bluuebunny/crossref_metadata_2025 huggingface dataset:
Noncontrast MR angiography for supraaortic arteries using inflow enhanced inversion recovery fast spin echo imaging
Authors: Takei Naoyuki , Miyoshi Mitsuharu , Kabasawa Hiroyuki
Published: December 2011

Purpose:

To depict supraaortic arteries using (3D fast spin echo (FSE) combined with slab selective inversion recovery for noncontrast magnetic resonance angiography (MRA) in healthy volunteers, and to investigate the property of the inflow enhanced inversion recovery FSE (IFIR‐FSE) for background suppression and inflow effects.

Materials and Methods:

IFIR‐FSE with no image subtraction was used to visualize the aortic arch, subclavian arteries, carotid arteries, and vertebral arteries in 10 healthy volunteers. Simulations were performed to achieve both high background suppression and inflow effects by adjusting the inversion time (TI) and wait time after data acquisition. The effect of inflow was investigated with TIs of 800, 1200, 1600, and 2000 msec. Contrast between artery and these background tissues were measured with scan protocols based on simulation results.

Results:

IFIR‐FSE images showed good visualization of the supraaortic arteries and allowed separation of arteries from veins without image subtraction. The proposed method demonstrated that a high contrast between arteries and background tissues can be acquired with various TIs, which was in good agreement with the simulation. A TI over 1600 msec was favorable in terms of background suppression, arterial signal intensity, and inflow effects.

Conclusion:

Inflow enhanced inversion recovery cardiac‐triggered 3D FSE imaging can be used for supraaortic artery imaging without contrast agents. J. Magn. Reson. Imaging 2012;35:957–962. © 2011 Wiley Periodicals, Inc.
Microwave thermolysis of sweat glands
Authors: Johnson Jessi E. , O'Shaughnessy Kathryn F. , Kim Steve
Published: December 2011

Background and Objectives

Hyperhidrosis is a condition that affects a large percentage of the population and has a significant impact on peoples' lives. This report presents a technical overview of a new noninvasive, microwave‐based device for creating thermolysis of sweat glands. The fundamental principles of operation of the device are presented, as well as the design and optimization of the device to target the region where the sweat glands reside.

Materials and Methods

An applicator was designed that consists of an array of four waveguide antennas, a cooling system, and a vacuum acquisition system. Initially, the performance of the antenna array was optimized via computer simulation such that microwave absorption was maximized near the dermal/hypodermal interface. Subsequently, hardware was implemented and utilized in pre‐clinical testing on a porcine model to optimize the thermal performance and analyze the ability of the system to create thermally affected zones of varying size yet centered on the target region.

Results

Computer simulation results demonstrated absorption profiles at a frequency of 5.8 GHz that had low amounts of absorption at the epidermis and maximal absorption at the dermal/hypodermal interface. The targeted zone was shown to be largely independent of skin thickness. Gross pathological and histological response from pre‐clinical testing demonstrated the ability to generate thermally affected zones in the desired target region while providing protection to the upper skin layers.

Conclusions

The results demonstrate that microwave technology is well suited for targeting sweat glands while allowing for protection of both the upper skin layers and the structures beneath the subcutaneous fat. Promising initial results from simulation and pre‐clinical testing demonstrate the potential of the device as a noninvasive solution for sweat gland thermolysis. Lasers Surg. Med. 44:20–25, 2012. © 2011 Wiley Periodicals, Inc.
IDEAL spiral CSI for dynamic metabolic MR imaging of hyperpolarized [1‐13C]pyruvate
Authors: Wiesinger Florian , Weidl Eliane , Menzel Marion I. , Janich Martin A. , Khegai Oleksandr , Glaser Steffen J. , Haase Axel , Schwaiger Markus , Schulte Rolf F.
Published: December 2011

Metabolic imaging with hyperpolarized [1‐13C]pyruvate offers the unique opportunity for a minimally invasive detection of cellular metabolism. Efficient and robust acquisition and reconstruction techniques are required for capturing the wealth of information present for the limited duration of the hyperpolarized state (∼1 min). In this study, the Dixon/IDEAL type of water–fat separation is expanded toward spectroscopic imaging of [1‐13C]pyruvate and its down‐stream metabolites. For this purpose, the spectral–spatial encoding is based on single‐shot spiral image encoding and echo‐time shifting in between excitations for the chemical‐shift encoding. In addition, also a free‐induction decay spectrum is acquired and the obtained chemical‐shift prior knowledge is efficiently used in the reconstruction. The spectral–spatial reconstruction problem is found to efficiently separate into a chemical‐shift inversion followed by a spatial reconstruction. The method is successfully demonstrated for dynamic, multislice [1‐13C]pyruvate metabolic MR imaging in phantom and in vivo rat experiments. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy
Authors: Rosenbaum Eli , Begum Shahnaz , Brait Mariana , Zahurak Marianna , Maldonado Leonel , Mangold Leslie A. , Eisenberger Mario A. , Epstein Jonathan I. , Partin Alan W. , Sidransky David , Hoque Mohammad O.
Published: December 2011

PURPOSE

To evaluate the prognostic significance of six epigenetic biomarkers (AIM1, CDH1, KIF1A, MT1G, PAK3, and RBM6 promoter hypermethlation) in a homogeneous group of prostate cancer patients, following radical prostatectomy (RP).

PATIENTS AND METHODS

Biomarker analyses were performed retrospectively on tumors from 95 prostate cancer patients all with a Gleason score of 3 + 4 = 7 and a minimum follow‐up period of 8 years. Using Quantitative Methylation Specific PCR (QMSP), we analyzed the promoter region of six genes in primary prostate tumor tissues. Time to any progression was the primary endpoint and development of metastatic disease and/or death from prostate cancer was a secondary endpoint. The association of clinicopathological and biomolecular risk factors to recurrence was performed using the Log‐rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used.

RESULTS

At a median follow‐up time of 10 years, 48 patients (50.5%) had evidence of recurrence: Biochemical/PSA relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression, the significant factors were: Older age, HR = 0.95 (95% CI: 0.91, 1.0) (P = 0.03), positive lymph nodes HR = 2.11 (95% CI: 1.05, 4.26) (P = 0.04), and decreased hypermethylation of AIM1 HR = 0.45 (95% CI: 0.2, 1.0) (P = 0.05).

CONCLUSIONS

Methylation status of AIM1 in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort. Prostate 72:1133–1139, 2012. © 2011 Wiley Periodicals, Inc.
Volcanic‐plutonic connections in a tilted nested caldera complex in Hong Kong
Authors: Sewell Roderick J. , Tang Denise L. K. , Campbell S. Diarmad G.
Published: December 2011

Exceptional exposures of four, precisely dated, Middle Jurassic to Early Cretaceous, silicic volcanic centers and their plutonic equivalents in Hong Kong have provided an excellent opportunity to examine close connections in time and space between magma chambers and their overlying calderas. Here, we describe a ∼14 km crustal section through a collapsed caldera in southeastern Hong Kong where the intracaldera fill suggests that the magmatic discharge was of supereruption scale. The main subvolcanic components that link a magma chamber with surface are revealed by well‐established field relationships, supplemented by high precision geochronology, whole‐rock geochemistry, and geophysical data. Exposures and outcrop patterns reveal kilometer‐scale caldera subsidence and evidence of the simultaneous evacuation of hundreds of cubic kilometers of high‐silica rhyolite magma through dike‐like conduits from a shallow subcrustal reservoir. The resultant volcanotectonic depression, within which is preserved a single cooling unit of massively columnar‐jointed densely welded tuff (High Island tuff), is interpreted to form part of a larger tilted Early Cretaceous nested caldera complex. The High Island eruption signaled the end of a 24 Myr‐period of voluminous, pulsed Middle Jurassic to Early Cretaceous silicic magmatism in the Hong Kong region characterized by four discrete ignimbrite ‘flare‐ups’.
Very high resolution regional climate model simulations over Greenland: Identifying added value
Authors: Lucas‐Picher Philippe , Wulff‐Nielsen Maria , Christensen Jens H. , Aðalgeirsdóttir Guðfinna , Mottram Ruth , Simonsen Sebastian B.
Published: December 2011

This study presents two simulations of the climate over Greenland with the regional climate model (RCM) HIRHAM5 at 0.05° and 0.25° resolution driven at the lateral boundaries by the ERA‐Interim reanalysis for the period 1989–2009. These simulations are validated against observations from meteorological stations (Danish Meteorological Institute) at the coast and automatic weather stations on the ice sheet (Greenland Climate Network). Generally, the temperature and precipitation biases are small, indicating a realistic simulation of the climate over Greenland that is suitable to drive ice sheet models. However, the bias between the simulations and the few available observations does not reduce with higher resolution. This is partly explained by the lack of observations in regions where the higher resolution is expected to improve the simulated climate. The RCM simulations show that the temperature has increased the most in the northern part of Greenland and at lower elevations over the period 1989–2009. Higher resolution increases the relief variability in the model topography and causes the simulated precipitation to be larger on the coast and smaller over the main ice sheet compared to the lower‐resolution simulation. The higher‐resolution simulation likely represents the Greenlandic climate better, but the lack of observations makes it difficult to validate fully. The detailed temperature and precipitation fields that are generated with the higher resolution are recommended for producing adequate forcing fields for ice sheet models, particularly for their improved simulation of the processes occurring at the steep margins of the ice sheet.
Beam distortion detection and deflectometry measurements of gigahertz surface acoustic waves
Authors: Higuet Julien , Valier-Brasier Tony , Dehoux Thomas , Audoin Bertrand
Published: December 2011

Gigahertz acoustic waves propagating on the surface of a metal halfspace are detected using different all-optical detection schemes, namely, deflectometry and beam distortion detection techniques. Both techniques are implemented by slightly modifying a conventional reflectometric setup. They are then based on the measurement of the reflectivity change but unlike reflectometric measurements, they give access to the sample surface displacement. A semi-analytical model, taking into account optical, thermal, and mechanical processes responsible for acoustic waves generation, allows analyzing the physical content of the detected waveforms.
Three-dimensional magnetohydrodynamics simulations of counter-helicity spheromak merging in the Swarthmore Spheromak Experiment
Authors: Myers C. E. , Belova E. V. , Brown M. R. , Gray T. , Cothran C. D. , Schaffer M. J.
Published: December 2011

Recent counter-helicity spheromak merging experiments in the Swarthmore Spheromak Experiment (SSX) have produced a novel compact torus (CT) with unusual features. These include a persistent antisymmetric toroidal magnetic field profile and a slow, nonlinear emergence of the n = 1 tilt mode. Experimental measurements are inconclusive as to whether this unique CT is a fully merged field-reversed configuration (FRC) with strong toroidal field or a partially merged “doublet CT” configuration with both spheromak- and FRC-like characteristics. In this paper, the SSX merging process is studied in detail using three-dimensional resistive MHD simulations from the Hybrid Magnetohydrodynamics (HYM) code. These simulations show that merging plasmas in the SSX parameter regime only partially reconnect, leaving behind a doublet CT rather than an FRC. Through direct comparisons, we show that the magnetic structure in the simulations is highly consistent with the SSX experimental observations. We also find that the n = 1 tilt mode begins as a fast growing linear mode that evolves into a slower-growing nonlinear mode before being detected experimentally. A simulation parameter scan over resistivity, viscosity, and line-tying shows that these parameters can strongly affect the behavior of both the merging process and the tilt mode. In fact, merging in certain parameter regimes is found to produce a toroidal-field-free FRC rather than a doublet CT.
Experimental quiescent drifting dusty plasmas and temporal dust acoustic wave growth
Authors: Heinrich J. R. , Kim S.-H. , Meyer J. K. , Merlino R. L.
Published: December 2011

We report on dust acoustic wave growth rate measurements taken in a dc (anode glow) discharge plasma device. By introducing a mesh with a variable bias 12–17 cm from the anode, we developed a technique to produce a drifting dusty plasma. A secondary dust cloud, free of dust acoustic waves, was trapped adjacent to the anode side of the mesh. When the mesh was returned to its floating potential, the secondary cloud was released and streamed towards the anode and primary dust cloud, spontaneously exciting dust acoustic waves. The amplitude growth of the excited dust acoustic waves was measured directly along with the wavelength and Doppler shifted frequency. These measurements were compared to fluid and kinetic dust acoustic wave theories. As the wave growth saturated a transition from linear to nonlinear waves was observed. The merging of the secondary and primary dust clouds was also observed.
Thermally induced nanoscale structural and morphological changes for atomic-layer-deposited Pt on SrTiO3(001)
Authors: Feng Zhenxing , Christensen Steven T. , Elam Jeffrey W. , Lee Byeongdu , Hersam Mark C. , Bedzyk Michael J.
Published: December 2011

Platinum grown by atomic layer deposition (ALD) on SrTiO3(001) surfaces was studied as a function of Pt coverage and post-deposition thermal treatment. The combination of atomic-force microscopy, scanning electron microscopy, x-ray fluorescence, x-ray reflectivity, and grazing-incidence small-angle x-ray scattering reveals significant changes in the nanoscale surface morphology and crystallinity for the differently prepared films. Surfaces with Pt coverages from 1 to 40 monolayers (ML) show different initial morphologies that evolve into different final Pt microstructures after annealing to 800 °C. These distinct nanoscale structural changes are explained by surface diffusion and the surface and interface energies for noble metals on oxides.
Complex magnetism and magneto-transport of RECoPO (RE = La, Nd, and Sm)
Authors: Pal Anand , Mehdi Syed Sajjad , Husain Mushahid , Gahtori Bhasker , Awana V. P. S.
Published: December 2011

We report the electrical, magnetotransport, and specific heat of the layered polycrystalline RECoPO (RE = La, Nd, and Sm) samples. These compounds are iso-structural to recently discovered superconductor LaFeAs(O/F). Bulk polycrystalline samples are synthesized by a solid state reaction route in an evacuated sealed quartz tube. All these compounds are crystallized in a tetragonal structure with space group P4/nmm. Cobalt in these compounds is in an itinerant state, with its paramagnetic moment above 1.4 μB and the same orders ferromagnetically (FM) with saturation moment of around 0.20 μB below, say, 80 K. Though, LaCoPO shows single paramagnetic (PM) to ferromagnetic (FM) transition near 35 K, the NdCoPO and SmCoPO exhibit successive PM-FM-anti-ferromagnetic (AFM) transitions. Both FM and AFM transition temperatures vary with applied fields. Although the itinerant ferromagnetism occurs with small saturation moment, typical anti-ferromagnetic (AFM) transitions (TN1, TN2) are observed at 60 K and 14 K for Nd and 70 K and 40 K for Sm. This FM-AFM transition of Co spins in NdCoPO and SmCoPO is both field and temperature dependent. The magneto-transport of NdCoPO and SmCoPO distinctly follows their successive PM-FM-AFM transitions. It is clear that Sm/Nd (4f) interacts with the Co (3d) in first-time-synthesized Sm/NdCoPO.
Spin reorientation transitions in Ho1-xDyxAl2 alloys
Authors: Khan Mahmud , Gschneidner K. A. , Pecharsky V. K.
Published: December 2011

HoAl2 undergoes a first order spin reorientation transition at 20 K, which is accompanied by a sharp peak in the heat capacity data. Here, we have explored the effect of Dy doping on the spin reorientation transitions in Ho1-xDyxAl2 alloys by heat capacity measurements. The first order spin reorientation transition in HoAl2 changes to a second order transition as Ho is partially replaced by Dy in Ho1-xDyxAl2. The Curie temperature shifts to higher temperatures while the spin reorientation transition shifts to lower temperatures with increasing Dy concentration. The observations are interpreted by taking into consideration the higher order Stevens factors that significantly contribute to the free energy of the system. The magnetocaloric properties of the Ho1-xDyxAl2 alloys have also been calculated.
Resistive cooling circuits for charged particle traps using crystal resonators
Authors: Kaltenbacher T. , Caspers F. , Doser M. , Kellerbauer A. , Pribyl W.
Published: December 2011

The paper addresses a novel method to couple a signal from charged particles in a Penning trap to a high Q resonant circuit using a crystal resonator. Traditionally, the trap capacity is converted into a resonator by means of an inductance. The tuned circuit's Q factor is directly linked to the input impedance “seen” by the trapped particles at resonance frequency. This parallel resonance impedance is a measure of the efficiency of resistive cooling and thus it should be optimized. We propose here a commercially available crystal resonator since it exhibits a very high Q value and a parallel resonance impedance of several MΩ. The possibility to tune the parallel resonance frequency of the quartz results in filter behavior that allows covering a range of some tens of its 3dB bandwidth by means of tuning.
A stiff scanning tunneling microscopy head for measurement at low temperatures and in high magnetic fields
Authors: White S. C. , Singh U. R. , Wahl P.
Published: December 2011

We have developed a measurement head for scanning tunneling microscopy (STM) and specifically for spectroscopic imaging STM which is optimized for high mechanical stiffness and good thermal conductivity by choice of material. The main components of the microscope head are made of sapphire. Sapphire has been chosen from several competing possibilities based on finite element modeling of the fundamental vibrational modes of the body. We demonstrate operation of the STM head in topographic imaging and tunneling spectroscopy at temperatures down to below 2 K.
Modeling of spin-torque driven magnetization dynamics in a spin-valve with combined in-plane and out-of-plane polarizers
Authors: Hou Zhiwei , Zhang Zongzhi , Zhang Jianwei , Liu Yaowen
Published: December 2011

Spin-torque (ST) driven magnetization dynamics have been investigated in a spin-valve structure that consists of an in-plane (IP) free layer and two fixed polarizers [magnetized IP and out-of-plane (OP)]. Three distinct dynamics including no switching, switching, and periodic oscillation are identified in a phase diagram governed by the ST parameters. The ST strengths which are able to switch the free layer have been analytically predicted and supported by simulations, showing that the torque originated from the OP polarizer should be much smaller than that from the IP polarizer. The free layer driven by the dual polarizers could switch 10 times faster than that by a single IP polarizer.
Entanglement generation and quantum state transfer between two quantum dot molecules mediated by quantum bus of plasmonic circuits
Authors: Cheng Mu-Tian , Ma Xiao-San , Luo Ya-Qin , Wang Pei-Zhen , Zhao Guang-Xing
Published: December 2011

We investigate theoretically entanglement generation between two distant quantum dot molecules (QDMs) mediated by quantum bus of metal nanoring with surface plasmon polaritons. We show that the two QDMs can be in an entangled state by adjusting the external gate voltage and the coupling strength between the QDMs and the surface plasmon polaritons. The quantum state transfer between the two QDMs is also discussed. Our scheme may find applications in on-chip quantum networks and integrated optoelectronics devices.
Transport properties in single-crystalline rutile TiO2 nanorods
Authors: Chen R. S. , Chen C. A. , Wang W. C. , Tsai H. Y. , Huang Y. S.
Published: December 2011

Electronic transport properties of the single-crystalline titanium dioxide (TiO2) nanorods (NRs) with single rutile phase have been investigated. The conductivity values for the individual TiO2 NRs grown by metal-organic chemical vapor deposition are in the range of 1−10 Ω−1 cm−1. The temperature-dependent measurement shows the presence of two shallow donor levels/bands with activation energies at 8 and 28 meV, respectively. On the photoconductivity (PC), the TiO2 NRs exhibit the much higher normalized PC gain and sensitive excitation-power dependence than the polycrystalline nanotubes. The results demonstrate the superior photoconduction efficiency and distinct mechanism in the monocrystalline one-dimensional TiO2 nanostructures in comparison to the polycrystalline or nanoporous counterparts.
Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways
Authors: D'Autréaux Fabien , Coppola Eva , Hirsch Marie-Rose , Birchmeier Carmen , Brunet Jean-François
Published: December 2011

Taste and most sensory inputs required for the feedback regulation of digestive, respiratory, and cardiovascular organs are conveyed to the central nervous system by so-called “visceral” sensory neurons located in three cranial ganglia (geniculate, petrosal, and nodose) and integrated in the hindbrain by relay sensory neurons located in the nucleus of the solitary tract. Visceral sensory ganglia and the nucleus of the solitary tract all depend for their formation on the pan-visceral homeodomain transcription factor Phox2b, also required in efferent neurons to the viscera. We show here, by genetically tracing

Phox2b
+

cells, that in the absence of the protein, many visceral sensory neurons (first- and second-order) survive. However, they adopt a fate—including molecular signature, cell positions, and axonal projections—akin to that of somatic sensory neurons (first- and second-order), located in the trigeminal, superior, and jugular ganglia and the trigeminal sensory nuclei, that convey touch and pain sensation from the oro-facial region. Thus, the cranial sensory pathways, somatic and visceral, are related, and
Phox2b
serves as a developmental switch from the former to the latter.
Atomic-level stress and induced growth of wurtzite zinc oxide using molecular dynamics simulation
Authors: Hong Zheng-Han , Fang Te-Hua , Hwang Shun-Fa
Published: December 2011

Molecular dynamics is used to simulate the film growth process of zinc oxide (ZnO) deposited on a ZnO substrate. In the work, the Buckingham-type interatomic potential is modelled to describe the interaction of Zn–O atoms. The effects of incident energy and substrate temperature on the layer coverage function, radial distribution function and residual stress are investigated. Results show that the crystal growth of the deposition film is a symmetric wurtzite lattice along the [0 0 0 1] direction due to charge transformation. Epitaxial-like growth only occurs at very low incident energies, while the intermixing process could start from an incident energy of 3 eV. The average stress of the Zn layer is a compressive stress that is close to zero. However, the average mean biaxial stress and the normal stress of the O layer are −4.49 GPa and −3.07 GPa, respectively. The simulation results are compared with experimental results available in the literature.
PGAP: pan-genomes analysis pipeline
Authors: Zhao Yongbing , Wu Jiayan , Yang Junhui , Sun Shixiang , Xiao Jingfa , Yu Jun
Published: December 2011

Summary: With the rapid development of DNA sequencing technology, increasing bacteria genome data enable the biologists to dig the evolutionary and genetic information of prokaryotic species from pan-genome sight. Therefore, the high-efficiency pipelines for pan-genome analysis are mostly needed. We have developed a new pan-genome analysis pipeline (PGAP), which can perform five analytic functions with only one command, including cluster analysis of functional genes, pan-genome profile analysis, genetic variation analysis of functional genes, species evolution analysis and function enrichment analysis of gene clusters. PGAP's performance has been evaluated on 11 Streptococcus pyogenes strains.

Availability:PGAP is developed with Perl script on the Linux Platform and the package is freely available from http://pgap.sf.net.

Contact:  junyu@big.ac.cn; xiaojingfa@big.ac.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
The structure of LsrB from Yersinia pestis complexed with autoinducer-2
Authors: Kavanaugh Jeffrey S. , Gakhar Lokesh , Horswill Alexander R.
Published: December 2011

The crystal structure of LsrB from Yersinia pestis complexed with autoinducer-2 (AI-2; space group P212121, unit-cell parameters a = 40.61, b = 61.03, c = 125.23 Å) has been solved by molecular replacement using the structure of LsrB from Salmonella typhimurium (PDB entry 1tjy) and refined to R = 0.180 (R
free = 0.213) at 1.75 Å resolution. The electron density for bound AI-2 and the stereochemistry of the AI-2-binding site are consistent with bound AI-2 adopting the (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran conformation, just as has been observed in the crystal structures of the Salmonella typhimurium and Sinorhizobium meliloti LsrB–AI-2 complexes.
Structure of the H107R variant of the extracellular domain of mouse NKR-P1A at 2.3 Å resolution
Authors: Kolenko Petr , Rozbeský Daniel , Vaněk Ondřej , Bezouška Karel , Hašek Jindřich , Dohnálek Jan
Published: December 2011

The structure of the H107R variant of the extracellular domain of the mouse natural killer cell receptor NKR-P1A has been determined by X-ray diffraction at 2.3 Å resolution from a merohedrally twinned crystal. Unlike the structure of the wild-type receptor in space group I4122 with a single chain per asymmetric unit, the crystals of the variant belonged to space group I41 with a dimer in the asymmetric unit. Different degrees of merohedral twinning were detected in five data sets collected from different crystals. The mutation does not have a significant impact on the overall structure, but led to the binding of an additional phosphate ion at the interface of the molecules.
Predicting cetuximab accumulation in KRAS wild‐type and KRAS mutant colorectal cancer using 64Cu‐labeled cetuximab positron emission tomography
Authors: Achmad Arifudin , Hanaoka Hirofumi , Yoshioka Hiroki , Yamamoto Shinji , Tominaga Hideyuki , Araki Takuya , Ohshima Yasuhiro , Oriuchi Noboru , Endo Keigo
Published: December 2011

Overexpression of epidermal growth factor receptor (EGFR) is common in colorectal cancer. However, cetuximab as an EGFR‐targeting drug is useful only for a subset of patients and currently no single predictor other than V‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status has been established. In the present study, we investigated cetuximab accumulation in colorectal tumors and major organs using 111In‐DOTA‐cetuximab. We also evaluated the potential of positron emission tomography (PET) imaging of 64Cu‐DOTA‐cetuximab. Colorectal tumor xenografts with a different EGFR expression level and KRAS mutation status were subjected to in vivo biodistribution study and PET imaging at 48 h post‐injection of radiolabeled cetuximab. The EGFR expression levels on colorectal tumors were determined by ex vivo immunoblotting and ELISA. We found that KRAS wild‐type tumors had significantly higher 111In‐DOTA‐cetuximab accumulation than KRAS mutant tumors (P < 0.001). Based on KRAS mutation status, a strong correlation was found between 111In‐DOTA‐cetuximab tumor uptake and EGFR expression level (KRAS wild type: r = 0.988; KRAS mutant: r = 0.829), and between 64Cu‐DOTA‐cetuximab tumor uptake with EGFR expression level (KRAS wild type: r = 0.838; KRAS mutant: r = 0.927). Significant correlation was also found between tumor uptake of 111In‐DOTA‐cetuximab and 64Cu‐DOTA‐cetuximab (r = 0.920). PET imaging with 64Cu‐DOTA‐cetuximab allowed clear visualization of tumors. Both radiolabeled cetuximab had effectively visualized cetuximab accumulation in colorectal tumors with a wide variety of EGFR expression levels and different KRAS mutation status as commonly encountered in the clinical setting. Our findings suggest that this radioimmunoimaging therefore can be clinically translated as an in vivo tool to predict cetuximab accumulation in colorectal cancer patients prior to cetuximab therapy. (Cancer Sci 2012; 103: 600–605)
Light exposure and cell viability in fluorescence microscopy
Authors: SCHNECKENBURGER H. , WEBER P. , WAGNER M. , SCHICKINGER S. , RICHTER V. , BRUNS T. , STRAUSS W.S.L. , WITTIG R.
Published: December 2011

Test systems for measuring cell viability in optical microscopy (based on colony formation ability or lysosomal integrity) were established and applied to native cells as well as to cells incubated with fluorescence markers or transfected with genes encoding for fluorescent proteins. Human glioblastoma and Chinese hamster ovary cells were irradiated by various light doses, and maximum doses where at least 90% of the cells survived were determined. These tolerable light doses were in the range between 25 J cm−2 and about 300 J cm−2 for native cells (corresponding to about 250−3000 s of solar irradiance and depending on the wavelength as well as on the mode of illumination, e.g. epi‐ or total internal reflection illumination) and decreased to values between 50 J cm−2 and less than 1 J cm−2 upon application of fluorescent markers, fluorescent proteins or photosensitizers. In high‐resolution wide field or laser scanning microscopy of single cells, typically 10−20 individual cell layers needed for reconstruction of a 3D image could be recorded with tolerable dose values. Tolerable light doses were also maintained in fluorescence microscopy of larger 3D samples, e.g. cell spheroids exposed to structured illumination, but may be exceeded in super‐resolution microscopy based on single molecule detection.
Biotin deficiency causes spontaneous cell death and activation of defense signaling
Authors: Li Jing , Brader Günter , Helenius Elina , Kariola Tarja , Palva E. Tapio
Published: December 2011

In addition to its essential metabolic functions, biotin has been suggested to play a critical role in regulating gene expression. The first committed enzyme in biotin biosynthesis in Arabidopsis, 7‐keto‐8‐aminopelargonic acid synthase, is encoded by At5g04620 (BIO4). We isolated a T‐DNA insertion mutant of BIO4 (bio4‐1) with a spontaneous cell death phenotype, which was rescued both by exogenous biotin and genetic complementation. The bio4‐1 plants exhibited massive accumulation of hydrogen peroxide and constitutive up‐regulation of a number of genes that are diagnostic for defense and reactive oxygen species signaling. The cell‐death phenotype was independent of salicylic acid and jasmonate signaling. Interestingly, the observed increase in defense gene expression was not accompanied by enhanced resistance to bacterial pathogens, which may be explained by uncoupling of defense gene transcription from accumulation of the corresponding protein. Characterization of biotinylated protein profiles showed a substantial reduction of both chloroplastic biotinylated proteins and a nuclear biotinylated polypeptide in the mutant. Our results suggest that biotin deficiency results in light‐dependent spontaneous cell death and modulates defense gene expression. The isolation and molecular characterization of the bio4‐1 mutant provides a valuable tool for elucidating new functions of biotin.
Renoprotective effect of erythropoietin in ischemia/reperfusion injury: Possible roles of the Akt/endothelial nitric oxide synthase‐dependent pathway
Authors: Oba Shigeyoshi , Suzuki Etsu , Nishimatsu Hiroaki , Kumano Shintaro , Hosoda Chihiro , Homma Yukio , Hirata Yasunobu
Published: December 2011

Objectives:  It has been reported that erythropoietin protects the kidneys from ischemia/reperfusion injury. In the present study, we examined the role of Akt and endothelial nitric oxide synthase in the protective effect of erythropoietin on ischemia/reperfusion injury of the kidney.

Methods:  Erythropoietin was injected in the peritoneal space of ICR mice after ischemia/reperfusion injury and its effect was assessed by measuring blood urea nitrogen and creatinine, and by histological analysis. Phosphorylation of Akt and endothelial nitric oxide synthase was examined by western blot analysis. Endothelial nitric oxide synthase gene null mice were also used to examine the role of endothelial nitric oxide synthase in the renoprotective effect of erythropoietin.

Results:  Erythropoietin administration significantly inhibited the increase in blood urea nitrogen and creatinine after ischemia/reperfusion injury compared with control mice. Accordingly, erythropoietin administration significantly ameliorated the histological damages, including apoptotic cell death. Erythropoietin significantly stimulated phosphorylation of Akt and endothelial nitric oxide synthase in the kidneys. When endothelial nitric oxide synthase gene null mice were subjected to ischemia/reperfusion injury, erythropoietin did not significantly suppress the increase in blood urea nitrogen or creatinine.

Conclusions:  Erythropoietin seems to activate the Akt/endothelial nitric oxide synthase‐dependent pathway in the kidneys. This pathway might be implicated in the renoprotective effect of erythropoietin in the ischemia/reperfusion injury model.
Ablation and Pacing: Improving Brain Perfusion and Cognitive Function in Patients with Atrial Fibrillation and Uncontrolled Ventricular Rates
Authors: EFIMOVA IRINA , EFIMOVA NATALIYA , CHERNOV VLADIMIR , POPOV SERGEY , LISHMANOV YURI
Published: December 2011

Background:
 The aim of our study was to determine if ablation and pacing improved brain perfusion (BP) and cognitive function (CF) in patients with medically refractory rapidly conducted atrial fibrillation (Med Refr RCAF).

Methods and Results:
 The study included 17 patients with Med Refr RCAF (average age 55.3 ± 4.5 years). All patients underwent brain single photon emission computed tomography scanning with 99mTc‐hexamethylpropylene amine oxime and comprehensive neuropsychological testing before and after 3 months following pacemaker implantation. The BP was significantly lower in all regions in patients with Med Refr RCAF compared with the control group. The greatest BP decrease was revealed in the inferior frontal (P = 0.002) and posterior parietal (P = 0.024) brain regions. These patients showed cognitive deficit in 94%. There was a direct correlation between BP and CF parameters. Ablation followed by pacemaker implantation had a positive effect on BP and CF in all patients with Med Refr RCAF. Thus, BP increased in the right inferior frontal (P = 0.01), in the left superior frontal (P = 0.007), and in the left temporal (P = 0.005) cortex. These patients demonstrated improvements in immediate and delayed verbal memory, immediate and delayed visual memory, abstract mentation, attention, psychomotor speed, as well as in learning.

Conclusions:
 Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF. (PACE 2011;1–7)
dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state
Authors: Fawaz Naglaa A. , Beshlawi Ismail O. , Al Zadjali Shoaib , Al Ghaithi Hamed K. , Elnaggari Mohamed A. , Elnour Ibtisam , Wali Yasser A. , Al‐Said Bushra B. , Rehman Jalil U. , Pathare Anil V. , Knox‐Macaulay Huxley , Alkindi Salam S.
Published: December 2011

Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride–bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis (dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5′‐maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort.
Mapping plant strategy types using remote sensing
Authors: Schmidtlein Sebastian , Feilhauer Hannes , Bruelheide Helge
Published: December 2011

Aims

The three‐strategy (CSR) model proposed by Grime constitutes one of the most established systems for plant functional types. The primary strategies (competitive ability, adaptation to severe stress and adaptation to disturbance) relate to the productivity and level of disturbance at a given site. Accordingly, their change in space and time may serve as an illustration and measure of key processes such as succession, eutrophication and habitat shift. Here, we make use of the known links between the three primary strategies to traits with potential relevance for canopy reflectance, and test whether remote sensing is able to reproduce the spatial pattern of strategy types.

Location

A raised bog and minerotrophic fen complex, Murnauer Moos, Germany.

Methods

Field data on the distribution of plant strategies in sample plots were regressed against canopy reflectance using partial least squares regression. The resulting models were validated and applied to airborne hyperspectral imagery on a per pixel basis. The resulting local maps for each strategy type and their combined representation in an RGB colour composite were interpreted in terms of plant species composition and environmental constraints.

Results

All three primary strategy types could be mapped using remote sensing. Reflectance spectra related to competitive ability and adaptation to severe stress suggest that typical traits linked to these strategies exerted a direct influence. On the other hand, species with low cover values played a decisive role for the strength of the statistical relationship between reflectance and strategies. Because these species have a low impact on canopy reflectance, their contribution is better explained by their role as proxies for covarying variables such as the total cover of dead plant material.

Conclusions

Our study demonstrates the potential to detect community strategy type composition using hyperspectral remote sensing, providing direct insights into spatial ecological patterns. By illustrating the exposure to stress, competition and disturbance, the derived maps of functional traits are potentially useful for applications in nature management and for the monitoring of functional shifts in ecosystems. As a next step, they can be easily combined into maps of functional diversity. Upcoming satellites with higher spectral resolution will improve access to this kind of spatial information.
Involvement of Perineuronal and Perisynaptic Extracellular Matrix in Alzheimer's Disease Neuropathology
Authors: Morawski Markus , Brückner Gert , Jäger Carsten , Seeger Gudrun , Matthews Russel T , Arendt Thomas
Published: December 2011

Brain extracellular matrix (ECM) is organized in specific patterns assumed to mirror local features of neuronal activity and synaptic plasticity. Aggrecan‐based perineuronal nets (PNs) and brevican‐based perisynaptic axonal coats (ACs) form major structural phenotypes of ECM contributing to the laminar characteristics of cortical areas. In Alzheimer's disease (AD), the deposition of amyloid proteins and processes related to neurofibrillary degeneration may affect the integrity of the ECM scaffold. In this study we investigate ECM organization in primary sensory, secondary and associative areas of the temporal and occipital lobe. By detecting all major PN components we show that the distribution, structure and molecular properties of PNs remain unchanged in AD. Intact PNs occurred in close proximity to amyloid plaques and were even located within their territory. Counting of PNs revealed no significant alteration in AD. Moreover, neurofibrillary tangles never occurred in neurons associated with PNs. ACs were only lost in the core of amyloid plaques in parallel with the loss of synaptic profiles. In contrast, hyaluronan was enriched in the majority of plaques. We conclude that the loss of brevican is associated with the loss of synapses, whereas PNs and related matrix components resist disintegration and may protect neurons from degeneration.
Blocking the evolution of insecticide‐resistant malaria vectors with a microsporidian
Authors: Koella Jacob C. , Saddler Adam , Karacs Thomas P. S.
Published: December 2011

Finding a way to block the evolution insecticide resistance would be a major breakthrough for the control of malaria. We suggest that this may be possible by introducing a stress into mosquito populations that restores the sensitivity of genetically resistant mosquitoes and that decreases their longevity when they are not exposed to insecticide. We use a mathematical model to show that, despite the intense selection pressure imposed by insecticides, moderate levels of stress might tip the evolutionary balance between costs and benefits of resistance toward maintaining sensitivity. Our experimental work with the microsporidian parasite Vavraia culicis infecting two lines of resistant mosquitoes and a sensitive line suggests that it may indeed be possible to stress the mosquitoes in the required way. The mortality of resistant mosquitoes 24 h after exposure to the insecticide was up to 8.8 times higher in infected than in uninfected ones; if mosquitoes were not exposed to the insecticide, resistant mosquitoes infected by the microsporidian lived about half as long as uninfected ones and insecticide‐sensitive mosquitoes (with or without the parasite). Our results suggest that biopesticides or other insecticides that interfere with the expression of resistance may help to manage insecticide resistance in programs of malaria control.
Genetic and maternal effects on tail spine and body length in the invasive spiny water flea (Bythotrephes longimanus)
Authors: Miehls Andrea L. J. , Peacor Scott D. , McAdam Andrew G.
Published: December 2011

Interest in the evolution of invasive species has grown in recent years, yet few studies have investigated sources of variation in invasive species traits experiencing natural selection. The spiny water flea, Bythotrephes longimanus, is an invasive zooplankton in the Great Lakes that exhibits seasonal changes in tail spine and body length consistent with natural selection. Evolution of Bythotrephes traits, however, depends on the presence and magnitude of quantitative genetic variation, which could change within or across years. Clonal analysis of wild‐captured Bythotrephes indicated that variance components for distal spine length were variable among but not within years. Spine length was always heritable but was not always influenced by maternal effects. In contrast, variance components for body length varied both within and among years, but likewise body length was always heritable and not always influenced by maternal effects. Results indicate that important Bythotrephes traits have heritable variation comparable to native species and other invasive species that would enable an evolutionary response to natural selection. This evolutionary capacity could contribute to the widespread success and dramatic effects of Bythotrephes invasion in systems with diverse biotic and abiotic conditions.
Defining Clinical Research Nursing Practice: Results of a Role Delineation Study
Authors: Bevans Margaret , Hastings Clare , Wehrlen Leslie , Cusack Georgie , Matlock Ann Marie , Miller‐Davis Claiborne , Tondreau Linda , Walsh Diane , Wallen Gwenyth R.
Published: December 2011

Clinical research nursing is a specialty nursing practice focused on the care of research subjects and implementation of clinical research. A five‐dimensional model (Clinical Practice [CP], Study Management, Care Coordination and Continuity, Contributing to the Science [CS], Human Subjects Protection) has been validated nationally to represent the domain of clinical research nursing practice. The purpose of this study was to describe the frequency and importance of activities within each dimension as performed by nurses in clinical research and to describe differences between roles. One thousand and four nurses from the NIH Intramural Campus in Bethesda, Maryland, were invited to participate in an anonymous web‐based survey. Participants (N = 412) were predominantly female (90%) with ≥11 years research experience (70%). Two hundred eighty‐eight respondents (70%) identified themselves as clinical research nurses (CRNs) and 74 (18%) as research nurse coordinators (RNCs). CP activities were reported most frequent and important whereas CS activities were least frequent and important. CRN and RNC activity frequency differed across all dimensions (p < 0.001) with CRNs reporting significantly higher levels of CP activities and significantly lower levels in other dimensions. Delineating specialty activities and practice across roles enhances the understanding of nurses’ role in clinical research and provides groundwork for role‐based training. Clin Trans Sci 2011; Volume 4: 421–427