bluuebunny/crossref_metadata_2025 huggingface dataset:
600-V 27-mΩ normally off SiC junction field effect transistors for high-efficiency power supply
Authors: Shimizu Haruka , Okino Hiroyuki , Akiyama Satoru , Katoh Kaoru , Yokoyama Natsuki , Ishikawa Katsumi
Published: February 2014

Normally-off SiC junction field effect transistors (JFETs) with high blocking voltage and low gate leakage current were developed by localized current-path doping (LCD). Numerical simulation of electric field revealed that LCD effectively decreases the on-resistance of SiC JFETs without degrading blocking voltage. On the basis of the obtained simulation results, 600-V 27-mΩ normally off SiC JFETs were fabricated by LDC. The gate leakage current of the fabricated JFETs was suppressed by surface oxynitridation. By applying in a server power supply, we found that these improved JFETs decreased power loss due to FETs by 66%.
Electrical conduction and mobility enhancement in p-type In-doped Cu2ZnSnSe4 bulks
Authors: Kuo Dong-Hau , Tsega Moges
Published: February 2014

Cu2Zn(Sn1−

x
In
x
)Se4 bulks with x = 0–0.6 were prepared by a liquid–phase reactive sintering method at 600 °C. Defect chemistry was studied by measuring electrical properties of In-doped CZTSe (In–CZTSe) as a function of dopant concentration. With increasing the x value from 0 to 0.6, the carrier concentration of In–CZTSe increased from 1017 to 1019 cm−3 but the hole mobility greatly increased from 1.23 cm2 V−1 s−1 to a maximum value of 8.0 cm2 V−1 s−1 then decreased to about 1.4 cm2 V−1 s−1 at x = 0.6. The largely increased carrier concentration and the slightly changed lattice parameters for In–CZTSe with increasing the In content are related to the precipitated In-rich Cu2
B
II
B
IVSe4 compound and the types of their defects such as InSn and B
Cu.
Anisotropic lateral growth of homoepitaxial diamond (111) films by plasma-enhanced chemical vapor deposition
Authors: Tokuda Norio , Ogura Masahiko , Yamsaki Satoshi , Inokuma Takao
Published: February 2014

Anisotropic growth is observed for homoepitaxial diamond (111) films by microwave plasma-enhanced chemical vapor deposition in the lateral growth mode. Using ex situ atomic force microscopy, we clearly show the motion of single bi-atomic layer steps owing to homoepitaxial diamond growth for the first time. An atomistic model of homoepitaxial lateral diamond growth is discussed.
Vesta surface thermal properties map
Authors: Capria M. T. , Tosi F. , De Sanctis M. C. , Capaccioni F. , Ammannito E. , Frigeri A. , Zambon F. , Fonte S. , Palomba E. , Turrini D. , Titus T. N. , Schröder S. E. , Toplis M. , Li J.‐Y. , Combe J.‐P. , Raymond C. A. , Russell C. T.
Published: February 2014

The first ever regional thermal properties map of Vesta has been derived from the temperatures retrieved by infrared data by the mission Dawn. The low average value of thermal inertia, 30 ± 10 J m−2 s−0.5 K−1, indicates a surface covered by a fine regolith. A range of thermal inertia values suggesting terrains with different physical properties has been determined. The lower thermal inertia of the regions north of the equator suggests that they are covered by an older, more processed surface. A few specific areas have higher than average thermal inertia values, indicative of a more compact material. The highest thermal inertia value has been determined on the Marcia crater, known for its pitted terrain and the presence of hydroxyl in the ejecta. Our results suggest that this type of terrain can be the result of soil compaction following the degassing of a local subsurface reservoir of volatiles.
Diurnal cycle of lake methane flux
Authors: Podgrajsek E. , Sahlée E. , Rutgersson A.
Published: February 2014

Air‐lake methane flux (FCH4) and partial pressure of methane in the atmosphere (pCH4a) were measured using the eddy covariance method over a Swedish lake for an extended period. The measurements show a diurnal cycle in both FCH4 and pCH4a with high values during nighttime (FCH4 ≈ 300 nmol m−2 s−1, pCH4a ≈ 2.5 µatm) and low values during day (FCH4 ≈ 0 nmol m−2 s−1, pCH4a ≈ 2.0 µatm) for a large part of the data set. This diurnal cycle persist in all open water season; however, the magnitude of the diurnal cycle is largest in the spring months. Estimations of buoyancy in the water show that high nighttime fluxes coincide with convective periods. Our interpretation of these results is that the convective mixing enhances the diffusive flux, in analogy to previous studies. We also suggest that the convection may bring methane‐rich water from the bottom to the surface and trigger bubble release from the sediment. A diurnal cycle is not observed for all convective occasions, indicating that the presence of convection is not sufficient for enhanced nighttime flux; other factors are also necessary. The observed diurnal cycle of pCH4a is explained with the variation of FCH4 and a changing internal boundary layer above the lake. The presence of a diurnal cycle of FCH4 stresses the importance of making long‐term continuous flux measurements. A lack of FCH4 measurements during night may significantly bias estimations of total CH4 emissions from lakes to the atmosphere.
Influence of Sulfur on the Recrystallization and {100}〈001〉 Cube Texture Formation in Fe48%Ni Alloys Tapes
Authors: Betanda Yanick Ateba , Helbert Anne‐Laure , Brisset François , Wehbi Mickael , Mathon Marie‐Hélène , Waeckerlé Thierry , Baudin Thierry
Published: February 2014

Hyper textured substrate tapes were prepared by cold rolling and annealing of a Fe48%Ni alloys in order to obtain Cube oriented substrate for photovoltaic thin films and superconductor cables in particular. In the present work, the effect of sulfur on recrystallization and sharp Cube texture formation has been investigated. Results show that the formation of Cube texture is favored by the addition of sulfur in the Fe48%Ni alloy. In order to explain this result, the development of Cube texture during recrystallization has been investigated by EBSD, furthermore, the stored energy has been measured using neutron diffraction on the deformed states. It appeared that MnS precipitates are at the origin of hardening that increases the stored energy gap between the Cube component and the other ones. This difference favors the Cube development.
Topological‐Structure Modulated Polymer Nanocomposites Exhibiting Highly Enhanced Dielectric Strength and Energy Density
Authors: Hu Penghao , Shen Yang , Guan Yuhan , Zhang Xuehui , Lin Yuanhua , Zhang Qiming , Nan Ce‐Wen
Published: February 2014

Dielectric materials with high electric energy densities and low dielectric losses are of critical importance in a number of applications in modern electronic and electrical power systems. An organic–inorganic 0–3 nanocomposite, in which nanoparticles (0‐dimensional) are embedded in a 3‐dimensionally connected polymer matrix, has the potential to combine the high breakdown strength and low dielectric loss of the polymer with the high dielectric constant of the ceramic fillers, representing a promising approach to realize high energy densities. However, one significant drawback of the composites explored up to now is that the increased dielectric constant of the composites is at the expense of the breakdown strength, limiting the energy density and dielectric reliability. In this study, by expanding the traditional 0–3 nanocomposite approach to a multilayered structure which combines the complementary properties of the constituent layers, one can realize both greater dielectric displacement and a higher breakdown field than that of the polymer matrix. In a typical 3‐layer structure, for example, a central nanocomposite layer of higher breakdown strength is introduced to substantially improve the overall breakdown strength of the multilayer‐structured composite film, and the outer composite layers filled with large amount of high dielectric constant nanofillers can then be polarized up to higher electric fields, hence enhancing the electric displacement. As a result, the topological‐structure modulated nanocomposites, with an optimally tailored nanomorphology and composite structure, yield a discharged energy density of 10 J/cm3 with a dielectric breakdown strength of 450 kV mm–1, much higher than those reported from all earlier studies of nanocomposites.
Aromatic Homologation by Non‐Chelate‐Assisted RhIII‐Catalyzed CH Functionalization of Arenes with Alkynes
Authors: Pham Manh V. , Cramer Nicolai
Published: February 2014

Larger condensed arenes are of interest owing to their electro‐ and photochemical properties. An efficient synthesis is the catalyzed aromatic annulation of a smaller arene with two alkyne molecules. Besides difunctionalized starting materials, directed CH functionalization can be used for such aromatic homologation. However, thus far the requirement of either pre‐functionalized substrates or suitable directing groups were limiting this approach. Herein, we describe a rhodium(III)‐catalyzed method allowing the use of completely unbiased arenes and internal alkynes. The reaction works best with copper(II) 2‐ethylhexanoate and decabromodiphenyl ether as the oxidant combination. This aromatic annulation tolerates a variety of functional groups and delivers homologated condensed arenes. Aside from simple benzenes, naphthalenes and higher condensed arenes provide access to highly substituted and highly soluble acenes structures having important electronic and photophysical properties.
Catalytic, Enantioselective Synthesis of 1,2‐anti‐Diols by Asymmetric Ring‐Opening/Cross‐Metathesis
Authors: Hartung John , Grubbs Robert H.
Published: February 2014

An enantioselective method for the synthesis of 1,2‐anti‐diols has been developed. A cyclometalated chiral‐at‐ruthenium complex catalyzes the asymmetric ring‐opening/cross‐metathesis of dioxygenated cyclobutenes, thus resulting in functionally rich synthetic building blocks. Syntheses of the insect pheromone (+)‐endo‐brevicomin and monosaccharide ribose demonstrate the synthetic utility of the 1,2‐anti‐diol fragments generated in the title reaction.
Engineering of P450pyr Hydroxylase for the Highly Regio‐ and Enantioselective Subterminal Hydroxylation of Alkanes
Authors: Yang Yi , Liu Ji , Li Zhi
Published: February 2014

Terminal‐selective cytochrome P450pyr has been successfully engineered through directed evolution for the subterminal hydroxylation of alkanes with excellent regio‐ and enantioselectivity. A sensitive colorimetric high‐throughput screening (HTS) assay was developed for the measurement of both the regioselectivity and the enantioselectivity of a hydroxylation reaction. By using the HTS assay and iterative saturation mutagenesis, sextuple‐mutant P450pyrSM1 was created for the hydroxylation of n‐octane (1) to give (S)‐2‐octanol (2) with 98 % ee and >99 % subterminal selectivity. The engineered P450 is the first enzyme for this type of highly selective alkane hydroxylation, being useful for the CH activation and functionalization of alkanes and the preparation of enantiopure alcohols. Molecular modeling provided structure‐based understanding of the fully altered regioselectivity and the excellent enantioselectivity. Another sextuple‐mutant P450pyrSM2 catalyzed the hydroxylation of propylbenzene (3) to afford (S)‐1‐phenyl‐2‐propanol (4) with 95 % ee and 98 % subterminal selectivity.
Activation of Matrix Metalloproteinases 2, 9, and 13 by Activated Protein C in Human Osteoarthritic Cartilage Chondrocytes
Authors: Jackson Miriam T. , Moradi Babak , Smith Margaret M. , Jackson Christopher J. , Little Christopher B.
Published: February 2014

Objective

Levels of activated protein C (APC) are elevated in the synovial fluid of patients with osteoarthritis (OA), and increased APC levels are correlated with the levels of active matrix metalloproteinase 2 (MMP‐2). This study sought to investigate whether APC is a relevant protein for activation of MMPs in the degradation of human OA cartilage, and to elucidate its mechanisms of action.

Methods

Human articular cartilage was cultured with or without interleukin‐1α (IL‐1α), in the presence or absence of APC or protein C, and an MMP or serine proteinase inhibitor. Aggrecan and collagen release and chondrocyte gene expression levels were quantified. Aggrecanase and MMP cleavage of aggrecan was examined with neoepitope‐specific antibodies, and MMP activity was measured using gelatin zymography and fluorogenic peptide assay.

Results

In human OA cartilage, APC induced aggrecan and collagen release, whereas in non‐OA cartilage, costimulation with IL‐1α was required. Inhibition of MMP activity reduced APC‐induced cartilage proteolysis, and MMP‐induced aggrecanolysis was confirmed by Western blotting. In cultures with APC alone, the activity of MMPs 2, 9, and 13 was significantly increased in OA cartilage, although APC could not directly activate MMPs 2 or 9. Expression of MMP1, MMP2, MMP9, MMP13, TIMP1, and TIMP3 was not altered by APC in OA cartilage. Human OA chondrocytes expressed messenger RNA for protein C, endothelial protein C receptor, thrombomodulin, and protease‐activated receptor 1, but these were unaltered or down‐regulated by APC. The induction of MMP activation and cartilage degradation by APC was dependent on its serine protease activity.

Conclusion

APC is a physiologically relevant activator of MMPs and cartilage breakdown in human OA. The effects of APC are dependent on its proteolytic activity and as‐yet‐undefined cell and/or cartilage matrix factors, and inhibition of this pathway may provide a novel therapeutic target to halt the progression of cartilage damage in OA.
Epigenome‐Wide Scan Identifies a Treatment‐Responsive Pattern of Altered DNA Methylation Among Cytoskeletal Remodeling Genes in Monocytes and CD4+ T Cells From Patients With Behçet's Disease
Authors: Hughes Travis , Ture‐Ozdemir Filiz , Alibaz‐Oner Fatma , Coit Patrick , Direskeneli Haner , Sawalha Amr H.
Published: February 2014

Objective

The pathogenesis of Behçet's disease (BD), an inflammatory disease with multisystem involvement, remains poorly understood. This study was undertaken to investigate whether there are DNA methylation abnormalities in BD that might contribute to the pathogenesis of the disease.

Methods

We examined genome‐wide DNA methylation patterns in monocytes and CD4+ T cells from 16 male patients with untreated BD and age, sex, and ethnicity–matched healthy controls. Additional samples were collected from 12 of the same BD patients after treatment and achievement of disease remission. Genome‐wide DNA methylation patterns were assessed using the Infinium HumanMethylation450 BeadChip array, which includes >485,000 individual methylation sites across the genome.

Results

We identified 383 CpG sites in monocytes, and 125 in CD4+ T cells, that were differentially methylated between BD patients and controls. Bioinformatic analysis revealed a pattern of aberrant DNA methylation among genes that regulate cytoskeletal dynamics, suggesting that aberrant DNA methylation of multiple classes of structural and regulatory proteins of the cytoskeleton might contribute to the pathogenesis of BD. Further, treatment of BD modified the differences in DNA methylation observed in patients compared to controls; indeed, among CpG sites that were differentially methylated after disease remission versus before treatment, there was widespread reversal of the direction of aberrant DNA methylation observed between the patient and control groups.

Conclusion

The results of this epigenome‐wide study—the first such study in BD—provide strong evidence that epigenetic modification of cytoskeletal dynamics underlies the pathogenesis of BD and its response to treatment.
Structure and Function of Renal Macrophages and Dendritic Cells From Lupus‐Prone Mice
Authors: Sahu Ranjit , Bethunaickan Ramalingam , Singh Satwinder , Davidson Anne
Published: February 2014

Objective

To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis.

Methods

We used a bead‐based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite production was examined using biochemical assays. The antigen‐presenting functions of the cells were determined using mixed lymphocyte reactions. Selected cytokine, chemokine, and Toll‐like receptor (TLR) profiles were examined using real‐time quantitative polymerase chain reaction.

Results

We identified 2 populations of macrophages and 3 populations of DCs in both of our murine models of lupus (NZB/NZW and [NZW × BXSB]F1 mice). F4/80high macrophages, which were resident in normal kidneys and found to be increased in number during nephritis, did not produce either arginase or nitrite upon cytokine stimulation and acquired a mixed proinflammatory and antiinflammatory functional phenotype during nephritis that resembles the constitutively activated phenotype of gut F4/80high macrophages. The various cell types differed in their expression of chemokine receptors and TLRs, consistent with variability in their renal location. Resident renal CD103+ DCs were the best antigen‐presenting cells and could easily be distinguished from CD11chigh myeloid DCs that accumulated in large numbers during nephritis.

Conclusion

Our study highlights the heterogeneity of the macrophage/DC infiltrate in chronic lupus nephritis and provides an initial phenotypic and functional analysis of the different cellular components that can now be used to define the role of each cell subset in nephritis progression or amelioration. Of note, the dominant macrophage population that accumulates during nephritis has an acquired phenotype that is neither M1 nor M2 and may reflect failure of resolution of inflammation.
Fault Prediction and Maintenance of Non‐Periodic Incipient Fault for Hydraulic Tube Tester
Authors: Zhao Zhen , Zhang Jun , Wang Shu , Chang Yuqing , Jia Mingxing
Published: February 2014

This paper is concerned with fault prediction and maintenance for the hydraulic tube tester according to the process variables. For the two types of incipient faults of this machine, it is more difficult to predict the non‐periodic incipient fault and make a predictive maintenance decision in comparison with the periodic incipient fault. For the non‐periodic incipient fault, a new probabilistic fault prediction method is proposed using a multivariate principle component analysis and Bayesian auto‐regression model. Then, a new predictive maintenance policy is developed, based on the results of the probabilistic fault prediction approach, which implies the evolvement of system deterioration caused by the non‐periodic incipient fault. Simulation results demonstrate the effectiveness of the method proposed in this paper.
Zonal rate model for axial and radial flow membrane chromatography, part II: Model‐based scale‐up
Authors: Ghosh Pranay , Lin Min , Vogel Jens H. , Choy Derek , Haynes Charles , von Lieres Eric
Published: February 2014

Membrane chromatography (MC) systems are finding increasing use in downstream processing trains for therapeutic proteins due to the unique mass‐transfer characteristics they provide. As a result, there is increased need for model‐based methods to scale‐up MC units using data collected on a scaled‐down unit. Here, a strategy is presented for MC unit scale‐up using the zonal rate model (ZRM). The ZRM partitions an MC unit into virtual flow zones to account for deviations from ideal plug‐flow behavior. To permit scale‐up, it is first configured for the specific device geometry and flow profiles within the scaled‐down unit so as to achieve decoupling of flow and binding related non‐idealities. The ZRM is then configured for the preparative‐scale unit, which typically utilizes markedly different flow manifolds and membrane architecture. Breakthrough is first analyzed in both units under non‐binding conditions using an inexpensive tracer to independently determine unit geometry related parameters of the ZRM. Binding related parameters are then determined from breakthrough data on the scaled‐down MC capsule to minimize sample requirements. Model‐based scale‐up may then be performed to predict band broadening and breakthrough curves on the preparative‐scale unit. Here, the approach is shown to be valid when the Pall XT140 and XT5 capsules serve as the preparative and scaled‐down units, respectively. In this case, scale‐up is facilitated by our finding that the distribution of linear velocities through the membrane in the XT140 capsule is independent of the feed flow rate and the type of protein transmitted. Introduction of this finding into the ZRM permits quantitative predictions of breakthrough over a range of industrially relevant operating conditions. Biotechnol. Bioeng. 2014;111: 1587–1594. © 2014 Wiley Periodicals, Inc.
Myoblast alignment on 2D wavy patterns: Dependence on feature characteristics and cell‐cell interaction
Authors: Grigola Michael S. , Dyck Casey L. , Babacan Derin S. , Joaquin Danielle N. , Hsia K. Jimmy
Published: February 2014

In this study, we investigate the effects of micron‐scale surface patterns on the alignment of individual cells and groups of cells. Using a simple replication molding process we produce a number of micron‐scale periodic wavy patterns with different pitch and depth. We observe C2C12 cells as they grow to confluence on these patterns and find that, for some geometries, cell‐cell interaction leads to global alignment in a confluent culture when individual cells would not align on the same pattern. Three types of alignment behavior are thus defined: no alignment, immediate alignment, and alignment upon confluence. To further characterize this response, we introduce a non‐dimensional parameter that describes the aligning power of a periodic pattern based on its geometry. The three types of alignment behavior can be distinguished by the value of the alignment parameter, and we identify values at which the transitions in alignment behavior occur. Applying this parameter to data from the current and several earlier studies reveals that the parameter successfully describes substrate aligning power over a wide range of length scales for both wavy and grooved features. Biotechnol. Bioeng. 2014;111: 1617–1626. © 2014 Wiley Periodicals, Inc.
Spatiotemporal distribution of SUMOylation components during mouse brain development
Authors: Hasegawa Yuta , Yoshida Daisuke , Nakamura Yuki , Sakakibara Shin‐ichi
Published: February 2014

Posttranslational modification of proteins might play an important role in brain cellular dynamics via the rapid turnover or functional change of critical proteins controlling neuronal differentiation or synaptic transmission. Small ubiquitin‐like modifier protein (SUMO) is a family of ubiquitin‐like small proteins that are covalently attached to target proteins to modify their function posttranslationally. Many cellular processes, such as transcription and protein trafficking, are regulated by SUMOylation, but its functional significance in the brain remains unclear. Although developmental regulation of SUMOylation levels in rat brain was recently demonstrated, no comparative immunohistochemical analysis of the cellular distribution profiles of SUMOylation components, including SUMO1, SUMO2/3, and Ubc9, has been undertaken so far. The present study used immunohistochemical and immunoblot analysis with the different developmental stages of mice and demonstrated the developmentally regulated distribution of SUMO1, SUMO2/3, and Ubc9 in the brain. During embryonic development, SUMOylation by SUMO1 and SUMO2/3 occurred in the nucleoplasm of nestin‐positive neural stem cells. Although the total amount of SUMO‐modified proteins decreased during postnatal brain development, intense and persistent accumulation of SUMO2/3 was detected throughout life in neural progenitor populations in neurogenic regions, including the subventricular zone and the hippocampal subgranular zone. In contrast, many neurons in the adult brain accumulated SUMO1 rather than SUMO2/3. Heavy immunoreactivity of SUMO1 was found in large projection neurons in the brainstem, whereas SUMO2/3 was almost absent from these areas. This heterogeneous distribution implies that both proteins play a specific and unique role in the brain. J. Comp. Neurol. 522:3020–3036, 2014. © 2014 Wiley Periodicals, Inc.
Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration
Authors: Samad Arbaz , Conway Andrea B. , Attam Rajeev , Jessurun Jose , Pambuccian Stefan E.
Published: February 2014

The “vacuolated cell pattern” has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytologic features of a case of pancreatic adenocarcinoma with “vacuolated cell pattern” occurring in a 60‐year‐old man. The aspirate smears and cell block sections from the EUS‐FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably‐sized crowded three‐dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20–50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non‐vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a “vacuolated cell pattern” adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU‐FNA samples allows its differentiation from primary and metastatic signet‐ring cell carcinomas. Diagn. Cytopathol. 2014;42:302–307. © 2014 Wiley Periodicals, Inc.
All lesions great and small, part 2. Diagnostic cytology in veterinary medicine
Authors: Sharkey Leslie C. , Seelig Davis M. , Overmann Jed
Published: February 2014

This is the second in a two‐part review of diagnostic cytopathology in veterinary medicine. As in human medicine, cytopathology is a minimally invasive, rapid, and cost‐effective diagnostic modality with broad utilization. In this second part, the diagnostic applications of cytology in respiratory, gastrointestinal, genitourinary, endocrine, ocular, and central nervous system tissues are discussed with a section describing fluid analysis in veterinary medicine. As noted in the previous manuscript, which characterized the cytology of the skin/subcutis, musculoskeletal, and lymphoid tissues, the interpretation of veterinary cytology samples must be undertaken with extensive knowledge of the breadth of animal species, including familiarity with the frequency and clinical progression of diseases, both of which can be influenced by species, breed, and husbandry conditions. Similar to part one, this review focuses on the most common domestic companion animal species (dog, cat, and horse) and highlights lesions that are either unique to veterinary species or have relevant correlates in people. The cytologic features and biological behavior of similar lesions are compared, and selected mechanisms of disease and ancillary diagnostics are reviewed when appropriate. Supporting figures illustrate a subset of lesions. While not an exhaustive archive of veterinary cytology, the goal is to give cytopathologists working in human medicine a general impression of correlates and unique entities in veterinary practice. Diagn. Cytopathol. 2014;42:544–552. © 2014 Wiley Periodicals, Inc.
trans‐Hexahydrobenzoxazolidinones in the Enantioselective Synthesis of β2‐Amino Acids Containing Proteinogenic Side Chains
Authors: Bandala Yamir , Reyes‐Rangel Gloria , Obregón‐Zúñiga Arturo , Cruz‐Hernández Carlos , Corzo Gerardo , Juaristi Eusebio
Published: February 2014

The use of enantiopure trans‐hexahydrobenzoxazolidinones as chiral auxiliaries in the enantioselective synthesis of two β2‐amino acids containing proteinogenic side chains (β2‐hPhenylalanine and β2‐hLysine), in both enantiomeric forms, is described. Absolute configurations were assigned on the basis of X‐ray diffraction analysis and chemical correlation methods.
Design, Synthesis, and X‐ray Structural Analyses of Diamantane Diammonium Salts: Guests for Cucurbit[n]uril (CB[n]) Hosts
Authors: Šekutor Marina , Molčanov Krešimir , Cao Liping , Isaacs Lyle , Glaser Robert , Mlinarić‐Majerski Kata
Published: February 2014

New bisprimary and bisquaternary diamantane‐1,6‐ and ‐4,9‐diammonium/diaminium salts were synthesized, and characterized by NMR spectroscopy and X‐ray crystallography. The impetus for these syntheses were previously reported X‐ray crystallographic investigations of adamantane mono‐ and bisquaternary ammonium ions [3,5‐diMeAda‐1‐NH3 or Ada‐1,3‐di(NMe3)] complexed with cucurbit[n]uril (n = 7, 8). The crystal structures were analyzed to ascertain possible structural hypotheses for high binding affinity guests bound within various diameter pumpkin‐shaped hosts. Although Diam‐4,9‐di(NMe3I) 5 could be readily prepared from the bisprimary precursor, corresponding Diam‐1,6‐di(NMe3I) 14 could not be obtained even under strong reaction conditions. Stereochemical analysis of this situation suggests very severe steric non‐bonding cis‐1,3‐diaxial type H···H interactions between the “axial”‐type NMe3 group and neighboring “axial” proton neighbors. These same interactions are found in Ada‐2,6‐di(NMe3I) analogues, but they are alleviated in this smaller polycyclic skeleton through tilting the axial C(methylene)–NMe3 bond away from its axial neighbors. However, similar structural relief for Diam‐1,6‐di(NMe3I) is not possible, because the C(methine)–NMe3 bond therein is ligated to the diamondoid's rigid skeleton.
Function‐Oriented Synthesis of Liponucleoside Antibiotics
Authors: Tanino Tetsuya , Yamaguchi Mayumi , Matsuda Akira , Ichikawa Satoshi
Published: February 2014

Function‐oriented synthesis of a class of liponucleoside antibiotics was investigated through rational simplification guided by previous structure–activity relationship studies of caprazamycins and muraymycins to address the issue associated with their molecular complexity. A lactam‐fused isoxazolidine scaffold was designed, and a diverse set of lactam‐fused isoxazolidines derivatives were constructed by intramolecular 1,3‐dipolar cycloaddition of alkenyl nitrones. Several analogues exhibited moderate activity against a range of Gram‐positive drug‐resistant bacterial pathogens.
Evaluation of the anti‐inflammatory and antinociceptive effects of myrtenol, a plant‐derived monoterpene alcohol, in mice
Authors: Silva Renan O. , Salvadori Mirian S. , Sousa Francisca Beatriz M. , Santos Maisa S. , Carvalho Nathalia S. , Sousa Damião P. , Gomes Bruno S. , Oliveira Francisco A. , Barbosa André Luiz R. , Freitas Rivelilson M. , de Almeida Reinaldo Nóbrega , Medeiros Jand‐Venes R.
Published: February 2014

Inflammation is characterized by vasodilatation, increase of blood flow and vascular permeability, migration of leucocytes to the inflammatory site, and production of cytokines. The aim of this study was evaluate the anti‐inflammatory and antinociceptive effects of (−)‐myrtenol, a plant‐derived monoterpene alcohol, in mice and its possible mechanisms. Myrtenol was used in classical models of inflammation (paw oedema induced by different agents, carrageenan‐induced peritonitis, myeloperoxidase levels and cytokine measurement) and nociception (acetic acid‐induced writhing, hot‐plate test, and paw licking induced by formalin, glutamate, and capsaicin). Pretreatment with myrtenol effectively inhibited paw oedema induced by carrageenan, compound 48/80, histamine, serotonin and prostaglandin E2. Myrtenol also reduced the cell counts, myeloperoxidase activity and cytokine levels (interleukin 1β, but not tumour necrosis factor‐α) of the peritoneal cavity induced by carrageenan. In addition, myrtenol inhibited acetic acid‐induced writhing, did not significantly prolong the latency time in the hot‐plate test, decreased licking time caused by an intraplantar injection of formalin (only in the second phase), glutamate and capsaicin. Myrtenol reduces the inflammatory response and nociception in mice due to the inhibition of the release of inflammatory mediators, cell migration and also to the signalling pathway of receptors involved in the transmission of pain. Copyright © 2014 John Wiley & Sons, Ltd.
Investigation of morphometric variability of subthalamic nucleus, red nucleus, and substantia nigra in advanced Parkinson's disease patients using automatic segmentation and PCA‐based analysis
Authors: Xiao Yiming , Jannin Pierre , D'Albis Tiziano , Guizard Nicolas , Haegelen Claire , Lalys Florent , Vérin Marc , Collins D. Louis
Published: February 2014

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective surgical therapy to treat Parkinson's disease (PD). Conventional methods employ standard atlas coordinates to target the STN, which, along with the adjacent red nucleus (RN) and substantia nigra (SN), are not well visualized on conventional T1w MRIs. However, the positions and sizes of the nuclei may be more variable than the standard atlas, thus making the pre‐surgical plans inaccurate. We investigated the morphometric variability of the STN, RN and SN by using label‐fusion segmentation results from 3T high resolution T2w MRIs of 33 advanced PD patients. In addition to comparing the size and position measurements of the cohort to the Talairach atlas, principal component analysis (PCA) was performed to acquire more intuitive and detailed perspectives of the measured variability. Lastly, the potential correlation between the variability shown by PCA results and the clinical scores was explored. Hum Brain Mapp 35:4330–4344, 2014. © 2014 Wiley Periodicals, Inc.
Summary of proceedings of the second World Congress on Thyroid Cancer
Authors: Czerwonka Lukasz , Freeman Jeremy , McIver Bryan , Randolph Gregory W. , Shah Jatin P. , Shaha Ashok R. , Sherman Steven I. , Tuttle R. Michael , Witterick Ian J.
Published: February 2014

The second World Congress on Thyroid Cancer was held from July 10 to July 14, 2013, in Toronto, Canada. Its purpose was to provide a platform for the multidisciplinary discussion on research, education, and patient management of thyroid malignancy. Herein, we summarize the latest major trends and controversies within the field of thyroid oncology as discussed in the Congress including the use of ultrasound, standardization of cytology, role of molecular testing, treatment options for small recurrence including ablation and observation, management of recurrent laryngeal nerve injury, importance of identification of the external branch of the superior laryngeal nerve, role of minimally invasive thyroid surgery, trends in radioactive iodine treatment, advancements in targeted agents, and the importance of personalizing treatment to individual patients. © 2014 Wiley Periodicals, Inc. Head Neck 36: 917–920, 2014
Survival in Infection-Related Acute-on-Chronic Liver Failure Is Defined by Extrahepatic Organ Failures
Authors: Bajaj Jasmohan S. , O'Leary Jacqueline G. , Reddy Rajender K. , Wong Florence , Biggins Scott W. , Patton Heather , Fallon Michael B. , Garcia-Tsao Guadalupe , Maliakkal Benedict , Malik Raza , Subramanian Ram M. , Thacker Leroy R. , Kamath Patrick S.
Published: February 2014

Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multicenter studies are required in order to improve prognostication and resource allocation. Using the North American Consortium for Study of End-stage Liver Disease (NACSELD) database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhosis patients hospitalized with an infection. We defined organ failures as 1) shock, 2) grade III/IV hepatic encephalopathy (HE), 3) need for dialysis and mechanical ventilation. Determinants of survival with these organ failures were analyzed. In all, 507 patients were included (55 years, 52% hepatitis C virus [HCV], 15.8% nosocomial infection, 96% Child score ≥7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were the most prevalent infections. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30 days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%), or four (4%) organ failures. The 30-day survival worsened with a higher number of extrahepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%), and all four (23%). I-ACLF was defined as ≥2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, Model for Endstage Liver Disease (MELD) score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count, and low albumin.

Conclusion :

Using multicenter study data in hospitalized decompensated infected cirrhosis patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor survival. (Hepatology 2014;60:250–256)
The biliary epithelium gives rise to liver progenitor cells
Authors: Rodrigo-Torres Daniel , Affò Silvia , Coll Mar , Morales-Ibanez Oriol , Millán Cristina , Blaya Delia , Alvarez-Guaita Anna , Rentero Carles , José Lozano Juan , Maestro Miguel Angel , Solar Myriam , Arroyo Vicente , Caballería Joan , van Grunsven Leo A. , Enrich Carlos , Ginès Pere , Bataller Ramon , Sancho-Bru Pau
Published: February 2014

Severe liver diseases are characterized by expansion of liver progenitor cells (LPC), which correlates with disease severity. However, the origin and role of LPC in liver physiology and in hepatic injury remains a contentious topic. We found that ductular reaction cells in human cirrhotic livers express hepatocyte nuclear factor 1 homeobox B (HNF1β). However, HNF1β expression was not present in newly generated epithelial cell adhesion molecule (EpCAM)-positive hepatocytes. In order to investigate the role of HNF1β-expressing cells we used a tamoxifen-inducible Hnf1βCreER/R26RYfp/LacZ mouse to lineage-trace Hnf1β+ biliary duct cells and to assess their contribution to LPC expansion and hepatocyte generation. Lineage tracing demonstrated no contribution of HNF1β+ cells to hepatocytes during liver homeostasis in healthy mice or after loss of liver mass. After acute acetaminophen or carbon tetrachloride injury no contribution of HNF1β+ cells to hepatocyte was detected. We next assessed the contribution of Hnf1β+-derived cells following two liver injury models with LPC expansion, a diethoxycarbonyl-1,4-dihydro-collidin (DDC)-diet and a choline-deficient ethionine-supplemented (CDE)-diet. The contribution of Hnf1β+ cells to liver regeneration was dependent on the liver injury model. While no contribution was observed after DDC-diet treatment, mice fed with a CDE-diet showed a small population of hepatocytes derived from Hnf1β+ cells that were expanded to 1.86% of total hepatocytes after injury recovery. Genome-wide expression profile of Hnf1β+-derived cells from the DDC and CDE models indicated that no contribution of LPC to hepatocytes was associated with LPC expression of genes related to telomere maintenance, inflammation, and chemokine signaling pathways. Conclusion: HNF1β+ biliary duct cells are the origin of LPC. HNF1β+ cells do not contribute to hepatocyte turnover in the healthy liver, but after certain liver injury, they can differentiate to hepatocytes contributing to liver regeneration. (Hepatology 2014;60:1367–1377)
Human T cells expressing BEND3 on their surface represent a novel subpopulation that preferentially produces IL‐6 and IL‐8
Authors: Shiheido Hirokazu , Kitagori Koji , Sasaki Chiyomi , Kobayashi Shio , Aoyama Takane , Urata Kozue , Oku Takuma , Hirayama Yoshitaka , Yoshitomi Hiroyuki , Hikida Masaki , Yoshifuji Hajime , Mimori Tsuneyo , Watanabe Takeshi , Shimizu Jun
Published: February 2014

BEN domain‐containing protein 3 (BEND3) has no transmembrane region, is localized in the cytoplasm, and is involved in chromatin function and transcription. We here identified a novel subpopulation of human T cells that expressed BEND3 on their cell surface (BEND3+ T cells). BEND3+ T cells consisted of approximately 3% of T cells in the peripheral blood, were present in both CD4+ and CD8+ T cells, and were also observed in cord blood. The stimulation of BEND3+ T cells through the TCR/CD3 complex led to the production of various kinds of cytokines; however, the levels of IL‐6 and IL‐8 produced by BEND3+ T cells were higher than those by BEND3− T cells. The proportion of BEND3+ T cells was also increased in some patients with inflammatory diseases. Taken together, these results indicate that BEND3+ T cells are a new subpopulation of T cells in terms of their cytokine profile. Further analyses on BEND3+ T cells may be of importance and useful in understanding human T cell immunology.
In vivo disposition of doxorubicin is affected by mouse Oatp1a/1b and human OATP1A/1B transporters
Authors: Durmus Selvi , Naik Jyoti , Buil Levi , Wagenaar Els , van Tellingen Olaf , Schinkel Alfred H.
Published: February 2014

Organic anion‐transporting polypeptides (OATPs) are important drug uptake transporters, mediating distribution of substrates to several pharmacokinetically relevant organs. Doxorubicin is a widely used anti‐cancer drug extensively studied for its interactions with various drug transporters, but not OATPs. Here, we investigated the role of OATP1A/1B proteins in the distribution of doxorubicin. In vitro, we observed ∼2‐fold increased doxorubicin uptake in HEK293 cells overexpressing human OATP1A2, but not OATP1B1 or OATP1B3. In mice, absence of Oatp1a/1b transporters led to up to 2‐fold higher doxorubicin plasma concentrations and 1.3‐fold higher plasma AUC. Conversely, liver AUC and liver‐to‐plasma ratios of Oatp1a/1b−/− mice were 1.4‐fold and up to 4.1‐fold lower than in wild‐type mice, respectively. Decreased doxorubicin levels in the small intestinal content reflected those in the liver, indicating a reduced biliary excretion of doxorubicin in Oatp1a/1b−/− mice. These results demonstrate important control of doxorubicin plasma clearance and hepatic uptake by mouse Oatp1a/1b transporters. This is unexpected, as the fairly hydrophobic weak base doxorubicin is an atypical OATP1A/1B substrate. Interestingly, transgenic liver‐specific expression of human OATP1A2, OATP1B1 or OATP1B3 could partially rescue the increased doxorubicin plasma levels of Oatp1a/1b−/− mice. Hepatic uptake and bile‐derived intestinal excretion of doxorubicin were completely reverted to wild‐type levels by OATP1A2, and partially by OATP1B1 and OATP1B3. Thus, doxorubicin is transported by hepatocyte‐expressed OATP1A2, −1B1 and −1B3 in vivo, illustrating an unexpectedly wide substrate specificity. These findings have possible implications for the uptake, disposition, therapy response and toxicity of doxorubicin, also in human tumors and tissues expressing these transporters.
Adsorption of Glycosaminoglycans to the Cell Surface Is Responsible for Cellular Donnan Effects
Authors: Hagenfeld Daniel , Kathagen Nadine , Prehm Peter
Published: February 2014

In previous publications, we showed that extracellular glycosaminoglycans reduced the membrane potential, caused cell blebbing and swelling and decreased the intracellular pH independently of cell surface receptors. These phenomena were explained by Donnan effects. The effects were so large that they could not be attributed to glycosaminoglycans in solution. Therefore, we tested the hypothesis that glycosaminoglycans were concentrated on the cell membrane and analysed the mechanism of adsorption by fluorescent hyaluronan, chondroitin sulphate and heparin. The influence of the CD44 receptor was evaluated by comparing CD44 expressing human fibroblasts with CD44 deficient HEK cells. Higher amounts of glycosaminoglycans adsorbed to fibroblasts than to HEK cells. When the membrane potential was annihilated by substituting NaCl by KCl in the medium, adsorption was reduced and intracellular pH decrease was abolished. To eliminate other cellular interfering factors, potential‐dependent adsorption was demonstrated for hyaluronan which adsorbed to inert gold foils in physiological salt concentrations at pH 7.2 and surface potentials up to 120 mV. From these results, we conclude that large cellular Donnan effects of glycosaminoglycans results from receptor mediated, hydrophobic and ionic adsorption to cell surfaces. J. Cell. Biochem. 115: 1334–1341, 2014. © 2014 Wiley Periodicals, Inc.
Fully atomistic molecular‐mechanical model of liquid alkane oils: Computational validation
Authors: Zahariev Tsvetan K. , Slavchov Radomir I. , Tadjer Alia V. , Ivanova Anela N.
Published: February 2014

Fully atomistic molecular dynamics simulations were performed on liquid n‐pentane, n‐hexane, and n‐heptane to derive an atomistic model for middle‐chain‐length alkanes. All simulations were based on existing molecular‐mechanical parameters for alkanes. The computational protocol was optimized, for example, in terms of thermo‐ and barostat, to reproduce properly the properties of the liquids. The model was validated by comparison of thermal, structural, and dynamic properties of the normal alkane liquids to experimental data. Two different combinations of temperature and pressure coupling algorithms were tested. A simple differential approach was applied to evaluate fluctuation‐related properties with sufficient accuracy. Analysis of the data reveals a satisfactory representation of the hydrophobic systems behavior. Thermodynamic parameters are close to the experimental values and exhibit correct temperature dependence. The observed intramolecular geometry corresponds to extended conformations domination, whereas the intermolecular structure demonstrates all characteristics of liquid systems. Cavity size distribution function was calculated from coordinates analysis and was applied to study the solubility of gases in hexane and heptane oils. This study provides a platform for further in‐depth research on hydrophobic solutions and multicomponent systems. © 2014 Wiley Periodicals, Inc.
Exchange coupling and magnetic anisotropy in a family of bipyrimidyl radical‐bridged dilanthanide complexes: Density functional theory and ab initio calculations
Authors: Zhang Yi‐Quan , Luo Cheng‐Lin , Zhang Qiang
Published: February 2014

The origin of the magnetic anisotropy energy barriers in a series of bpym− (bpym = 2,2′‐bipyrimidine) radical‐bridged dilanthanide complexes [(Cp*2Ln)2(μ‐bpym)]+ [Cp* = pentamethylcyclopentadienyl; Ln = GdIII (1), TbIII (2), DyIII (3), HoIII (4), ErIII (5)] has been explored using density functional theory (DFT) and ab initio methods. DFT calculations show that the exchange coupling between the two lanthanide ions for each complex is very weak, but the antiferromagnetic Ln‐bpym− couplings are strong. Ab initio calculations show that the effective energy barrier of 2 or 3 mainly comes from the contribution of a single TbIII or DyIII fragment, which is only about one third of a single Ln energy barrier. For 4 or 5, however, both of the two HoIII or ErIII fragments contribute to the total energy barrier. Thus, it is insufficient to only increase the magnetic anisotropy energy barrier of a single Ln ion, while enhancing the Ln‐bpym− couplings is also very important. © 2014 Wiley Periodicals, Inc.