bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical analysis of E‐cadherin and zeste homolog 2 expression in endoscopic ultrasound‐guided fine‐needle aspiration of pancreatic adenocarcinoma
Authors: Gao Ling , Antic Tatjana , Hyjek Elizabeth , Gong Can , Mueller Jeffrey , Waxman Irving , DeMay Richard M. , Reeves Ward
Published: May 2013

BACKGROUND

Recent studies have demonstrated that partial or complete loss of E‐cadherin (EC) and nuclear accumulation of zeste homolog 2 (EZH2) are hallmarks of poorly differentiated pancreatic adenocarcinoma (PAC). Depletion of EZH2 sensitizes cancer cells to chemotherapy in vitro. The objective of this study was to determine EC and EZH2 expression by immunohistochemistry (IHC) in samples obtained by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) as potential biomarkers for treatment and disease prognosis.

METHODS

Thirty‐eight EUS‐FNA samples from patients with a PAC diagnosis were analyzed by IHC for EC and EZH2 expression. Seven corresponding surgical resection specimens were included in the study. The intensity of EZH2 and EC expression in PAC and in normal gastrointestinal pick‐ups (internal positive control) was scored by using a 4‐tier grading system.

RESULTS

EC demonstrated a focal, weak‐to‐moderate decrease in 24 PAC samples. Complete loss of EC expression was observed in the poorly differentiated areas represented by single tumor cells. The average staining intensity of EC in samples of poorly differentiated PAC was significantly lower than that of moderately differentiated PAC samples (P = .0005). EZH2 was variably positive in 31 of 38 PAC samples. The average staining intensity of EZH2 in moderately and poorly differentiated PACs did not differ significantly (P = .81).

CONCLUSIONS

EC and EZH2 expression was determined reliably by IHC on paraffin sections of EUS‐FNA cell block specimens. The current results were consistent with prior reports indicating a decrease or loss of EC expression in poorly differentiated PAC. However, EZH2 expression did not always correlate inversely with EC expression and was more heterogeneous. Cancer (Cancer Cytopathol) 2013;121:644–52. © 2013 American Cancer Society.
Extraction of Noble and Rare‐Earth Metals from Aqueous Solutions by DNA Cross‐Linked Hydrogels
Authors: Maeda Yuko , Zinchenko Anatoly , Lopatina Larisa I. , Sergeyev Vladimir G. , Murata Shizuaki
Published: May 2013

Invited for this month’s cover is the group of Prof. Shizuaki Murata and Dr. Anatoly Zinchenko from Nagoya University and the group of Prof. Vladimir Sergeyev from Moscow State University. The cover picture shows the accumulation of noble and rare‐earth metals by DNA cross‐linked hydrogel. Read the full text of the article on page 619 ff..
Benchmark of Simplified Formulations for the Electrical Conductivity of Non‐Ideal Plasmas
Authors: Clérouin J.
Published: May 2013

We discuss simplified formulations for the electrical conductivity [1] and compare them with experimental results of various expanded metals recently published [2]. We use formulations designed for fully ionized hydrogen in a broader range of non‐fully ionized materials of various atomic number through the use of an effective coupling parameter based on estimations of the ionization. The ionizations are deduced from average‐atom calculations and compared with faster Thomas‐Fermi‐Dirac estimations. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Calculation of Canonical Properties of a Quantum System by Path Integral Numerical Methods
Authors: Voznesenskiy M. A. , Vorontsov‐Velyaminov P. N.
Published: May 2013

We propose a new approach in obtaining the partition function of a system of several interacting particles (fermions) in external field within path integral Monte Carlo method based on direct averaging of the exchange contributions over the positive weight determined by non‐closed trajectories. This procedure is performed at fixed temperatures, ranging to rather low values. The complete partition function for each temperature is then obtained within an expanded ensemble procedure. We found a good agreement of data obtained by the new method with results of previously proposed path‐integral‐expanded‐ensemble Monte Carlo calculations [1, 2]. The new approach allows to reach observably lower temperatures compared to method [1, 2], thus providing a significant reduce of the sign problem. It yields an independent way to treat thermal properties of quantum systems, so the good agreement with previous data [1, 2] allows us to test and state the validity of both approaches. Simulations for systems of 2 up to 5 non‐interacting particles and particles interacting with Coulomb repulsion in 3D harmonic field were performed. The presented approach allows one to carry out calculations for low temperatures that makes it possible to extract data for the ground‐state energy and low‐temperature thermodynamics. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electron Kinetics in Femtosecond X‐Ray Irradiated SiO2
Authors: Medvedev N. , Ziaja B. , Cammarata M. , Harmand M. , Toleikis S.
Published: May 2013

A theoretical study of the ultrafast electron kinetics in solid SiO2, irradiated with a femtosecond X‐ray laser pulse, is presented. A Monte Carlo code for event‐by‐event simulations of individual particles is applied to model the electron kinetics within the irradiated SiO2 bulk. The simulation includes photoionization, elastic and inelastic scatterings of electrons, Auger decays of core holes, and electron‐hole recombination via exciton self‐trapping mechanism. Transient electron density is followed, at different photon energies and pulse durations. The change of the optical properties (reflectance, transmittance) of the material is estimated with the help of the Drude model. The analysis of the results allows us to conclude that within the X‐ray excited dielectric, the holes in the valence band give the predominant contribution to the transient changes of optical properties within the material. The increase rate of the free electron density is limited by the duration of secondary electron cascading. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Atomistic Modelling and Simulation of Warm Dense Matter. Conductivity and Reflectivity
Authors: Norman G. , Saitov I. , Stegailov V. , Zhilyaev P.
Published: May 2013

Warm dense matter conductivity and reflectivity are investigated by means of density functional theory. Both one‐ and two‐temperature cases are considered. One‐temperature mode is related to equilibrium state where temperature of electrons and ions are equal. As an example of one‐temperature system xenon plasma is studied. The reflectivity of shock‐compressed dense xenon plasma is calculated and compared with experimental data. Two‐temperature mode is associated with different temperature of electrons and ions. The thermal conductivity of aluminium and gold in such mode is examined. The comparison of obtained results with theoretical model based on Boltzmann equation is conducted. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
SAHA‐S Thermodynamic Model of Solar Plasma
Authors: Gryaznov V.K. , Iosilevskiy I.L. , Fortov V.E. , Starostin A.N. , Roerich V.K. , Baturin V. A. , Ayukov S. V.
Published: May 2013

The model SAHA‐S based on the chemical picture for the equation of state of the solar plasma is presented. The effects of Coulomb interaction, exchange and diffraction effects, free electron degeneracy, relativistic corrections, radiation pressure contributions are taken into account. The solar model based on SAHA‐S taking into account extended element composition and variation of heavy element abundance is represented and discussed. The comparison of the SAHA‐S equation of state data for a hydrogen plasma with the results of other models applicable to the description of the solar plasma equation of state and the results obtained with the first principle methods are demonstrated and discussed. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamic Screening, Coulomb Singularity and Drude Model of Absorption
Authors: Mulser P. , Murakami M.
Published: May 2013

The Debye screening potential is generalized for an arbitrary isotropic distribution function and the dynamic screening for a cold streaming plasma is calculated. In both cases the structure of the screening length is the same, however the potentials are different. For the warm plasma under arbitrary drift the ballistic model is compared with the self consistent dielectric model. The validity of the Drude ansatz is shown to hold as long as the electron oscillations parallel to its motion are negligible. Their energy is by twice the Coulomb logarithm lower than in perpendicular direction. Finally, the problem of the Coulomb singularity is addressed. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hypernetted Chain Calculations for Multi‐Component and NonEquilibrium Plasmas
Authors: Bredow R. , Bornath Th. , Kraeft W.‐D. , Redmer R.
Published: May 2013

We solve the Ornstein‐Zernike equation within the hypernetted chain approximation for dense multi‐component plasmas using effective pair potentials. The method is used to study structural properties of plasmas, for instance in order to explain and predict X‐ray Thomson scattering spectra. Corresponding experiments are performed at free electron lasers such as FLASH Hamburg and LCLS Stanford, or at facilities using energetic optical lasers such as Omega in Rochester and Janus in Livermore. Results for pair distribution functions and static structure factors for dense hydrogen, beryllium, carbon and carbonhydride plasmas are presented. Furthermore, calculations for non‐equilibrium two‐temperature plasmas are performed as well, which are relevant for laserplasma interaction and relaxation phenomena on short time scales. We propose a consistent treatment for the electron‐ion coupling term which leads to a more realistic description of correlation effects. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Structural and Transport Properties of Dust Formation in Plasma of Noble Gases Mixture in Radio Frequency Discharge
Authors: Dosbolayev M.K. , Utegenov A. U. , Ramazanov T. S. , Daniyarov T. T.
Published: May 2013

In the present paper properties of dust formation in RF discharges of pure helium and helium‐argon mixture are investigated. Analysis of macroscopic properties of dust formation at different pressures of background gas reveals a change of properties of dust formation in the mixture of gases in comparison with discharge in pure helium. As possible mechanisms for observed behavior, a change of ion jet content and a friction of neutral component are considered. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Composition of Dense Beryllium, Boron and Carbon Plasmas
Authors: Gabdullin M.T. , Ramazanov T.S. , Redmer R. , Akhtanova G.B.
Published: May 2013

In the present paper we determine the composition of dense beryllium, boron and carbon plasma by solving the Saha equations with corrections due to non‐ideality. The lowering of the ionization potentials is calculated on the basis of effective potentials by taking into account screening and quantum diffraction effects. The considered range of density and temperature covers plasmas with a very low degree of ionization up to full ionization with ions having the maximum ionization state. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dust Particles Behavior in an Electrodynamic Trap
Authors: Lapitsky D. S. , Filinov V. S. , Deputatova L. V. , Vasilyak L. M. , Vladimirov V. I. , Pecherkin V. Ya.
Published: May 2013

The behavior of the charged dust particles in the linear Paul trap was simulated by Brownian dynamics for reasonable choice of the particle parameters and trap electrode voltages. Regions of these parameters needed for particle confinement at normal atmosphere conditions (pressure and temperatures) have been obtained. An influence of air viscosity, particle masses and charges, frequency and alternating voltage on regions of confinement were investigated. Obtained regions of the particle confinement agree with our experimental results for linear Paul trap. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Low‐Density Equation of State for Water from a Chemical Model
Authors: Schöttler M. , Redmer R. , French M.
Published: May 2013

We calculate the free energy and other basic thermodynamic properties of water within a model in the chemical picture. The respective mass‐action laws between several molecular, atomic, and ionic species are solved analytically, and purely temperature‐dependent partition functions are used for all species. It is shown that such an ideal gas‐like model is able to describe the thermodynamic properties in relatively good agreement with ab initio simulations, provided that the density of the system is sufficiently low. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Atomic Layer Deposition of W:Al2O3 Nanocomposite Films with Tunable Resistivity
Authors: Mane Anil U. , Elam Jeffrey W.
Published: May 2013

Nanocomposite tungsten‐aluminum oxide (W:Al2O3) thin films were prepared by atomic layer deposition (ALD) using tungsten hexafluoride (WF6) and disilane (Si2H6) for the W ALD and trimethyl aluminum (TMA) and H2O for the Al2O3 ALD. Quartz crystal microbalance (QCM) measurements performed using various W cycle percentages revealed that the W ALD inhibits the Al2O3 ALD and vice versa. Despite this inhibition, the relationship between W content and W cycle percentage was close to that predicted by theoretical calculations based on the growth per cycle values of binary compounds. Depth profiling XPS showed that the (W:Al2O3) films were uniform in composition and contained Al, O, and metallic W as expected, but also included significant F and C. Cross‐sectional TEM revealed the composite film structure to be metallic nanoparticles (∼1 nm) embedded in an amorphous matrix. The resistivity of these composite films could be tuned in the range of 1012–108 Ω cm by adjusting the W cycle percentage between 10% and 30%W. These films have applications in electron multipliers as well as electron and ion optics.
Bcl‐2 level as a biomarker for 13q14 deletion in CLL
Authors: Degheidy Heba A. , Gadalla Shahinaz M. , Farooqui Mohammed Z. H. , Abbasi Fatima , Arthur Diane C. , Bauer Steven R. , Wilson Wyndham H. , Wiestner Adrian , Stetler‐Stevenson M. A. , Marti Gerald E.
Published: May 2013

Background

Deletion 13q14.3 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL). Previously it was reported that miR‐15/16 is the target of 13q14 deletions and plays a tumor suppressor role by suppressing Bcl‐2. Therefore, Bcl‐2 expression was examined more closely to determine whether it would predict 13q14 deletion status.

Methods

A multi‐color flow panel consisting of anti‐Bcl‐2/anti‐lambda/anti‐kappa/CD19/CD5/CD3/CD20 was performed. The ability of Bcl‐2 to predict 13q14 deletion was tested using the conventional Bcl‐2 index (c‐index): mean fluorescence intensity (MFI) of CLL clone/MFI of residual T cells. Fifty‐four untreated CLL/MBL patients were studied. Bimodal Bcl‐2 expression was evaluated to test the ability of Bcl‐2 to detect intraclonal heterogeneity. Other CLL prognostic markers including CD38, CD49d, CD26, and CD69 were evaluated. FISH was performed on selected sorted populations.

Results

The Bcl‐2 c‐index strongly predicts del13q14 P < 0.0001. A statistically significant association was observed between the percentage of cells carrying the deletion and the level of Bcl‐2 expression P < 0.05. Cells sorted based on Bcl‐2 expression showed enrichment of both hemizygous and homozygous del 13q14 cells. Also, we observed that an alteration in Bcl‐2 level over time predicts changes in 13q14 deletion status. And a statistically significant correlation between the bimodal pattern of CD69 expression and the presence of 13q14 deletion was found P < 0.0001.

Conclusion

Bcl‐2 expression using the c‐index strongly predicts 13q14 deletion and can be used to distinguish homozygous, heterozygous, and diploid CLL clonal cells. Further systematic studies of this biomarker are needed for confirmation and expansion of these findings. Published 2013 Wiley‐Periodicals, Inc.
Stabilization media increases recovery in paucicellular cerebrospinal fluid specimens submitted for flow cytometry testing
Authors: Greig B. , Stetler‐Stevenson M. , Lea J.
Published: May 2013

Background

Flow cytometric immunophenotpying (FCI) of cerebrospinal fluid (CSF) and other paucicellular fluids has been demonstrated to have increased sensitivity in detection of lymphoma and leukemia when compared to cytomorphology [(1) de Graaf et al., Cytometry Part B 2011, 80B:271–281; (2) Szamosi et al., CLSI Document H56‐A—Body Fluid Analysis for Cellular Composition; Approved Guideline, Wayne, PA: Clinical and Laboratory Standards Institute, 2006; (3) Kraan et al., Flow Cytometric Immunophenotyping of Cerebrospinal Fluid. Current Protocols in Cytometry, Hoboken, NJ: Wiley, 2008]. However, low cellularity has been an historical problem with these samples. Several studies indicate that immediate addition of a stabilization media (e.g., RPMI with fetal calf serum (FCS)) to CSF improves the cell yield for FCI [(1) de Graaf et al.]. Such stabilization medias can, however, significantly increase cost.

Methods

We compared FCI results in CSF stabilized with RPMI 1640 (without additional additives) to results obtained using non‐stabilized CSF. Samples were processed according to published CLSI guidelines [(2) Szamosi et al.].

Results

About 98/105 (93%) CSF specimens stabilized with RPMI had adequate numbers of viable cells (>100) for performing FCI. About 65/217 (30%) CSF specimens without stabilization had adequate numbers of viable cells for analysis (70% either quantity not sufficient (QNS) or specimen viability below analytical limits).

Conclusions

Utilizing RMPI without FCS as a stabilization media results in increased cell yield and improved FCI results. We have found FCS is not required to achieve high quality results in FCI of paucicellular CSF specimens. © 2013 International Clinical Cytometry Society
Mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory T cells
Authors: Thakur Reva S. , Tousif Sultan , Awasthi Vikky , Sanyal Anirban , Atul P. K. , Punia Parveen , Das Jyoti
Published: May 2013

Plasmodium spp. parasites, the causative agents of malaria, survive and replicate in human hosts by modulating host protective immune responses. In a rodent model, malaria manifests as a severe splenomegaly, with infiltration of cells and lympho‐proliferation as major contributing factors of the immunopathology. However, the cellular contents and the functions of these cells have not been well studied. Here, we report that Plasmodium berghei infection of mice leads to massive recruitment of mesen‐chymal stem cells (MSCs) in secondary lymphoid organs. Infusion of these cells into naïve mice was able to confer host resistance against malaria. Furthermore, MSCs augmented interleukin (IL)‐12 production but suppressed IL‐10 production in recipient animals. In addition, we observed dramatic reductions of regulatory T (Treg) cells in animals that received MSCs. Taken together, our findings have identified recruitment of MSCs as a novel host protective mechanism adopted by the host to combat malaria by modulating Treg‐cell responses.
p300, but not PCAF, collaborates with IRF‐1 in stimulating TRIM22 expression independently of its histone acetyltransferase activity
Authors: Gao Bo , Xu Wei , Zhong Linmao , Zhang Qilin , Su Ya , Xiong Sidong
Published: May 2013

Tripartite motif (TRIM) 22 plays an important role in IFN‐mediated antiviral activity. We previously demonstrated that IFN regulatory factor‐1 (IRF‐1) was crucial for constitutive and IFN‐induced TRIM22 expression via binding to a special cis‐element named 5′ extended IFN‐stimulating response element. Here, we further investigate the molecular mechanisms of TRIM22 with a focus on the co‐activators of IRF‐1. Using an in vitro DNA affinity binding assay and an in vivo chromatin immunoprecipitation assay, we found that IFN‐γ stimulation significantly enhanced the binding of p300 and p300/CBP‐associated factor, but not other co‐activators such as general control nondepressible 5, steroid receptor co‐activator‐1, and activator of thyroid and retinoic, to the 5′ extended IFN‐stimulating response element containing TRIM22 promoter region together with IRF‐1. Overexpression and knockdown analysis demonstrated that it was p300, but not p300/CBP‐associated factor, that functioned as a transcriptional co‐activator of IRF‐1 in IFN‐γ induction of TRIM22. We further show that p300 contributed to both IFN‐γ‐ and IRF‐1‐mediated TRIM22 transcription independent of its histone acetyltransferase activity, however, it was required for the recruitment of RNA polymerase II to TRIM22 promoter region. These data indicate that p300 plays a critical role in IFN‐γ‐induced TRIM22 expression via recruiting RNA polymerase II to the TRIM22 promoter, and might serve as a bridge between IRF‐1 and the basal transcriptional apparatus in TRIM22 induction.
Chemotaxis of bone marrow derived eosinophils in vivo: A novel method to explore receptor‐dependent trafficking in the mouse
Authors: Sturm Eva M. , Dyer Kimberly D. , Percopo Caroline M. , Heinemann Akos , Rosenberg Helene F.
Published: May 2013

Here, we describe a novel method via which ex vivo cultured mouse bone marrow derived eosinophils (bmEos) can be adoptively transferred into recipient mice in order to study receptor‐dependent recruitment to lung tissue in vivo. Intratracheal instillation of recombinant human eotaxin‐2 (hCCL24) prior to introduction of bmEos via tail vein injection resulted in an approximately fourfold increase in Siglec F‐positive/CD11c‐negative eosinophils in the lungs of eosinophil‐deficient ΔdblGATA recipient mice compared with controls. As anticipated, bmEos generated from CCR3‐gene‐deleted mice did not migrate to the lung in response to hCCL24 in this model, indicating specific receptor dependence. BmEos generated from GFP‐positive BALB/c mice responded similarly to hCCL24 in vitro and were detected in lung tissue of BALB/c WT as well as BALB/c ΔdblGATA eosinophil‐deficient recipient mice, at approximately fourfold (at 5 h post‐injection) and approximately threefold (at 24 h postinjection) over baseline, respectively. Comparable results were obtained with GFP‐positive C57BL/6 bmEos responding to intratracheal hCCL24 in C57BL/6 ΔdblGATA recipient mice. The use of ex vivo cultured bmEos via one or more of these methods offers the possibility of manipulating bmEos prior to transfer into a WT or gene‐deleted recipient host. Thus, this chemotaxis model represents a novel and robust tool for pharmacological studies in vivo.
Hydrogen Evolution Catalyzed by Aluminum‐Bridged Cobalt Diglyoximate Complexes
Authors: Kelley Paul , Day Michael W. , Agapie Theodor
Published: May 2013

The syntheses of several cobalt diglyoximate complexes connected by one or two aluminum bridges are described. The aluminum centers are supported by tunable tetradentate diamine bisphenoxide ligands. Electrochemical investigations revealed that the number of aluminum bridges and the nature of the substituents on the phenoxide ligands significantly affect the cobalt reduction potentials. The present aluminum–cobalt compounds are electrocatalysts for proton reduction to hydrogen at potentials negative relative to those of the boron‐ and proton‐bridged analogs. The reported synthetic strategies allow modulation of the reduction potentials and the secondary coordination sphere interactions by tuning the ancillary ligands bound to aluminum.
Temporal variability of in situ methane concentrations in gas hydrate‐bearing sediments near Bullseye Vent, Northern Cascadia Margin
Authors: Lapham Laura , Wilson Rachel , Riedel Michael , Paull Charles K. , Holmes M. Elizabeth
Published: May 2013

To assess the temporal variability in the methane fluxes from marine sediments that overly gas hydrate bearing sediments and the factors that might control its rate, in situ methane concentrations were measured near Bullseye Vent on the Northern Cascadia continental margin. A long‐term sampling device collected overlying water and pore‐fluid samples from 25 cm above seafloor, at the sediment‐water interface (SWI), and 7 cmbsf (centimeters below seafloor) over a 9 month period (August 2009–May 2010). These samples provide a record at ∼4 day resolution of in situ methane, ethane, propane, sulfate, and chloride concentrations, as well as stable carbon isotope ratios of methane (δ13C‐CH4) and dissolved inorganic carbon (δ13C‐DIC). We show that pore fluids near the SWI are saturated or supersaturated with respect to methane (∼80 mM) and the methane flux from the seabed is variable over time. We hypothesized that regional seismic activity controlled this variable CH4 flux in the Northern Cascadia continental margin setting. However, we found no direct correlation between earthquakes and CH4 flux. We also posited alternative controls on CH4 flux variability, such as storms, regional oceanography and microbial activity. Again, no direct correlation was seen. This study takes first steps toward exploring which physical factors play a role in methane flux from hydrate‐bearing sediments.
Mass transport‐dominated sedimentation in a foreland basin, the Hidaka Trough, northern Japan
Authors: Noda Atsushi , TuZino Taqumi , Joshima Masato , Goto Shusaku
Published: May 2013

Mass transport is an important process of sediment redistribution from shallow to deep sea basins. It is vital to understand this process for disaster prevention and protection of economic interests in coastal and offshore areas. We describe mass transport‐dominated sedimentation in an active foreland basin, the Hidaka Trough, which developed from collision between the northeastern Japan arc and the Kuril arc. The basin is deformed by east‐west compression associated with large, frequent earthquakes. The trough is filled with thick (>4.5 km) sediments, ranging from coal‐bearing Cretaceous terrestrial strata to modern diatomaceous hemipelagic mud and volcanic ash. Bottom‐simulating reflectors and the distribution of mud volcanoes, pockmarks, and acoustic wipe‐out zones on the seismic records suggest the presence of subsurface gases in the sediments. The basin features stacked mass transport deposits (MTDs), but no channel‐levee systems have developed. The MTDs are relatively thin (<30 m) and are derived from three sides of the basin margin. Initiation of submarine slope failure in this area may be controlled by multiple factors that increase driving forces and decrease resistance of the slopes. The driving forces include oversteepening of the margin slope as a result of thrusting and folding, and additional downslope gravitational acceleration caused by cyclic shaking during earthquakes. Decreased resistance in the slopes may be caused by the accumulation of excess pore‐water pressure driven by a high‐sedimentation rate, gas hydrate dissociation accompanying changes in sea level or seawater temperature, and liquefaction in coarse‐grained beds during earthquakes.
Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and alzheimer's disease dementia
Authors: Wang Pei‐Ning , Chou Kun‐Hsien , Chang Ni‐Jung , Lin Ker‐Neng , Chen Wei‐Ta , Lan Gong‐Yau , Lin Ching‐Po , Lirng Jiing‐Feng
Published: May 2013

Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single‐domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Hum Brain Mapp 35:1529–1543, 2014. © 2013 Wiley Periodicals, Inc.
Assessing the function of the fronto‐parietal attention network: Insights from resting‐state fMRI and the attentional network test
Authors: Markett Sebastian , Reuter Martin , Montag Christian , Voigt Gesine , Lachmann Bernd , Rudorf Sarah , Elger Christian E. , Weber Bernd
Published: May 2013

In the recent past, various intrinsic connectivity networks (ICN) have been identified in the resting brain. It has been hypothesized that the fronto‐parietal ICN is involved in attentional processes. Evidence for this claim stems from task‐related activation studies that show a joint activation of the implicated brain regions during tasks that require sustained attention. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate that functional connectivity within the fronto‐parietal network at rest directly relates to attention. We applied graph theory to functional connectivity data from multiple regions of interest and tested for associations with behavioral measures of attention as provided by the attentional network test (ANT), which we acquired in a separate session outside the MRI environment. We found robust statistical associations with centrality measures of global and local connectivity of nodes within the network with the alerting and executive control subfunctions of attention. The results provide further evidence for the functional significance of ICN and the hypothesized role of the fronto‐parietal attention network. Hum Brain Mapp 35:1700–1709, 2014. © 2013 Wiley Periodicals, Inc.
The spontaneous fluctuation of the excitability of a single node modulates the internodes connectivity: A TMS‐EEG study
Authors: Giambattistelli Federica , Tomasevic Leo , Pellegrino Giovanni , Porcaro Camillo , Melgari Jean Marc , Rossini Paolo Maria , Tecchio Franca
Published: May 2013

Brain effective connectivity can be tracked by cerebral recruitments evoked by transcranial magnetic stimulation (TMS), as measured by simultaneous electroencephalography (TMS‐EEG). When TMS is targeting the primary motor area, motor evoked potentials (MEPs) can be collected from the “target” muscles. The aim of this study was to measure whether or not effective brain connectivity changes with the excitability level of the corticospinal motor pathway (CSMP) as parameterized by MEP amplitude. After averaging two subgroups of EEG‐evoked responses corresponding to high and low MEP amplitudes, we calculated the individual differences between them and submitted the grand average to sLORETA algorithm obtaining localized regions of interest (RoIs). Statistical differences of RoI recruitment strength between low and high CSMP excitation was assessed in single subjects. Preceding the feedback arrival, neural recruitment for stronger CSMP activation were weaker at 6–10 ms of homotopic sensorimotor areas BA3/4/5 of the right nonstimulated hemisphere (trend), weaker at 18–25 ms of left parietal BA2/3/40, and stronger at 26–32 ms of bilateral frontal motor areas BA6/8. The proposed method enables the tracking of brain network connectivity during stimulation of one node by measuring the strength of the connected recruited node activations. Spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. The effective connectivity within bilateral circuits orchestrating hand control appeared dynamically modulated in time even in resting state as probed by TMS. Hum Brain Mapp 35:1740–1749, 2014. © 2013 Wiley Periodicals, Inc.
Grasping with the foot: Goal and motor expertise in action observation
Authors: Senna Irene , Bolognini Nadia , Maravita Angelo
Published: May 2013

Action observation typically induces an online inner simulation of the observed movements. Here we investigate whether action observation merely activates, in the observer, the muscles involved in the observed movement or also muscles that are typically used to achieve the observed action goal. In a first experiment, hand and foot motor areas were stimulated by means of transcranial magnetic stimulation, while participants viewed a typical hand action (grasping) or a nonspecific action (stepping over an object) performed by either a hand or a foot. Hand motor evoked potentials (MEPs) increased for grasping and stepping over actions performed by the hand and for grasping actions performed by the foot. Conversely, foot MEPs increased only for actions performed by the foot. In a second experiment, participants viewed a typical hand action (grasping a pencil) and a typical foot action (pressing a foot‐pedal) performed by either a hand or a foot. Again, hand MEPs increased not only during the observation of both actions performed by the hand but also for grasping actions performed by the foot. Foot MEPs increased not only during the observation of grasping and pressing actions performed by the foot but also for pressing actions performed by the hand. This evidence indicates that motor activations by action observation occur also in the muscles typically used to perform the observed action, even when the action is executed by an unusual effector, hence suggesting a double coding of observed actions: a strict somatotopic coding and an action goal coding based on the observer's motor expertise. Hum Brain Mapp 35:1750–1760, 2014. © 2013 Wiley Periodicals, Inc.
Characterization of disease‐related covariance topographies with SSMPCA toolbox: Effects of spatial normalization and PET scanners
Authors: Peng Shichun , Ma Yilong , Spetsieris Phoebe G. , Mattis Paul , Feigin Andrew , Dhawan Vijay , Eidelberg David
Published: May 2013

To generate imaging biomarkers from disease‐specific brain networks, we have implemented a general toolbox to rapidly perform scaled subprofile modeling (SSM) based on principal component analysis (PCA) on brain images of patients and normals. This SSMPCA toolbox can define spatial covariance patterns whose expression in individual subjects can discriminate patients from controls or predict behavioral measures. The technique may depend on differences in spatial normalization algorithms and brain imaging systems. We have evaluated the reproducibility of characteristic metabolic patterns generated by SSMPCA in patients with Parkinson's disease (PD). We used [18F]fluorodeoxyglucose PET scans from patients with PD and normal controls. Motor‐related (PDRP) and cognition‐related (PDCP) metabolic patterns were derived from images spatially normalized using four versions of SPM software (spm99, spm2, spm5, and spm8). Differences between these patterns and subject scores were compared across multiple independent groups of patients and control subjects. These patterns and subject scores were highly reproducible with different normalization programs in terms of disease discrimination and cognitive correlation. Subject scores were also comparable in patients with PD imaged across multiple PET scanners. Our findings confirm a very high degree of consistency among brain networks and their clinical correlates in PD using images normalized in four different SPM platforms. SSMPCA toolbox can be used reliably for generating disease‐specific imaging biomarkers despite the continued evolution of image preprocessing software in the neuroimaging community. Network expressions can be quantified in individual patients independent of different physical characteristics of PET cameras. Hum Brain Mapp 35:1801–1814, 2014. © 2013 Wiley Periodicals, Inc.
MODELING THE EFFECTS OF IMMUNIZATIONS TIMING ON CHILD HEALTH OUTCOMES IN INDIA
Authors: Bhargava Alok , Guntupalli Aravinda M. , Lokshin Michael , Howard Larry L.
Published: May 2013

Timely vaccinations of children in developing countries are important for reducing morbidity and mortality, which are Millennium Development Goals. However, a majority of children do not possess vaccination cards compiling information on timing. We investigated the benefits of vaccination cards for the uptake of immunizations against diphtheria, pertussis and tetanus (DPT), polio, tuberculosis (BCG), and measles using data on over 200,000 Indian children from the District Level Health and Facility Survey 3. Methodological issues such as whether parents of children with higher morbidity levels may have them vaccinated were investigated. The results from the models for DPT, polio, measles, and BCG vaccinations showed significant beneficial effects of maternal education, household possessions, and access to health care facilities. Moreover, models for children's ages at the time of vaccination showed significant interactions between maternal education and access to and availability of health care facilities. Finally, models for child morbidity due to diarrhea, cough, and fever showed that timely vaccinations against DPT, access to piped water, and cooking with electricity or natural gas were associated with lower morbidity. Overall, issuing paper or electronic vaccination cards to children is likely to enhance timely uptake of various immunizations thereby reducing child morbidity. Copyright © 2013 John Wiley & Sons, Ltd.
A new method to characterize the spatial structure of soil macropore networks in effects of cultivation using computed tomography
Authors: Hu Youbing , Feng Jie , Yang Tao , Wang Chao
Published: May 2013

Soil macropore networks are subsurface connected void spaces caused by processes such as fracture of soils, micro‐erosion and fauna burrows. Axial X‐ray computed tomography (CT) scanning provides a convenient means of recording the spatial structure of soil macropore networks. The objective of this study were to (1) based on CT technique and GIS digitized image method, construction a new technique for tracing, visualizing and measuring the soil macropore networks and (2) investigate the effects of farming activities on soil macropore networks characteristics. Our technique uses left‐turning and nine‐direction judgment methods, a combination of the layer‐by‐layer analysis method and the up‐down tracking algorithm. The characteristics for the overall structure patterns of macropores, the spatial distribution of the macropore networks and each single macropore network can be conveniently identified by our technique. Eight undisturbed soil columns from fields with two distinct land uses (under cultivation and not been cultivated) and four different depths (0–20, 20–40, 40–60 and 60–80 cm) were investigated. The soil columns were scanned using X‐ray CT at a voxel resolution of 0.075 × 0.075 × 3.000 mm. Results indicate that farming activities can destroy the initial structure of macropores, and those remaining are mainly small‐sized and medium‐sized networks with lower extension and hydraulic conductivity. The network properties show a significant difference between upper and lower layer. The results can provide beneficial reference to further research centered on non‐equilibrium flow prediction and chemical transport modeling in field soils. Copyright © 2013 John Wiley & Sons, Ltd.
Regulation of cardiac autophagy by insulin‐like growth factor 1
Authors: Troncoso Rodrigo , Díaz‐Elizondo Jessica , Espinoza Sandra P. , Navarro‐Marquez Mario F. , Oyarzún Alejandra P. , Riquelme Jaime A. , Garcia‐Carvajal Ivonne , Díaz‐Araya Guillermo , García Lorena , Hill Joseph A. , Lavandero Sergio
Published: May 2013

Insulin‐like growth factor‐1 (IGF‐1) signaling is a key pathway in the control of cell growth and survival. Three critical nodes in the IGF‐1 signaling pathway have been described in cardiomyocytes: protein kinase Akt/mammalian target of rapamycin (mTOR), Ras/Raf/extracellular signal‐regulated kinase (ERK), and phospholipase C (PLC)/inositol 1,4,5‐triphosphate (InsP3)/Ca2+. The Akt/mTOR and Ras/Raf/ERK signaling arms govern survival in the settings of cardiac stress and hypertrophic growth. By contrast, PLC/InsP3/Ca2+ functions to regulate metabolic adaptability and gene transcription. Autophagy is a catabolic process involved in protein degradation, organelle turnover, and nonselective breakdown of cytoplasmic components during nutrient starvation or stress. In the heart, autophagy is observed in a variety of human pathologies, where it can be either adaptive or maladaptive, depending on the context. We proposed the hypothesis that IGF‐1 protects the heart by rescuing the mitochondrial metabolism and the energetics state, reducing cell death and controls the potentially exacerbate autophagic response to nutritional stress. In light of the importance of IGF‐1 and autophagy in the heart, we review here IGF‐1 signaling and autophagy regulation in the context of cardiomyocyte nutritional stress. © 2013 IUBMB Life, 65(7):593–601, 2013.
Bayesian integrated testing strategy to assess skin sensitization potency: from theory to practice
Authors: Jaworska Joanna , Dancik Yuri , Kern Petra , Gerberick Frank , Natsch Andreas
Published: May 2013

Frameworks to predictin vivoeffects by integration ofin vitro,in silicoandin chemicoinformation using mechanistic insight are needed to meet the challenges of 21stcentury toxicology. Expert‐based approaches that qualitatively integrate multifaceted data are practiced under the term ’weight of evidence’, whereas quantitative approaches remain rare. To address this gap we previously developed a methodology to design an Integrated Testing Strategy (ITS) in the form of a Bayesian Network (BN). This study follows up on our proof of concept work and presents an updated ITS to assess skin sensitization potency expressed as local lymph node assay (LLNA) potency classes. Modifications to the ITS structure were introduced to include better mechanistic information. The parameters of the updated ITS were calculated from an extended data set of 124 chemicals. A detailed validation analysis and a case study were carried out to demonstrate the utility of the ITS for practical application. The improved BN ITS predicted correctly 95% and 86% of chemicals in a test set (n = 21) for hazard and LLNA potency classes, respectively. The practical value of using the BN ITS is far more than a prediction framework when all data are available. The BN ITS can develop a hypothesis using subsets of data as small as one data point and can be queried on the value of adding additional tests before testing is commenced. The ITS represents key steps of the skin sensitization process and a mechanistically interpretable testing strategy can be developed. These features are illustrated in the manuscript via practical examples. Copyright © 2013 John Wiley & Sons, Ltd.
Assessment of the biocompatibility and stability of a gold nanoparticle collagen bioscaffold
Authors: Grant Sheila A. , Spradling Claire S. , Grant Daniel N. , Fox Derek B. , Jimenez Luis , Grant David A. , Rone Rebecca J.
Published: May 2013

Collagen has been utilized as a scaffold for tissue engineering applications due to its many advantageous properties. However, collagen in its purified state is mechanically weak and prone to rapid degradation. To mitigate these effects, collagen can be crosslinked. Although enhanced mechanical properties and stability can be achieved by crosslinking, collagen can be rendered less biocompatible either due to changes in the overall microstructure or due to the cytotoxicity of the crosslinkers. We have investigated crosslinking collagen using gold nanoparticles (AuNPs) to enhance mechanical properties and resistance to degradation while also maintaining its natural microstructure and biocompatibility. Rat tail type I collagen was crosslinked with AuNPs using a zero‐length crosslinker, 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC). Several characterization studies were performed including electron microscopy, collagenase assays, ROS assays, and biocompatibility assays. The results demonstrated that AuNP‐collagen scaffolds had increased resistance to degradation as compared to non‐AuNP‐collagen while still maintaining an open microstructure. Although the biocompatibility assays showed that the collagen and AuNP‐collagen scaffolds are biocompatible, the AuNP‐collagen demonstrated enhanced cellularity and glycoaminoglycans (GAG) production over the collagen scaffolds. Additionally, the Reactive Oxygen Species (ROS) assays indicated the ability of the AuNP‐collagen to reduce oxidation. Overall, the AuNP‐collagen scaffolds demonstrated enhanced biocompatibility and stability over non‐AuNP scaffolds. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 332–339, 2014.
Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM
5 gene
Authors: Grover Monica , Campeau Philippe M , Lietman Caressa Dee , Lu James T , Gibbs Richard A , Schlesinger Alan E , Lee Brendan H
Published: May 2013

Osteogenesis imperfecta (OI) is typically caused by mutations in type 1 collagen genes, but in recent years new recessive and dominant forms caused by mutations in a plethora of different genes have been characterized. OI type V is a dominant form caused by the recurrent (c.-14C > T) mutation in the 5'UTR of the IFITM5 gene. The mutation adds five residues to the N-terminus of the IFITM5, but the pathophysiology of the disease remains to be elucidated. Typical clinical features present in the majority of OI type V patients include interosseous membrane calcification between the radius and ulna and between the tibia and fibula, radial head dislocation, and significant hyperplastic callus formation at the site of fractures. We report a 5-year-old child with clinical features of OI type III or severe OI type IV (characteristic facies, gray sclerae, typical fractures) and absence of classical features of OI type V with a de novo recurrent IFITM5 mutation (c.-14C > T), now typical of OI type V. This highlights the variability of OI caused by IFITM5 mutations and suggests screening for mutations in this gene in most cases of OI where type 1 collagen mutations are absent. © 2013 American Society for Bone and Mineral Research.
The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides
Authors: Elzagallaai Abdelbaset A. , Koren Gideon , Rieder Michael J.
Published: May 2013

Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte toxicity assay (LTA) have been used but are time‐consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet toxicity assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS‐sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration‐dependent toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.