bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Temperature Programs for Surface Carbonization of Si(111) and Their Effects on 3C-SiC Film Growth
Authors: Nguyen Nam Giang , Liu Chie-Sheng , Hu Ming-Shien , Hong Lu-Sheng
Published: July 2013

We have studies of the changes in the surface states of carbonized Si(111) substrates treated under various temperature programs prior to high-temperature 3C-SiC film growth in a low pressure chemical vapor deposition system using SiH4, C2H2, and H2 as reactant gases. The carbonized Si surface underwent a change in bonding from SiC to disordered graphite, together with the formation of etch pits, when heated directly from the carbonization temperature of 1343 K to the growth temperature of 1523 K under a H2 flow over a period of 5 min; this transformation deteriorated the quality of the subsequent 3C-SiC growth. In contrast, a void-free stoichiometric SiC surface was preserved when we inserted a rapid cooling step, to near room temperature, under a H2 flow of 352 sccm within a period of 15 min after shutting off the C2H2 gas flow at the end of the surface carbonization process. The sharp temperature decrease in this program sealed off the carbonized substrate surface and, thus, led to a high film quality for subsequent 3C-SiC(111) growth.
Study of Adsorption Behavior of Disulfide on the Surface of Au Nanoparticle by X-ray Photoelectron Spectroscopy
Authors: Suzuki Shuichi , Sakaue Hiroyuki , Suzuki Hitoshi , Takahagi Takayuki
Published: July 2013

The surface of Au nanoparticles (NPs) modified with nitrilotriacetic acid (NTA), which is used for site-specific labeling in protein structural analysis, was analyzed using X-ray photoelectron spectroscopy. The S 2p3/2 spectrum consisted of two components assigned to the Au–S and S–S bonds. The energies of the Au–S and S–S components were determined to be 161.7 and 163.2 eV, respectively. The FWHM of the component of the Au–S bond was 0.2 eV narrower than that of the S–S bond. It was found that NTA-modified Au NP solution included many unbound precursor molecules of NTA, which can be reduced by repeated cycles of ultrafiltration.
Simulations and Experiments on O Density and Distribution in Ashing Process Using Surface Plasma Excited by Microwave
Authors: Takagi Shigeyuki , Yamazaki Osamu , Yamauchi Kenji , Shinmura Tadashi
Published: July 2013

Simulation methods for the density and spatial distribution of O atoms have been developed to analyze high-density plasma (1011cm-3) excited by two microwave sources. The density of O atoms, that react with photoresist, was calculated in a gas mixture of CF4and O2, and the density has a maximum value at 10% CF4partial pressure. For the distribution simulation, the rate of reaction between O atoms and photoresist was measured in a small cell, and the sticking coefficient was estimated to be 0.002. The O atom distribution on a glass substrate was calculated by the simulator, where the sticking coefficient was input, focusing on the density under a beam that connected the microwave sources and had no plasma source. The results of both the simulations are in good agreement with the experimental results. The simulations were applied to optimize the chamber configuration and process conditions. As a result, a high ashing rate of over 1430 nm with a uniformity of ±9.3% was obtained.
Quantification of Nitrogen in Silicon by Luminescence Activation Using Aluminum Ion Implantation
Authors: Tajima Michio , Kamata Yohei
Published: July 2013

A photoluminescence method is proposed for quantification of N in Czochralski-grown Si. We transformed N impurities on the order of 1013–1015 cm-3 into radiative centers responsible for the A-line at 1.1223 eV by forming an isoelectronic Al–N pair using Al ion implantation. The relative intensity of the A-line to the free exciton line increases with the N concentration. We suggest that this relationship can be used as a calibration curve for quantifying N impurities. Effect of dopant and O impurities and appropriate annealing conditions after ion implantation are discussed.
Temperature Dependence of Young's Modulus of Silicon
Authors: Shirai Koun
Published: July 2013

The effect of stress on defect formation in the crystal growth of Si is currently a controversial issue. One confusing matter is the temperature dependence of the Young's modulus. The physical meaning of this dependence has been theoretically studied in terms of the anharmonic effect of phonons.
Duplication of the Xq27.3–q28 region, including the FMR1 gene, in an X‐linked hypogonadism, gynecomastia, intellectual disability, short stature, and obesity syndrome
Authors: Hickey Scott E. , Walters‐Sen Lauren , Mosher Theresa Mihalic , Pfau Ruthann B. , Pyatt Robert , Snyder Pamela J. , Sotos Juan F. , Prior Thomas W.
Published: July 2013

In 1979 a “new” syndrome characterized by X‐linked inheritance, hypogonadism, gynecomastia, intellectual disability, obesity, and short stature was described. The now‐36‐year‐old propositus was recently referred to the genetics clinic for profound intellectual disability. Fragile X testing initially demonstrated a duplication of the FMR1 region, and upon further testing we identified an Xq27.3–q28 8.05 Mb‐long duplication responsible for a syndrome. Our report describes the molecular and clinical aspects of the X‐linked syndrome. Our results suggest that male patients with intellectual disability, hypogonadism, short stature, and gynecomastia should be further investigated for rearrangements in the Xq27.3–q28 region. In the future, when more cases of the duplication are identified, it may become possible to more accurately determine the specific genes affected by overexpression and responsible for the phenotype. © 2013 Wiley Periodicals, Inc.
Narrative medicine: A call to pens
Authors: Nowaczyk Małgorzata J.M. , Carey John C.
Published: July 2013

An call for papers on the topic of narrative medicine as it pertains to the practice of clinical genetics, this article briefly reviews the tenets of narrative medicine and the ethical issues associated with publishing patients' and doctors' stories. It is an invitation to the readership of the American Journal of Medical Genetics to share its stories of caring for and living with genetic conditions in our new column called Frameshifts. © 2013 Wiley Periodicals, Inc.
Macrophage Migration Inhibitory Factor Receptor CD74 Mediates Alphavirus‐Induced Arthritis and Myositis in Murine Models of Alphavirus Infection
Authors: Herrero Lara J. , Sheng Kuo‐Ching , Jian Peng , Taylor Adam , Her Zhisheng , Herring Belinda L. , Chow Angela , Leo Yee‐Sin , Hickey Michael J. , Morand Eric F. , Ng Lisa F. P. , Bucala Richard , Mahalingam Suresh
Published: July 2013

Objective

Arthrogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) circulate worldwide. This virus class causes debilitating illnesses that are characterized by arthritis, arthralgia, and myalgia. In previous studies, we identified macrophage migration inhibitory factor (MIF) as a critical inflammatory factor in the pathogenesis of alphaviral diseases. The present study was undertaken to characterize the role of CD74, a cell surface receptor of MIF, in both RRV‐ and CHIKV‐induced alphavirus arthritides.

Methods

Mouse models of RRV and CHIKV infection were used to investigate the immunopathogenesis of arthritic alphavirus infection. The role of CD74 was assessed using histologic analysis, real‐time polymerase chain reaction, flow cytometry, and plaque assay.

Results

In comparison to wild‐type mice, CD74−/− mice developed only mild clinical features and had low levels of tissue damage. Leukocyte infiltration, characterized predominantly by inflammatory monocytes and natural killer cells, was substantially reduced in the infected tissue of CD74−/− mice, but production of proinflammatory cytokines and chemokines was not decreased. CD74 deficiency was associated with increased monocyte apoptosis, but had no effect on monocyte migratory capacity. Consistent with these findings, alphaviral infection resulted in a dose‐dependent up‐regulation of CD74 expression in human peripheral blood mononuclear cells, and serum MIF levels were significantly elevated in patients with RRV or CHIKV infection.

Conclusion

CD74 appears to regulate immune responses to alphaviral infection through its effects on cellular recruitment and survival. These findings suggest that both MIF and CD74 play a critical role in mediating alphaviral disease, and blocking these factors with novel therapeutic agents could substantially ameliorate the pathologic manifestations.
Methotrexate Normalizes Up‐Regulated Folate Pathway Genes in Rheumatoid Arthritis
Authors: Blits Marjolein , Jansen Gerrit , Assaraf Yehuda G. , van de Wiel Mark A. , Lems Willem F. , Nurmohamed Mike T. , van Schaardenburg Dirkjan , Voskuyl Alexandre E. , Wolbink Gert‐Jan , Vosslamber Saskia , Verweij Cornelis L.
Published: July 2013

Objective

The folate antagonist methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA), but its mechanism of action with regard to the impact on folate metabolism remains elusive. The aim of the present study was to investigate the cellular pharmacologic impact of MTX on peripheral blood cells, by comparing MTX‐treated RA patients to MTX‐naive RA patients and healthy controls.

Methods

Gene expression microarray data were used to investigate the expression of 17 folate pathway genes by peripheral blood cells from a cohort of 25 RA patients treated with MTX, 10 MTX‐naive RA patients starting treatment with MTX, and 15 healthy controls (test cohort). Multiplex real‐time polymerase chain reaction was used to validate the results in an independent cohort, consisting of 151 RA patients treated with MTX, 28 MTX‐naive RA patients starting treatment with MTX, and 24 healthy controls (validation cohort).

Results

Multiple folate metabolism–related genes were consistently and significantly altered between the 3 groups in both cohorts. Concurrent with evidence of an immune‐activation gene signature in MTX‐naive RA patients, significant up‐regulation of the folate‐metabolizing enzymes γ‐glutamyl hydrolase and dihydrofolate reductase, as well as the MTX/folate efflux transporters ABCC2 and ABCC5, was observed in the MTX‐naive RA group compared to healthy controls. Strikingly, MTX treatment of RA patients normalized these differential gene expression levels to the levels observed in healthy controls.

Conclusion

These results suggest that under inflammatory conditions, basal folate metabolism in the peripheral blood cells of RA patients is markedly up‐regulated, and treatment with MTX restores folate metabolism to normal levels. Identification of this novel gene signature provides insight into the mechanism of action of MTX, thus paving the way for development of novel folate metabolism–targeted therapies.
Transplantation of Achilles Tendon Treated With Bone Morphogenetic Protein 7 Promotes Meniscus Regeneration in a Rat Model of Massive Meniscal Defect
Authors: Ozeki Nobutake , Muneta Takeshi , Koga Hideyuki , Katagiri Hiroki , Otabe Koji , Okuno Makiko , Tsuji Kunikazu , Kobayashi Eiji , Matsumoto Kenji , Saito Hirohisa , Saito Tomoyuki , Sekiya Ichiro
Published: July 2013

Objective

This study was undertaken to examine whether bone morphogenetic protein 7 (BMP‐7) induces ectopic cartilage formation in the rat tendon, and whether transplantation of tendon treated with BMP‐7 promotes meniscal regeneration. Additionally, we analyzed the relative contributions of host and donor cells on the healing process after tendon transplantation in a rat model.

Methods

BMP‐7 was injected in situ into the Achilles tendon of rats, and the histologic findings and gene profile were evaluated. Achilles tendon injected with 1 μg of BMP‐7 was transplanted into a meniscal defect in rats. The regenerated meniscus and articular cartilage were evaluated at 4, 8, and 12 weeks. Achilles tendon from LacZ‐transgenic rats was transplanted into the meniscal defect in wild‐type rats, and vice versa.

Results

Injection of BMP‐7 into the rat Achilles tendon induced the fibrochondrocyte differentiation of tendon cells and changed the collagen gene profile of tendon tissue to more closely approximate meniscal tissue. Transplantation of the rat Achilles tendon into a meniscal defect increased meniscal size. The rats that received the tendon treated with BMP‐7 had a meniscus matrix that exhibited increased Safranin O and type II collagen staining, and showed a delay in articular cartilage degradation. Using LacZ‐transgenic rats, we determined that the regeneration of the meniscus resulted from contribution from both donor and host cells.

Conclusion

Our findings indicate that BMP‐7 induces ectopic cartilage formation in rat tendons. Transplantation of Achilles tendon treated with BMP‐7 promotes meniscus regeneration and prevents cartilage degeneration in a rat model of massive meniscal defect. Native cells in the rat Achilles tendon contribute to meniscal regeneration.
ADAMTS‐4_v1 Is a Splice Variant of ADAMTS‐4 That Is Expressed as a Protein in Human Synovium and Cleaves Aggrecan at the Interglobular Domain
Authors: Wainwright Shane D. , Bondeson Jan , Caterson Bruce , Hughes Clare E.
Published: July 2013

Objective

We previously described a messenger RNA variant of ADAMTS4 (ADAMTS4_v1) in human synovial cell cocultures obtained from patients with osteoarthritis (OA). This RNA message has been found only in OA synovium and, if translated, would result in a protein identical to ADAMTS‐4, except that the C‐terminal spacer domain would be different. The purpose of this study was to determine whether ADAMTS4_v1 is translated into a protein, is expressed in vivo, and acts as a functional aggrecanase.

Methods

Polyclonal antibodies were raised against unique C‐terminal sequences of ADAMTS‐4_v1. An immunohistochemical study of human OA synovium was performed. A mammalian expression vector coding for FLAG‐tagged human ADAMTS4 was mutated to contain the different sequences of ADAMTS4_v1, and the resultant plasmid was used to transfect HEK 293 cells. ADAMTS‐4_v1 produced by these cells was purified via the FLAG epitope, and the ability of this recombinant protein to cleave aggrecan, biglycan, and decorin was investigated.

Results

An antibody specific for ADAMTS‐4_v1 was found to bind to the synovial membrane surface on cryosections, and the protein was detected in cell lysates from synovium obtained from OA patients. The recombinant ADAMTS‐4_v1 demonstrated enzyme activity toward the target substrate in a commercial aggrecanase 1 enzyme‐linked immunosorbent assay and was also found to cleave aggrecan at the pathologically important Glu373↓374Ala aggrecanase site.

Conclusion

ADAMTS‐4_v1 is expressed as a protein in vivo in human OA synovium, functions as an aggrecanase, and cleaves other proteoglycan substrates. This splice variant may be a major contributor to loss of aggrecan from the superficial zone of OA cartilage.
Analytic hierarchy process application in selecting the mode of transport for a logistics company
Authors: Kumru Mesut , Kumru Pınar Yıldız
Published: July 2013

As a multi‐criteria decision‐making (MCDM) method, the analytic hierarchy process (AHP) has been used considerably to solve hierarchical or network‐based decision problems in socio‐economic fields. Following an in‐depth explanation of the transport function in logistics and an overview of the MCDM methods, the AHP model is employed in the paper for a logistics company in selecting the most suitable way of transportation between two given locations in Turkey. The criteria used in the selection of transportation modes are identified as the cost, speed, safety, accessibility, reliability, environmental friendliness, and flexibility. Several cost parameters (transportation, storage, handling, bosphorus crossover) are incorporated into the decision‐making process. The application is carried out in instructional character. The results of the study indicate that the railway transportation, which is not widely used in Turkey, is also an alternative and suitable means of transportation. Copyright © 2013 John Wiley & Sons, Ltd.
Micro‐computed tomography imaging and analysis in developmental biology and toxicology
Authors: Wise L. David , Winkelmann Christopher T. , Dogdas Belma , Bagchi Ansuman
Published: July 2013

Micro‐computed tomography (micro‐CT) is a high resolution imaging technique that has expanded and strengthened in use since it was last reviewed in this journal in 2004. The technology has expanded to include more detailed analysis of bone, as well as soft tissues, by use of various contrast agents. It is increasingly applied to questions in developmental biology and developmental toxicology. Relatively high‐throughput protocols now provide a powerful and efficient means to evaluate embryos and fetuses subjected to genetic manipulations or chemical exposures. This review provides an overview of the technology, including scanning, reconstruction, visualization, segmentation, and analysis of micro‐CT generated images. This is followed by a review of more recent applications of the technology in some common laboratory species that highlight the diverse issues that can be addressed. Birth Defects Research (Part C) 99:71–82, 2013. © 2013 Wiley Periodicals, Inc.
Engineered genetic selection links in vivo protein folding and stability with asparagine‐linked glycosylation
Authors: Mansell Thomas J. , Guarino Cassandra , DeLisa Matthew P.
Published: July 2013

Predicting the structural consequences of site‐specific glycosylation remains a major challenge due in part to the lack of convenient experimental tools for rapidly determining how glycosylation influences protein folding. To address this shortcoming, we developed a genetic selection that directly links the in vivo folding of asparagine‐linked (N‐linked) glycoproteins with antibiotic resistance. Using this assay, we identified three known or putative glycoproteins from Campylobacter jejuni (Peb3, CjaA, and Cj0610c) whose folding was significantly affected by N‐glycosylation. We also used the genetic selection to isolate a glycoengineered variant of the Escherichia coli colicin E7 immunity protein (Im7) whose intracellular folding and stability were enhanced as a result of N‐glycosylation. In addition to monitoring the effect of glycan attachment on protein folding in living cells, this strategy could easily be extended for optimizing protein folding in vivo and engineering glycosylation enzymes, pathways, and hosts for optimal performance.

See accompanying commentary by Danielle Tullman‐Ercek DOI: 10.1002/biot.201300319
Peptide‐based ligand screening and functional analysis of protein kinase C
Authors: Ohashi Nami , Nomura Wataru , Narumi Tetsuo , Tamamura Hirokazu
Published: July 2013

Protein kinase C (PKC) plays an important role in cell signaling pathways and is implicated in disorders ranging from cancer to Alzheimer's disease. Highly potent PKC ligands as therapeutic drugs have not been developed to date and useful methodologies for controlling PKC activation in defined areas are necessary to analyze precise PKC functions in cells. Studies focused on the development of PKC ligand screening systems and methods for regulation of PKC activation have been performed in our laboratory. In this review, our ligand screening methods involving synthetic peptides and solvatochromic fluorescent dye‐labeled small compounds are summarized and the technique of spatio‐temporal manipulation of PKC activation by caging strategies is introduced. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 613–620, 2013.
Analysis of N‐amino‐imidazolin‐2‐one peptide turn mimic 4‐position substituent effects on conformation by X‐ray crystallography
Authors: Proulx Caroline , Lubell William D.
Published: July 2013

N‐Amino‐imidazolin‐2‐ones, a new class of turn mimics onto which side chains of different amino acids may be added conveniently, have been analyzed by X‐ray crystallography. 4‐Methyl and 4‐benzyl N‐amino‐imidazolin‐2‐one tetrapeptide models 2 and 3 were examined to study the influence of the 4‐position substituent on turn conformation and the chi dihedral angle of the neighbouring C‐terminal residue side‐chain. The nature of the 4‐position substituent caused substantial effects on the ψi + 2 main chain and C‐terminal Phe χ1 side‐chain dihedral angle values, giving a preference for β‐ and γ‐turn conformers for the methyl‐ and benzyl‐substituted imidazolin‐2‐ones, respectively. Conformational analysis in the solid state has provided insight to guide application of N‐amino‐imidazolin‐2‐ones in peptide mimicry. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 7–15, 2014.
When “IUPs” were “BAPs”: How to study the nonconformation of intrinsically unfolded polyaminoacid chains
Authors: Pastore Annalisa , Temussi Pierandrea
Published: July 2013

Ideas often recur. It has been pointed out recently that proteins are not always the well‐structured entities we have become accustomed to from crystallographic studies, but may be intrinsically unstructured or contain unstructured regions. This feature, far from making these proteins less interesting, is an essential requirement for their function. Fascinating though it may be, the concept of so‐called intrinsically unfolded (or unordered) proteins (IUPs), also often referred to as intrinsically disordered proteins (IDPs), is not new: it directly links back to the 1970s when the attention of many structural biologists was focused on biologically active peptides, which like IUPs lack a specific defined conformation. The recurrent nature of this concept may now be of topical interest since it suggests the transfer, upon suitable adaptation, of old tools to develop new ideas. Here, we review some of the approaches that were developed for the study of peptides and discuss how they could inspire powerful new methodologies for the study of IUPs. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 592–600, 2013.
Charge‐Transfer Solids Using Nucleobases: Supramolecular Architectures Composed of Cytosine and [Ni(dmit)2] Assembled by Multiple Hydrogen Bonds and Heteroatomic Contacts
Authors: Yoshida Yukihiro , Maesato Mitsuhiko , Ishikawa Manabu , Nakano Yoshiaki , Hiramatsu Takaaki , Yamochi Hideki , Saito Gunzi
Published: July 2013

Protonated species of the nucleobase cytosine (C), namely the monoprotonated CH+ and the hemiprotonated CHC+, were used to obtain four charge‐transfer complexes of [Ni(dmit)2] (dmit: 1,3‐dithiole‐2‐thione‐4,5‐dithiolate). Diffusion methods afforded two semiconducting [Ni(dmit)2]− salts; (CH)[Ni(dmit)2](CH3CN) (1) and (CHC)[Ni(dmit)2] (2). In salt 1, the [Ni(dmit)2]− ions with a S=1/2 spin construct a uniform one‐dimensional array along the molecular long axis, and the significant intermolecular interaction along the face‐to‐face direction results in a spin‐singlet ground state. In contrast, salt 2 exhibits the Mott insulating behavior associated with uniform 1D arrays of [Ni(dmit)2]−, which assemble a two‐dimensional layer that is sandwiched between the layers of hydrogen‐bonded CHC+ ribbons. Multiple hydrogen bonds between CHC+ and [Ni(dmit)2]− seem to result in the absence of structural phase transition down to 0.5 K. Electrooxidation of [Ni(dmit)2]− afforded the polymorphs of the [Ni(dmit)2]0.5− salts, (CHC+)[{Ni(dmit)2}0.5−]2 (3 and 4), which are the first mixed‐valence salts of nucleobase cations with metal complex anions. Similar to 2, salt 3 contains CHC+ ribbons that are sandwiched between the 2D [Ni(dmit)2]0.5− layers. In the layer, the [Ni(dmit)2]0.5− ions form dimers with a S=1/2 spin and the narrow electronic bandwidth causes a semiconducting behavior. In salt 4, the CHC+ units form an unprecedented corrugated 2D sheet, which is sandwiched between the 2D [Ni(dmit)2]0.5− layers that involve ring‐over‐atom and spanning overlaps. In contrast to 3, salt 4 exhibits metallic behavior down to 1.8 K, associated with a wide bandwidth and a 2D Fermi surface. The ability of hydrogen‐bonded CHC+ sheets as a template for the anion radical arrangements is demonstrated.
Enthalpy and Entropy Barriers Explain the Effects of Topology on the Kinetics of Zeolite‐Catalyzed Reactions
Authors: Van der Mynsbrugge Jeroen , De Ridder Jeroen , Hemelsoet Karen , Waroquier Michel , Van Speybroeck Veronique
Published: July 2013

The methylation of ethene, propene, and trans‐2‐butene on zeolites H‐ZSM‐58 (DDR), H‐ZSM‐22 (TON), and H‐ZSM‐5 (MFI) is studied to elucidate the particular influence of topology on the kinetics of zeolite‐catalyzed reactions. H‐ZSM‐58 and H‐ZSM‐22 are found to display overall lower methylation rates compared to H‐ZSM‐5 and also different trends in methylation rates with increasing alkene size. These variations may be rationalized based on a decomposition of the free‐energy barriers into enthalpic and entropic contributions, which reveals that the lower methylation rates on H‐ZSM‐58 and H‐ZSM‐22 have virtually opposite reasons. On H‐ZSM‐58, the lower methylation rates are caused by higher enthalpy barriers, owing to inefficient stabilization of the reaction intermediates in the large cage‐like pores. On the other hand, on H‐ZSM‐22, the methylation rates mostly suffer from higher entropy barriers, because excessive entropy losses are incurred inside the narrow‐channel structure. These results show that the kinetics of crucial elementary steps hinge on the balance between proper stabilization of the reaction intermediates inside the zeolite pores and the resulting entropy losses. These fundamental insights into their inner workings are indispensable for ultimately selecting or designing better zeolite catalysts.
Intramolecular Participation of Amino Groups in the Cleavage and Isomerization of Ribonucleoside 3′‐Phosphodiesters: The Role in Stabilization of the Phosphorane Intermediate
Authors: Lain Luigi , Lönnberg Harri , Lönnberg Tuomas
Published: July 2013

A dinucleoside‐3′,5′‐phosphodiester model, 5′‐amino‐4′‐aminomethyl‐5′‐deoxyuridylyl‐3′,5′‐thymidine, incorporating two aminomethyl functions in the 4′‐position of the 3′‐linked nucleoside has been prepared and its hydrolytic reactions studied over a wide pH range. The amino functions were found to accelerate the cleavage and isomerization of the phosphodiester linkage in both protonated and neutral form. When present in protonated form, the cleavage of the 3′,5′‐phosphodiester linkage and its isomerization to a 2′,5′‐linkage are pH‐independent and 50–80 times as fast as the corresponding reactions of uridylyl‐3′,5′‐uridine (3′,5′‐UpU). The cleavage of the resulting 2′,5′‐isomer is also accelerated, albeit less than with the 3′,5′‐isomer, whereas isomerization back to the 3′,5′‐diester is not enhanced. When the amino groups are deprotonated, the cleavage reactions of both isomers are again pH‐independent and up to 1000‐fold faster than the pH‐independent cleavage of UpU. Interestingly, the 2′‐ to 3′‐isomerization is now much faster than its reverse reaction. The mechanisms of these reactions are discussed. The rate accelerations are largely accounted for by electrostatic and hydrogen‐bonding interactions of the protonated amino groups with the phosphorane intermediate.
Particles motion in a cascading rotary drum dryer
Authors: Hamawand Ihsan , Yusaf Talal
Published: July 2013

A mathematical model was built and used to show the motion of particles in a cascade rotary drum dryer. In a cascade rotary drum the flights pick up the particles at a number of points in the lower half of the drum while, in the upper half, the particles fall freely. A model is derived where the drag force exerted on the particles throughout the falling period is emphasised. The motion of the particles in a rotary drum is described by three actions: Cascade; Kiln and Bouncing. In this study a horizontal rotary drum was used where both the kiln and bouncing actions have minimal effect, therefore, the focus is on the cascade motion of the particles. A characteristic of the model is the “falling number” which is found to be dependent on the curtain properties. The model has demonstrated its ability to predict the effect of many important parameters such as drying medium velocity, drum rotation speed, particle size and feeding flow rate. It has been shown that increasing the drying medium velocity by 2.5 times results in an 85% decrease in the residence time. Also, the number of falling is shown to be limited and a function of the drum rotation speed, in this case 0.59 falling per second. An important feature of this model is the ability to predict the mean resident time, contact time interval and the resting time interval. The maximum error between the predicted and the measured data was <10%.
Axonal transcription factors: Novel regulators of growth cone‐to‐nucleus signaling
Authors: Ji Sheng‐Jian , Jaffrey Samie R.
Published: July 2013

Developing axons contain transcripts that are locally translated to influence the axonal proteome. Recent studies have shown that axonal transcripts include mRNAs encoding transcription factors. These mRNAs are translated to produce transcription factors that can be retrogradely trafficked back to the nucleus, where they regulate gene expression programs. These findings point to a novel mechanism of growth cone‐to‐nucleus signaling that occurs when growth cones encounter extracellular signaling molecules that stimulate local translation of these transcription factors, thereby influencing gene transcription. Here we summarize recent findings on local translation of transcription factors in axons and their roles in different neuronal processes such as neuronal specification, survival, and axon regeneration. Comprehensive axonal transcriptome studies have revealed transcripts that encode many more transcription factors and cofactors, suggesting a potentially broad role for this type of signaling. We review the progress on the approaches and tools that have been developed to study local translation and retrograde trafficking of transcription factors. We also highlight the challenges in the field and discuss the potential routes to resolving them. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 245–258, 2014
Identification of axon‐enriched MicroRNAs localized to growth cones of cortical neurons
Authors: Sasaki Yukio , Gross Christina , Xing Lei , Goshima Yoshio , Bassell Gary J.
Published: July 2013

There is increasing evidence that localized mRNAs in axons and growth cones play an important role in axon extension and pathfinding via local translation. A few studies have revealed the presence of microRNAs (miRNAs) in axons, which may control local protein synthesis during axon development. However, so far, there has been no attempt to screen for axon‐enriched miRNAs and to validate their possible localization to growth cones of developing axons from neurons of the central nervous system. In this study, the localization of miRNAs in axons and growth cones in cortical neurons was examined using a “neuron ball” culture method that is suitable to prepare axonal miRNAs with high yield and purity. Axonal miRNAs prepared from the neuron ball cultures of mouse cortical neurons were analyzed by quantitative real‐time RT‐PCR. Among 375 miRNAs that were analyzed, 105 miRNAs were detected in axons, and six miRNAs were significantly enriched in axonal fractions when compared with cell body fractions. Fluorescence in situ hybridization revealed that two axon‐enriched miRNAs, miR‐181a‐1* and miR‐532, localized as distinct granules in distal axons and growth cones. The association of these miRNAs with the RNA‐induced silencing complex further supported their function to regulate mRNA levels or translation in the brain. These results suggest a mechanism to localize specific miRNAs to distal axons and growth cones, where they could be involved in local mRNA regulation. These findings provide new insight into the presence of axonal miRNAs and motivate further analysis of their function in local protein synthesis underlying axon guidance. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 397–406, 2014
Mixed functional characteristics correlating with TCR‐ligand koff‐rate of MHC‐tetramer reactive T cells within the naive T‐cell repertoire
Authors: Hombrink Pleun , Raz Yotam , Kester Michel G. D. , de Boer Renate , Weißbrich Bianca , von dem Borne Peter A. , Busch Dirk H. , Schumacher Ton N. M. , Falkenburg J. H. Frederik , Heemskerk Mirjam H. M.
Published: July 2013

The low frequency of antigen‐specific naïve T cells has challenged numerous laboratories to develop various techniques to study the naïve T‐cell repertoire. Here, we combine the generation of naïve repertoire‐derived antigen‐specific T‐cell lines based on MHC‐tetramer staining and magnetic‐bead enrichment with in‐depth functional assessment of the isolated T cells. Cytomegalovirus (CMV) specific T‐cell lines were generated from seronegative individuals. Generated T‐cell lines consisted of a variety of immunodominant CMV‐epitope‐specific oligoclonal T‐cell populations restricted to various HLA‐molecules (HLA‐A1, A2, B7, B8, and B40), and the functional and structural avidity of the CMV‐specific T cells was studied. Although all CMV‐specific T cells were isolated based on their reactivity toward a specific peptide‐MHC complex, we observed a large variation in the functional avidity of the MHC‐tetramer positive T‐cell populations, which correlated with the structural avidity measured by the recently developed Streptamer koff‐rate assay. Our data demonstrate that MHC‐tetramer staining is not always predictive for specific T‐cell reactivity, and challenge the sole use of MHC‐tetramers as an indication of the peripheral T‐cell repertoire, independent of the analysis of functional activity or structural avidity parameters.
Unexpected Coordination Behaviour of 3,5‐Di(2‐pyridyl)‐1,2,4‐oxadiazole
Authors: Klingele Julia , Kaase Dominic , Schmucker Maximilian , Meier Lea
Published: July 2013

The coordination behaviour of 3,5‐di(2‐pyridyl)‐1,2,4‐oxadiazole (L′) has been studied and compared with that of the 2,5‐di(2‐pyridyl)‐1,3,4‐chalcadiazolesLO,LSandLSe[LO= 2,5‐di(2‐pyridyl)‐1,3,4‐oxadiazole,LS= 2,5‐di(2‐pyridyl)‐1,3,4‐thiadiazole,LSe= 2,5‐di(2‐pyridyl)‐1,3,4‐selenadiazole]. LigandL′and the new complexes [CuII(L′)3](ClO4)2·1.5MeOH·H2O (1·1.5MeOH·H2O),1·MeCN, [CoII(L′)2(MeOH)2](ClO4)2(2), [CoII(LO)2(MeOH)2](ClO4)2(3), [CuII(L′)2Cl2] (4), [CuII(L′)2Br2] (5) and [CuII(LSe)2Cl2]·MeOH (6·MeOH) have been structurally characterised by single‐crystal X‐ray diffraction analyses. With the help of DFT calculations and the analyses of metal–ligand bond lengths of similar complexes ofL′,LO,LSandLSethe binding capacities have been determined asL′ <<LO <LS <LSe.
Reductive Deoxygenation of Alcohols: Catalytic Methods Beyond Barton–McCombie Deoxygenation
Authors: Herrmann Josef M. , König Burkhard
Published: July 2013

Deoxygenation is an extensively studied field in organic chemistry, and over the last decades many methods such as the Barton–McCombie deoxygenation reaction or deoxygenation with alkali metals in liquid ammonia have been established. Within this microreview, we discuss different strategies for the chemoselective catalytic deoxygenation of alcohols with special attention to their scope and limitations. The deoxygenation of derivatives of alcohols and their direct deoxygenation as step‐economic alternative are covered with current examples. Catalytic methods can serve as convenient and economic alternatives for established methods in the reduction of carbon–oxygen single bonds.
Flexural properties after exposure to elevated temperatures of a ground granulated blast furnace slag concrete incorporating steel fibers and polypropylene fibers
Authors: Gao Danying , Yan Dongming , Li Xiangyu
Published: July 2013

Experiments were carried out to investigate the flexural properties of fiber‐reinforced ground granulated blast furnace slag (GGBFS) concrete after exposure to high temperatures. On the basis of experimental observation, the effect of GGBFS content, the steel fiber dosage, the polypropylene (PP) fiber dosage, and the strength grade on the residual strength of concrete after exposure to elevated temperatures were systematically examined. Test data indicate that exposure to high temperatures causes deterioration in the flexural strength of concrete; inclusion of GGBFS, PP fibers, and steel fibers, all effectively improve the residual flexural strength of concrete after fire. The optimum amounts of GGBFS, PP fibers, and steel fibers are identified respectively for better fire resistance of concrete. The strength losses of concretes characterized by different strength grades are very close to one another. Equations are proposed to predict the residual flexural strength of concrete incorporating GGBFS, PP fibers, and steel fibers after being heated to temperatures up to 800°C. Copyright © 2013 John Wiley & Sons, Ltd.
Automated MRI parcellation of the frontal lobe
Authors: Ranta Marin E. , Chen Min , Crocetti Deana , Prince Jerry L. , Subramaniam Krish , Fischl Bruce , Kaufmann Walter E. , Mostofsky Stewart H.
Published: July 2013

Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub‐regions is a fundamental goal in neuropsychiatry. Here, we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS‐CRUISE(T‐C), based on the manual method described in Ranta et al. [2009]: Psychiatry Res 172:147‐154 in which sulcal‐gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field, and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex [OFC] and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T‐C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof‐of‐principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub‐regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions. Hum Brain Mapp 35:2009–2026, 2014. © 2013 Wiley Periodicals, Inc.
Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults
Authors: Ito Kiyoaki , Yotsuyanagi Hiroshi , Yatsuhashi Hiroshi , Karino Yoshiyasu , Takikawa Yasuhiro , Saito Takafumi , Arase Yasuji , Imazeki Fumio , Kurosaki Masayuki , Umemura Takeji , Ichida Takafumi , Toyoda Hidenori , Yoneda Masashi , Mita Eiji , Yamamoto Kazuhide , Michitaka Kojiro , Maeshiro Tatsuji , Tanuma Junko , Tanaka Yasuhito , Sugiyama Masaya , Murata Kazumoto , Masaki Naohiko , Mizokami Masashi
Published: July 2013

The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance.

Conclusion :

Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies.
Suspended sediment and total dissolved solid yield patterns at the headwaters of Urumqi River, northwestern China: a comparison between glacial and non‐glacial catchments
Authors: Gao Wenhua , Gao Shu , Li Zhongqin , Lu X. X. , Zhang Mingjun , Wang Shengjie
Published: July 2013

In order to understand the differences in the suspended sediment and total dissolved solid (TDS) yield patterns between the glacial and non‐glacial catchments at the headwaters of Urumqi River, northwestern China, water samples were collected from a glacier catchment and an empty cirque catchment within the region, during three melting seasons from 2006 to 2008. These samples were analyzed to estimate suspended sediment and TDS concentrations, fluxes and erosion rates in the two adjoining catchments. There were remarked differences in suspended sediment and TDS yield patterns between the two catchments. Suspended sediment concentrations were controlled mainly by the sediment source, whereas TDS concentrations were primarily related to the hydrologic interaction with soil minerals. Generally, the glacial catchment had much higher suspended sediment and TDS yields, together with higher denudation rates, than the non‐glacial catchment. Overall, glacial catchment was mainly dominated by physical denudation process, whereas the non‐glacial catchment was jointly influenced by physical and chemical denudation processes. The observed differences in material delivery patterns were mainly controlled by the runoff source and the glacial processes. The melting periods of glacier and snow were typically the most important time for the suspended sediment and TDS yields. Meanwhile, episodic precipitation events could generate disproportionately large yields. Subglacial hydrology dynamics, glaciers pluck and grind processes could affect erodibility, and the large quantities of dust stored on the glacier surface provided additional sources for suspended sediment transport in the glacial catchment. These mechanisms imply that, in response to climate change, the catchment behaviour will be modified significantly in this region, in terms of material flux. Copyright © 2013 John Wiley & Sons, Ltd.
Determination of telaprevir in plasma of HCV‐infected patients by HPLC‐UV
Authors: Tempestilli Massimo , Milano Elisa , D'Offizi Gianpiero , Montalbano Marzia , D'Avolio Antonio , Gasperi Tecla , Narciso Pasquale , Ascenzi Paolo , Pucillo Leopoldo P.
Published: July 2013

Telaprevir is a direct acting antiviral agent, used with pegylated interferon and ribavirin for the management of chronic hepatitis C virus (HCV) genotype 1 infection, in patients not responding to therapy with pegylated interferon and ribavirin only. Although 75% of patients achieve a sustained virological response after treatment with telaprevir, adverse drug–drug interactions and undesirable events often occur. Therefore, telaprevir monitoring is pivotal to improve the management of HCV infection. Here, the first High‐Performance Liquid Chromatography‐Ultraviolet (HPLC‐UV) method to quantify telaprevir in human plasma of HCV‐genotype 1‐infected patients is reported. The volume of the plasma sample was 700 μL. This method involved automated solid‐phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N‐vinylpyrrolidone). The extracted samples were reconstituted with 150 μL of 60/40 water/acetonitrile. Thirty microliters of these samples was injected into a HPLC‐UV system, and the analytes were eluted on a X Terra® RP18 column (250 mm × 4.6 mm i.d.) with a particle size of 5 μm. The mobile phase (ammonium acetate buffer, 150 mM, pH 8.0, and methanol:acetonitrile 50:50) was delivered at 1.0 mL/min with linear gradient elution. The total run time for a single analysis was 16 min; telaprevir was detected by UV at 276 and 286 nm. The calibration curve was linear from 312.5 to 20,000 ng/mL (r2 > 0.996). The absolute recovery of telaprevir ranged between 89 and 93% at concentrations of quality control samples of 800, 4,000, 8,000, and 16,000 ng/mL. Both precision and accuracy were always <15%. The HPLC‐UV method reported here: (i) has been validated, (ii) is currently applied to monitor telaprevir in plasma of HCV‐infected patients, and (iii) appears useful in a routine laboratory. © 2013 IUBMB Life, 65(9):800–805, 2013
Induction of Dopaminergic Neurons From Human Wharton's Jelly Mesenchymal Stem Cell by Forskolin
Authors: Paldino Emanuela , Cenciarelli Carlo , Giampaolo Adele , Milazzo Luisa , Pescatori Mario , Hassan Hamisa Jane , Casalbore Patrizia
Published: July 2013

The purpose of this study was to investigate the Wharton's jelly mesenchymal stem cells differentiation ability toward neuronal fate. Human Wharton's jelly mesenchymal stem cells (hWJMSC) have been isolated from human umbilical cord of full‐term births and characterized by flow cytometry analysis for their stem mesenchymal properties through specific surface markers expression (CD73, CD90, and CD105). hWJMSC mesodermal lineage differentiation ability and karyotype analysis were assessed. The trans‐differentiation of hWJMSC into neural lineage was investigated in presence of forskolin, an agent known to increase the intracellular levels of cAMP. A molecular profile of differentiated hWJMSC was performed by microarray technology which revealed 1,532 statistically significant modulated genes respect to control cells. Most of these genes are mainly involved in functional neuronal signaling pathways and part of them are specifically required for the neuronal dopaminergic induction. The acquisition of the dopaminergic phenotype was evaluated via immunocytochemistry and Western blot analysis revealed the significant induction of Nurr1, NeuroD1, and TH proteins expression in forskolin‐induced hWJMSC. Moreover, the treatment with forskolin promoted, in hWJMSC, a strong upregulation of the neurotrophin Trk receptors related to the high release of brain‐derived neurotrophic factor. Taken together these findings show that hWJMSC may be represent an optimal therapeutic strategy for neurological diseases. J. Cell. Physiol. 229: 232–244, 2014. © 2013 Wiley Periodicals, Inc.