model (DRGM) provides a better prediction of scalar variance transfers than the standard gradient model. The DRGM is then evaluated in a series of large-eddy simulations. This shows a substantial improvement for various scalar statistics predictions.
Polarization sensitive optical low-coherence reflectometry for blood glucose monitoring in human subjects
Authors: Solanki Jitendra , Choudhary Om Prakash , Sen P. , Andrews J. T.
Published: July 2013

A device based on polarization sensitive optical low-coherence reflectometry is developed to monitor blood glucose levels in human subjects. The device was initially tested with tissue phantom. The measurements with human subjects for various glucose concentration levels are found to be linearly dependent on the ellipticity obtainable from the home-made phase-sensitive optical low-coherence reflectometry device. The linearity obtained between glucose concentration and ellipticity are explained with theoretical calculations using Mie theory. A comparison of results with standard clinical methods establishes the utility of the present device for non-invasive glucose monitoring.
Energy and shape relaxation in binary atomic systems with realistic quantum cross sections
Authors: Sospedra-Alfonso Reinel , Shizgal Bernie D.
Published: July 2013

We use the spatially homogeneous linear Boltzmann equation to study the time evolution of an initial non-equilibrium distribution function of an ensemble of test particles dilutely dispersed in a background gas at thermal equilibrium. The systems considered are energetic N in He and Xe in He. We employ the quantum mechanical differential cross section to define the collision operator in the Boltzmann equation. The Boltzmann equation is solved with a moment method based on the expansion of the distribution function in the Sonine (Laguerre) polynomials as well as with a direct simulation Monte Carlo method. The moment method provides the approximate eigenvalues and eigenfunctions of the linear Boltzmann collision operator. The reciprocal of the eigenvalues is a measure of the relaxation times to equilibrium. For hard sphere cross sections, the relaxation of the average energy and the shape of the distribution function can be characterized by a single time scale determined by the momentum transfer cross section. We show that this is also the case for realistic quantum cross sections with dominant small angle scattering contributions.
Non-linear interplay between exchange-bias-induced unidirectional anisotropy and oblique-deposition-induced uniaxial anisotropy
Authors: Phuoc Nguyen N. , Ong C. K.
Published: July 2013

A systematic investigation of the non-linear interplay between the uniaxial magnetic anisotropy induced by oblique deposition and the unidirectional magnetic anisotropy induced by exchange bias coupling in NiFe/MnIr bilayers was performed. It was found that depending on the oblique angle, the uniaxial anisotropy induced by oblique deposition may play a vital role in defining the orientation of exchange bias. In particular, when the oblique angle is in the range from 31° to 45°, the oblique-deposition-induced anisotropy is large enough to reorient the easy axis of exchange bias to the direction perpendicular to the deposition field leading to the appearance of double-shifted loops. When the oblique angle is less than 30° or higher than 45°, normal exchange bias is observed with typical behavior. The dynamic permeability spectra are also presented and discussed in conjunction with the static magnetic properties.
Impact-ionization-based resistive transition model for thin TiO2 films
Authors: Omura Yasuhisa , Kondo Yusuke
Published: July 2013

This study tries to reproduce the unipolar “forming” process and the “reset” process of the Pt/TiO2/Pt capacitor. It is assumed that the impact ionization process triggers the “forming” process (so-called breakdown), and that the thermal energy generated by the conductive filament yields the “reset” process through the annihilation of oxygen vacancies. Simulations of I–V characteristics successfully reproduce the unipolar “forming” and “reset” processes. It is demonstrated that the “forming” voltage rises as TiO2 film thickness increases, and that the “reset” voltage is insensitive to film thickness. The rise of the “forming” voltage stems from the increase in filament length and width. The insensitivity of “reset” voltage strongly suggests that the reaction energy of the oxygen ion with the vacancy is the critical parameter.
Nanostructures with the Hilbert curve geometry as surface enhanced Raman scattering substrates
Authors: Grigorenko Ilya
Published: July 2013

In this work, we consider fractal substrates for Surface Enhanced Raman Scattering measurements. The shape of the substrates is based on self-similar space filling Hilbert curves, which possess properties of both one dimensional and two dimensional geometries. The dielectric response of a doped semiconductor nanostructure, where conducting electrons are trapped in an effective potential having the geometry of the Hilbert curve is calculated and analysed. It is found that the system may exhibit electronic collective excitations specific for either a two dimensional or one dimensional system, depending on the excitation frequency.
Lattice vacancies in silicon film exposed to external electric field
Authors: Mao Yuliang , Caliste Damien , Pochet Pascal
Published: July 2013

Density functional calculations based on wavelet basis set are performed to investigate the structure, internal electric-charge distribution, and formation energy of lattice vacancies in silicon film under electric fields. It was found that the formation energies of vacancies both in JT⊥ (Jahn-Teller distortion orthogonal to electric field) and JT‖ (Jahn-Teller distortion parallel to electric field) distortions are decreased with the increasing of field strength, due to the charge polarization in the whole space of silicon film. For the split vacancy, it can lower its energy by moving further away from the split space to form a tetragonal JT⊥ vacancy under electric field. Our results also demonstrate the importance of the potential fluctuations induced by the electric fields on the charge redistribution within the vacancy defects.
Enhancement of proton acceleration field in laser double-layer target interaction
Authors: Gu Y. J. , Kong Q. , Kawata S. , Izumiyama T. , Li X. F. , Yu Q. , Wang P. X. , Ma Y. Y.
Published: July 2013

A mechanism is proposed to enhance a proton acceleration field in laser plasma interaction. A double-layer plasma with different densities is illuminated by an intense short pulse. Electrons are accelerated to a high energy in the first layer by the wakefield. The electrons accelerated by the laser wakefield induce the enhanced target normal sheath (TNSA) and breakout afterburner (BOA) accelerations through the second layer. The maximum proton energy reaches about 1 GeV, and the total charge with an energy higher than 100 MeV is about several tens of μC/μm. Both the acceleration gradient and laser energy transfer efficiency are higher than those in single-target-based TNSA or BOA. The model has been verified by 2.5D-PIC simulations.
Insight into Age and Growth of Northern Snakehead in the Potomac River
Authors: Odenkirk John , Lim Catherine , Owens Steve , Isel Mike
Published: July 2013

A Northern Snakehead Channa argus population was documented in the Potomac River system in 2004. Since that time, the population has expanded in range and number, yet relatively little is known about key population variables including age and growth. Lack of known-age fish with which to compare otoliths from the sampled population has hindered verification, and Northern Snakehead otoliths can be difficult to interpret. We compared growth increments (mm/d) of recaptured fish marked with T-bar anchor tags (n = 51; mean time at large, 310 d [SD = 302]) to otolith annuli from fish sacrificed in 2011 and 2012 (n = 192). While immersed (solution of 80% water and 20% glycerin) otolith transverse perspectives were viewed “cracked” with transmitted light. Readings from fish aged 1–4 years suggested initial growth was much faster than previously reported, but length at age was highly variable. Annual growth increments for fish aged 1–4 (mean length at age of fish, respectively: 394, 563, 644, and 721 mm TL) were converted to estimated daily growth (mm/d), which was reasonably similar to the daily growth of recaptured tagged fish. Von Bertalanffy growth parameters were L∞ = 780, K = 0.48, and t  0 = −0.56, where L∞ is the asymptotic length, K is a growth coefficient, and t  0 is a time coefficient at which length would theoretically be zero. The implications of rapid growth include the potential for the earlier onset of sexual maturity, which could represent enhanced chances for successful colonization.

Received November 20, 2012; accepted May 15, 2013
Effect of Varying the Number and Location of Alcohol-Based Hand Rub Dispensers on Usage in a General Inpatient Medical Unit
Authors: Chan Benjamin P. , Homa Karen , Kirkland Kathryn B.
Published: July 2013

We sequentially increased the number of wall-mounted alcohol-based hand rub dispensers in a small medical unit to evaluate effects on hand hygiene performance. Above a certain point, addition of more dispensers did not increase hand hygiene frequency, which appeared to be influenced more by location than by total number of dispensers.
Innovative Technique for the Placement of the Drainage Tube for Microendoscopic Spinal Decompression
Authors: Mizuno Kentaro , Mikami Yasuo , Hase Hitoshi , Ikeda Takumi , Nagae Masateru , Tonomura Hitoshi , Shirai Toshiharu , Fujiwara Hiroyoshi , Kubo Toshikazu
Published: July 2013

Study Design:

A technical note and retrospective study.

Objectives:

The objectives were to describe a new method of drainage tube placement during microendoscopic spinal decompression, and compare the positioning and fluid discharge obtained with this method and the conventional method.

Summary of Background Data:

To prevent postoperative epidural hematoma after microendoscopic decompression, a drainage tube must be placed in a suitable location. However, the narrow operative field makes precise control of the position of the tube technically difficult. We developed a method to reliably place the tube in the desired location.

Materials and Methods:

We use a Deschamps aneurysm needle with a slightly curved tip, which we call a drain passer. With the microendoscope in position, the drain passer, with a silk thread passed through the eye at the needle tip, is inserted percutaneously into the endoscopic field of view. The drainage tube is passed through the loop of silk thread protruding from the inside of the tubular retractor, and the thread is pulled to the outside, guiding the end of the drainage tube into the wound. This method was used in 23 cases at 44 intervertebral levels (drain passer group), and the conventional method in 20 cases at 32 intervertebral levels (conventional group). Postoperative plain radiographs were taken, and the amount of fluid discharge at postoperative hour 24 was measured.

Results:

Drainage tube positioning was favorable at 43 intervertebral levels (97.7%) in the drain passer group and 26 intervertebral levels (81.3%) in the conventional group. Mean fluid discharge was 58.4±32.2 g in the drain passer group and 38.4±23.0 g in the conventional group. Positioning was significantly better and fluid discharge was significantly greater in the drain passer group.

Conclusion:

The results indicate that this method is a useful drainage tube placement technique for preventing postoperative epidural hematoma.
Reliability and Usefulness of Intraoperative 3-Dimensional Imaging by Mobile C-Arm With Flat-Panel Detector
Authors: Fujimori Takahito , Iwasaki Motoki , Nagamoto Yukitaka , Kashii Masafumi , Takao Masaki , Sugiura Tsuyoshi , Yoshikawa Hideki
Published: July 2013

Study Design:

Reliability and agreement study.

Objective:

To assess the reliability of intraoperative 3-dimensional imaging with a mobile C-arm (3D C-arm) equipped with a flat-panel detector.

Summary of Background Data:

Pedicle screws are widely used in spinal surgery. Postoperative computed tomography (CT) is the most reliable method to detect screw misplacement. Recent advances in imaging devices have enabled surgeons to acquire 3D images of the spine during surgery. However, the reliability of these imaging devices is not known.

Methods:

A total of 203 screws were used in 22 consecutive patients who underwent surgery for scoliosis. Screw position was read twice with a 3D C-arm and twice with CT in a blinded manner by 2 independent observers. Screw positions were classified into 4 categories at every 2 mm and then into 2 simpler categories of acceptable or unacceptable. The degree of agreement with respect to screw positions between the double readings was evaluated by κ value. With unanimous agreement between 2 observers regarding postoperative CT readings considered the gold standard, the sensitivity of the 3D C-arm for determining screw misplacement was calculated.

Results:

A total 804 readings were performed. For the 4-category classification, the mean κ value for the 2 interobserver readings was 0.52 for the 3D C-arm and 0.46 for CT. For the 2-category classification, the mean κ value for the 2 interobserver readings was 0.80 for the 3D C-arm and 0.66 for CT. The sensitivity, specificity, positive predictive value, and negative predictive value of intraoperative imaging with the 3D C-arm were 70%, 95%, 44%, and 98%, respectively. With respect to screws with perforation ≥4 mm, the sensitivity was 83%. No revision surgery was performed.

Conclusions:

Intraoperative imaging with a 3D C-arm was reliable for detecting screw misplacement and helpful in decreasing the rate of revision surgery for screw misplacement.
Restoration recovers population structure and landscape genetic connectivity in a dispersal‐limited ecosystem
Authors: Reynolds Laura K. , Waycott Michelle , McGlathery Karen J.
Published: July 2013

Ecological restoration assists the recovery of degraded ecosystems; however, restoration can have deleterious effects such as outbreeding depression when source material is not chosen carefully and has non‐local adaptations.

We surveyed 23 eelgrass (Zostera marinaL.) populations along the North American Atlantic coast to evaluate genetic structure and connectivity among restored and naturally recruited populations.

While populations along the North America Atlantic coast were genetically distinctive, significant migration was detected among populations. All estimates of connectivity (FST, migration rate base on rare alleles, and Bayesian modelling) showed a general north to south pattern of migration, corresponding to the typical long‐shore currents in this region.

Individual naturally recruited meadows in the Virginia coastal bays appear to be the result of dispersal from different meadows north of the region. This supports the hypothesis that recruitment into this region is typically a slow, episodic process rather than a permanent, continuous connection between the populations.

While natural recovery of populations that were catastrophically lost in the 1930s has been slow, large‐scale seed‐based restoration has been very successful at quickly restoring landscape‐scale areal coverage (over 1600 ha in just 10 years). Our results show that restoration was also successful at restoring meadows with high genetic diversity. Naturally recruited meadows were less diverse and exhibited signs of genetic drift.

Synthesis. Our analyses demonstrate that metapopulation dynamics are important to the natural recovery of seagrass ecosystems that have experienced catastrophic loss over large spatial scales; however, natural recovery processes are slow and inefficient at recovering genetic diversity and population structure when recruitment barriers exist, such as a limited seed source. Seed‐based restoration provides a greater abundance of propagules, rapidly facilitates the recovery of populations with higher genetic diversity, and when seed sources are chosen carefully protects regional genetic structure. First‐order estimates indicated that the genetic diversity achieved by active restoration in 10 years would have otherwise taken between 125 and 185 years to achieve through natural recruitment events.
Predicting the optimal depth of left‐sided central venous catheters in children
Authors: Kim H. , Jeong C‐H. , Byon H‐J. , Shin H. K. , Yun T. J. , Lee J‐H. , Park Y‐H. , Kim J‐T.
Published: July 2013

The aim of this study was to predict the optimal depth for insertion of a left‐sided central venous catheter in children. Using 3D chest computed tomography angiography, we measured the distance from a point where the internal jugular vein is at the superior border of the clavicle, and from a point where the subclavian vein is inferior to the anterior border of the clavicle, to the junction of the superior vena cava and the right atrium in 257 children. Linear regression analysis revealed that the distances correlated with age, weight and height. Simple formulae for the depth of a central venous catheter via the left internal jugular vein (0.07 × height (cm)) and the left subclavian vein (0.08 × height (cm)) were developed to predict placement of the central venous catheter tip at the junction of the superior vena cava with the right atrium. Using these fomulae, the proportion of catheter tips predicted to be correctly located was 98.5% (95% CI 96.8–100%) and 94.0% (95% CI 90.8–97.3%), respectively.
There is no relation between the occurrence of proliferative vitreoretinopathy and the location of the donor site after transplantation of a free autologous retinal pigment epithelium–choroid graft
Authors: van Zeeburg Elsbeth J. T. , Maaijwee Kristel , van Meurs Jan C.
Published: July 2013

Purpose:  A free autologous retinal pigment epithelium (RPE)–choroid graft can be harvested during transplantation surgery from a 6 or 12 o’clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro‐inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy.

Methods:  Retrospective analysis of a prospective cohort of 246 patients with exudative age‐related macular degeneration treated with an RPE–choroid graft transplantation and a lighter‐than‐water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two‐tailed Fisher’s exact test was used for statistical analysis.

Results:  Thirty‐nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p = 0.8).

Conclusion:  Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.
Diagnosis and complications of Cushing's disease: gender‐related differences
Authors: Zilio Marialuisa , Barbot Mattia , Ceccato Filippo , Camozzi Valentina , Bilora Franca , Casonato Alessandra , Frigo Anna Chiara , Albiger Nora , Daidone Viviana , Mazzai Linda , Mantero Franco , Scaroni Carla
Published: July 2013

Objective

Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female‐to‐male ratio of 3–8:1. The aim of this study was to evaluate gender‐related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease.

Methods

We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values).

Results

We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0·001) and ACTH values (P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0·05), hypercoagulable state and osteoporosis at lumbar spine (P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures.

Conclusions

Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties.
Reliability and validity of short‐term performance tests for wheelchair‐using children and adolescents with cerebral palsy
Authors: Verschuren Olaf , Zwinkels Maremka , Obeid Joyce , Kerkhof Nicky , Ketelaar Marjolijn , Takken Tim
Published: July 2013

Aim

To investigate the test–retest reproducibility of the Muscle Power Sprint Test (MPST), the 10 × 5‐m sprint test, and the arm‐cranking Wingate Anaerobic Test (WAnT) in children and adolescents with cerebral palsy (CP). A secondary objective was to assess the construct validity of the MPST.

Method

Twenty‐three participants with spastic CP (mean age 13y 3mo, range 7‐18y, SD 3.6y; 18 males, five females, two classified as having spastic unilateral CP, 21 as having spastic bilateral CP) using a manual wheelchair for at least part of the day were recruited and tested in different rehabilitation settings in the Netherlands. Participants were classified as in Gross Motor Function Classification System Expanded and Revised (GMFCS‐E&R) levels III and IV.

Results

Intraclass correlation coefficients (range 0.93–0.99; 95% confidence interval 0.82–1.0) for all variables indicated highly acceptable reproducibility. Limits of agreement analysis revealed satisfactory levels of agreement. The MPST variables demonstrated very strong significant positive correlations for peak power and mean power from both tests (peak power: r=0.91, p<0.001; mean power: r=0.88, p<0.001).

Interpretation

The MPST, the 10 × 5‐m sprint test, and the arm‐cranking WAnT are reproducible tests for measuring anaerobic performance and agility in adolescents with spastic CP who self‐propel a manual wheelchair. The MPST has been shown to be a valid test to measure anaerobic performance in this population.
Pneumopericardium Secondary to Esophago‐Pericardial Fistula
Authors: Caselli Stefano , Serdoz Andrea , Palumbo Barbara , Todi Fiammetta , Palma Mario Di , Serdoz Roberto
Published: July 2013

Mini‐Abstract

We report the clinical case of a 63‐year‐old woman with a squamous cell carcinoma in the distal esophagus complicated by an esophago‐pericardial fistula and pneumopericardium. This is a rarely observed condition usually associated with a high mortality because may result in cardiac tamponade. However, as the esophago‐pericardial fistula was open and the air was free to enter and exit throughout the cardiac and respiratory cycle without significantly increasing pericardial pressure, our patient showed only a mild hemodynamic impairment without overt clinical signs of cardiac tamponade.
Multimerization of anti‐(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers
Authors: Asano Ryutaro , Hagiwara Yasuyo , Koyama Noriaki , Masakari Yosuke , Orimo Ryota , Arai Kyoko , Ogata Hiromi , Furumoto Shozo , Umetsu Mitsuo , Kumagai Izumi
Published: July 2013

The construction of antibody fragments has the potential to reduce the high cost of therapeutic antibody production, but the structures of these fragments, with monovalency and the lack of an Fc region, can lead to reduced function. Multimerization is one strategy for recovering function that also yields better tumor‐to‐blood ratios than IgGs or monomeric antibody fragments because of rapid tumor uptake and clearance. Here, we constructed single‐chain variable fragment (scFv) multimers by modifying the linker length and domain order of humanized anti‐(epidermal growth factor receptor) IgG 528 (h528) and tested their ability to inhibit tumor growth. h528 scFv multimers, expressed using a bacterial expression system, were successfully fractionated and inhibited cancer growth in a multimerization‐dependent manner, whereas the h528 scFv monomer showed no inhibition. h528 scFv trimers with variable heavy–light domain order and no linkers showed the highest in vitro and in vivo antitumor effects, which were comparable with those of the approved anti‐(epidermal growth factor receptor) therapeutic IgG Cetuximab and Panitumumab. The trimers were also structurally stable in vitro and in vivo, which may be attributable to a strong interaction between the variable heavy and variable light domains of h528 Fv. Thus, h528 scFv multimers, especially trimers, are attractive as the next generation of anti‐(epidermal growth factor receptor) therapeutic IgG and offer the possibility of low‐cost production.
Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells
Authors: Sattu Kamaraj , Hochgräfe Falko , Wu Jianmin , Umapathy Ganesh , Schönherr Christina , Ruuth Kristina , Chand Damini , Witek Barbara , Fuchs James , Li Pui‐Kai , Hugosson Fredrik , Daly Roger J. , Palmer Ruth H. , Hallberg Bengt
Published: July 2013

Activation of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is a key oncogenic mechanism in a growing number of tumor types. In the majority of cases, ALK is activated by fusion with a dimerizing partner protein as a result of chromosomal translocation events, most studied in the case of the nucleophosmin–ALK and echinoderm microtubule‐associated protein‐like 4–ALK oncoproteins. It is now also appreciated that the full‐length ALK receptor can be activated by point mutations and by deletions within the extracellular domain, such as those observed in neuroblastoma. Several studies have employed phosphoproteomics approaches to find substrates of ALK fusion proteins. In this study, we used MS‐based phosphotyrosine profiling to characterize phosphotyrosine signaling events associated with the full‐length ALK receptor. A number of previously identified and novel targets were identified. One of these, signal transducer and activator of transcription 3 (STAT3), has previously been observed to be activated in response to oncogenic ALK signaling, but the significance of this in signaling from the full‐length ALK receptor has not been explored further. We show here that activated ALK robustly activates STAT3 on Tyr705 in a number of independent neuroblastoma cell lines. Furthermore, knockdown of STAT3 by RNA interference resulted in a reduction in myelocytomatosis neuroblastom (MYCN) protein levels downstream of ALK signaling. These observations, together with a decreased level of MYCN and inhibition of neuroblastoma cell growth in the presence of STAT3 inhibitors, suggest that activation of STAT3 is important for ALK signaling activity in neuroblastoma.
Microbial mat controls on infaunal abundance and diversity in modern marine microbialites
Authors: Tarhan L. G. , Planavsky N. J. , Laumer C. E. , Stolz J. F. , Reid R. P.
Published: July 2013

Microbialites are the most abundant macrofossils of the Precambrian. Decline in microbialite abundance and diversity during the terminal Proterozoic and early Phanerozoic has historically been attributed to the concurrent radiation of complex metazoans. Similarly, the apparent resurgence of microbialites in the wake of Paleozoic and Mesozoic mass extinctions is frequently linked to drastic declines in metazoan diversity and abundance. However, it has become increasing clear that microbialites are relatively common in certain modern shallow, normal marine carbonate environments—foremost the Bahamas. For the first time, we present data, collected from the Exuma Cays, the Bahamas, systematically characterizing the relationship between framework‐building cyanobacteria, microbialite fabrics, and microbialite‐associated metazoan abundance and diversity. We document the coexistence of diverse microbialite and infaunal metazoan communities and demonstrate that the predominant control upon both microbialite fabric and metazoan community structure is microbial mat type. These findings necessitate that we rethink prevalent interpretations of microbialite–metazoan interactions and imply that microbialites are not passive recipients of metazoan‐mediated alteration. Additionally, this work provides support for the theory that certain Precambrian microbialites may have been havens of early complex metazoan life, rather than bereft of metazoans, as has been traditionally envisaged.
Pressureless Sintering of Carbon Nanofibre/SiC Composites and Their Properties
Authors: Xu Guosheng , Yamakami Tomohiko , Yamaguchi Tomohiro , Endo Morinobu , Taruta Seiichi , Kubo Isao
Published: July 2013

To enhance the fracture toughness of silicon carbide (SiC) ceramics and prevent the generation of cracks and chippings in the SiC ceramics during machining process, carbon nanofibres (CNFs) were compounded with SiC. The densification and microstructure development of the CNFs/SiC composites pressureless sintered in Ar atmosphere were investigated. The fracture toughness of SiC ceramics was enhanced by the addition of 1–3 wt% CNFs, which resulted from the pullout and/or bridging effect of CNFs bonded much more closely with SiC. The addition of 3 wt% CNFs prevented the chippings from generating in the composite during precision machining process.
Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis
Authors: Patrício Patrícia , Ramalho‐Carvalho João , Costa‐Pinheiro Pedro , Almeida Mafalda , Barros‐Silva João Diogo , Vieira Joana , Dias Paula Cristina , Lobo Francisco , Oliveira Jorge , Teixeira Manuel R. , Henrique Rui , Jeronimo Carmen
Published: July 2013

Expression of PAX2 (Paired‐box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax‐2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes—clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma—but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax‐2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT‐PCR. PAX2 promoter methylation status was assessed by methylation‐specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax‐2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut‐off, Pax‐2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax‐2 immunoexpression. We concluded that Pax‐2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax‐2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC.
Safety Assessment of Enterococcus faecium and Enterococcus faecalis Strains Isolated from Turkish Tulum Cheese
Authors: Inoğlu Zehra Nur , Tuncer Yasin
Published: July 2013

The aim of this study was to evaluate several genetic and phenotypic traits of clinical significance in 21 Enterococcus faecium and seven E. faecalis strains previously isolated from Turkish Tulum Cheese. Enterococcus strains were tested for the presence of 14 virulence genes and two vancomycin resistance genes by polymerase chain reaction (PCR). Biogenic amine production was also investigated by decarboxylase medium and PCR. Investigation of virulence factors by PCR amplification revealed the presence of genes encoding for gelatinase (gelE), cell wall adhesin (efaAfm and efaAfs), sex pheromone (ccf), cell wall‐associated protein (espfm and espfs) and aggregation substance (agg). Other presumed virulence genes (cpd, cob, cad, ace, cylM, cylB and cylA) were not detected. At least one virulence gene was detected in all strains. The ccf (85.7%), efaAfm (75.0%) and gelE (32.1%) were detected most frequently present virulence genes in enterococcal strains. Phenotypic gelatinase testing revealed the existence of apparently silent gelE gene. None of the strains carried the vanA and vanB genes. Enterococcus strains did not decarboxylate histidine, lysine or ornithine, but the majority of strains (92.9%) produced tyramine from tyrosine. The tyrosine decarboxylase gene (tdc) was detected in all tyraminogenic strains.

Practical Application

Enterococci are lactic acid bacteria that are important both in food and clinical microbiology. Enterococci species especially E. faecium and E. faecalis play an important role in the development of sensory characteristics of different traditional fermented foods such as dairy and meat products. On the other hand, E. faecium and E. faecalis are recognized as nosocomial pathogens. Results of this study indicated that E. faecium and E. faecalis strains isolated from Turkish Tulum Cheese carried some virulence genes and most of them produce tyramine. The findings of our study suggest that E. faecium and E. faecalis strains isolated from Turkish Tulum Cheese may be potential risk factors for consumer health. For this reason, use of Enterococcus strains as starter cultures requires thorough safety evaluation.
Association Between a Geriatric Trauma Resuscitation Protocol Using Venous Lactate Measurements and Early Trauma Surgeon Involvement and Mortality Risk
Authors: Bar‐Or David , Salottolo Kristin M. , Orlando Alessandro , Mains Charles W. , Bourg Pamela , Offner Patrick J.
Published: July 2013

Objectives

To investigate whether implementing a geriatric resuscitation protocol that uses lactate‐guided therapy with early trauma surgeon involvement is associated with lower mortality through the early recognition of occult hypoperfusion (OH).

Design

Prospective cohort study.

Setting

Level I trauma center.

Participants

All hemodynamically stable individuals with blunt trauma aged 65 and older admitted to the Level I trauma center from October 1, 2008, through December 31, 2011 (n = 1,998).

Measurements

Mortality over time (according to quarter) was analyzed using an adjusted logarithmic regression model stratified according to the presence of OH. OH was defined as lactate of 2.5 mM or greater.

Results

Overall mortality was 3.9% (n = 78). Admission venous lactate was collected in 73.5% of participants, of whom 20.5% had OH (n = 301). In participants with OH, a significant decrease in mortality was observed over time (adjusted coefficient of determination (R2) = 0.66, P = .002). A smaller yet significant decrease in mortality rates in participants with normal perfusion status was also observed (adjusted R2 = 0.55, P = .01).

Conclusion

Early identification and treatment of OH in elderly adults with trauma using venous lactate‐guided therapy coupled with early trauma surgeon involvement was associated with significantly lower mortality. A protocol that uses lactate‐guided therapy with early trauma surgeon involvement should be followed to improve the care of elderly adults with trauma.
Variations in Self‐Reported Practice of Physicians Providing Clinical Care to Individuals with Dementia: A Systematic Review
Authors: Sivananthan Saskia N. , Puyat Joseph H. , McGrail Kimberlyn M.
Published: July 2013

Objectives

To determine to what extent actual practice as reported in the literature is consistent with clinical guidelines for dementia care.

Design

A systematic review of empirical studies of clinical services provided by physicians to older adults with a diagnosis of dementia.

Setting

All settings involving primary care physicians in which a diagnosis of dementia is provided.

Participants

Physicians providing care to individuals aged 60 and older with a primary or secondary diagnosis of dementia.

Intervention

Seven dementia care processes recommended by guidelines: formal memory testing, imaging, laboratory testing, interventions, counseling, community service, and specialist referrals.

Measurements

Web of Knowledge, PubMed, Science Direct, MedLine, PsychINFO, EMBASE, and Google Scholar databases were searched for articles in English published before March 1, 2012.

Results

Twelve studies met the final inclusion criteria, all of which were self‐reported cross‐sectional surveys. There was broad variation in the proportion of physicians who reported conducting each dementia care process, with the widest variation in formal memory testing (4–96%). Recently published studies reflected a shift in scope of care, reporting that high proportions of physicians provided interventions, counseling, and referrals to specialist.

Conclusion

Despite the availability and dissemination of established best practice guidelines, there is still wide variation in physician practice patterns in dementia care. The quality of currently available studies limits the ability to draw strong conclusions. Better information on practice patterns and their relationship to outcomes for individuals with dementia and their caregivers using more‐robust study designs is needed to address the needs of the increasing number of individuals who will require dementia care.
Age, Renal Dysfunction, Cardiovascular Disease, and Antihyperglycemic Treatment in Type 2 Diabetes Mellitus: Findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study
Authors: Solini Anna , Penno Giuseppe , Bonora Enzo , Fondelli Cecilia , Orsi Emanuela , Trevisan Roberto , Vedovato Monica , Cavalot Franco , Cignarelli Mauro , Morano Susanna , Ferrannini Ele , Pugliese Giuseppe ,   Renal Insufficiency and Cardiovascular Events Study Group
Published: July 2013

Objectives

To assess the distribution of antihyperglycemic treatments according to age and renal function and its relationship with cardiovascular disease in type 2 diabetes mellitus (T2DM).

Design

Cross‐sectional analysis.

Setting

Nineteen hospital‐based diabetes mellitus clinics in 2007 and 2008.

Participants

Fifteen thousand seven hundred thirty‐three individuals with T2DM from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.

Measurements

Current antihyperglycemic treatments were recorded. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Albuminuria was measured using immunonephelometry or immunoturbidimetry. Prevalence of major acute cardiovascular events was calculated according to age quartiles, treatments, and categories of eGFR (1 = ≥90; 2 = 60–89; 3 = 30–59; and 4 = <30 mL/min per 1.73 m2).

Results

Across age quartiles, eGFR declined progressively at a time‐linear rate, with an acceleration in older adults, whereas albuminuria increased; age and eGFR were associated with cardiovascular events independently of other confounders. With increasing age, percentage of participants using lifestyle treatments for their T2DM and taking metformin or glitazones fell; percentage taking sulphonylureas and repaglinide rose, and percentage taking insulin remained stable. In eGFR categories 3 and 4, use of metformin was 41.4% and 14.5%, respectively, and that of sulphonylureas was 34.2% and 18.1%, respectively. Inappropriate prescription of these agents, especially sulphonylureas, increased with age. Metformin was independently associated with lower prevalence of cardiovascular disease for any age quartile and eGFR category than all other treatments.

Conclusion

In real‐life conditions, use of agents that are not recommended in elderly adults with diabetes mellitus with moderate to severe renal impairment is frequent, but metformin is associated with lower cardiovascular event rates even in these individuals.
Do‐Not‐Hospitalize Orders for Individuals with Advanced Dementia: Healthcare Proxies' Perspectives
Authors: Mann Elizabeth , Goff Sarah L. , Colon‐Cartagena Wanda , Bellantonio Sandra , Rothberg Michael B.
Published: July 2013

Objectives

To determine how well healthcare proxies (HCPs) understand do‐not‐hospitalize (DNH) orders and why they may or may not initiate them.

Design

Semistructured qualitative interviews.

Setting

Two nursing homes in western Massachusetts.

Participants

HCPs of nursing home residents with advanced dementia.

Measurement

In‐depth interviews were audiotaped and transcribed verbatim. Data were qualitatively analyzed in an iterative process, and emergent concepts were conceptually ordered into explanatory categories. Pertinent demographic and clinical information was collected from the Minimum Data Set (MDS) and patient charts.

Results

Sixteen of 31 eligible HCPs were interviewed. Major findings included barriers to and facilitators of initiating DNH orders. Barriers included a perceived lack of physician involvement in decision‐making and limited understanding of DNH orders and the resident's prognosis. Facilitators included a HCPs' personal experience in health care, understanding the prognosis of advanced dementia, and a desire to limit resident distress.

Conclusion

The potential barriers to and facilitators of HCPs initiating DNH orders identified in this study suggest that HCPs may benefit from more in‐depth discussions with healthcare providers when making this decision. Interventions to address these barriers may improve the capacity of HCPs to make informed decisions about DNH orders that reflect individuals' values and wishes.
Quick‐and‐clean article figures with FigureJ
Authors: MUTTERER J. , ZINCK E.
Published: July 2013

We created FigureJ a new ImageJ plugin dedicated to scientific article figures preparation. Building a convincing figure is a demanding task that covers different steps ranging from content acquisition to figure assembly in editing software. Notions of image processing are required when it comes to even simple tasks such as cropping or resizing images and assembling them in a single figure. Scientific images are typically well handled in dedicated software but poorly supported in software used for laying out the final version of a figure for submission to review process.