bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary supplement use and colorectal cancer risk: A systematic review and meta‐analyses of prospective cohort studies
Authors: Heine‐Bröring Renate C. , Winkels Renate M. , Renkema Jacoba M.S. , Kragt Lea , van Orten‐Luiten Anne‐Claire B. , Tigchelaar Ettje F. , Chan Doris S.M. , Norat Teresa , Kampman Ellen
Published: October 2014

Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta‐analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer‐reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. “Use‐no use”(U‐NU), “highest‐lowest”(H‐L) and “dose‐response”(DR) meta‐analyses were performed. Random‐effects models were used to estimate summary estimates. In total, 24 papers were included in the meta‐analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U‐NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U‐NU: RR = 0.86; 95% CI: 0.79,0.95; H‐L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta‐analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.
Chronic liver inflammation and hepatocellular carcinogenesis are independent of S100A9
Authors: De Ponti Aurora , Wiechert Lars , Stojanovic Ana , Longerich Thomas , Marhenke Silke , Hogg Nancy , Vogel Arndt , Cerwenka Adelheid , Schirmacher Peter , Hess Jochen , Angel Peter
Published: October 2014

The S100A8/A9 heterodimer (calprotectin) acts as a danger signal when secreted into the extracellular space during inflammation and tissue damage. It promotes proinflammatory responses and drives tumor development in different models of inflammation‐driven carcinogenesis. S100A8/A9 is strongly expressed in several human tumors, including hepatocellular carcinoma (HCC). Apart from this evidence, the role of calprotectin in hepatocyte transformation and tumor microenvironment is still unknown. The aim of this study was to define the function of S100A8/A9 in inflammation‐driven HCC. Mice lacking S100a9 were crossed with the Mdr2−/− model, a prototype of inflammation‐induced HCC formation. S100a9−/− Mdr2−/− (dKO) mice displayed no significant differences in tumor incidence or multiplicity compared to Mdr2−/− animals. Chronic liver inflammation, fibrosis and oval cell activation were not affected upon S100a9 deletion. Our data demonstrate that, although highly upregulated, calprotectin is dispensable in the onset and development of HCC, and in the maintenance of liver inflammation.
Are You Ready for Digital Currency?
Authors: Smith Antoinette , Weismann Miriam F.
Published: October 2014

Increasingly, companies and customers are beginning to hear, “We accept all major credit cards and Bitcoins.” Virtual or digital currency is a new financial “black box” product that has seeped into the retail market and is slowly becoming the currency of choice for nation states like Iceland. As the cash or treasury manager of your organization, are you ready to take on Bitcoin currency—or any virtual currency, for that matter?
New Strategies for “Trapped” Excess Cash
Authors: Le Guyader Louis P.
Published: October 2014

U.S. companies continue accumulating cash offshore, with liquidity balances now setting new record highs. This trend is about half a decade old. But the U.S. corporate tax code has not changed, with the effect that earnings are now taxed in the United States at one of the highest rates in the world. And companies bringing earnings home will still be hit by the U.S. foreign “repatriation tax.” From the shareholders' point of view, this means the cash is “trapped” offshore. New strategies and tactics are needed. What are they?© 2014 Wiley Periodicals, Inc.
Stockpiling Cash: How Much Is Enough?
Authors: Cole Cathy J.
Published: October 2014

We all know that companies have been stockpiling cash. But how much is enough? What is optimal? The author of this article reminds us that while the cash on U.S. companies' balance sheets may have risen in recent years as a precautionary reaction to the global financial crisis, the rise in cash holdings at U.S. companies is not just a recent phenomenon. And when addressing significant cash balances in management discussion and analysis (MD&A), companies must consider limitations on cash accessibility and changes or trends in liquidity that may be particularly relevant as the economy improves. Regarding the size of cash balances, recent studies in finance and accounting have developed models to predict optimal cash levels, which may be useful in assessing the levels of cash on company balance sheets.
Tax Refunds on Overstated Earnings: A Valuation Puzzle
Authors: Churyk Natalie Tatiana , Mantzke Katrina L. , Johnson James M. , Reinstein Alan
Published: October 2014

The number of financial statement restatements practically doubled from 1998 to 2002 (Huron Consulting Group, ). Approximately 37% of these restatements are related to revenue recognition, with most of these resulting in an original overstatement of earnings. From 2000 to 2009, the Securities and Exchange Commission (SEC), on average, issued 200 Accounting and Auditing Enforcement Releases (AAERs) each year (see SEC.gov). Most AAERs lead to restatements. While prior literature focused on the negative consequences to firms from reporting a restatement, the authors' study looks for a mitigating effect from reporting good news along with the bad.
PCAOB Proposes Significant Changes to Auditor's Reporting Model
Authors: Lawson Bradley P. , Schwartz William C.
Published: October 2014

The Public Company Accounting Oversight Board (PCAOB) recently proposed significant changes to the audit report. These changes would impact the financial reporting and auditing process for companies' management, audit committees, and auditors. The proposals require auditors to disclose company‐specific critical audit matters and expand their evaluation of other information outside the audited financial statements. Could this change the fundamental nature of the audit process and increase audit costs, as some suggest?
The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells
Authors: Alayev Anya , Berger Sara Malka , Kramer Melissa Y. , Schwartz Naomi S. , Holz Marina K.
Published: October 2014

Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) is a frequent event in breast cancer and current efforts are aimed at targeting the mTORC1 signaling pathway in combination with other targeted therapies. However, patients often develop drug resistance in part due to activation of the oncogenic Akt signaling and upregulation of autophagy, which protects cancer cells from apoptosis. In the present study we investigated the effects of combination therapy of rapamycin (an allosteric mTORC1 inhibitor) together with resveratrol (a phytoestrogen that inhibits autophagy). Our results show that combination of these drugs maintains inhibition of mTORC1 signaling, while preventing upregulation of Akt activation and autophagy, causing apoptosis. Additionally, this combination was effective in estrogen receptor positive and negative breast cancer cells, underscoring its versatility. J. Cell. Biochem. 116: 450–457, 2015. © 2014 Wiley Periodicals, Inc.
Regulation of Ribosomal Gene Expression in Cancer
Authors: Nguyen Le Xuan Truong , Raval Aparna , Garcia Jacqueline S. , Mitchell Beverly S.
Published: October 2014

The ability of a cell to undergo malignant transformation is both associated with and dependent on a concomitant increase in protein synthesis due to increased cell division rates and biosynthetic activities. Protein synthesis, in turn, depends upon the synthesis of ribosomes and thus ultimately on the transcription of ribosomal RNA by RNA polymerase I that occurs in the nucleolus. Enlargement of nucleoli has long been considered a hallmark of the malignant cell, but it is only recently that the rate of synthesis of rRNA in the nucleolus has been recognized as both a critical regulator of cellular proliferation and a potential target for therapeutic intervention. As might be expected, the factors regulating rRNA synthesis are both numerous and complex. It is the objective of this review to highlight recent advances in understanding how rRNA synthesis is perturbed in transformed mammalian cells and to consider the impact of these findings on the development of new approaches to the treatment of malignancies. In‐depth analysis of the process of rRNA transcription itself may be found in several recently published reviews (Drygin et al., 2010, Annu Rev Pharmacol Toxicol 50:131–156; Bywater et al., 2013,Cancer Cell 22: 51–65; Hein et al., 2013,Trends Mol Med 19:643–654). J. Cell. Physiol. 230: 1181–1188, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Liability impact of the hospitalist model of care
Authors: Schaffer Adam C. , Puopolo Ann Louise , Raman Supriya , Kachalia Allen
Published: October 2014

BACKGROUND

An increasingly large proportion of inpatient care is provided by hospitalists. The care discontinuities inherent to hospital medicine raise concerns about malpractice risk. However, little published data exist on the medical liability risks associated with care by hospitalists.

OBJECTIVE

We sought to determine the risks and outcomes of malpractice claims against hospitalists in internal medicine.

DESIGN

Retrospective observational analysis.

MEASUREMENTS

Using claims data from a liability insurer‐maintained database of over 52,000 malpractice claims, we measured the rates of malpractice claims against hospitalists compared to other physician specialties, types of allegations against hospitalists, contributing factors, and the severity of injury in and outcomes of these claims.

RESULTS

Hospitalists had a malpractice claims rate of 0.52 claims per 100 physician coverage years (PCYs), which was significantly lower than that of nonhospitalist internal medicine physicians (1.91 claims per 100 PCYs), emergency medicine physicians (3.50 claims per 100 PCYs), general surgeons (4.70 claims per 100 PCYs), and obstetricians‐gynecologists (5.56 claims per 100 PCYs) (P < 0.001 for all comparisons). The most common allegation types made against hospitalists were for errors in medical treatment (41.5%) and diagnosis (36.0%). The most common contributing factors underlying claims were deficiencies in clinical judgment (54.4%) and communication (36.4%). Of the claims made against hospitalists, 50.4% involved the death of the patient.

CONCLUSIONS

Despite fears of increased liability from the hospitalist model of care, hospitalists in internal medicine are subject to medical malpractice claims less frequently when compared to other internal medicine physicians and specialties. Journal of Hospital Medicine 2014;9:750–755. © 2014 Society of Hospital Medicine
Alternative role of HuD splicing variants in neuronal differentiation
Authors: Hayashi Satoru , Yano Masato , Igarashi Mana , Okano Hirotaka James , Okano Hideyuki
Published: October 2014

HuD is a neuronal RNA‐binding protein that plays an important role in neuronal differentiation of the nervous system. HuD has been reported to have three RNA recognition motifs (RRMs) and three splice variants (SVs) that differ in their amino acid sequences between RRM2 and RRM3. This study investigates whether these SVs have specific roles in neuronal differentiation. In primary neural epithelial cells under differentiating conditions, HuD splice variant 1 (HuD‐sv1), which is a general form, and HuD‐sv2 were expressed at all tested times, whereas HuD‐sv4 was transiently expressed at the beginning of differentiation, indicating that HuD‐sv4 might play a role compared different from that of HuD‐sv1. Indeed, HuD‐sv4 did not promote neuronal differentiation in epithelial cells, whereas HuD‐sv1 did promote neuronal differentiation. HuD‐sv4 overexpression showed less neurite‐inducing activity than HuD‐sv1 in mouse neuroblastoma N1E‐115 cells; however, HuD‐sv4 showed stronger growth‐arresting activity. HuD‐sv1 was localized only in the cytoplasm, whereas HuD‐sv4 was localized in both the cytoplasm and the nuclei. The Hu protein has been reported to be involved in translation and alternative splicing in the cytoplasm and nuclei, respectively. Consistent with this observation, HuD‐sv1 showed translational activity on p21, which plays a role in growth arrest and neuronal differentiation, whereas HuD‐sv4 did not. By contrast, HuD‐sv4 showed stronger pre‐mRNA splicing activity than did HuD‐sv1 on Clasp2, which participates in cell division. Therefore, HuD SVs might play a role in controlling the timing of proliferation/differentiation switching by controlling the translation and alternative splicing of target genes. © 2014 Wiley Periodicals, Inc.
Formulation, synthesis and characterization of boron phosphate (BPO4) compounds as raw materials to develop slow‐release boron fertilizers
Authors: Abat Margaret , Degryse Fien , Baird Roslyn , McLaughlin Michael J.
Published: October 2014

We investigated the use of boron phosphate (BPO4) as a slow‐release boron (B) source. Boron phosphate compounds were synthesized by mixing boric acid (H3BO3) and phosphoric acid (H3PO4) and heating at temperatures of 25 to 1000°C for 1 or 24 h. X‐ray diffraction (XRD) patterns and chemical analysis confirmed the formation of BPO4. The crystallinity of these compounds increased with increasing temperature and heating time. The compounds synthesized at 300°C or less were hygroscopic and clumped together, while those synthesized at 500 to 1000°C were non‐hygroscopic and free‐flowing. The solubility of these compounds was assessed at different pH and P concentrations, and compared to the solubility of ulexite and colemanite. The solubility of the BPO4 compounds decreased with increasing synthesis temperature and with decreasing pH. The solubility and the kinetics of B release from BPO4 compounds synthesized at 500 and 800°C were slower than for most commonly used B sources. Given their slow dissolution, the BPO4 compounds may have potential to continuously supply B to crops in environments where B leaching is a problem. The compounds synthesized at 500 and 800°C show potential for co‐granulation with macronutrient fertilizers such as mono‐ammonium phosphate to produce slow‐release B‐enriched granules.
Individual glass shard trace element analyses confirm that all known Toba tephra reported from India is from the c. 75‐ka Youngest Toba eruption
Authors: PEARCE NICHOLAS J. G. , WESTGATE JOHN A. , GATTI EMMA , PATTAN JINNAPPA N. , PARTHIBAN GOPAL , ACHYUTHAN HEMA
Published: October 2014

Uncertainty over the identity and age of Toba tephras across peninsular India persists, with radiometric age dates contradicting earlier compositional data, which have been used to identify this important stratigraphic marker as the Youngest Toba Tuff (YTT). To address this issue, new single glass shard analyses have been performed for samples from Morgaon and Bori (north‐western India), which have recently been dated at c. 800 ka. These, and indeed all Toba tephra samples thus far analysed from India, show the presence of four populations of glass shards (defined by their Ba/Y ratio), which uniquely identifies them as products of the c. 75‐ka Youngest Toba eruption. Confirmation that the YTT fingerprint is characteristic comes from new analyses of Oldest Toba Tuff (OTT) glass shards from five sites in the Indian Ocean. These are compositionally identical to Layer D from the ODP site 758 sediment core (c. 800 ka), and belong to a single, low‐Ba population, clearly different from YTT. These analyses show that there is essentially no reworked OTT material in the YTT eruption, and indicate unequivocally that all known Toba tephra occurrences in India belong to the c. 75‐ka Youngest Toba eruption.
Development of 8‐in. oxide‐TFT‐driven flexible AMOLED display using high‐performance red phosphorescent OLED
Authors: Nakajima Yoshiki , Nakata Mitsuru , Takei Tatsuya , Fukagawa Hirohiko , Motomura Genichi , Tsuji Hiroshi , Shimizu Takahisa , Fujisaki Yoshihide , Kurita Taiichiro , Yamamoto Toshihiro
Published: October 2014

An 8‐in. flexible active‐matrix organic light‐emitting diode (AMOLED) display driven by oxide thin‐film transistors (TFTs) has been developed. In‐Ga‐Zn‐O (IGZO)‐TFTs used as driving devices were fabricated directly on a plastic film at a low temperature below 200 °C. To form a SiOx layer for use as the gate insulator of the TFTs, direct current pulse sputtering was used for the deposition at a low temperature. The fabricated TFT shows a good transfer characteristic and enough carrier mobility to drive OLED displays with Video Graphic Array pixels. A solution‐processable photo‐sensitive polymer was also used as a passivation layer of the TFTs. Furthermore, a high‐performance phosphorescent OLED was developed as a red‐light‐emitting device. Both lower power consumption and longer lifetime were achieved in the OLED, which used an efficient energy transfer from the host material to the guest material in the emission layer. By assembling these technologies, a flexible AMOLED display was fabricated on the plastic film. We obtained a clear and uniform moving color image on the display.
A course on thin‐film transistor circuit design for modern displays
Authors: Guo Xiaojun , Wang Yanwei , Chen Li
Published: October 2014

A new subject‐specific course on thin‐film transistor (TFT) circuit design is introduced, covering related knowledge of display technologies, TFT device physics, processing, characterization, modeling and circuit design. A design project is required for students to deepen the understanding even more and get hands‐on design experience. This course can be an intense 1‐week course to offer a full training of design engineers in an organized way to meet the ever‐increasing needs in display industry for TFT circuit design specialists. It can also be organized in one semester for electrical engineering Master's and Ph.D. students.
Truly wearable display comprised of a flexible battery, flexible display panel, and flexible printed circuit
Authors: Tajima Ryota , Miwa Takuya , Oguni Teppei , Hitotsuyanagi Aya , Miyake Hiroyuki , Katagiri Haruki , Goto Yuugo , Saito Yumiko , Goto Junya , Kaneyasu Makoto , Hiroki Masaaki , Takahashi Minoru , Yamazaki Shunpei
Published: October 2014

In an effort to create a truly flexible and wearable display having a flexible battery as well as a flexible organic light‐emitting diode panel and a flexible printed circuit, a flexible lithium‐ion battery has been developed, and a prototype wrist‐wearable or arm‐wearable display has been fabricated. Owing to improvements in the internal structure and exterior of the lithium‐ion battery, no remarkable changes in charge and discharge curves and the internal state of the electrodes were observed even after conducting a 10,000‐cycle bending test. Therefore, this flexible lithium‐ion battery prototype demonstrated remarkable bending resistance. Thus, we succeeded in fabricating a truly flexible and wearable display comprised of a flexible organic light‐emitting diode panel, a flexible printed circuit, and a flexible battery.
On evolutionary equations with material laws containing fractional integrals
Authors: Picard Rainer , Trostorff Sascha , Waurick Marcus
Published: October 2014

A well‐posedness result for a time‐shift invariant class of evolutionary operator equations involving material laws with fractional time‐integrals of order α ϵ ]0, 1[ is considered. The fractional derivatives are defined via a function calculus for the (time‐)derivative established as a normal operator in a suitable L2 type space. Employing causality, we show that the fractional derivatives thus obtained coincide with the Riemann‐Liouville fractional derivative. We exemplify our results by applications to a fractional Fokker‐Planck equation, equations describing super‐diffusion and sub‐diffusion processes, and a Kelvin‐Voigt type model in fractional visco‐elasticity. Moreover, we elaborate a suitable perspective to deal with initial boundary value problems. Copyright © 2014 John Wiley & Sons, Ltd.
Analysis of fractional order differential coupled systems
Authors: Wang JinRong , Zhang Yuruo
Published: October 2014

In this paper, we investigate the existence of solutions to nonlinear fractional order differential coupled systemswith the classical nonlocal initial conditions.We introduce a useful vector norm, named β·B‐vector norm,which is not only a novelty but also provides another way to deal with a large number of problems not limit to integer and noninteger differential systems and singular integral systems. Copyright © 2014 John Wiley & Sons, Ltd.
Dynamical analysis of public health education on HIV/AIDS transmission
Authors: Ostadzad M.H. , Shahmorad S. , Erjaee G.H.
Published: October 2014

An Human Immunodeficiency Virus/Acquired Immuno‐Deficiency Syndrome (HIV/AIDS) epidemic model for sexual transmission with asymptomatic and symptomatic phase is proposed as a system of differential equations. The threshold and steady state for the model are determined and stabilities of disease free steady state is investigated. We use the model and study the effect of public health education on the spread of HIV/AIDS as a single‐strategy in HIV prevention. The education, including basic reproduction number
for the model with public health education, is compared with the basic reproduction number
for the HIV/AIDS in the absence of public health education. By comparing these two values, influence of public health education appears. According to property of
, threshold proportion of educated adolescents, education rate for susceptible individuals and education efficacy is obtained. Copyright © 2014 John Wiley & Sons, Ltd.
Stability and Hopf bifurcation analysis of immune response delayed HIV type 1 infection model with two target cells
Authors: Balasubramaniam P. , Prakash M. , Tamilalagan P.
Published: October 2014

This manuscript presents the HIV‐1 infection model along with cause of differentiation of cytotoxic T lymphocyte response, the total carrying capacity of CD4C+ T‐cells, logistic growth term, effect of combination of antiretroviral therapy and discrete type immune response delay. The possibility of existence of multiple equilibriums for the proposed model is analyzed. Asymptotic stability of the non‐delayed infection model is proved from the roots of characteristic equation which are obtained by employing the Jacobian matrix method. The existence of Hopf bifurcation due to immune activation delay is proved. The stability switching is studied by choosing immune activation delay as a bifurcation parameter. Utilizing normal formtheory and centermanifold , we derive the explicit formulae for determining the stability and direction of the periodic solutions bifurcating from Hopf bifurcations. Numerical simulations are executed to verify the derived analytical results. Copyright © 2014 John Wiley & Sons, Ltd.
All traveling wave exact solutions of three kinds of nonlinear evolution equations
Authors: Meng Fanning , Zhang Liming , Wu Yonghong , Yuan Wenjun
Published: October 2014

In this article, we employ the complex method to obtain all meromorphic exact solutions of complex Klein–Gordon (KG) equation, modified Korteweg‐de Vries (mKdV) equation, and the generalized Boussinesq (gB) equation at first, then find all exact solutions of the Equations KG, mKdV, and gB. The idea introduced in this paper can be applied to other nonlinear evolution equations. Our results show that all rational and simply periodic solutions are solitary wave solutions, the complex method is simpler than other methods, and there exist some rational solutions w2r,2(z) and simply periodic solutions w1s,2(z),w2s,1(z) in these equations such that they are not only new but also not degenerated successively by the elliptic function solutions. We have also given some computer simulations to illustrate our main results. Copyright © 2014 John Wiley & Sons, Ltd.
On the fractional Schrödinger problem with non‐symmetric potential
Authors: Yang Jing
Published: October 2014

We study the semilinear equation

urn:x-wiley:mma:media:mma3309:mma3309-math-0001
where 0 < s < 1,
, V(x) is a sufficiently smooth non‐symmetric potential with
, and ϵ > 0 is a small number. Letting U be the radial ground state of (−Δ)sU + U − Up=0 in
, we build solutions of the form

urn:x-wiley:mma:media:mma3309:mma3309-math-0005
for points ϑj,j = 1,⋯,m, using a Lyapunov–Schmidt variational reduction. Copyright © 2014 John Wiley & Sons, Ltd.
Global weak solutions for the Vlasov–Poisson system with a point charge
Authors: Chen Jing , Zhang Xianwen , Wei Jinbo
Published: October 2014

We study the dynamics of three‐dimensional Vlasov‐Poisson system in the presence of a point charge with attractive interaction. Compared to the repulsive interaction,we cannot get a priori conversation law. Nevertheless,we are able to obtain bound of kinetic energy by introducing a Lyapunov functional. Combining this result with the concept of Diperna‐Lions flow, we establish global existence of weak solutions for this system. Copyright © 2014 John Wiley & Sons, Ltd.
Sulforaphane suppresses cardiac hypertrophy by inhibiting GATA4/GATA6 expression and MAPK signaling pathways
Authors: Kee Hae Jin , Kim Gwi Ran , Kim In Kyeom , Jeong Myung Ho
Published: October 2014

Scope

Sulforaphane (SFN) is a naturally occurring isothiocynate compound found in cruciferous vegetables. Here, we report the effect of SFN on cardiac hypertrophy and propose an underlying mechanism.

Methods and results

SFN suppresses cardiomyocyte hypertrophy induced by hypertrophic stimuli in vitro and in vivo. SFN suppresses the expression of fetal genes, including atrial natriuretic peptide, brain natriuretic peptide, and beta myosin heavy chain. We used an siRNA technique and atrial natriuretic peptide promoter with mutated GATA binding sites to demonstrate that SFN mediates cardiac hypertrophy by modulating transcription factors GATA4/6.

Conclusion

These results suggest that SFN has the potential to prevent cardiac hypertrophy by downregulating GATA4/6 and mitogen‐activated protein kinase signaling pathways.
Chiral discrimination of secondary alcohols and carboxylic acids by NMR spectroscopy
Authors: Pal Indrani , Chaudhari Sachin R. , Suryaprakash Nagaraja Rao
Published: October 2014

The manuscript reports two novel ternary ion‐pair complexes, which serve as chiral solvating agents, for enantiodiscrimination of secondary alcohols and carboxylic acids. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4‐dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP and a carboxylic acid. The designed protocols also permit accurate measurement of enantiomeric composition. Copyright © 2014 John Wiley & Sons, Ltd.
Multiparametric MRI reveals dynamic changes in molecular signatures of injured spinal cord in monkeys
Authors: Wang Feng , Qi Hui‐Xin , Zu Zhongliang , Mishra Arabinda , Tang Chaohui , Gore John C. , Chen Li Min
Published: October 2014

Purpose

To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multiparametric MRI methods.

Methods

Quantitative MRI imaging including diffusion tensor imaging, magnetization transfer (MT), and chemical exchange saturation transfer (CEST) were conducted in anesthetized squirrel monkeys at 9.4T. The structural, cellular, and molecular features of the spinal cord were examined before and at different time points after a dorsal column lesion in each monkey.

Results

Images with MT contrast enhanced visualization of the gray and white matter boundaries and the lesion and permitted differentiation of core and rim compartments within an abnormal volume (AV). In the early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient, decreased fractional anisotropy, decreased MT ratio, decreased nuclear Overhauser effect, and large CEST effects. Over time, cellular density and fiber density increased, whereas amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst.

Conclusion

Multiparametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury. Magn Reson Med 74:1125–1137, 2015. © 2014 Wiley Periodicals, Inc.
Generalized Robin–Neumann explicit coupling schemes for incompressible fluid‐structure interaction: Stability analysis and numerics
Authors: Fernández Miguel A. , Mullaert Jimmy , Vidrascu Marina
Published: October 2014

We introduce a new class of explicit coupling schemes for the numerical solution of fluid‐structure interaction problems involving a viscous incompressible fluid and an elastic structure. These methods generalize the arguments reported in [Comput. Methods Appl. Mech. Engrg., 267:566–593, 2013, Numer. Math., 123(1):21–65, 2013] to the case of the coupling with thick‐walled structures. The basic idea lies in the derivation of an intrinsic interface Robin consistency at the space semi‐discrete level, using a lumped‐mass approximation in the structure. The fluid–solid splitting is then performed through appropriate extrapolations of the solid velocity and stress on the interface. Based on these methods, a new, parameter‐free, Robin–Neumann iterative procedure is also proposed for the partitioned solution of implicit coupling. A priori energy estimates, guaranteeing the stability of the schemes and the convergence of the iterative procedure, are established within a representative linear setting. The accuracy and performance of the methods are illustrated in several numerical examples. Copyright © 2014 John Wiley & Sons, Ltd.
Quantitative phosphoproteomics of Alzheimer's disease reveals cross‐talk between kinases and small heat shock proteins
Authors: Dammer Eric B. , Lee Andrew K. , Duong Duc M. , Gearing Marla , Lah James J. , Levey Allan I. , Seyfried Nicholas T.
Published: October 2014

Abnormal phosphorylation contributes to the formation of neurofibrillary tangles in Alzheimer's disease (AD), but may play other signaling roles during AD pathogenesis. In this study, we employed IMAC followed by LC‐MS/MS to identify phosphopeptides from eight individual AD and eight age‐matched control postmortem human brain tissues. Using this approach, we identified 5569 phosphopeptides in frontal cortex across all 16 cases in which phosphopeptides represented 80% of all peptide spectral counts collected following IMAC enrichment. Marker selection identified 253 significantly altered phosphopeptides by precursor intensity, changed by at least 1.75‐fold relative to controls, with an empirical false discovery rate below 7%. Approximately 21% of all significantly altered phosphopeptides in AD tissue were derived from tau. Of the other 142 proteins hyperphosphorylated in AD, membrane, synapse, cell junction, and alternatively spliced proteins were overrepresented. Of these, we validated differential phosphorylation of HSP 27 (HSPB1) and crystallin‐alpha‐B (CRYAB) as hyperphosphorylated by Western blotting. We further identified a network of phosphorylated kinases, which coenriched with phosphorylated small HSPs. This supports a hypothesis that a number of kinases are regulating and/or regulated by the small HSP folding network.
Directional Interactions of α‐Particles with FOX‐7. A DFT Study
Authors: Türker Lemi
Published: October 2014

FOX‐7 is exposed to the effects of α‐particles from selected directions of approach. Various energies and properties of these composite FOX‐7 systems (FOX‐7+α‐particle) are obtained. The effect of α‐particles on FOX‐7 is drastic. The CC double bond turns into a single bond and one of the CNO2 bonds highly elongates. The approach from the side of amino groups results more stable composite system compared to the approach from the side of nitro groups.
Structural insight into the transmembrane segments 3 and 4 of the hERG potassium channel
Authors: Li Qingxin , Wong Ying Lei , Ng Hui Qi , Gayen Shovanlal , Kang CongBao
Published: October 2014

The hERG (human ether‐a‐go‐go related gene) potassium channel is a voltage‐gated potassium channel containing an N‐terminal domain, a voltage‐sensor domain, a pore domain and a C‐terminal domain. The transmembrane segment 4 (S4) is important for sensing changes of membrane potentials through positively charge residues. A construct containing partial S2–S3 linker, S3, S4 and the S4–S5 linker of the hERG channel was purified into detergent micelles. This construct exhibits good quality NMR spectrum when it was purified in lyso‐myristoyl phosphatidylglycerol (LMPG) micelles. Structural study showed that S3 contains two short helices with a negatively charged surface. The S4 and S4–S5 linker adopt helical structures. The six positively charged residues in S4 localize at different sides, suggesting that they may have different functions in channel gating. Relaxation studies indicated that S3 is more flexible than S4. The boundaries of S3–S4 and S4–S4–S5 linker were identified. Our results provided structural information of the S3 and S4, which will be helpful to understand their roles in channel gating. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Improving Cu2ZnSnS4 (CZTS) solar cell performance by an ultrathin ZnO intermediate layer between CZTS absorber and Mo back contact
Authors: Liu Xiaolei , Cui Hongtao , Li Wei , Song Ning , Liu Fangyang , Conibeer Gavin , Hao Xiaojing
Published: October 2014

The effects of an ultrathin ZnO intermediate layer deposited at the CZTS/Mo interface on CZTS solar cell performance have been investigated in this work. The ZnO layer inhibits the generation of MoS2 layer and the formation of voids in the CZTS absorber. Consequently, the incorporation of this layer reduces the series resistance and increases the shunt resistance, which boosts photovoltaic conversion efficiency from 1.13% to 4.3%. (© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Morphological Awareness in Vocabulary Acquisition Among Chinese‐Speaking Children: Testing Partial Mediation via Lexical Inference Ability
Authors: Zhang Haomin (Stanley)
Published: October 2014

The goal of this study was to investigate the effect of Chinese‐specific morphological awareness on vocabulary acquisition among young Chinese‐speaking students. The participants were 288 Chinese‐speaking second graders from three different cities in China. Multiple regression analysis and mediation analysis were used to uncover the mediated and unmediated effects of morphological awareness on reading vocabulary knowledge. Results showed that both morphological awareness and lexical inference ability significantly contributed to reading vocabulary knowledge after each factor was controlled for. The ability to extract sublexical morphological information (in the form of derivational awareness and compound awareness) significantly predicted the students' reading vocabulary. More importantly, the study revealed that morphological awareness made a significant indirect contribution to reading vocabulary via lexical inference ability. Findings suggest that morphological awareness enhances young Chinese students' reading vocabulary acquisition by the partial mediation of their lexical inference ability.
The height of random k‐trees and related branching processes
Authors: Cooper Colin , Frieze Alan , Uehara Ryuhei
Published: October 2014

We consider the height of random k‐trees and k‐Apollonian networks. These random graphs are not really trees, but instead have a tree‐like structure. The height will be the maximum distance of a vertex from the root. We show that w.h.p. the height of random k‐trees and k‐Apollonian networks is asymptotic to c log t, where t is the number of vertices, and c = c(k) is given as the solution to a transcendental equation. The equations are slightly different for the two types of process. In the limit as k →∞ the height of both processes is asymptotic to . © 2014 Wiley Periodicals, Inc. Random Struct. Alg., 45, 675–702, 2014
P2X7 Receptors Mediate Innate Phagocytosis by Human Neural Precursor Cells and Neuroblasts
Authors: Lovelace Michael D. , Gu Ben J. , Eamegdool Steven S. , Weible Michael W. , Wiley James S. , Allen David G. , Chan-Ling Tailoi
Published: October 2014

During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68+ microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin+ (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7highDCXlow hNPCs and P2X7highDCXhigh neuroblasts, derived from primary cultures of human fetal telencephalon, phagocytosed targets including latex beads, apoptotic ReNcells, and apoptotic hNPC/neuroblasts. Pretreatment of neuroblasts and hNPCs with 1 mM adenosine triphosphate (ATP), 100 µM OxATP (P2X7 antagonist), or siRNA knockdown of P2X7 inhibited phagocytosis of these targets. Our results show that P2X7 functions as a scavenger receptor under serum-free conditions resembling those in early neurogenesis. This is the first demonstration that hNPCs and neuroblasts may participate in clearance of apoptotic corpses during pre target-dependent neurogenesis and mediate phagocytosis using P2X7 as a scavenger receptor. Stem Cells  2015;33:526–541
Functional Regulation of Adipose-Derived Stem Cells by PDGF-D
Authors: Hye Kim Ji , Gyu Park Sang , Kim Wang-Kyun , Song Sun U. , Sung Jong-Hyuk
Published: October 2014

Platelet-derived growth factor-D (PDGF-D) was recently identified, and acts as potent mitogen for mesenchymal cells. PDGF-D also induces cellular transformation and promotes tumor growth. However, the functional role of PDGF-D in adipose-derived stem cells (ASCs) has not been identified. Therefore, we primarily investigated the autocrine and paracrine roles of PDGF-D in this study. Furthermore, we identified the signaling pathways and the molecular mechanisms involved in PDGF-D-induced stimulation of ASCs. It is of interest that PDGF-B is not expressed, but PDGF-D and PDGF receptor-β are expressed in ASCs. PDGF-D showed the strongest mitogenic effect on ASCs, and PDGF-D regulates the proliferation and migration of ASCs through the PI3K/Akt pathways. PDGF-D also increases the proliferation and migration of ASCs through generation of mitochondrial reactive oxygen species (mtROS) and mitochondrial fission. mtROS generation and fission were mediated by p66Shc phosphorylation, and BCL2-related protein A1 and Serpine peptidase inhibitor, clade E, member 1 mediated the proliferation and migration of ASCs. In addition, PDGF-D upregulated the mRNA expression of diverse growth factors such as vascular endothelial growth factor A, fibroblast growth factor 1 (FGF1), FGF5, leukemia inhibitory factor, inhibin, beta A, interleukin 11, and heparin-binding EGF-like growth factor. Therefore, the preconditioning of PDGF-D enhanced the hair-regenerative potential of ASCs. PDGF-D-induced growth factor expression was attenuated by a pharmacological inhibitor of mitogen-activated protein kinase pathway. In summary, PDGF-D is highly expressed by ASCs, where it acts as a potent mitogenic factor. PDGF-D also upregulates growth factor expression in ASCs. Therefore, PDGF-D can be considered a novel ASC stimulator, and used as a preconditioning agent before ASC transplantation. Stem Cells  2015;33:542–556
Human Mesenchymal Stromal Cells Attenuate Graft-Versus-Host Disease and Maintain Graft-Versus-Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Authors: Auletta Jeffery J. , Eid Saada K. , Wuttisarnwattana Patiwet , Silva Ines , Metheny Leland , Keller Matthew D. , Guardia-Wolff Rocio , Liu Chen , Wang Fangjing , Bowen Theodore , Lee Zhenghong , Solchaga Luis A. , Ganguly Sudipto , Tyler Megan , Wilson David L. , Cooke Kenneth R.
Published: October 2014

We sought to define the effects and underlying mechanisms of human, marrow-derived mesenchymal stromal cells (hMSCs) on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity. Irradiated B6D2F1 mice given C57BL/6 BM and splenic T cells and treated with hMSCs had reduced systemic GvHD, donor T-cell expansion, and serum TNFα and IFNγ levels. Bioluminescence imaging demonstrated that hMSCs redistributed from lungs to abdominal organs within 72 hours, and target tissues harvested from hMSC-treated allogeneic BMT (alloBMT) mice had less GvHD than untreated controls. Cryoimaging more precisely revealed that hMSCs preferentially distributed to splenic marginal zones and regulated T-cell expansion in the white pulp. Importantly, hMSCs had no effect on in vitro cytotoxic T-cell activity and preserved potent GvL effects in vivo. Mixed leukocyte cultures containing hMSCs exhibited decreased T-cell proliferation, reduced TNFα, IFNγ, and IL-10 but increased PGE2 levels. Indomethacin and E-prostanoid 2 (EP2) receptor antagonisms both reversed while EP2 agonism restored hMSC-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following alloBMT abrogated the protective effects of hMSCs. Together, our data show that hMSCs preserve GvL activity and attenuate GvHD and reveal that hMSC biodistribute to secondary lymphoid organs wherein they attenuate alloreactive T-cell proliferation likely through PGE2 induction. Stem Cells  2015;33:601–614
Comparative FAIRE-seq Analysis Reveals Distinguishing Features of the Chromatin Structure of Ground State- and Primed-Pluripotent Cells
Authors: Murtha Matthew , Strino Francesco , Tokcaer-Keskin Zeynep , Sumru Bayin N. , Shalabi Doaa , Xi Xiangmei , Kluger Yuval , Dailey Lisa
Published: October 2014

Both pluripotent embryonic stem cells (ESCs), established from preimplantation murine blastocysts, and epiblast stem cells (EpiSCs), established from postimplantation embryos, can self-renew in culture or differentiate into each of the primary germ layers. While the core transcription factors (TFs) OCT4, SOX2, and NANOG are expressed in both cell types, the gene expression profiles and other features suggest that ESCs and EpiSCs reflect distinct developmental maturation stages of the epiblast in vivo. Accordingly, “naïve” or “ground state” ESCs resemble cells of the inner cell mass, whereas “primed” EpiSCs resemble cells of the postimplantation egg cylinder. To gain insight into the relationship between naïve and primed pluripotent cells, and of each of these pluripotent states to that of nonpluripotent cells, we have used FAIRE-seq to generate a comparative atlas of the accessible chromatin regions within ESCs, EpiSCs, multipotent neural stem cells, and mouse embryonic fibroblasts. We find a distinction between the accessible chromatin patterns of pluripotent and somatic cells that is consistent with the highly related phenotype of ESCs and EpiSCs. However, by defining cell-specific and shared regions of open chromatin, and integrating these data with published gene expression and ChIP analyses, we also illustrate unique features of the chromatin of naïve and primed cells. Functional studies suggest that multiple stage-specific enhancers regulate ESC- or EpiSC-specific gene expression, and implicate auxiliary TFs as important modulators for stage-specific activation by the core TFs. Together these observations provide insights into the chromatin structure dynamics accompanying transitions between these pluripotent states. Stem Cells  2015;33:378–391
Pwp1 Is Required for the Differentiation Potential of Mouse Embryonic Stem Cells Through Regulating Stat3 Signaling
Authors: Shen Junwei , Jia Wenwen , Yu Yangyang , Chen Jie , Cao Xinkai , Du Yanhua , Zhang Xiaobai , Zhu Songcheng , Chen Wen , Xi Jiajie , Wei Tingyi , Wang Guiying , Yuan Detian , Duan Tao , Jiang Cizhong , Kang Jiuhong
Published: October 2014

Leukemia inhibitory factor/Stat3 signaling is critical for maintaining the self-renewal and differentiation potential of mouse embryonic stem cells (mESCs). However, the upstream effectors of this pathway have not been clearly defined. Here, we show that periodic tryptophan protein 1 (Pwp1), a WD-40 repeat-containing protein associated with histone H4 modification, is required for the exit of mESCs from the pluripotent state into all lineages. Knockdown (KD) of Pwp1 does not affect mESC proliferation, self-renewal, or apoptosis. However, KD of Pwp1 impairs the differentiation potential of mESCs both in vitro and in vivo. PWP1 chromatin immunoprecipitation-seq results revealed that the PWP1-occupied regions were marked with significant levels of H4K20me3. Moreover, Pwp1 binds to sites in the upstream region of Stat3. KD of Pwp1 decreases the level of H4K20me3 in the upstream region of Stat3 gene and upregulates the expression of Stat3. Furthermore, Pwp1 KD mESCs recover their differentiation potential through suppressing the expression of Stat3 or inhibiting the tyrosine phosphorylation of STAT3. Together, our results suggest that Pwp1 plays important roles in the differentiation potential of mESCs. Stem Cells  2015;33:661–673