bluuebunny/crossref_metadata_2025 huggingface dataset:
TAT‐modified mixed micelles as biodegradable targeting and delivering system for cancer therapeutics
Authors: Li Xiaoyuan , Wang Mingzhe , Liu Changbai , Jing Xiabin , Huang Yubin
Published: July 2013

A mixed micellar system of novel function was designed and synthesized by co‐assembling TAT (cell penetrating peptide)‐modified poly (ethylene glycol)‐poly(l‐lactide) (PEG‐PLA) copolymer with the drug‐conjugated poly(ethylene glycol)‐b‐poly(l‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylene carbonate) (mPEG‐b‐P(LA‐co‐MCC)) copolymer. UV‐Vis, Matrix‐assisted laser desorption/ionization time‐of‐flight, and XPS were used to ensure the successful modification of the copolymers with TAT and anti‐tumor drugs. The size of spherical nanomicelles increased from 50 to 60 nm as of empty polymeric micelles to 100–150 nm as of drug‐loaded ones, determined by dynamic light scattering and TEM. Daunorubicin was selected as model drug for in vitro evaluations on different cell lines. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay clearly indicated an improved cell growth inhibition of the TAT‐modified mixed micelles. While green fluorescent protein was used as a marker for the mixed micelle, small amount of DMSO was necessary to enhance the accumulation of the mixed micelles in cell lines Caski. Mediated by TAT, mixed micelles containing Apoptin (a tumor‐specific apoptosis drug) showed higher level of tumor cell internalization and growth inhibition than that of mixed micelles without TAT modification. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4598–4607, 2013
Effect of processing conditions on physical properties of 3‐aminophenoxyphthalonitrile/epoxy laminates
Authors: Guo Heng , Chen Zhiran , Liu Xiaobo
Published: July 2013

To develop high performances of polymer composite laminates, differential scanning calorimetry and dynamic rheological analysis studies were conducted to show curing behaviors of 3‐aminophenoxyphthalonitrile/epoxy resin (3‐APN/EP) matrix and define cure parameters of manufacturing processes. Glass fiber reinforced 3‐APN/EP (GF/3‐APN/EP) composite laminates were successfully prepared through different processing conditions with three parameters such as pressures, temperatures, and time. Based on flexure tests, dynamic mechanical analysis, thermal gravimetric analysis, and scanning electron microscope, the complementary catalytic effect of the three processing parameters is investigated by studying mechanical behavior, thermomechanical behavior, thermal behavior, and fracture morphology of GF/3‐APN/EP laminates. The 50/50 GF/3‐APN/EP laminates showed a significant improvement in flexural strength, glass transition temperature (Tg), and thermal stability with favorable processing parameters. It was also found that the Tg and thermal stability were significantly improved by the postheated treatment method. The effect of manufacturing process provides a new and simple route for the polymer–matrix composites application, which indicates that the composites can be manufactured at low temperatures. But, they can be used in a high temperature environment. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39746.
Phase I, Randomized, Double‐Blind, Placebo‐Controlled, Multiple Intravenous, Dose‐Ascending Study of Sirukumab in Cutaneous or Systemic Lupus Erythematosus
Authors: Szepietowski Jacek C. , Nilganuwong Surasak , Wozniacka Anna , Kuhn Annegret , Nyberg Filippa , van Vollenhoven Ronald F. , Bengtsson Anders A. , Reich Adam , de Vries Dick E. , van Hartingsveldt Bart , Robinson Donald W. , Gordon Robert , Hsu Benjamin
Published: July 2013

Objective

We undertook a 2‐part, phase I, double‐blind, placebo‐controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab, a human anti–interleukin‐6 monoclonal antibody, in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE).

Methods

In part A, patients with histologically confirmed CLE were randomized to 4 infusions of placebo or 1, 4, or 10 mg/kg sirukumab every 2 weeks. In part B, SLE patients diagnosed according to American College of Rheumatology criteria with a score of 5–12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index were randomized to 4 infusions of placebo or 10 mg/kg sirukumab every 2 weeks.

Results

We treated 31 CLE patients (23 with sirukumab, 8 with placebo) and 15 SLE patients (10 with sirukumab, 5 with placebo). Adverse events (AEs) occurred more often with sirukumab than placebo in CLE patients (91% versus 63%) and in SLE patients (90% versus 80%). Sirukumab led to sustained, dose‐independent decreases in white blood cell counts, absolute neutrophil counts (neutropenia), and platelet counts (thrombocytopenia) and to minor elevations in total cholesterol levels. The majority of infections were mild respiratory infections. which were reported similarly across CLE cohorts but more often in sirukumab‐treated than in placebo‐treated SLE patients. Two serious AEs of infection occurred (pneumonia in the 10 mg/kg–treated group and iatrogenic wound infection in the 4 mg/kg–treated group). Sirukumab showed linear pharmacokinetics in CLE patients. Systemic exposure and half‐life were comparable between CLE and SLE patients. No patient developed antibodies to sirukumab through 22 weeks. C‐reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14.

Conclusion

Treatment with intravenous sirukumab infusions was generally well tolerated in both CLE and SLE patients with mild, stable, active disease. Sirukumab demonstrated linear pharmacokinetics over the dose range studied and comparable systemic exposure and half‐life in CLE and SLE patients.
Comparative effects of 1α‐hydroxyvitamin D3 and 1,25‐dihydroxyvitamin D3 on transporters and enzymes in fxr(+/+) and fxr(‐/‐) mice
Authors: Chow Edwin C.Y. , Durk Matthew R. , Maeng Han‐Joo , Pang K. Sandy
Published: July 2013

Previous studies have shown that 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3] treatment in mice resulted in induction of intestinal and renal Cyp24a1 and Trpv6 expression, increased hepatic Cyp7a1 expression and activity, as well as higher renal Mdr1/P‐gp expression. The present study compared the equimolar efficacies of 1α‐hydroxyvitamin D3 [1α(OH)D3] (6 nmol/kg i.p. q2d × 4), a lipophilic precursor with a longer plasma half‐life that is converted to 1,25(OH)2D3, and 1,25(OH)2D3 on vitamin D receptor (VDR) target genes. To clarify whether changes in VDR genes was due to VDR and not secondary, farnesoid X receptor (FXR)‐directed effects, namely, lower Cyp7a1 expression in rat liver due to increased bile acid absorption, wildtype [fxr(+/+)] and FXR knockout [fxr(‐/‐)] mice were used to distinguish between VDR and FXR effects. With the exception that hepatic Sult2a1 mRNA was increased equally well by 1α(OH)D3 and 1,25(OH)2D3, 1α(OH)D3 treatment led to higher increases in hepatic Cyp7a1, renal Cyp24a1, VDR, Mdr1 and Mrp4, and intestinal Cyp24a1 and Trpv6 mRNA expression in both fxr(+/+) and fxr(‐/‐) mice compared to 1,25(OH)2D3 treatment. A similar induction in protein expression and microsomal activity of hepatic Cyp7a1 and renal P‐gp and Mrp4 protein expression was noted for both compounds. A higher intestinal induction of Trpv6 was observed, resulting in greater hypercalcemic effect following 1α(OH)D3 treatment. The higher activity of 1α(OH)D3 was explained by its rapid conversion to 1,25(OH)2D3 in tissue sites, furnishing higher plasma and tissue 1,25(OH)2D3 levels compared to following 1,25(OH)2D3‐treatment. In conclusion, 1α(OH)D3 exerts a greater effect on VDR gene induction than equimolar doses of 1,25(OH)2D3 in mice. Copyright © 2013 John Wiley & Sons, Ltd.
Ultrasound imaging in research and clinical medicine
Authors: Schellpfeffer Michael A.
Published: July 2013

The use of ultrasound imaging in clinical obstetrics continues to grow at an almost exponential rate. Ultrasound imaging in developmental biology has only begun to be used to enhance the traditional methodologies to study the developing embryo/fetus. The various modalities of ultrasound imaging are reviewed as they apply to current uses in clinical obstetrics and developmental biologic research. New modalities are also discussed in both clinical obstetrics and developmental biologic research as well as the current limitations of ultrasound imaging faced in both of these fields. Birth Defects Research (Part C) 99:83–92, 2013. © 2013 Wiley Periodicals, Inc.
Cyclotide discovery in Gentianales revisited—identification and characterization of cyclic cystine‐knot peptides and their phylogenetic distribution in Rubiaceae plants
Authors: Koehbach Johannes , Attah Alfred F. , Berger Andreas , Hellinger Roland , Kutchan Toni M. , Carpenter Eric J. , Rolf Megan , Sonibare Mubo A. , Moody Jones O. , Wong Gane Ka‐Shu , Dessein Steven , Greger Harald , Gruber Christian W.
Published: July 2013

Cyclotides are a unique class of ribosomally synthesized cysteine‐rich miniproteins characterized by a head‐to‐tail cyclized backbone and three conserved disulfide‐bonds in a knotted arrangement. Originally they were discovered in the coffee‐family plant Oldenlandia affinis (Rubiaceae) and have since been identified in several species of the violet, cucurbit, pea, potato, and grass families. However, the identification of novel cyclotide‐containing plant species still is a major challenge due to the lack of a rapid and accurate analytical workflow in particular for large sampling numbers. As a consequence, their phylogeny in the plant kingdom remains unclear. To gain further insight into the distribution and evolution of plant cyclotides, we analyzed ∼300 species of >40 different families, with special emphasis on plants from the order Gentianales. For this purpose, we have developed a refined screening methodology combining chemical analysis of plant extracts and bioinformatic analysis of transcript databases. Using mass spectrometry and transcriptome‐mining, we identified nine novel cyclotide‐containing species and their related cyclotide precursor genes in the tribe Palicoureeae. The characterization of novel peptide sequences underlines the high variability and plasticity of the cyclotide framework, and a comparison of novel precursor proteins from Carapichea ipecacuanha illustrated their typical cyclotide gene architectures. Phylogenetic analysis of their distribution within the Psychotria alliance revealed cyclotides to be restricted to Palicourea, Margaritopsis, Notopleura, Carapichea, Chassalia, and Geophila. In line with previous reports, our findings confirm cyclotides to be one of the largest peptide families within the plant kingdom and suggest that their total number may exceed tens of thousands. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 438–452, 2013.
Molecular Rotors of Coronene in Charge‐Transfer Solids
Authors: Yoshida Yukihiro , Shimizu Yasuhiro , Yajima Takeshi , Maruta Goro , Takeda Sadamu , Nakano Yoshiaki , Hiramatsu Takaaki , Kageyama Hiroshi , Yamochi Hideki , Saito Gunzi
Published: July 2013

Ten types of neutral charge transfer (CT) complexes of coronene (electron donor; D) were obtained with various electron acceptors (A). In addition to the reported 7,7,8,8‐tetracyanoquinodimethane (TCNQ) complex of 1:1 stoichiometry with a DA‐type alternating π column, TCNQ also afforded a 3:1 complex, in which a face‐to‐face dimer of parallel coronenes (Cor‐As) is sandwiched between TCNQs to construct a DDA‐type alternating π column flanked by another coronene (Cor‐B). Whereas solid‐state 2H NMR spectra of the 1:1 TCNQ complex formed with deuterated coronene confirmed the single in‐plane 6‐fold flipping motion of the coronenes, two unsynchronized motions were confirmed for the 3:1 TCNQ complex, which is consistent with a crystallographic study. Neutral [Ni(mnt)2] (mnt: maleonitriledithiolate) as an electron acceptor afforded a 5:2 complex with a DDA‐type alternating π column flanked by another coronene, similar to the 3:1 TCNQ complex. The fact that the Cor‐As in the [Ni(mnt)2] complex arrange in a non‐parallel fashion must cause the fast in‐plane rotation of Cor‐A relative to that of Cor‐B. This is in sharp contrast to the 3:1 TCNQ complex, in which the dimer of parallel Cor‐As shows inter‐column interactions with neighboring Cor‐As. The solid‐state 1H NMR signal of the [Ni(mnt)2] complex suddenly broadens at temperatures below approximately 60 K, indicating that the in‐plane rotation of the coronenes undergoes down to approximately 60 K; the rotational rate reaches the gigahertz regime at room temperature. Rotational barriers of these CT complexes, as estimated from variable‐temperature spin–lattice relaxation time (T1) experiments, are significantly lower than that of pristine coronene. The investigated structure–property relationships indicate that the complexation not only facilitates the molecular rotation of coronenes but also provides a new solid‐state rotor system that involves unsynchronized plural rotators.
Enantiomer‐Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)
Authors: Connors Kristin A. , Du Bowen , Fitzsimmons Patrick N. , Chambliss C. Kevin , Nichols John W. , Brooks Bryan W.
Published: July 2013

The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well‐studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). No biotransformation was observed forrac‐,R‐, orS‐fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans,S(−)‐propranolol was more rapidly cleared than theR(+)‐ enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed.Chirality 25:763–767, 2013, © 2013 Wiley Periodicals, Inc.
Response to Incremental Predictive Value of Red Cell Distribution Width for 12‐Month Clinical Outcome After Acute Myocardial Infarction
Authors: Demirkol Sait , Balta Sevket , Kucuk Ugur , Kurt Omer , Sarlak Hakan , Kucuk Hilal Olgun
Published: July 2013

Lee JH et al. Clin Cardiol. 2013;36:336–341.
Removal of Heavy Metal Quaternary Cations Systems on Zeolite A and X Mixtures Prepared from Local Kaolin
Authors: Hegazy Eman Z. , Abdelmaksod Islam H. , Kosa Samia A.
Published: July 2013

The use of a mixture of zeolites A and X was utilized to study the selectivity and the removal efficiency of a mixture of a quaternary cations solution containing Ca2+, Cu2+, Co2+, and Ni2+. The selectivity varied according to the mixture content. The total amount removed was found to follow the second order equation. Different mixtures of zeolites were examined for the removal efficiency of quaternary system of cations. The normalized selectivity varied according to the percent of the mixture. Pure zeolite A showed a non‐selective behavior while zeolite X was highly selective for Cu2+. The in‐between mixtures showed a variety of selectivity. The % mixture of two zeolites could be used for the selection of optimum conditions for the actual cases based on % of cations. A program was written to calculate the % removal of each cation in the solution. The mixture was examined on several synthetic wastewater solutions containing the quaternary system of these cations and on a real wastewater sample. It is found that the program could expect the % removal of the quartenary cation with more than 99% precision.
Neuropeptides in the antennal lobe of the yellow fever mosquito, Aedes aegypti
Authors: Siju K.P. , Reifenrath Anna , Scheiblich Hannah , Neupert Susanne , Predel Reinhard , Hansson Bill S. , Schachtner Joachim , Ignell Rickard
Published: July 2013

For many insects, including mosquitoes, olfaction is the dominant modality regulating their behavioral repertoire. Many neurochemicals modulate olfactory information in the central nervous system, including the primary olfactory center of insects, the antennal lobe. The most diverse and versatile neurochemicals in the insect nervous system are found in the neuropeptides. In the present study, we analyzed neuropeptides in the antennal lobe of the yellow fever mosquito, Aedes aegypti, a major vector of arboviral diseases. Direct tissue profiling of the antennal lobe by matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry indicated the presence of 28 mature products from 10 different neuropeptide genes. In addition, immunocytochemical techniques were used to describe the cellular location of the products of up to seven of these genes within the antennal lobe. Allatostatin A, allatotropin, SIFamide, FMRFamide‐related peptides, short neuropeptide F, myoinhibitory peptide, and tachykinin‐related peptides were found to be expressed in local interneurons and extrinsic neurons of the antennal lobe. Building on these results, we discuss the possible role of neuropeptide signaling in the antennal lobe of Ae. aegypti. J. Comp. Neurol. 522:592–608, 2014. © 2013 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.
Differential content of vesicular glutamate transporters in subsets of vagal afferents projecting to the nucleus tractus solitarii in the rat
Authors: Hermes Sam M. , Colbert James F. , Aicher Sue A.
Published: July 2013

The vagus nerve contains primary visceral afferents that convey sensory information from cardiovascular, pulmonary, and gastrointestinal tissues to the nucleus tractus solitarii (NTS). The heterogeneity of vagal afferents and their central terminals within the NTS is a common obstacle for evaluating functional groups of afferents. To determine whether different anterograde tracers can be used to identify distinct subpopulations of vagal afferents within NTS, we injected cholera toxin B subunit (CTb) and isolectin B4 (IB4) into the vagus nerve. Confocal analyses of medial NTS following injections of both CTb and IB4 into the same vagus nerve resulted in labeling of two exclusive populations of fibers. The ultrastructural patterns were also distinct. CTb was found in both myelinated and unmyelinated vagal axons and terminals in medial NTS, whereas IB4 was found only in unmyelinated afferents. Both tracers were observed in terminals with asymmetric synapses, suggesting excitatory transmission. Because glutamate is thought to be the neurotransmitter at this first primary afferent synapse in NTS, we determined whether vesicular glutamate transporters (VGLUTs) were differentially distributed among the two distinct populations of vagal afferents. Anterograde tracing from the vagus with CTb or IB4 was combined with immunohistochemistry for VGLUT1 or VGLUT2 in medial NTS and evaluated with confocal microscopy. CTb‐labeled afferents contained primarily VGLUT2 (83%), whereas IB4‐labeled afferents had low levels of vesicular transporters, VGLUT1 (5%) or VGLUT2 (21%). These findings suggest the possibility that glutamate release from unmyelinated vagal afferents may be regulated by a distinct, non‐VGLUT, mechanism. J. Comp. Neurol. 522:642–653, 2014. © 2013 Wiley Periodicals, Inc.
Classification of retinal ganglion cells in the southern hemisphere lamprey Geotria australis (Cyclostomata)
Authors: Fletcher Lee Norman , Coimbra João Paulo , Rodger Jennifer , Potter Ian C. , Gill Howard S. , Dunlop Sarah A. , Collin Shaun P.
Published: July 2013

ABSRACT

Lampreys are one of two extant representatives of the earliest group of vertebrates, the agnathans or jawless fishes. The single species of the southern hemisphere lamprey family Geotriidae, Geotria australis, possesses the potential for pentachromatic color discrimination opposed to the mono‐ or dichromacy found in other lampreys. However, little is known of the retinal ganglion cell types that contribute to visual processing in G. australis. A quantitative morphological approach was used to distinguish and describe retinal ganglion cell types in G. australis. The morphology of retinal ganglion cells was revealed by retrograde biocytin labeling from the optic disc. Cells were digitally reconstructed, and somatic area and position and dendritic field size, density, tortuosity, and stratification were subjected to quantitative morphometric analyses. Cluster analysis, in conjunction with similarity profile analysis (SIMPROF), statistically identified five discrete monostratified retinal ganglion cell types, one of which may comprise two subtypes. Two bistratified types were identified separately, including a biplexiform and a bistratified subtype. The use of cluster analysis with SIMPROF provided a robust statistical technique for objectively identifying cell types whose characteristics were similar and significantly different from those of other types and thus provides an objective resolution of the problems posed by “lumpers vs. splitters” when designating cell types. The diversity of retinal ganglion cells suggests that visual information in the lamprey G. australis is processed in parallel streams, as in gnathostomes. These findings, together with the results of previous studies, indicate that the visual system of the lamprey G. australis represents the upper limit of visual complexity in extant agnathans. J. Comp. Neurol. 522:750–771, 2014. © 2013 Wiley Periodicals, Inc.
Geographic routing protocol for vehicular ad hoc networks in city scenarios: a proposal and analysis
Authors: Li C. , Zhao C. , Zhu L. , Lin H. , Li J.
Published: July 2013

The characteristics of vehicular ad hoc networks (VANETs) make the design of routing protocol a great challenge. In this paper, we propose a vehicle density and load aware routing protocol for VANETs called VDLA. VDLA adopts sequential selection of junctions to construct the route. The selection is based on the real‐time vehicle density, the traffic load, and the distance to the destination. The network information is collected by a decentralized mechanism. Through factoring in these metrics, the packets are avoided being sent to roads where network is disconnected, and the network load is balanced to mitigate network congestion. The intermediate junctions are selected before the packet reaches a junction to reduce the unnecessary hops. Our study also investigates the impact of the high mobility of the nodes. An analytical framework is proposed to analyze the mobility. Based on the analysis, the traditional Hello scheme is enhanced to improve the accuracy of the neighbor table. In the simulation, we compare VDLA with greedy perimeter coordinator routing and GpsrJ+, which are geographic routings protocols proposed for VANETs. The results validate the superiority of VDLA in terms of end‐to‐end delay and packet delivery rate. And the superiority holds in different scenarios. Copyright © 2013 John Wiley & Sons, Ltd.
Fully secure constructions of spatial encryption with vector privacy
Authors: Zhang Mingwu , Wang Chunzhi , Yang Bo , Takagi Tsuyoshi
Published: July 2013

An encryption scheme is a tuple of algorithms used to ensure secrecy while exchanging messages over a public channel. Spatial encryption is a generalized extension of id‐based encryption with the ability of partial order role delegation. In this paper, we propose an efficient spatial encryption with vector privacy preservation, which is derived from the technique of static assumption from dual system encryption in composite order groups. The proposed scheme achieves the cryptosystem properties of message confidentiality, recipient anonymity, adaptively full security, and short constant ciphertext. Provable security in our setting consists of three steps: the first one is giving a rigorous definition of security, the second one is giving the construction of a scheme, and the last one is giving a rigorous mathematical proof showing that the scheme satisfies the security definition given in the first stage. Compared with related schemes, our proposed scheme has a comparable advantage in security while it holds an approximate computing efficiency and communicating payload such as public parameters, private keys, and ciphertexts. Copyright © 2013 John Wiley & Sons, Ltd.
Generation and characterization of a tamoxifen‐inducible EomesCreER mouse line
Authors: Pimeisl Inga‐Marie , Tanriver Yakup , Daza Ray A. , Vauti Franz , Hevner Robert F. , Arnold Hans‐Henning , Arnold Sebastian J.
Published: July 2013

Transgenic mouse lines expressing inducible forms of Cre‐recombinase in a tissue‐specific manner are powerful genetic tools for studying aspects of development and various processes in the adult. The T‐box transcription factor eomesodermin (Eomes) plays critical roles for maintenance and differentiation of different pools of stem and progenitor cells from early embryonic stages to adulthood. These include trophoblast stem cells, epiblast cells during the generation of the primary germ layers, neurogenic intermediate progenitor cells in embryonic and adult cortical neurogenesis, and maturing natural killer and T cells. Here, we report on the generation and analysis of an EomesCreER‐targeted allele by placing the tamoxifen‐activatable Cre‐recombinase (CreER) under the control of the Eomes genomic locus. We demonstrate that CreER expression recapitulates endogenous Eomes transcription within different progenitor cell populations. Tamoxifen administration specifically labels Eomes‐expressing cells and their progeny as demonstrated by crossing EomesCreER animals to different Cre‐inducible reporter strains. In summary, this novel EomesCreER allele can be used as elegant genetic tool that allows to follow the fate of Eomes‐positive cells and to genetically manipulate them in a temporal specific manner. genesis 51:725–733. © 2013 Wiley Periodicals, Inc.
Hydrolysis of Dipeptides Catalyzed by a Zirconium(IV)‐Substituted Lindqvist Type Polyoxometalate
Authors: Ly Hong Giang T. , Absillis Gregory , Bajpe Sneha R. , Martens Johan A. , Parac‐Vogt Tatjana N.
Published: July 2013

The hydrolysis of a series of unactivated dipeptides in the presence of a zirconium(IV)‐substituted Lindqvist type polyoxometalate, (Me4N)2[W5O18Zr(H2O)3] (designated as ZrW5), was studied by kinetic experiments and NMR spectroscopy. Among the dipeptides examined, those with the X–Ser amino acid sequence were most effectively hydrolyzed. The kinetics of the hydrolysis of histidylserine (His–Ser) was studied in detail; a rate constant of 95.3 (± 0.1) × 10–7 s–1 (pD 7.4 and 60 °C) in the presence of an equimolar amount of ZrW5 was calculated. The binding of His–Ser to ZrW5 was examined by UV/Vis, 1H, 13C, and 183W NMR spectroscopy, and the data indicate that at physiological pD His–Ser chelates the ZrIV through its imidazole nitrogen, amine nitrogen, and amide carbonyl oxygen. In the presence of ZrW5, the pD profile of kobs is bell‐shaped, with a maximum reaction rate at pD 7.5. At high pD values an inactive complex is formed as a result of the deprotonation of the amide nitrogen, resulting in inhibition of His–Ser hydrolysis. The effects of pH, temperature, inhibitors, and ionic strength on the hydrolysis rate constant were also investigated, and a full account of the mechanism of this novel reaction is given.
Identification and antioxidant activity of sinapic acid derivatives in Brassica napus L. seed meal extracts
Authors: Siger Aleksander , Czubinski Jaroslaw , Dwiecki Krzysztof , Kachlicki Piotr , Nogala‐Kalucka Malgorzata
Published: July 2013

Sinapic acid and its derivatives are main phenolic compounds present in rapeseed. Identification and quantitative determination of those compounds were carried out in crude extracts as well as extracts after basic and acidic hydrolysis. The total phenolic content in the crude extracts, expressed as sinapic acid equivalent, ranged from 1577 to 1705 mg/100 g for cv. Visby and Bellevue, respectively. An increase in total phenolics contents was observed in extracts after hydrolysis in comparison to crude extracts. The predominant phenolic acids in rapeseed samples were trans‐sinapic and cis‐sinapic acids. The highest concentration of sinapic acid methyl ester (2533–2702 mg/100 g) was detected in the extract after basic hydrolysis. In turn, two sinapic acid derivatives, i.e., kaempferol 3‐dihexoside‐7‐sinapoyl‐hexoside and 3‐hexoside‐7‐sinapoyl‐hexoside, were detected in the hydrolysed extracts. Total peroxyl radical‐trapping potential (TRAP) of the investigated crude extracts amounted to 20.21 and 27.05 μM Trolox Eq/g in the case of cv. Visby and Bellevue, respectively. The increase in antioxidant activity of the analyzed extracts after basic and acidic hydrolysis was probably a result of the release of free phenolic compounds from their conjugates (esters, glycosides).

Practical applications: The content and qualitative composition of the phenolic compounds in rapeseed have much influence on the stability, sensory, and nutritional characteristics of the products. During oil production process phenolic compounds may be transferred into final products and inhibit lipid oxidation. Rapeseed oil, among all commercially available oils, has the highest content of phenolic compounds, especially sinapic acid and their derivatives. That is why the antioxidant activity of phenolic compounds was investigated in the presented study. Determination of polar phenolics before and after hydrolysis indicates which compounds are responsible for antioxidant effect in oils and which are available for the human organism after digestion in the digestive tract.
D–π–A Dye Sensitizers Made of Polymeric Metal Complexes Containing 1,10‐Phenanthroline and Alkylfluorene or Alkoxybenzene: Synthesis, Characterization and Photovoltaic Performance for Dye‐Sensitized Solar Cells
Authors: Yu Xiaoguang , Jin Xueliang , Tang Guipeng , Zhou Jun , Zhang Wei , Peng Dahai , Hu Jiaomei , Zhong Chaofan
Published: July 2013

Four polymeric metal complexes (P1–P4) based on 1,10‐phenanthroline metal complexes and alkylfluorene or alkoxybenzene were synthesized by the Heck coupling reaction and were developed for dye‐sensitized solar cell applications. The target dyes use alkoxybenzene or alkylfluorene as the electron donor, a C=C moiety as the π linker, and the phenanthroline derivative complex was used as the electron acceptor. Bipyridine derivatives were ancillary ligands as well as providing anchoring groups. The thermal, photophysical, electrochemical and photovoltaic properties of these copolymers were investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), C–V curves and I–V curves. Dye‐sensitized solar cells with these polymeric metal complexes as dye sensitizers exhibited considerable power conversion efficiencies (PCE). The dyes containing alkoxybenzenes (P3, P4) exhibited higher PCE values than the corresponding target polymers containing alkylfluorenes (P1, P2), The dye P3 showed the maximal power conversion efficiency of 2.12 % (Jsc = 4.91 mA/cm2, Voc = 0.69 V, FF = 62.5). In addition, the four polymers possessed excellent stabilities, and their thermal decomposition temperatures all exceeded 300 °C, indicating that these polymeric metal complexes are suitable for the fabrication processes of optoelectronic devices.
A Convenient Microwave‐Assisted Propylphosphonic Anhydride (T3P®) Mediated One‐Pot Pyrazolone Synthesis
Authors: Desroses Matthieu , Jacques‐Cordonnier Marie‐Caroline , Llona‐Minguez Sabin , Jacques Sylvain , Koolmeister Tobias , Helleday Thomas , Scobie Martin
Published: July 2013

This paper describes a facile, efficient, and clean synthesis of various pyrazolones by employing T3P® as a catalyst and performing the reaction under microwave irradiation. This two‐step, one‐pot reaction proceeded readily and tolerated a variety of functional groups. A wide range of pyrazolone derivatives were obtained in good to excellent yields.
Investigation of BOLD fMRI resonance frequency shifts and quantitative susceptibility changes at 7 T
Authors: Bianciardi Marta , van Gelderen Peter , Duyn Jeff H.
Published: July 2013

Although blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments of brain activity generally rely on the magnitude of the signal, they also provide frequency information that can be derived from the phase of the signal. However, because of confounding effects of instrumental and physiological origin, BOLD related frequency information is difficult to extract and therefore rarely used. Here, we explored the use of high field (7 T) and dedicated signal processing methods to extract frequency information and use it to quantify and interpret blood oxygenation and blood volume changes. We found that optimized preprocessing improves detection of task‐evoked and spontaneous changes in phase signals and resonance frequency shifts over large areas of the cortex with sensitivity comparable to that of magnitude signals. Moreover, our results suggest the feasibility of mapping BOLD quantitative susceptibility changes in at least part of the activated area and its largest draining veins. Comparison with magnitude data suggests that the observed susceptibility changes originate from neuronal activity through induced blood volume and oxygenation changes in pial and intracortical veins. Further, from frequency shifts and susceptibility values, we estimated that, relative to baseline, the fractional oxygen saturation in large vessels increased by 0.02–0.05 during stimulation, which is consistent to previously published estimates. Together, these findings demonstrate that valuable information can be derived from fMRI imaging of BOLD frequency shifts and quantitative susceptibility changes. Hum Brain Mapp 35:2191–2205, 2014. © 2013 Wiley Periodicals, Inc.
River temperature regimes of England and Wales: spatial patterns, inter‐annual variability and climatic sensitivity
Authors: Garner Grace , Hannah David M. , Sadler Jonathan P. , Orr Harriet G.
Published: July 2013

Identification of the most sensitive hydrological regions to a changing climate is essential to target adaptive management strategies. This study presents a quantitative assessment of spatial patterns, inter‐annual variability and climatic sensitivity of the shape (form) and magnitude (size) of annual river/stream water temperature regimes across England and Wales. Classification of long‐term average (1989–2006) annual river (air) temperature regime dynamics at 88 (38) stations within England and Wales identified spatially differentiable regions. Emergent river temperature regions were used to structure detailed hydroclimatological analyses of a subset of 38 paired river and air temperature stations. The shape and magnitude of air and water temperature regimes were classified for individual station‐years; and a sensitivity index (SI, based on conditional probability) was used to quantify the strength of associations between river and air temperature regimes. The nature and strength of air–river temperature regime links differed between regions. River basin properties considered to be static over the timescale of the study were used to infer modification of air–river temperature links by basin hydrological processes. The strongest links were observed in regions where groundwater contributions to runoff (estimated by basin permeability) were smallest and water exposure time to the atmosphere (estimated by basin area) was greatest. These findings provide a new large‐scale perspective on the hydroclimatological controls driving river thermal dynamics and, thus, yield a scientific basis for informed management and regulatory decisions concerning river temperature within England and Wales. © 2013 The Authors. Hydrological Processes published by John Wiley & Sons, Ltd.
Angiotensin converting enzyme 2: A new important player in the regulation of glycemia
Authors: Chhabra Kavaljit H. , Chodavarapu Harshita , Lazartigues Eric
Published: July 2013

In spite of the novel antidiabetic drugs available on the market, type 2 diabetes mellitus (T2DM) affects nearly 25 million people in the USA and causes about 5% of all deaths globally each year. Given the rate and proportion by which T2DM is affecting human beings, it is indispensable to identify new therapeutic targets that can control the disease. Recent preclinical and clinical studies suggest that attenuating the activity of the renin–angiotensin system (RAS) could improve glycemia in diabetic patients. Angiotensin‐converting enzyme 2 (ACE2) counteracts RAS overactivity by degrading angiotensin‐II (Ang‐II), a vasoconstrictor, to Ang‐(1–7) which is a vasodilator. A decrease in ACE2 and an increase in A disintegrin and metalloproteinase (ADAM17)‐mediated shedding activity have been observed with the progression of T2DM, suggesting the importance of this mechanism in the disease. Indeed, restoration of ACE2 improves glycemia in db/db and Ang‐II‐infused mice. The beneficial effects of ACE2 can be attributed to reduced oxidative stress and ADAM17 expression in the islets of Langerhans in addition to the improvement of blood flow to the β‐cells. The advantage of ACE2 over other RAS blockers is that ACE2 not only counteracts the negative effects of Ang‐II but also increases Ang‐(1–7)/Mas receptor (MasR) [a receptor through which Ang‐(1–7) produces its actions] signaling in the cells. Increased Ang‐(1–7)/MasR signaling has been reported to improve insulin sensitivity and glycemia in diabetic animals. Altogether, ACE2/Ang‐(1–7)/MasR axis of the RAS appears to be protective in T2DM and strategies to restore ACE2 levels in the disease seem to be a promising therapy for Ang‐II‐mediated T2DM. © 2013 IUBMB Life, 65(9):731–738, 2013
Fighting an old war with a new weapon—silencing transposons by Piwi‐interacting RNA
Authors: Guo Manhong , Wu Yuliang
Published: July 2013

Discovered six decades ago, transposons are known to selfishly multiply within and between chromosomes. Although they may play a creative role in building new functional parts of the genome, transposons usually cause insertional mutagenesis and/or turn nearby genes on or off. To maintain genome integrity, cells use a variety of strategies to defend against the proliferation of transposons. A class of small noncoding RNA, discovered seven years ago and called piRNA, is a new player in the war to silence transposons. piRNA is made via two biogenesis pathways: the primary processing pathway and the ping‐pong amplification loop. These pathways are critically involved in transposon RNA degradation, DNA methylation, and histone modification machinery that represses transposons. In this review, we briefly introduce transposon‐caused genomic instability and summarize our current understanding of the piRNA pathway, focusing on its key function in transposon silencing. © 2013 IUBMB Life, 65(9):739–747, 2013
Targeting RAS/RAF/MEK/ERK signaling in metastatic melanoma
Authors: Wang Ao‐Xue , Qi Xiao‐Yi
Published: July 2013

The RAS/RAF/MEK/ERK pathway has been reported to be activated in over 80% of all cutaneous melanomas, making it the focus of many scientific studies in the melanoma field. Discoveries of mutations and aberrant expression of components in this cascade, in particular, BRAF and NRAS render a deeper understanding of the mechanisms responsible for oncogenesis and provide new therapeutic strategies for this deadly disease. This review starts with a comprehensive discussion on the role of this pathway in initiation and progress of melanoma. Mechanistically, mutated BRAF and NRAS exert most of the oncogenic effects through the activation of the MAPK pathway, which both drive the uncontrolled growth of melanoma cells and regulate the cell survival. In a subsequent section, clinical efficacy of targeted small‐molecule inhibitors is highlighted. BRAF‐targeted therapies (e.g., vemurafenib, dabrafenib) have showed impressive results in systemic therapy for melanoma harboring activating BRAF V600E mutations. MEK inhibitors show limited activity in phase I trials, and inhibitors directly targeting mutated NRAS, to date, have not been realized. Furthermore, the emerging mechanisms underlying both intrinsic and acquired drug resistance as well as approaches to prevent or abrogate the onset of therapeutic escape are addressed. Finally, the promising vistas and major challenges involving small‐molecule inhibitors targeting this MAPK pathway in melanoma therapy are briefly discussed. It can be envisaged that disseminated melanoma is no longer such a bleak prognosis in future given the research and development of new signal transduction inhibitors based on our evolving understanding of melanoma genetics and intracellular signaling. © 2013 IUBMB Life, 65(9):748–758, 2013
LED‐activated methylene blue‐loaded Pluronic‐nanogold hybrids for in vitro photodynamic therapy
Authors: Simon Timea , Boca‐Farcau Sanda , Gabudean Ana‐Maria , Baldeck Patrice , Astilean Simion
Published: July 2013

In this work we introduce a new class of multifunctional photodynamic agents based on the coupling of photosensitizer molecules with noble metal nanoparticles, which can be efficiently activated under low light intensity. The favourable modification of the photophysical properties of methylene blue (MB) in MB‐loaded Pluronic‐nanogold hybrids (Au‐PF127‐MB) increases the probability of singlet oxygen generation, which in turn allows the use of a light emitting diode (LED) irradiation source instead of commonly used, more invasive lasers. In this regard, Au‐PF127‐MB treated human lung carcinoma cells (HTB 177) were irradiated at different light doses, using a 660 nm LED source, the results indicating a dose dependent therapeutic effect, decreasing the cell viability down to 13%. Owing to their effectiveness, biocompatibility and integrated imaging and therapeutic functionalities, Au‐PF127‐MB could represent an important development in the field of biophotonic applications. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pigeon responding in fixed‐interval and response‐initiated fixed‐interval schedules
Authors: Fox Adam E. , Kyonka Elizabeth G. E.
Published: July 2013

In fixed‐interval (FI) and response‐initiated fixed‐interval (RIFI) schedules of reinforcement, a response is required after an interval has elapsed for delivery of reinforcement. In RIFI schedules, a response is required to initiate each interval as well. The objective of this experiment was a systematic comparison of performance in the two schedule types over a range of interval durations. Four pigeons were exposed to FI and RIFI schedules of 15, 30, 60, 120 and 240 s. Interfood intervals were longer and more variable in RIFI than corresponding FI schedules. In addition, response rates early in the RIFI schedules were higher than in corresponding FI schedules. However, the distribution of first‐response latencies, mean breakpoints, and normalized response gradients suggest that temporal discrimination was equivalent in the two schedules.
Computational model of selection by consequences: Patterns of preference change on concurrent schedules
Authors: Kulubekova Saule , McDowell J. J
Published: July 2013

The computational model of selection by consequences is an ontogenetic dynamic account of adaptive behavior based on the Darwinian principle of selection by consequences. The model is a virtual organism based on a genetic algorithm, a class of computational algorithms that instantiate the principles of selection, fitness, reproduction and mutation. The computational model has been thoroughly tested in experiments with a variety of single alternative and concurrent schedules. A number of published reports demonstrate that the model generates patterns of behavior that are quantitatively equivalent to the findings from live organisms. The experiments and analyses in this study assess the behavior of the computational model for evidence of preference change phenomena in environments with rapidly changing reinforcement rate ratios. Molar and molecular effects of behavioral adjustment were consistent with those observed in live organisms. The results of this study provide strong evidence supporting the selectionist account of adaptive behavior.
A novel approach to improve numerical weather prediction skills by using anomaly integration and historical data
Authors: Peng Xindong , Che Yuzhang , Chang Jun
Published: July 2013

Using the concept of anomaly integration and historical climate data, we have developed a novel operational framework to implement deterministic numerical weather prediction within 15 days. Real‐case validation shows pronounced improvements in the forecasts of global geopotential heights in 20 out of 30 cases with the Community Atmosphere Model version 3.0. Seven other cases are marginally improved, and only three are deteriorated, in which all are ameliorated within the first‐week period. The average of the 30 cases shows an obvious increase of anomaly correlation coefficient (ACC) and a decrease of root mean square error (RMSE) of the geopotential height over global, hemispherical, and tropical zones. Significant amelioration on tropical circulation is displayed within the first‐week prediction. The forecasting skill is extended by 0.6 day in terms of days of the ACC greater than 0.6 for 500 hPa 30 case averaged geopotential height on global scale. The 30 case mean ACC and RMSE of 500 hPa temperature show the increment of 0.2 and −1.6 K, respectively, in the first‐week prediction. In the case of January 2008, much more reasonable horizontal distribution and vertical structure are achieved in bias‐corrected model geopotential height, temperature, relative humidity, and horizontal wind components in comparison to reanalysis data. In spite of a need for additional storage of historical modeling data, the new method does not increase computational costs and therefore is suitable for routine application.
Application of spectral analysis techniques in the intercomparison of aerosol data: 1. An EOF approach to analyze the spatial‐temporal variability of aerosol optical depth using multiple remote sensing data sets
Authors: Li Jing , Carlson Barbara E. , Lacis Andrew A.
Published: July 2013

Many remote sensing techniques and passive sensors have been developed to measure global aerosol properties. While instantaneous comparisons between pixel‐level data often reveal quantitative differences, here we use Empirical Orthogonal Function (EOF) analysis, also known as Principal Component Analysis, to demonstrate that satellite‐derived aerosol optical depth (AOD) data sets exhibit essentially the same spatial and temporal variability and are thus suitable for large‐scale studies. Analysis results show that the first four EOF modes of AOD account for the bulk of the variance and agree well across the four data sets used in this study (i.e., Aqua MODIS, Terra MODIS, MISR, and SeaWiFS). Only SeaWiFS data over land have slightly different EOF patterns. Globally, the first two EOF modes show annual cycles and are mainly related to Sahara dust in the northern hemisphere and biomass burning in the southern hemisphere, respectively. After removing the mean seasonal cycle from the data, major aerosol sources, including biomass burning in South America and dust in West Africa, are revealed in the dominant modes due to the different interannual variability of aerosol emissions. The enhancement of biomass burning associated with El Niño over Indonesia and central South America is also captured with the EOF technique.