bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser‐induced volume changes during confocal Raman microscopy of whey‐protein‐stabilized emulsions and their relationship to protein content and particle diameters
Authors: Iljina Marija , Euston Stephen R. , Bookey Henry T.
Published: June 2013

The use of confocal Raman microscopy is applied to the study of whey‐protein‐stabilized oil‐in‐water emulsions. The stability of emulsions is an important parameter for many applications and is dependent on several factors including protein content and particle size. Emulsions were prepared with varying particle size ranging from 0.8 to 10.0 µm. Changes in sample volume due to laser‐induced heating were monitored and correlated to protein content in samples and to particle diameters. It was found that samples with the lowest protein content and larger particle diameters experienced the largest volume changes. The newly developed approach is of a potential predictive use. Copyright © 2013 John Wiley & Sons, Ltd.
Flexible AMOLEDs with low‐temperature‐processed TFT backplane technologies
Authors: Hsieh Hsing‐Hung , Tsai Chih‐Hung , Yang Chao‐Shun , Liu Chan‐Jui , Lin Jian‐Hong , Wu Yen‐Yu , Fang Chun‐Hsiung , Chuang Ching‐Sang
Published: June 2013

Developments of backplane technologies, which are one of the challenging topics, toward the realization of flexible active matrix organic light‐emitting diodes (AMOLEDs) are discussed in this paper. Plastic substrates including polyimide are considered as a good candidate for substrates of flexible AMOLEDs. The fabrication process flows based on plastic substrates are explained. Limited by the temperature that plastic substrates can sustain, TFT technologies with maximum processing temperature below 400 °C must be developed. Considering the stringent requirements of AMOLEDs, both oxide thin‐film transistors (TFTs) and ultra‐low‐temperature poly‐silicon TFTs (U‐LTPS TFTs) are investigated. First, oxide TFTs with representative indium gallium zinc oxide channel layer are fabricated on polyimide substrates. The threshold voltage shifts under bias stress and under bending test are small. Thus, a 4.0‐in. flexible AMOLED is demonstrated with indium gallium zinc oxide TFTs, showing good panel performance and flexibility. Further, the oxide TFTs based on indium tin zinc oxide channel layer with high mobility and good stability are discussed. The mobility can be higher than 20 cm2/Vs, and threshold voltage shifts under both voltage stress and current stress are almost negligible, proving the potential of oxide TFT technology. On the other hand, the U‐LTPS TFTs are also developed. It is confirmed that dehydrogenation and dopant activation can be effectively performed at a temperature within 400 °C. The performance of U‐LTPS TFTs on polyimide is compatible to those of TFTs on glass. Also, the performance of devices on polyimide can be kept intact after devices de‐bonded from glass carrier. Finally, a 4.3‐in. flexible AMOLED is also demonstrated with U‐LTPS TFTs.
Tunable Shell Thickness in Silica Nanospheres Functionalized by a Hydrophobic PMMA‐PSt Diblock Copolymer Brush via Activators Generated by Electron Transfer for Atom Transfer Radical Polymerization
Authors: Zhang Lei , Zhou Guowei , Sun Bin , Chen Fengjiao , Zhao Minnan , Li Tianduo
Published: June 2013

An improved strategy to synthesize SiO2‐PMMA nanoparticles with tunable shell thickness is demonstrated, via iron (III) catalyst‐mediated activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP). To investigate the effect of the content monomer and ligand on the PMMA shell thickness, hydrophobic PMMA‐PSt diblock copolymer brushes on the surface of the silica nanospheres are designed and synthesized by AGET ATRP. Transmission electron microscopy (TEM) and field‐emission scanning electron microscopy (FESEM) show that the product has a core‐shell‐like structure and that the average shell thickness of the PMMA can easily be tuned by simply adjusting the amount of monomer or ligand. In addition, the Mn of the PMMA can be tuned from 37 800 to 62 400 g mol−1 by changing the shell thickness, and the PDI is 1.213–1.473. These results confirm the living nature of the polymerization.

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Functional ROMP‐Derived Poly(cyclopentene)s
Authors: Herz Katharina , Imbrich Dominik A. , Unold Jörg , Xu Guangjuan , Speiser Maria , Buchmeiser Michael R.
Published: June 2013

Functional polyolefins are prepared from poly‐CPE via ROMP by the action of a designed Ru‐alkylidene initiator followed by quantitative hydroboration with 9‐borabicyclo[3.3.1]nonane. The borylated polymers prepared in this way are then converted into hydroxy‐, amino‐, and silyloxy‐functionalized polyolefins. With increasing polarity of the substituents, the glass‐transition temperatures of the modified polymers increase significantly. Perhydrobrominated poly‐CPE is prepared from poly‐CPE and HBr and subjected to Cu(I)‐mediated ATRP‐based grafting to yield poly(tert‐butyl acrylate)‐grafted polyethylene (PE). The synthetic routes reported here present a straightforward access to functional and polar olefins.

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Tailoring Cellulose Surfaces by Controlled Polymerization Methods
Authors: Carlmark Anna
Published: June 2013

Cellulose, with its excellent mechanical properties and low weight, would be highly advantageous to employ in bioplastics and biocomposites applications. However, to expand the utilization of cellulose beyond its traditional uses, a modification of the fiber surface is often a prerequisite. One approach is to graft polymer chains on the surface in order to compatibilize the fibers with a non‐polar polymer matrix or to introduce functionalities. By exploiting controlled polymerization methods such as ATRP, RAFT, ROP, and ROMP, the surface of the fibers can be carefully tailored. Herein, an overview on controlled, heterogeneous grafting of cellulose fibers and fibrils employing both “grafting from” and “grafting to” methodologies is provided, focusing on the latest findings

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Correlation Between Reactive Modification Conditions and Degree of Long‐Chain Branching in Chemically Modified Linear Low Density Polyethylene Using Response Surface Experimental Design
Authors: Golriz Mahdi , Khonakdar Hossein Ali , Morshedian Jalil , Abedini Hossein , Jafari Seyed Hassan , Lederer Albena , Wagenknecht Udo
Published: June 2013

Changes induced in the molecular architecture of linear low‐density polyethylene during early stages of peroxide modification in a microcompounder are monitored by means of size exclusion chromatography and dynamic shear oscillatory measurements as a function of peroxide concentration, mixing temperature and resident time. By the use of a response surface method and according to a box Behnken statistical design, various contour plots are constructed to establish correlations between the processing parameters and degree of long‐chain branching. All investigated process parameters are shown to have a significant effect on the degree of long‐chain branching, the order of significance being concentration > temperature > mixing time. The interactive effects of these factors are determined.
Compressed sensing CPMG with group‐sparse reconstruction for myelin water imaging
Authors: Chen Henry S. , Majumdar Angshul , Kozlowski Piotr
Published: June 2013

Purpose

Myelin content is a marker for nervous system pathology and is quantifiable by myelin water imaging using multi‐echo CPMG sequence, which is inherently slow. One way to accelerate the scan is to utilize compressed sensing. However, reconstructing the images piecemeal by standard compressed sensing methods is not the optimal solution, because it only exploits intraimage spatial redundancy. It does not recognize that the different T2 weighted images are scans of the same anatomical volume and hence correlated. The purpose of this work is to test the feasibility of compressed sensed CPMG with group‐sparsity promoting optimization for myelin water imaging.

Methods

Group‐sparse reconstruction was performed at various simulated and actual undersampling factors for an electronic phantom, ex vivo rat spinal cord, and in vivo rat spinal cord. Normalized mean square error was used as the metric for comparison.

Results

For both simulated undersampling and the actual undersampling, the method was found to minimally impact myelin water fraction map quality (normalized mean square error < 0.25) when acceleration factor was below two.

Conclusion

Compressed sensed CPMG with group‐sparse reconstruction is useful for achieving a shorter scan time than traditionally possible. Magn Reson Med 71:1166–1171, 2014. © 2013 Wiley Periodicals, Inc.
Local specific absorption rate (SAR), global SAR, transmitter power, and excitation accuracy trade‐offs in low flip‐angle parallel transmit pulse design
Authors: Guérin Bastien , Gebhardt Matthias , Cauley Steven , Adalsteinsson Elfar , Wald Lawrence L.
Published: June 2013

Purpose

We propose a constrained optimization approach for designing parallel transmit (pTx) pulses satisfying all regulatory and hardware limits. We study the trade‐offs between excitation accuracy, local and global specific absorption rate (SAR), and maximum and average power for small flip‐angle pTx (eight channels) spokes pulses in the torso at 3 T and in the head at 7 T.

Methods

We compare the trade‐offs between the above‐mentioned quantities using the L‐curve method. We use a primal‐dual algorithm and a compressed set of local SAR matrices to design radio‐frequency (RF)
pulses satisfying all regulatory (including local SAR) and hardware constraints.

Results

Local SAR can be substantially reduced (factor of 2 or more) by explicitly constraining it in the pulse design process compared to constraining global SAR or pulse power alone. This often comes at the price of increased pulse power.

Conclusion

Simultaneous control of power and SAR is needed for the design of pTx pulses that are safe and can be played on the scanner. Constraining a single quantity can create large increase in the others, which can then rise above safety or hardware limits. Simultaneous constraint of local SAR and power is fast enough to be applicable in a clinical setting. Magn Reson Med 71:1446–1457, 2014. © 2013 Wiley Periodicals, Inc.
Political radio and television advertisements in a young democracy: the 2009 South African national election campaign
Authors: Fourie Lynnette
Published: June 2013

It is argued that political parties in a developing democracy should contribute to sustaining democracy through their informational and motivational functions during election campaigns. Rather than debating the merit of issue messages, it is argued that cognitive and emotional campaign messages should be integrated, in order to not only attract voters' attention but also to inform the voter, to foster democratic values, to stimulate debate and to motivate voters to vote.

It was found that in the 2009 South African general election, South African political parties did not effectively integrate emotional and cognitive messages, but references to democratic values were integrated with the emotional messages. Few of the parties encouraged voters to participate in the election for the sake of sustaining the democracy. Copyright © 2013 John Wiley & Sons, Ltd.
Antipsychotics in the treatment of schizophrenia
Authors: Parker Caroline
Published: June 2013

In the first of a new series of updated articles on the major psychiatric drug groups, produced in association with the College of Mental Health Pharmacy (www.cmhp.org.uk), Caroline Parker summarises the use of antipsychotics through a review of the clinical literature. Pharmacology, interactions and side‐effects as well as drug choice and information to give to patients are discussed.
Fast and effective copper(0)‐mediated simultaneous chain‐ and step‐growth radical polymerization at ambient temperature
Authors: Zhang Xiaomin , Dou Heqin , Zhang Zhengbiao , Zhang Wei , Zhu Xiulin , Zhu Jian
Published: June 2013

Vinyl‐conjugated monomer (methyl acrylate, MA) and allyl 2‐bromopropanoate (ABP)‐possessing unconjugated CC and active CBr bonds were polymerized via the Cu(0)‐mediated simultaneous chain‐ and step‐growth radical polymerization at ambient temperature using Cu(0) as catalyst, N,N,N′,N″,N″‐pentamethyldiethylenetriamine as ligand and dimethyl sulfoxide as solvent. The conversion was reached higher than 98% within 20 h. The obtained polymers showed block structure consisting of polyester and vinyl polymer moieties. The Cu(0)‐catalyzed simultaneous chain‐ and step‐growth radical polymerization mechanism was demonstrated by NMR, matrix‐assisted laser desorption ionization time‐of‐flight, and GPC analyses. Furthermore, the obtained copolymers of MA and ABP were further modified with poly(N‐isopropylamide) through radical thiol‐ene “click” chemistry from the terminal double bond. The thermoresponsive behavior of this block copolymer was investigated. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3907–3916
Retracted: Climate Change and Internal Migration in India: Response of the State, Market, and the Civil Society
Authors: Jha Anil Kumar
Published: June 2013

Climate change has become a major concern for the international community. Among its consequences, its impact on migration is the object of increasing attention from both policymakers and researchers. Yet knowledge in this field remains limited and fragmented. This article, therefore, provides an overview of the climate change–migration nexus in India. It investigates the key issues at stake, including the social and political context in which the topic emerged. It further investigates the responses of the state, market and the civil society. Two major interconnected arguments arise. The first regards the weight of environmental and climatic factors in migration and their relationship to other push or pull factors, whether of social, political, or economic nature. The second is about the political framework in which such migration flows should take place and the manner in which to treat the people who move in connection with environmental factors. The two issues are deeply intertwined, as the extent to which the environment determines migration is intimately connected to the status to be associated with the people concerned. The ISMW Act is an obsolete piece of legislation by the Government of India in this regard. Some of the work that civil society is doing—for instance, the move to issue migrants an ID, provide them with skills training, offer legal protection, and financial services—is highly scaleable. They are not unique to a specific geography; they are fairly universal solutions that can be taken to any geography and any group of migrants across the country. Of course, civil society is limited by its resources, its networks, and its ability to deliver. Therefore, it can partner well with governments to deliver these services.
Elites and Poverty in the Neoliberal Era: The Case of Mexico
Authors: Medrano Anahely
Published: June 2013

Mexico is an upper‐middle‐income country, an OECD member, and the homeland of the richest man on earth, yet most Mexicans are poor. This article explores how Mexican elites perceive poverty and the poor, and how such perceptions are linked to particular policy preferences. Findings suggest that when Mexican elites talk about poverty, some things often remain unsaid. Mainstream perceptions of poverty were chiefly silent about power and inequality. In other words, depoliticized views of poverty seem to be prevailing among Mexican elites. This qualitative analysis contributes to understanding the specific nature of policies implemented to tackle this social problem in Mexico.
Dedication of This Issue to the Late U.S. Senator, Ambassador, Democratic Candidate for President of the United States, and Tireless Worker for Peace and Against War and Poverty, The Hon. George S. McGovern
Authors: Skidmore Max J.
Published: June 2013

In 1972, George McGovern challenged Richard M. Nixon for the presidency of the United States, and it went down as one of the greatest defeats in American presidential history. Years later, in response to a question whether he was embarrassed to have lost so badly, he said that everything had to be put into perspective. Many times, he said, he had met people who remarked, “I voted for Nixon. But if I had known then what I know now, I would have voted for you.” I doubt, he remarked, that Nixon ever met anyone who said, “I voted for McGovern, but if I had known then what I know now, I would have voted for you.”

George McGovern died on October 21, 2012, at the age of 90. Somewhat more than two years previously, on April 7, 2010, the Norwegian Nobel Institute acknowledged receipt of a nomination for the Nobel Peace Prize for Senator McGovern that Professor Robert P. Watson of Lynn University and I prepared. United States Representative Dennis Moore, then representing the Third Congressional District of Kansas, strongly endorsed, and submitted, the nomination.

Unfortunately, the timing was not good, because an American, President Barack Obama, had received the prize the previous year; the prize has only rarely been awarded to recipients of the same country in two consecutive years. In his honor, we believe it appropriate to reproduce here our nomination of Senator McGovern, and the tribute that it includes.
Protein–protein alternative binding modes do not overlap
Authors: Kundrotas Petras J. , Vakser Ilya A.
Published: June 2013

Proteins often bind other proteins in more than one way. Thus alternative binding modes is an essential feature of protein interactions. Such binding modes may be detected by X‐ray crystallography and thus reflected in Protein Data Bank. The alternative binding is often observed not for the protein itself but for its structural homolog. The results of this study based on the analysis of a comprehensive set of co‐crystallized protein–protein complexes show that the alternative binding modes generally do not overlap, but are spatially separated. This effect is based on molecular recognition characteristics of the protein structures. The results are also in excellent agreement with the intermolecular energy funnel size estimates obtained previously by an independent methodology. The results provide an important insight into the principles of protein association, as well as potential guidelines for modeling of protein complexes and the design of protein interfaces.
Selective interaction between nanotubes and perylene‐based surfactant
Authors: Ernst Friederike , Heeg Sebastian , Heek Timm , Setaro Antonio , Haag Rainer , Reich Stephanie
Published: June 2013

We recently reported a significant deviation in the photoluminescence intensities of HiPco nanotubes solubilized with a perylene‐based surfactant, C16, compared to bile salt surfactants. For C16, the photoluminescence emission of chiralities (9,5), (10,3), and (11,1) is enhanced by up to 430%. Resonant Raman spectroscopy is less sensitive to bundling state and also yields disparate chirality intensity ratios: The (11,0) zigzag tube signal increases by 100% compared to (8,6), (9,4), and (10,2) after suspension with C16. We also report the change in photoluminescence intensity distribution after the swelling of bile salt suspended nanotubes with a series of small organic chromophores in DCM. These changes are attributed to chromophore‐induced surfactant reorganization, resulting in better nanotube individualization. The chirality for which the PL intensity is most enhanced is (11,1) for all chromophores, a chirality also increased by 300% in the C16‐solubilized sample. Conjointly, these measurements indicate that both preferential solubilization and enhanced debundling contribute to the PL intensity distribution in the C16‐solubilized nanotube sample. This has wide ranging implications for the design of chirally selective surfactants and the demonstration of their selectivity, which is typically only shown through luminescence measurements. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Using trusted computing in trusted mail transfer protocol
Authors: Mohamed Fady A. , Hemayed Elsayed E.
Published: June 2013

In this era, hacking techniques have become more dangerous and more widely used across the Internet. If we want to send and receive a trusted email, our current techniques would not be efficient. In this paper, we propose a new protocol for trusting our emails based on Trusted Computing. We combine the hardware‐based cryptography of the Trusted Platform Module and the Remote Attestation with the email protocols. The details of the proposed protocol and its security analysis are discussed in this paper. Copyright © 2013 John Wiley & Sons, Ltd.
Signer‐admissible strong designated verifier signature from bilinear pairings
Authors: Wang Huaqun
Published: June 2013

In the designated verifier signature, the validity of signature can be proved by the specific verifier although the verifier has no ability to prove this to others. On the other hand, strong designated verifier signature (SDVS) can only be verified by the designated verifier. It will not be verified without the designated verifier's private key. The third party cannot tell who generates the signature. Even if the true signer signs a message by using SDVS, he has no ability to show any evidence. In some cases, the true signer wants to admit the signature if the admission can bring about reward. On the basis of the idea, this paper proposes the new concept of signer‐admissible SDVS. By utilizing bilinear pairings and the modified ElGamal signature, we design an efficient identity‐based SDVS scheme with signer‐admission property. Compared with the existing identity‐based SDVS schemes, our scheme supports the signer‐admission property, and it is efficient. Copyright © 2013 John Wiley & Sons, Ltd.
Collaborative agglomerative document clustering with limited information disclosure
Authors: Su Chunhua , Zhou Jianying , Bao Feng , Takagi Tsuyoshi , Sakurai Kouichi
Published: June 2013

Document clustering is a practical and powerful data mining technique to analyze large amount of documents and large sets of text or hypertext documents. However, it also brings the problem of sensitive information leaking in disregard of privacy, especially when it is executed in distributed environment. In this paper, we propose a cryptography‐based framework to realize privacy‐preserving document clustering among the users under the distributed environment; there are two parties, each having his private document database, want to collaboratively execute agglomerative document clustering without disclosing their private contents. We provide two implementations of such a framework, one is with more precision and stronger security but requires more computational resources. The other is a simplified version with less computational complexity and achieves higher processing speed. Additionally, we provide the security proofs and experimental analysis of precision and scalability of our proposal. Copyright © 2013 John Wiley & Sons, Ltd.
Adjustment for measurement error in evaluating diagnostic biomarkers by using an internal reliability sample
Authors: White Matthew T. , Xie Sharon X.
Published: June 2013

Biomarkers are often measured with error due to imperfect lab conditions or temporal variability within subjects. Using an internal reliability sample of the biomarker, we develop a parametric bias‐correction approach for estimating a variety of diagnostic performance measures including sensitivity, specificity, the Youden index with its associated optimal cut‐point, positive and negative predictive values, and positive and negative diagnostic likelihood ratios when the biomarker is subject to measurement error. We derive the asymptotic properties of the proposed likelihood‐based estimators and show that they are consistent and asymptotically normally distributed. We propose confidence intervals for these estimators and confidence bands for the receiver operating characteristic curve. We demonstrate through extensive simulations that the proposed approach removes the bias due to measurement error and outperforms the naïve approach (which ignores the measurement error) in both point and interval estimation. We also derive the asymptotic bias of naïve estimates and discuss conditions in which naïve estimates of the diagnostic measures are biased toward estimates produced when the biomarker is ineffective (i.e., when sensitivity equals 1 − specificity) or are anticonservatively biased. The proposed method has broad biomedical applications and is illustrated using a biomarker study in Alzheimer's disease. We recommend collecting an internal reliability sample during the biomarker discovery phase in order to adequately evaluate the performance of biomarkers with careful adjustment for measurement error. Copyright © 2013 John Wiley & Sons, Ltd.
Graphene‐Like MoS2/Graphene Composites: Cationic Surfactant‐Assisted Hydrothermal Synthesis and Electrochemical Reversible Storage of Lithium
Authors: Huang Guochuang , Chen Tao , Chen Weixiang , Wang Zhen , Chang Kun , Ma Lin , Huang Feihe , Chen Dongyun , Lee Jim Yang
Published: June 2013

A cationic surfactant‐assisted hydrothermal route is developed for the facile synthesis of graphene‐like MoS2/graphene (GL‐MoS2/G) composites based on the hydrothermal reduction of Na2MoO4 and graphene oxide sheets with L‐cysteine in the presence of cetyltrimethylammonium bromide (CTAB), following by annealling in N2 atmosphere. The GL‐MoS2/G composites are characterized by X‐ray diffraction, electron microscopy, high‐resolution transmission electron microscopy, and Raman spectroscopy. The effects of CTAB concentration on the microstructures and electrochemical performances of the composites for reversible Li+ storage are investigated. It is found that the layer number of MoS2 sheets decreases with increasing CTAB concentration. The GL‐MoS2 sheets in the composites are few‐layer in the case of 0.01∼0.03 mol L−1 CTAB of hydrothermal solution and single‐layer in the case of 0.05 mol L−1 CTAB. The GL‐MoS2/G composites prepared with 0.01–0.02 mol·L−1 of CTAB solution exhibit a higher reversible capacity of 940–1020 mAh g−1, a greater cycle stability, and a higher rate capability than other samples. The exceptional electrochemical performance of GL‐MoS2/G composites for reversible Li+ storage could be attributed to an effective integration of GL‐MoS2 sheets and graphene that maximizes the synergistic interaction between them.
The lost intrinsic fragmentation of MAT1 protein during granulopoiesis promotes the growth and metastasis of leukemic myeloblasts
Authors: Lou Siyue , Liu Gang , Shimada Hiroyuki , Yang Xiaochun , He Qiaojun , Wu Lingtao
Published: June 2013

MAT1, an assembly factor and targeting subunit of both cyclin-dependent kinase-activating kinase (CAK) and general transcription factor IIH (TFIIH) kinase, regulates cell cycle and transcription. Previous studies show that expression of intact MAT1 protein is associated with expansion of human hematopoietic stem cells (HSC), whereas intrinsically programmed or retinoic acid (RA)-induced MAT1 fragmentation accompanies granulocytic differentiation of HSC or leukemic myeloblasts. Here we determined that, in humanized mouse microenvironment, MAT1 overexpression resisted intrinsic MAT1 fragmentation to sustain hematopoietic CD34+ cell expansion while preventing granulopoiesis. Conversely, we mimicked MAT1 fragmentation in vitro and in a mouse model by overexpressing a fragmented 81-aa MAT1 polypeptide (pM9) that retains the domain for assembling CAK but cannot affix CAK to TFIIH-core. Our results showed that pM9 formed ΔCAK by competing with MAT1 for CAK assembly to mimic MAT1 fragmentation-depletion of CAK. This resulting ΔCAK acted as a dominant negative to inhibit the growth and metastasis of different leukemic myeloblasts, with or without RA resistance, by concurrently suppressing CAK and TFIIH kinase activities to inhibit cell cycle and gene transcription. These findings suggest that the intrinsically programmed MAT1 expression and fragmentation regulate granulopoiesis by inversely coordinating CAK and TFIIH activities, whereas pM9 shares a mechanistic resemblance with MAT1 fragmentation in suppressing myeloid leukemogenesis.
Brief Report: VGLL4 Is a Novel Regulator of Survival in Human Embryonic Stem Cells
Authors: Tajonar Adriana , Maehr René , Hu Guang , Sneddon Julie B. , Rivera-Feliciano José , Cohen Dena E. , Elledge Stephen J. , Melton Douglas A.
Published: June 2013

Human embryonic stem cells (hESCs) are maintained in a self-renewing state by an interconnected network of mechanisms that sustain pluripotency, promote proliferation and survival, and prevent differentiation. We sought to find novel genes that could contribute to one or more of these processes using a gain-of-function screen of a large collection of human open reading frames. We identified Vestigial-like 4 (VGLL4), a cotranscriptional regulator with no previously described function in hESCs, as a positive regulator of survival in hESCs. Specifically, VGLL4 overexpression in hESCs significantly decreases cell death in response to dissociation stress. Additionally, VGLL4 overexpression enhances hESC colony formation from single cells. These effects may be attributable, in part, to a decreased activity of initiator and effector caspases observed in the context of VGLL4 overexpression. Additionally, we show an interaction between VGLL4 and the Rho/Rock pathway, previously implicated in hESC survival. This study introduces a novel gain-of-function approach for studying hESC maintenance and presents VGLL4 as a previously undescribed regulator of this process. Stem Cells  2013;31:2833–2841
Stimulation of Somatic Cell Reprogramming by ERas-Akt-FoxO1 Signaling Axis
Authors: Yu Yong , Liang Dan , Tian Qing , Chen Xiaona , Jiang Bo , Chou Bin-Kuan , Hu Ping , Cheng Linzhao , Gao Ping , Li Jinsong , Wang Gang
Published: June 2013

Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) shares much similarity to the cancer initiation process, and the molecular mechanisms underlying both processes remain to be elucidated. Here, we report that a tumor- or embryonic stem cell-specific Ras gene ERas, which encodes a constitutively active form of GTPase, and its downstream Phosphoinositide-3 kinase/Akt signaling pathway are important facilitators for the somatic reprogramming process. We found that overexpression of ERas retrovirally enhanced mouse iPSC induction while ERas knockdown repressed it. Modulation of Akt signaling by genetic or chemical means greatly impacted the reprogramming efficiency. Forced expression of a constitutively active Akt1 gene could rescue the reduced efficiency resulting from ERas knockdown, and point-mutation analyses further revealed that ERas is tightly coupled with Akt signaling to enhance reprogramming. Mechanistically, the forkhead transcription factor FoxO1 can function as a barrier to the iPSC induction, and the inactivation of FoxO1 by Akt-dependent phosphorylation largely accounts for the enhancing effect of ERas-Akt signaling on reprogramming. Collectively, these results unravel the significance of the ERas-Akt-FoxO1 signaling axis in iPSC generation, suggesting a possibly shared molecular basis for both somatic reprogramming and cancer initiation. Stem Cells  2014;32:349–363
Chemerin neutralization blocks hematopoietic stem cell osteoclastogenesis
Authors: Muruganandan Shanmugam , Dranse Helen J. , Rourke Jillian L. , McMullen Nichole M. , Sinal Christopher J.
Published: June 2013

Bone is a dynamic tissue that is continuously remodeled through the action of formative osteoblasts and resorptive osteoclasts. Chemerin is a secreted protein that activates chemokine-like receptor 1 (CMKLR1), a G protein-coupled receptor expressed by various cell types including adipocytes, osteoblasts, mesenchymal stem cells (MSCs), and macrophages. Previously, we identified chemerin as a regulator of adipocyte and osteoblast differentiation of MSCs. Herein we examined the role of chemerin in Lin− Sca1+ c-kit+ CD34+ hematopoietic stem cell (HSC) osteoclastogenesis. We found that HSCs expressed both chemerin and CMKLR1 mRNA and secreted chemerin protein into the extracellular media. Neutralization of chemerin with a blocking antibody beginning prior to inducing osteoclast differentiation resulted in a near complete loss of osteoclastogenesis as evidenced by reduced marker gene expression and matrix resorption. This effect was conserved in an independent model of RAW264.7 cell osteoclastogenesis. Reintroduction of chemerin by reversal of neutralization rescued osteoclast differentiation indicating that chemerin signaling is essential to permit HSC differentiation into osteoclasts but following blockade the cells maintained the potential to differentiate into osteoclasts. Mechanistically, neutralization of chemerin blunted the early receptor activator of nuclear factor-kappa B ligand induction of nuclear factor of activated T-cells 2 (NFAT2), Fos, Itgb3, and Src associated with preosteoclast formation. Consistent with a central role for NFAT2, induction or activation of NFAT2 by forced expression or stimulation of intracellular calcium release rescued the impairment of HSC osteoclastogenesis caused by chemerin neutralization. Taken together, these data support a novel autocrine/paracrine role for chemerin in regulating osteoclast differentiation of HSCs through modulating intracellular calcium and NFAT2 expression/activation.
Concise review: Adult mesenchymal stromal cell therapy for inflammatory diseases: How well are we joining the dots?
Authors: Griffin Matthew D. , Elliman Stephen J. , Cahill Emer , English Karen , Ceredig Rhodri , Ritter Thomas
Published: June 2013

Mesenchymal stromal (stem) cells (MSCs) continue to be a strong area of focus for academic- and industry-based researchers who share the goal of expanding their therapeutic use for diverse inflammatory and immune-mediated diseases. Recently, there has been an accelerated rate of scientific publication, clinical trial activity, and commercialisation in the field. This has included the reporting of exciting new developments in four areas that will be of key importance to future successful use of MSC-based therapies in large numbers of patients: (a) fundamental biology of the primary cells in bone marrow and other tissues that give rise to MSCs in culture. (b) Mechanisms by which MSCs modulate immune and inflammatory responses in vivo. (c) Insights into MSC kinetics, safety, and efficacy in relevant animal disease models. (d) Isolation, definition, and clinical trial-based testing of human MSCs by biomedical companies and academic medical centers. Despite this progress, it remains unclear whether MSCs will enter mainstream therapeutic practice as a frequently used alternative to pharmacotherapy or surgical/radiological procedures in the foreseeable future. In this review, we summarize some of the most significant new developments for each of the four areas that contribute to the process of translating MSC research to the clinical arena. In the context of this recent progress, we discuss key challenges and specific knowledge gaps which, if not addressed in a coordinated fashion, may hinder the creation of robust “translational pipelines” for consolidating the status of MSC-based therapies.
Metabotropic glutamate receptor 2 and corticotrophin‐releasing factor receptor‐1 gene expression is differently regulated by BDNF in rat primary cortical neurons
Authors: Jørgensen Christinna V. , Klein Anders B. , EL‐Sayed Mona , Knudsen Gitte M. , Mikkelsen Jens D.
Published: June 2013

Brain‐derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We are particularly interested in the regulation of the 5‐hydroxytryptamine receptor 2A (5‐HT2AR). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin‐releasing factor receptor 1 (CRF‐R1). The effect of BDNF on gene expression for all these receptors, as well as a number of immediate‐early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF‐R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5‐HT2AR mRNA was seen. The effects were dose‐dependent with half‐maximal effective concentrations (EC50) around 1 ng/ml. After 24 h of incubation with BDNF, CRF‐R1 mRNA levels had returned to baseline levels, whereas mGluR2 mRNA levels remained low. A significant reduction of all three receptor transcripts was observed after neuronal depolarization produced by high potassium. This study emphasizes the role of BDNF as an important regulator of receptor compositions in the synapse and provides further evidence that BDNF directly regulates important drug targets involved in cognition and mood. Synapse 67:794–800, 2013.. © 2013 Wiley Periodicals, Inc.
Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta‐analysis
Authors: Voskamp B. J. , Fleurke‐Rozema H. , Oude‐Rengerink K. , Snijders R. J. M. , Bilardo C. M. , Mol B. W. J. , Pajkrt E.
Published: June 2013

Objective

To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid‐trimester anomaly scan.

Methods

We searched MEDLINE (1948–2012), EMBASE (1980–2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI.

Results

We identified three cohort studies and four case–control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case–control studies. Compared to fetuses with a three‐vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97–2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9–4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, –154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy.

Conclusion

In view of the non‐significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large‐scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work‐up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
The politics of climate change in China
Authors: Qi Ye , Wu Tong
Published: June 2013

This article reviews recent studies on the politics of climate change in China. We explain the evolution of policy‐making and implementation processes and mechanisms over the past two decades, and discuss how they have eventuated in contemporary trends and challenges. Within the unitary hierarchy of the Chinese political system, the central government is responsible for making major policies, and subnational and local governments are responsible for the implementation. The policy‐making process is characterized by a consensus building at the center, in contrast to the open public and partisan debate in Western democracies. Climate policy implementation has been based on a so‐called ‘target responsibility system’, which disaggregates targets amongst all levels of local governments and related enterprises. While this system has proven effective in achieving the national targets set by the central government, the high costs associated with it have been a source of concern. The key challenge in making and implementing climate policy is to balance economic growth and environmental protection. This challenge is of critical importance in central–local political interactions. Clean energy development has been proposed as a ‘win–win’ solution to help balance economic development and climate change mitigation, and to satisfy both central and local government prerogatives, but the sustainability of such a model is questioned when the global and domestic economy experience difficulties. The central government is trying to translate its consensus in climate change and green development into priorities for local governments through policy pilots and market instruments; the real results will soon be seen. WIREs Clim Change 2013, 4:301–313. doi: 10.1002/wcc.221

This article is categorized under:

The Carbon Economy and Climate Mitigation > Policies, Instruments, Lifestyles, Behavior

Policy and Governance > National Climate Change Policy
The politics of climate change in Germany: ambition versus lobby power
Authors: Michaelowa Axel
Published: June 2013

In 30 years of climate policy in Germany, a high level of declared ambition has coexisted with an eclectic mix of climate policy measures. Well‐organized lobbies were either exempt from policy instruments such as the energy tax or directly benefitted from them, as in the case of the renewable feed‐in tariff or windfall profits from free allocation of emissions allowances. As a result, German emissions mitigation is much more costly than it would have to be. Moreover, the challenges because of the imminent phase‐out of nuclear power are increasing due to failures in a number of relevant policy fields such as offshore wind, grid reinforcement, and carbon capture and storage (CCS). WIREs Clim Change 2013, 4:315–320. doi: 10.1002/wcc.224

This article is categorized under:

The Carbon Economy and Climate Mitigation > Policies, Instruments, Lifestyles, Behavior

Policy and Governance > National Climate Change Policy
Biometric face recognition: from classical statistics to future challenges
Authors: Givens Geof H. , Beveridge J. Ross , Lui Yui Man , Bolme David S. , Draper Bruce A. , Phillips P. Jonathon
Published: June 2013

Face recognition involves at least three major concepts from statistics: dimension reduction, feature extraction, and prediction. A selective review of algorithms, from seminal to state‐of‐the‐art, explores how these concepts persist as organizing principles in the field. Algorithms based directly upon classical statistical techniques include linear methods like principal component analysis and linear discriminant analysis. Nonlinear manifold methods, such as Laplacianfaces and Stiefel quotients, offer considerable performance improvements. Other noteworthy ideas include three‐dimensional morphable models, methods using local regions and/or alternative feature spaces (e.g., elastic bunch graph matching and local binary patterns) and sparse representation approaches. Opportunities for innovative statistical and collaborative research in face recognition are expanding in tandem with the growing complexity and diversity of applications.WIREs Comput Stat2013, 5:288–308. doi: 10.1002/wics.1262

This article is categorized under:

Applications of Computational Statistics > Defense and National Security

Software for Computational Statistics > Artificial Intelligence and Expert Systems

Applications of Computational Statistics > Signal and Image Processing and Coding
Specificity factors in cytoplasmic polyadenylation
Authors: Charlesworth Amanda , Meijer Hedda A. , de Moor Cornelia H.
Published: June 2013

Poly(A) tail elongation after export of an messenger RNA (mRNA) to the cytoplasm is called cytoplasmic polyadenylation. It was first discovered in oocytes and embryos, where it has roles in meiosis and development. In recent years, however, has been implicated in many other processes, including synaptic plasticity and mitosis. This review aims to introduce cytoplasmic polyadenylation with an emphasis on the factors and elements mediating this process for different mRNAs and in different animal species. We will discuss the RNA sequence elements mediating cytoplasmic polyadenylation in the 3′ untranslated regions of mRNAs, including the CPE, MBE, TCS, eCPE, and C‐CPE. In addition to describing the role of general polyadenylation factors, we discuss the specific RNA binding protein families associated with cytoplasmic polyadenylation elements, including CPEB (CPEB1, CPEB2, CPEB3, and CPEB4), Pumilio (PUM2), Musashi (MSI1, MSI2), zygote arrest (ZAR2), ELAV like proteins (ELAVL1, HuR), poly(C) binding proteins (PCBP2, αCP2, hnRNP‐E2), and Bicaudal C (BICC1). Some emerging themes in cytoplasmic polyadenylation will be highlighted. To facilitate understanding for those working in different organisms and fields, particularly those who are analyzing high throughput data, HUGO gene nomenclature for the human orthologs is used throughout. Where human orthologs have not been clearly identified, reference is made to protein families identified in man. WIREs RNA 2013, 4:437–461. doi: 10.1002/wrna.1171

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

Translation > Translation Regulation

RNA Processing > 3' End Processing
U6 RNA biogenesis and disease association
Authors: Mroczek Seweryn , Dziembowski Andrzej
Published: June 2013

U6 snRNA is one of five uridine‐rich noncoding RNAs that form the major spliceosome complex. Unlike other U‐snRNAs, it reveals many distinctive aspects of biogenesis such as transcription by RNA polymerase III, transcript nuclear retention and particular features of transcript ends: monomethylated 5′‐guanosine triphosphate as cap structure and a 2′,3′‐cyclic phosphate moiety (>P) at the 3′ termini. U6‐snRNA plays a central role in splicing and thus its transcription, maturation, snRNP formation, and recycling are essential for cellular homeostasis. U6 snRNA enters the splicing cycle as part of the tri‐U4/U6.U5snRNP complex, and after significant structural arrangements forms the catalytic site of the spliceosome together with U2 snRNA and Prp8. U6 snRNA also contributes to the splicing reaction by coordinating metal cations required for catalysis. Many human diseases are associated with altered splicing processes. Disruptions of the basal splicing machinery can be lethal or lead to severe diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, or retinitis pigmentosa. Recent studies have identified a new U6 snRNA biogenesis factor Usb1, the absence of which leads to poikiloderma with neutropenia (PN) (OMIM 604173), an autosomal recessive skin disease. Usb1 is an evolutionarily conserved 3′→5′ exoribonuclease that is responsible for removing 3′‐terminal uridines from U6 snRNA transcripts, which leads to the formation of a 2′,3′ cyclic phosphate moiety (>P). This maturation step is fundamental for U6 snRNP assembly and recycling. Usb1 represents the first example of a direct association between a spliceosomal U6 snRNA biogenesis factor and human genetic disease.WIREs RNA 2013, 4:581–592. doi: 10.1002/wrna.1181

This article is categorized under:

RNA Processing > 3' End Processing

RNA in Disease and Development > RNA in Disease