bluuebunny/crossref_metadata_2025 huggingface dataset:
All Kinds of Reactivity: Recent Breakthroughs in Metal‐Catalyzed Alkyne Chemistry
Authors: Anaya de Parrodi Cecilia , Walsh Patrick J.
Published: April 2009

Alkynes of reactions: Recent breakthroughs in metal‐catalyzed alkyne reactions, which expand the synthetic utility of alkynes, have been achieved. These approaches broaden the range of alkynes that are accessible by CN and CC bond‐forming reactions and demonstrate that the use of bifunctional heterobimetallic catalysts can lead to new reactivity and excellent enantioselectivity (see scheme).

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Helikite aerial photography – a versatile means of unmanned, radio controlled, low‐altitude aerial archaeology
Authors: Verhoeven Geert J. J. , Loenders Jo , Vermeulen Frank , Docter Roald
Published: April 2009

During the past 100 years, various devices have been developed and applied in order to acquire archaeologically useful aerial imagery from low altitudes (e.g. balloons, kites, poles). This paper introduces Helikite aerial photography (HAP), a new form of close range aerial photography suitable for site or defined area photography, based on a camera suspended from a Helikite: a combination of both a helium balloon and kite wings. By largely overcoming the drawbacks of conventional kite‐ and balloon‐based photography, HAP allows for a very versatile, remotely controlled approach to low‐altitude aerial photography (LAAP). In addition to a detailed outline of the whole HAP system, its working procedure and possible improvements, some of the resulting imagery is shown to demonstrate the usefulness of HAP for several archaeological applications. Copyright © 2009 John Wiley & Sons, Ltd.
Artificial Restriction DNA Cutters as New Tools for Gene Manipulation
Authors: Katada Hitoshi , Komiyama Makoto
Published: April 2009

The final cut. Two types of artificial tools (artificial restriction DNA cutter and zinc finger nuclease) that cut double‐stranded DNA through hydrolysis of target phosphodiester linkages, have been recently developed. The chemical structures, preparation, properties, and typical applications of these two man‐made tools are reviewed.

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Two types of artificial tools that cut double‐stranded DNA through hydrolysis of target phosphodiester linkages have been recently developed. One is the chemistry‐based artificial restriction DNA cutter (ARCUT) that is composed of a CeIV–EDTA complex, which catalyses DNA hydrolysis, and a pair of pseudo‐complementary peptide nucleic acid fragments for sequence recognition. Another type of DNA cutter, zinc finger nuclease (ZFN), is composed of the nuclease domain of naturally occurring FokI restriction endonuclease and a designed zinc finger DNA‐binding domain. For both of these artificial tools, the scission site and specificity can be freely chosen according to our needs, so that even huge genomic DNA sequences can be selectively cut at the target site. In this article, the chemical structures, preparation, properties, and typical applications of these two man‐made tools are described.
Petroleum Residue Upgrading Via Delayed Coking: A Review
Authors: Sawarkar Ashish N. , Pandit Aniruddha B. , Samant Shriniwas D. , Joshi Jyeshtharaj B.
Published: April 2009

World petroleum residue processing capacity has reached about 725 million metric tons per annum (MMTPA). The high demand for transportation fuels and the ever‐rising heavy nature of crude oil have resulted in a renewed interest in the bottom‐of‐the‐barrel processing using various conversion processes. Delayed coking, known for processing virtually any refinery stream (which not only poses a serious threat to environment, but also involves a disposal cost) has garnered tremendous importance in the current refining scenario. Needle coke obtained from delayed coking process is a highly sought‐after product, which is used in electric arc furnaces (in the form of graphite electrodes) in steel making applications. In the present communication, the published literature has been extensively analyzed and a state‐of‐the‐art review has been written that includes: (1) importance and place of delayed coking as a residue upgrading process in the current refining scenario; (2) coking mechanism and kinetics; (3) design aspects; (4) feedstocks suitable for the production of needle coke; (5) characteristics of needle coke; (6) factors affecting needle coke quality and quantity; and (7) future market for needle coke. An attempt has been made to get the above‐mentioned aspects together in a coherent theme so that the information is available at a glance and could be of significant use for researchers and practising refiners.
Activity–Structure Correlation of Pt/Ru Catalysts for the Electrodecomposition of Methanol: The Importance of RuO2and PtRu Alloying
Authors: Wei Yu‐Chen , Liu Chen‐Wei , Wang Kuan‐Wen
Published: April 2009

Bimetallic catalysts:The effect of PtRu alloying and the influence of RuO2species on the methanol oxidation activity of PtRu/C catalysts is studied. Different heat treatments—utilizing either N2or air—are applied to the bimetallic materials to enhance the degree of alloying or produce RuO2(see picture). The catalysts with the best performance are characterized by a small particle size, a high degree of PtRu alloying, and the presence of a Pt‐related species on their surface.

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Herein, we study the effect of both PtRu alloying and the presence of RuO2species on the promotion of the methanol oxidation activity of PtRu/C catalysts. Bimetallic catalysts composed of 15 wt % PtRu/CexC (x=0 or 10) are prepared by using the precipitation–deposition method and activated through hydrogen reduction at 470 K. Different heat treatments, utilizing either N2or air, are applied to the as‐prepared catalysts to enhance the degree of alloying or produce RuO2, respectively. The electrocatalytic properties, the structure, and the surface composition of the alloys are investigated systematically by means of electrochemical measurements coupled with X‐ray diffraction (XRD) and temperature‐programmed reduction (TPR) experiments. We find that the N2heat treatment improves the catalytic activity of the alloys more significantly than the air heat treatment. Also, the current density and long‐term durability toward methanol oxidation can be significantly enhanced by combining a loading of 10 % CeO2and N2with a heat treatment at 570 K. Physical characterization performed by means of TPR reveals that the surface of the N2‐treated sample is covered with Pt, thereby presenting a higher methanol oxidation current than the air‐treated sample whose surface is composed of RuO2and some alloy species. Moreover, a model for describing the physical structures of the deposited bimetallic crystallites obtained after the N2and air treatments is proposed. This model suggests that the catalysts with the best performance should have a small particle size and exhibit a structure characterized by a high degree of PtRu alloying and a Pt‐related surface species. Therefore, we can conclude that the effect of PtRu alloying on the electro‐oxidation activity of the catalysts is superior to that of the presence of RuO2species under practical conditions.
Synthesis of α‐Hydroxyallenes by Copper‐Catalyzed SN2′ Substitution of Propargylic Dioxolanones
Authors: Tang Xiaoping , Woodward Simon , Krause Norbert
Published: April 2009

A new catalytic method for the synthesis of α‐hydroxyallenes is described. Efficient SN2′ substitution of propargylic dioxolanones has been achieved with a copper(I)/P(OBu)3 catalyst using Grignard reagents as the nucleophiles. The reaction tolerates a wide variety of propargylic dioxolanones, the corresponding primary and secondary α‐hydroxyallenes are obtained in good to excellent yields and excellent diastereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
The effects of interdune vegetation changes on eolian dune field evolution: a numerical‐modeling case study at Jockey's Ridge, North Carolina, USA
Authors: Pelletier Jon D. , Mitasova Helena , Harmon Russell S. , Overton Margery
Published: April 2009

Changes in vegetation cover within dune fields can play a major role in how dune fields evolve. To better understand the linkage between dune field evolution and interdune vegetation changes, we modified Werner's (Geology, 23, 1995: 1107–1110) dune field evolution model to account for the stabilizing effects of vegetation. Model results indicate that changes in the density of interdune vegetation strongly influence subsequent trends in the height and area of eolian dunes. We applied the model to interpreting the recent evolution of Jockey's Ridge, North Carolina, where repeat LiDAR surveys and historical aerial photographs and maps provide an unusually detailed record of recent dune field evolution. In the absence of interdune vegetation, the model predicts that dunes at Jockey's Ridge evolve towards taller, more closely‐spaced, barchanoid dunes, with smaller dunes generally migrating faster than larger dunes. Conversely, the establishment of interdune vegetation causes dunes to evolve towards shorter, more widely‐spaced, parabolic forms. These results provide a basis for understanding the increase in dune height at Jockey's Ridge during the early part of the twentieth century, when interdune vegetation was sparse, followed by the decrease in dune height and establishment of parabolic forms from 1953‐present when interdune vegetation density increased. These results provide a conceptual model that may be applicable at other sites with increasing interdune vegetation cover, and they illustrate the power of using numerical modeling to model decadal variations in eolian dune field evolution. We also describe model results designed to test the relative efficacy of alternative strategies for mitigating dune migration and deflation. Installing sand‐trapping fences and/or promoting vegetation growth on the stoss sides of dunes are found to be the most effective strategies for limiting dune advance, but these strategies must be weighed against the desire of many park visitors to maintain the natural state of the dunes. Copyright © 2009 John Wiley & Sons, Ltd.
Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?
Authors: Kumar Pasupulati Anil , Reddy Geereddy Bhanuprakash
Published: April 2009

Cataract, loss of eye lens transparency, is the leading cause of blindness worldwide. α‐Crystallin, initially known as one of the major structural proteins of the eye lens, is composed of two homologous subunits αA‐ and αB‐crystallins. It is convincingly established now that α‐crystallin functions like a chaperone and plays a decisive role in the maintenance of eye lens transparency. The functional ability of α‐crystallin subunits is to act in cooperation as molecular chaperones to prevent the cellular aggregation and/or inactivation of client proteins under variety of stress conditions. However, chaperone‐like activity of α‐crystallin could be deteriorated or lost during aging or under certain clinical conditions because of various genetic and environmental factors. This review will focus specifically on relevance of α‐crystallin chaperone function to lens transparency. In particular, we reviewed the studies that demonstrate the modulation of α‐crystallin chaperone‐like activity and discussed the possibility of chaperone‐like activity of α‐crystallin as a potential target to prevent or delay the cataractogenesis. © 2009 IUBMB IUBMB Life, 61(5): 485–495, 2009
Novel oncogenic actions of TRβ mutants in tumorigenesis
Authors: Guigon Celine J. , Cheng Sheue‐yann
Published: April 2009

The thyroid hormone, T3, plays important roles in metabolism, growth, and differentiation. Germline mutations in thyroid hormone receptor beta (TRβ) have been identified in many individuals with resistance to thyroid hormone, a syndrome of reduced sensitivity to T3. A close association of somatic mutations of TRβ with several human cancers has become increasingly apparent, but how TRβ mutants could be involved in the carcinogenesis in vivo has not been addressed. The creation of a mouse model (TRβPV/PV mouse) that harbors a knockin mutation of TRβ (denoted TRβPV) has facilitated the study of the molecular actions of TRβ mutants in vivo. The striking phenotype of thyroid cancer and the development of pituitary tumors exhibited by TRβPV/PV mice have uncovered novel functions of a TRβ mutant in tumorigenesis. It led to the important findings that the oncogenic action of TRβPV is mediated by both genomic and nongenomic actions to alter gene expression and signaling pathways activity. © 2009 IUBMB IUBMB Life, 61(5): 528–536, 2009
Retinal deimination in aging and disease
Authors: Bhattacharya Sanjoy K.
Published: April 2009

Deimination is a posttranslational modification and refers to the conversion of protein bound arginine into citrulline. In the retina, deimination is predominantly catalyzed by Peptidylarginine deiminase type 2 (PAD2). PAD2 expression and deimination are found in many different retinal layers: choroid, retinal pigment epithelium (RPE), photoreceptors, inner plexiform layer, inner nuclear layer, and retinal ganglion cell (RGC) layer. Although decreased retinal deimination and PAD2 expression have been found during normal aging, elevated PAD2 expression and deimination have been observed in age‐related neurodegenerative diseases. The role of deimination in normal physiology and in late‐onset and progressive ocular or retinal degenerative diseases, such as glaucoma and experimental autoimmune encephalomyelitis remains to be elucidated. © 2009 IUBMB IUBMB Life, 61(5): 504–509, 2009
GABA increases Ca2+ in cerebellar granule cell precursors via depolarization: Implications for proliferation
Authors: Dave Kathleen A. , Bordey Angélique
Published: April 2009

The amino acids glutamate and gamma‐aminobutyric acid (GABA) have primarily been characterized as the most prevalent excitatory and inhibitory, respectively, neurotransmitters in the vertebrate central nervous system. However, the role of these signaling molecules extends far beyond the synapse. GABA, glutamate, and their complement of receptors are essential signaling molecules that regulate developmental processes in both embryonic and young adult mammals. In this review, we describe the current knowledge on the role of GABA and glutamate in development, focusing on the perinatal cerebellum. We will then present novel data suggesting that GABA depolarizes granule cell precursors via GABAA receptors, which leads to calcium increases in these cells. Finally, we will consider the role of GABA and glutamate signaling on cell proliferation and perhaps neural cancers. From our review of the literature and these data, we hypothesize that GABAA receptors and metabotropic glutamate receptors may be a novel target for the pharmacological regulation of the cerebellar tumors, medulloblastomas. © 2009 IUBMB IUBMB Life, 61(5): 496–503, 2009
GSK‐3: A key player in neurodegeneration and memory
Authors: Giese Karl Peter
Published: April 2009

Abnormalities in molecular signalling have been implicated in neurodegeneration. It is emerging that glycogen synthase kinase‐3 (GSK‐3) is a key signalling molecule that induces neurodegeneration and deficits in memory formation related to Alzheimer's disease (AD). Early stages of AD are associated with deficits in memory formation before neuronal cell death is detectable. Recent studies in rodents have suggested that these impairments in memory formation might result from increased GSK‐3 signalling, because enhanced GSK‐3 activity impairs hippocampal memory formation. GSK‐3 activity blocks synaptic long‐term potentiation and induces long‐term depression. Furthermore, increased GSK‐3 signalling is likely to be a key contributor to the formation of the pathological hallmarks in AD, neurofibrillary tangles (NFTs) and amyloid plaques. Recent studies with mouse models have indicated that GSK‐3, but not cyclin‐dependent kinase 5, is critical for hyperphosphorylation of the cytoskeletal protein tau, which is the prerequisite for NFT formation in AD. Furthermore, increased GSK‐3 signalling in AD mice causes abnormal processing of the amyloid precursor protein so that amyloid peptide production augments and neurotoxicity is induced. Taken together, the current evidences suggest that increased GSK‐3 signalling may be responsible for the deficits in memory formation in early stages of AD and neurodegeneration in later stages of the disease. © 2009 IUBMB IUBMB Life 61(5): 516–521, 2009
Oxidized proteins: Mechanisms of removal and consequences of accumulation
Authors: Dunlop Rachael A. , Brunk Ulf T. , Rodgers Kenneth J.
Published: April 2009

Elevated levels of oxidized proteins are reported in diseased tissue from age‐related pathologies such as atherosclerosis, neurodegenerative disorders, and cataract. Unlike the precise mechanisms that exist for the repair of nucleic acids, lipids, and carbohydrates, the primary pathway for the repair of oxidized proteins is complete catabolism to their constitutive amino acids. This process can be inefficient as is evidenced by their accumulation. It is generally considered that damaged proteins are degraded by the proteasome; however, this is only true for mildly oxidized proteins, because substrates must be unfolded to enter the narrow catalytic core. Rather, evidence suggests that moderately or heavily oxidized proteins are endocytosed and enter the endosomal/lysosomal system, indicating co‐operation between the proteasomes and the lysosomes. Heavily modified substrates are incompletely degraded and accumulate within the lysosomal compartments resulting in the formation of lipofuscin‐like, autofluorescent aggregates. Accumulation eventually results in impaired turnover of large organelles such as proteasomes and mitochondria, lysosomal destablization, leakage of proteases into the cytosol and apoptosis. In this review, we summarize reports published since our last assessments of the field of oxidized protein degradation including a role for modified proteins in the induction of apoptosis. © 2009 IUBMB IUBMB Life, 61(5): 522–527, 2009
Exploring enantioselective molecular recognition mechanisms with chemoinformatic techniques
Authors: Del Rio Alberto
Published: April 2009

A comprehensive review of chemoinformatic techniques and studies applied to the field of enantioselective molecular recognition is presented. Several approaches such as enantiophores/pharmacophore modelling, QSPRs, CoMFA and other insightful data mining procedures are discussed. The review focuses on the central role of chemoinformatic approaches on the establishment of connections between available experimental data, mainly HPLC separation data, and these algorithms that describe properties of chiral molecules. The general overview of the aforementioned calculations account for a use of these techniques as a valuable strategy to achieve reliable prediction systems, infer the mechanisms of chiral recognition, generate insight for the conception of new chiral receptors and corroborate and assist experimental techniques such as chiral LC. Moreover, it is pointed out that computer methods in this field promise a wide range of applications for both academia and industry, ranging from enantioselective reactions, drug discovery and analysis of high‐throughput screenings, to analytical and semi‐preparative separations or large‐scale production of enantiopure compounds.
Comparative proteomic and regulatory network analyses of the elongating pig conceptus
Authors: Degrelle Séverine A. , Blomberg Le Ann , Garrett Wesley M. , Li Robert W. , Talbot Neil C.
Published: April 2009

Embryo loss during peri‐implantation can approach 20% in swine following artificial insemination or natural mating and coincides with rapid conceptus elongation. The objective of the present study was to establish a comprehensive profile of the abundant proteins of the pig conceptus at the time prior to implantation and identify stage‐specific changes during elongation. The abundant proteins of a homogenous population of gestational day‐11 ovoid (0.7–1 cm) and gestational day‐12 filamentous (15–20 cm) porcine concepti were compared by extracting proteins from three independent conceptus pools and separating the proteins by 2‐DE. Proteins in 305 spots were analyzed by MALDI‐TOF or additionally by LC‐MS/MS and 275 were positively identified representing 174 distinct proteins. The proteins could be classified into the following functional categories: cell proliferation/differentiation, cytoskeleton, metabolism, and stress response. Based on spot density, 35 proteins associated with cell proliferation, differentiation, apoptosis, and embryo/maternal signaling, were found to be differentially expressed between ovoid and filamentous concepti. A comparison of the protein expression profile with transcriptomic data from pig concepti of the same developmental stages identified similarities and dissimilarities between protein and mRNA expression profiles. This proteomic study helps to elucidate the biological mechanisms underlying the early embryonic development of the pig.
High efficiency solid state laser cooling in Yb3+:ZBLANP fiber with tilted fiber Bragg grating structures
Authors: Nemova Galina , Kashyap Raman
Published: April 2009

An optimized fiber structure for use in anti‐Stokes laser cooling of solids is presented. The sample is an optical fiber fabricated from a fluorozirconate glass ZBLANP (ZrF4‐BaF2‐LaF3‐AlF3‐NaF‐PbF2) with a core doped with Yb3+ ions and optimized to achieve the largest temperature change in the sample starting at room temperature.

It is shown that the change in the temperature of the sample is a function of the geometry of the fiber. For each pump power there is an optimized diameter of the fiber core, for which the largest drop occurs in the temperature of the sample. A titled Bragg grating imprinted into the fiber core is suggested to prevent the re‐absorption of anti‐Stokes photons. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Temperature dependence of carrier traps in high sensitivity HARP photoconductive film
Authors: Ohkawa Yuji , Miyakawa Kazunori , Matsubara Tomoki , Kikuchi Kenji , Suzuki Shirou , Kubota Misao , Egami Norifumi , Kobayashi Akira
Published: April 2009

Amorphous selenium (a‐Se) avalanche multiplication photoconductive film, what we call HARP (high‐gain avalanche rushing amorphous photoconductor) photoconductive film, has been investigated for the purpose of reporting breaking news at night and producing nature and science programs. The purpose of our work is to develop more sensitive HARP films with high reliability. 15‐μm‐thick HARP film with an avalanche multiplication factor of about 200 that is thicker and more sensitive than the previous 8‐μm‐thick one has been studied. However, the thick film has a problem that defects easily occurred during shooting of intense spot lights. The defects are caused by trapped electrons which makes an enhanced internal electric field around the incident light side interface of the film. Defects are suppressed by operating the film at high temperatures, because the thermal energy releases the trapped electrons. This paper describes the relationship between the defect occurrence and the temperature dependence of carries trap in the film. To investigate it, the defect occurrence and dark current characteristics were measured. As a result, it was found that the number of released electrons exceeds that of trapped ones at temperatures over 28.5 °C and that defect occurrence is suppressed by operating the film at over 27.5 °C. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Noise analysis of a novel hybrid active‐passive pixel sensor for medical X‐ray imaging
Authors: Safavian N. , Izadi M. H. , Sultana A. , Wu D. , Karim K. S. , Nathan A. , Rowlands J. A.
Published: April 2009

Passive pixel sensor (PPS) is one of the most widely used architectures in large area amorphous silicon (a‐Si) flat panel imagers. It consists of a detector and a thin film transistor (TFT) acting as a readout switch. While the PPS is advantageous in terms of providing a simple and small architecture suitable for high‐resolution imaging, it directly exposes the signal to the noise of data line and external readout electronics, causing significant increase in the minimum readable sensor input signal. In this work we present the operation and noise performance of a hybrid 3‐TFT current programmed, current output active pixel sensor (APS) suitable for real‐time X‐ray imaging. The pixel circuit extends the application of a‐Si TFT from conventional switching element to on‐pixel amplifier for enhanced signal‐to‐noise ratio and higher imager dynamic range. The capability of operation in both passive and active modes as well as being able to compensate for inherent instabilities of the TFTs makes the architecture a good candidate for X‐ray imaging modalities with a wide range of incoming X‐ray intensities. Measurement and theoretical calculations reveal a value for input refferd noise below the 1000 electron noise limit for real‐time fluoroscopy. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Time evolution of absorption process in nonlinear metallic photonic crystals
Authors: Singh Mahi R. , Hatef Ali
Published: April 2009

The time evolution of the absorption coefficient in metallic photonic crystals has been studied numerically. These crystals are made from metallic spheres which are arranged periodically in air. The refractive index of the metallic spheres depends on the plasma frequency. Probe and pump fields are applied to monitor the absorption process. Ensembles of three‐level particles are embedded in the crystal. Nanoparticles are interactiing with the metallic crystals via the electron‐photon interaction. It is found that when the resonance states lie away from the band edges system goes to transparent sate. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ag‐photodoping in nano‐structured GeO2‐GeS2 glasses
Authors: Terakado Nobuaki , Tanaka Keiji
Published: April 2009

Composition dependence of Ag‐photodoping in x GeO2‐(100–x)GeS2 glasses has been studied. The doping rate decreases with an increase in x, and becomes negligible at x ≥ 60. This photodoping disappearance can be related with transformation from percolated GeS2 networks in the heterogeneous oxy‐chalcogenide glasses to isolated nano‐scale clusters. Remarks on photodoping processes and overall composition dependences are also given. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Near‐field modulation of AlGaInP laser diode emissions by an aperture probe of near‐field optical microscope
Authors: Kamiyama Yasushi , Tomioka Akihiro , Anzai Takahiro , Iwamoto Kazuhisa , Susaki Wataru
Published: April 2009

In situ emission profiles of AlGaInP multiple quantum well laser diodes (LD's) observed by a near‐field scanning optical microscope (NSOM) aperture probe shows a single broad elliptic profile similar to a far‐field observation, whereas the local emission spectrum was different depending where the aperture probe was positioned within the emission profile. This observation suggests the existence of a near‐field coupling between the aperture and the LD cavity, which modulates the lasing wavelength among the longitudinal multimodes determined by the LD cavity length. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Radiation‐induced optically stimulated luminescence in Mn2+ and Eu2+ doped RbMgF3
Authors: Williams G. V. M. , Dotzler C. , Robinson J.
Published: April 2009

Radiation‐induced optically stimulated luminescence is observed in RbMgF3 when doped with Mn2+ or Eu2+. This compound can be used for radiation dosimetry where the dose information can be optically read and reset. The main difference between RbMgF3:Mn2+ and RbMgF3:Eu2+ is due to the fact that RbMgF3:Mn2+ has deep traps when compared with RbMgF3:Eu2+ that are evident as high temperature peaks in the thermoluminescence data. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A multistate approach for estimating the incidence of human immunodeficiency virus by using HIV and AIDS French surveillance data
Authors: Sommen Cécile , Alioum Ahmadou , Commenges Daniel
Published: April 2009

Before the introduction of highly active antiretroviral therapy (HAART) in 1996, monitoring the epidemics of HIV infection was extensively based on back‐calculating the number of new HIV infections from AIDS surveillance data and knowledge of the AIDS incubation period distribution. However, the increase in the AIDS incubation period induced by HAART has complicated the use of AIDS diagnosis data only, and made it necessary to supplement these data with HIV diagnosis data. We explore the advantage of combining HIV and AIDS surveillance data in the context where the HIV diagnosis data are available only for the most recent years. Extending the earlier work of Aalenet al. (Statist. Med.1997;16(19):2191–2210) based on a discrete‐time Markov model that describes simultaneously disease progression, HIV diagnosis and treatment intake, we propose a penalized likelihood approach to estimate smooth HIV incidence, together with HIV diagnosis rates. The smoothing parameter is chosen using an approximated cross‐validation criterion. In a simulation study, we show that incorporation of HIV test information improves the precision of the estimation of the incidence of infections in recent periods. The method is illustrated using HIV and AIDS surveillance data collected by the Institut de Veille Sanitaire, France. Copyright © 2009 John Wiley & Sons, Ltd.
Antigen-Specific T-Cell Response from Dendritic Cell Vaccination Using Cancer Stem-Like Cell-Associated Antigens
Authors: Xu Qijin , Liu Gentao , Yuan Xiangpeng , Xu Minlin , Wang Hongqiang , Ji Jianfei , Konda Bindu , Black Keith L. , Yu John S.
Published: April 2009

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body's own immune system to target cancers and could overcome the limitations of conventional treatments. One active immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T-cell-mediated antitumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression, and resistance to current treatments. However, whether using human CSC antigens may improve the antitumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced antitumor immunity. We found that CSCs express high levels of tumor-associated antigens as well as major histocompatibility complex molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T-cell responses against CSCs. DC vaccination-induced interferon-γ production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced cytotoxic T lymphocytes (CTLs) against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior antitumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.

Disclosure of potential conflicts of interest is found at the end of this article.
Wnt3a-Induced Mesoderm Formation and Cardiomyogenesis in Human Embryonic Stem Cells
Authors: Tran Thanh H. , Wang Xiurong , Browne Carol , Zhang Yunyu , Schinke Martina , Izumo Seigo , Burcin Mark
Published: April 2009

In vitro differentiation of human embryonic stem cells (hESCs) into pure human cardiomyocytes (hESCMs) would present a powerful tool to further the creation of cell models designed to advance preclinical drug development. Here, we report a novel differentiation method to substantially increase hESCM yield. Upon early and transient treatment of hESCs with Wnt3a, embryoid body and mesendoderm formation is enhanced, leading to greater differentiation toward cardiomyocytes. Moreover, the generated beating clusters are highly enriched with cardiomyocytes (50%) and express genes characteristic of cardiac cells, providing evidence that these hESCMs are competent to develop in vitro into functional and physiologically relevant cardiomyocytes. In summary, this protocol not only has the potential to guarantee a renewable supply of enriched cardiomyocyte populations for developing novel and more predictive cell models, but it also should provide valuable insights into pathways critical for cardiac regeneration.

Disclosure of potential conflicts of interest is found at the end of this article.
EpCAM Is Involved in Maintenance of the Murine Embryonic Stem Cell Phenotype
Authors: González Bárbara , Denzel Sabine , Mack Brigitte , Conrad Marcus , Gires Olivier
Published: April 2009

Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is expressed on subsets of normal epithelia, numerous stem- and progenitor-type cells, and most carcinomas and highly overexpressed on cancer-initiating cells. The role of EpCAM in early development, particularly in stem-like cells, has remained unclear. Here, we show that the maintenance of self-renewal in murine embryonic stem (ES) cells depends on the high-level expression of EpCAM. Cultivation of ES cells under differentiation conditions in the absence of leukemia inhibitory factor (LIF) caused down-regulation of EpCAM along with decreased expression of cellular myelocytomatosis oncogene (c-Myc), Sex-determining region Y-Box 2, Octamer 3/4 (Oct3/4), and Stat3. As a consequence ES cells were morphologically differentiated and ceased to proliferate. RNA interference-mediated inhibition of EpCAM expression under self-renewal conditions resulted in quantitatively decreased proliferation, decreased Oct3/4, SSEA-1, and c-Myc expression, and diminished alkaline phosphatase activity. Conversely, exogenous expression of EpCAM partially compensated for the requirement of ES cells for LIF to retain a stem cell phenotype. Thus, murine EpCAM is a transmembrane protein, which is essential but by itself is not sufficient for maintenance of the ES cell phenotype.

Disclosure of potential conflicts of interest is found at the end of this article.
Proliferation of Human Glioblastoma Stem Cells Occurs Independently of Exogenous Mitogens
Authors: Kelly John J. P. , Stechishin Owen , Chojnacki Andrew , Lun Xueqing , Sun Beichen , Senger Donna L. , Forsyth Peter , Auer Roland N. , Dunn Jeff F. , Cairncross J. Gregory , Parney Ian F. , Weiss Samuel
Published: April 2009

Primary glial tumors of the central nervous system, most commonly glioblastoma multiforme (GBM), are aggressive lesions with a dismal prognosis. Despite identification and isolation of human brain tumor stem cells (BTSCs), characteristics that distinguish BTSCs from neural stem cells remain to be elucidated. We cultured cells isolated from gliomas, using the neurosphere culture system, to understand their growth requirements. Both CD133+ and CD133− adult GBM BTSCs proliferated in the absence of exogenous mitogenic stimulation and gave rise to multipotent GBM spheres that were capable of self-renewal. Epidermal growth factor (EGF) and fibroblast growth factor-2 enhanced GBM BTSC survival, proliferation, and subsequent sphere size. Blockade of EGF receptor (EGFR) signaling reduced exogenous mitogen-independent GBM sphere growth. Implantation of as few as 10 exogenous mitogen-independent GBM BTSCs led to the formation of highly invasive intracranial tumors, which closely resembled human GBMs, in immunocompromised mice. These results demonstrate that exogenous mitogen independence, mediated in part through EGFR signaling, is one characteristic that distinguishes CD133+ and CD133− GBM BTSCs from neural stem cells. This novel experimental system will permit the elucidation of additional constitutively activated mechanisms that promote GBM BTSC survival, self-renewal, and proliferation.

Disclosure of potential conflicts of interest is found at the end of this article.
Regulation of Neural Specification from Human Embryonic Stem Cells by BMP and FGF
Authors: LaVaute Timothy M. , Yoo Young Dong , Pankratz Matthew T. , Weick Jason P. , Gerstner Jason R. , Zhang Su-Chun
Published: April 2009

Inhibition of bone morphogenetic protein (BMP) signaling is required for vertebrate neural induction, and fibroblast growth factors (FGFs) may affect neural induction through phosphorylation at the linker region of Smad1, thus regulating BMP signaling. Here we show that human embryonic stem cells efficiently convert to neuroepithelial cells in the absence of BMP antagonists, or even when exposed to high concentrations of exogenous BMP4. Molecular and functional analyses revealed multiple levels of endogenous BMP signaling inhibition that may account for the efficient neural differentiation. Blocking FGF signaling inhibited neural induction, but did not alter the phosphorylation of the linker region of Smad1, suggesting that FGF enhances human neural specification independently of BMP signaling.

Disclosure of potential conflicts of interest is found at the end of this article.
Congenital disorder of glycosylation type Ia: Heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency
Authors: Shanti B. , Silink M. , Bhattacharya K. , Howard N. J. , Carpenter K. , Fietz M. , Clayton P. , Christodoulou J.
Published: April 2009

We describe three patients with congenital disorder of glycosylation (CDG) type Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to diazoxide therapy as a common feature. The first patient, an infant girl, presented with recurrent vomiting, failure to thrive, liver impairment, hypothyroidism and a pericardial effusion. The second patient, also female, had a milder disease with single organ involvement, presenting as isolated hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment. The third patient, a boy presented with multi‐organ manifestations including congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia, coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All three patients had a type 1 serum transferrin isoform pattern, and were subsequently found to have low phosphomannomutase activity, confirming the diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as a differential diagnosis in patients with persistent hyperinsulinaemic hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia.
Intraguild predation of water scorpion Laccotrephes japonensis (Nepidae: Heteroptera)
Authors: Ohba Shin‐ya , Swart Charles C.
Published: April 2009

Previous work on community structure of the invertebrate fauna of Japanese wetlands indicates the presence of intraguild predation between the heteropterans Laccotrephes japonensis (Nepidae) and Kirkaldyia deyrolli (Belostomatidae). We designed a series of experiments to understand the biotic interactions of several species of sympatric heteroptera and their shared prey. Adult Laccotrephes japonensis (Nepidae), first‐instar nymph of Kirkaldyia (=Lethocerus) deyrolli (Belostomatidae), Hyla japonica tadpole, and fourth‐instar nymph of Appasus japonicus (Belostomatidae) have been shown to be intraguild predator, intraguild prey, common prey, and prey of L. japonensis, respectively. To further understand the factors affecting prey preference by L. japonensis, we also examined the comparison of swimming speed in the three prey animals (K. deyrolli first‐instar nymph, A. japonicus fourth‐instar nymph, and H. japonica tadpole), and effects of prey animals on weight gain of L. japonensis adult. Despite there being no significant difference in weight gain or swimming speed of the three prey species, L. japonensis exhibited a strong preference for the 1st‐instar nymph of K. deyrolli. We suggested that this may be evidence for one of elimination of a potential competitor, K. deyrolli, by L. japonensis through intraguild predation.
Intense Red Catho- and Photoluminescence from 200 nm Thick Samarium Doped Amorphous AlN Thin Films
Authors: Maqbool Muhammad , Ali Tariq
Published: April 2009

Samarium (Sm) doped aluminum nitride (AlN) thin films are deposited on silicon (100) substrates at 77 K by rf magnetron sputtering method. Thick films of 200 nm are grown at 100–200 watts RF power and 5–8 m Torr nitrogen, using a metal target of Al with Sm. X-ray diffraction results show that films are amorphous. Cathodoluminescence (CL) studies are performed and four peaks are observed in Sm at 564, 600, 648, and 707 nm as a result of4G5/2→6H5/2,4G5/2→6H7/2,4G5/2→6H9/2, and4G5/2→6H11/2transitions. Photoluminescence (PL) provides dominant peaks at 600 and 707 nm while CL gives the intense peaks at 600 nm and 648 nm, respectively. Films are thermally activated at 1,200 K for half an hour in a nitrogen atmosphere. Thermal activation enhances the intensity of luminescence.
Ultra-fast Microwave Synthesis of ZnO Nanowires and their Dynamic Response Toward Hydrogen Gas
Authors: Qurashi Ahsanulhaq , Tabet N , Faiz M , Yamzaki Toshinari
Published: April 2009

Ultra-fast and large-quantity (grams) synthesis of one-dimensional ZnO nanowires has been carried out by a novel microwave-assisted method. High purity Zinc (Zn) metal was used as source material and placed on microwave absorber. The evaporation/oxidation process occurs under exposure to microwave in less than 100 s. Field effect scanning electron microscopy analysis reveals the formation of high aspect-ratio and high density ZnO nanowires with diameter ranging from 70 to 80 nm. Comprehensive structural analysis showed that these ZnO nanowires are single crystal in nature with excellent crystal quality. The gas sensor made of these ZnO nanowires exhibited excellent sensitivity, fast response, and good reproducibility. Furthermore, the method can be extended for the synthesis of other oxide nanowires that will be the building block of future nanoscale devices.
Enhanced Luminescence of Eu-Doped TiO2Nanodots
Authors: Luo Ming , Cheng Kui , Weng Wenjian , Song Chenlu , Du Piyi , Shen Ge , Xu Gang , Han Gaorong
Published: April 2009

Monodisperse and spherical Eu-doped TiO2nanodots were prepared on substrate by phase-separation-induced self-assembly. The average diameters of the nanodots can be 50 and 70 nm by changing the preparation condition. The calcined nanodots consist of an amorphous TiO2matrix with Eu3+ions highly dispersed in it. The Eu-doped TiO2nanodots exhibit intense luminescence due to effective energy transfer from amorphous TiO2matrix to Eu3+ions. The luminescence intensity is about 12.5 times of that of Eu-doped TiO2film and the luminescence lifetime can be as long as 960 μs.
Differential expression of Dicer and Argonaute genes duringthe differentiation of human neuroblastoma cells
Authors: Potenza Nicoletta , Papa Umberto , Russo Aniello
Published: April 2009

Dicer and Argonaute 1–4 proteins are key components of the cytoplasmic enzyme machinery responsible for biogenesis and performance of microRNAs. To gain insight into the roles of these proteins in cell differentiation, we investigated possible changes in the expression levels of Dicer and Argonaute 1–4 genes during the differentiation of cultured neural and glial cells. The results show that the 5 genes are differentially expressed along the 2 differentiation pathways and suggest a prevalent role of Dicer and Argonaute 4 in neural cell differentiation.
Background ELF magnetic fields in incubators: A factor of importance in cell culture work
Authors: Mild Kjell Hansson , Wilén Jonna , Mattsson Mats‐Olof , Simko Myrtill
Published: April 2009

Extremely low frequency (ELF) magnetic fields in cell culture incubators have been measured. Values of the order of tens of μT were found which is in sharp contrast to the values found in our normal environment (0.05–0.1 μT). There are numerous examples of biological effects found after exposure to MF at these levels, such as changes in gene expression, blocked cell differentiation, inhibition of the effect of tamoxifen, effects on chick embryo development, etc. We therefore recommend that people working with cell culture incubators check for the background magnetic field and take this into account in performing their experiments, since this could be an unrecognised factor of importance contributing to the variability in the results from work with cell cultures.
Comparison of murine dental follicle precursor and retinal progenitor cells after neural differentiation in vitro
Authors: Ernst Wolfgang , Saugspier Michael , Felthaus Oliver , Driemel Oliver , Morsczeck Christian
Published: April 2009

Human dental stem or precursor cells can differentiate into multiple cell types like adipocytes, osteoblasts or chondrocytes. Recently, a number of different human dental stem cell lines were differentiated into neurons. This makes dental stem cells interesting as possible cell‐based therapeutics for neural degenerative diseases. To test this hypothesis, we have investigated the neural differentiation potential of murine dental follicle precursor cells (mDFPCs). The mDFPC cell line was newly established without cell immortalization. After differentiation, neural cell marker expression in mDFPCs was checked and compared with that of murine retinal progenitor cells (mRPCs). Differentiated mDFPCs became neuron‐like cells with small cell bodies and long/branching neurites, similar to differentiated mRPCs. However, mRPCs showed more complete neural differentiation. Furthermore, 5% of the differentiated mDFPCs and 37% of the differentiated mRPCs were positive for the glia cell marker GFAP (glial fibrillary acidic protein). The data presents new evidence of neural differentiation of mDFPCs, but only a small percentage of mDFPCs differentiated into glia cells, unlike mRPCs.
Effect of FK506 and cyclosporine A on the expression of BDNF, tyrosine kinase B and p75 neurotrophin receptors in astrocytes exposed to simulated ischemia in vitro
Authors: Gabryel Bozena , Bernacki Jacek
Published: April 2009

We investigated whether the immunosuppressive drugs, FK506 and cyclosporine A, increase BDNF protein and/or mRNA expression in ischemic astrocytes and if an increase could be related to changes in the nuclear expression of p‐CREB, p‐Erk1/2 and p‐Akt. The influence of these immunosuppressants on protein and mRNA levels of TrkB and p75NTR receptors was also examined. On day 21, cultures of rat astrocytes were subjected to ischemic conditions simulated in vitro (combined oxygen glucose deprivation, OGD) for 8 h and exposed to FK506 (10–1000 nM) and cyclosporine A (0.25–10 μM). FK506 and cyclosporine A (at 1000 nM and 0.25 μM, respectively) stimulated the expression and release of BDNF in cultured rat cerebral cortical astrocytes exposed to OGD. The immunosuppressants at these doses simultaneously increased p‐CREB and p‐Erk1/2 expression in the nuclear fraction of astrocytes. The results RT‐PCR and Western blot analysis provided further evidence of a modulating influence of the drugs on the expression of trkB and p75NTR genes and their protein products in ischemic astrocytes.
Three key variables involved in feeder preparation for the maintenance of human embryonic stem cells
Authors: Zhou Di , Liu Tiancheng , Zhou Xiaoying , Lu Guangxiu
Published: April 2009

Although the development of a feeder‐free culture system for future applications of human embryonic stem cells (hESCs), at present the regular culture system uses mitotically inactivated mouse embryonic fibroblasts (mEFs) as feeder cells for maintaining undifferentiated hESCs. Mitomycin C (MMC) is used to inactivate mEFs, but this causes DNA damage, and it is unclear whether MMC remains in the culture system after several washes. Three variables have been evaluated with respect to feeder preparation and MMC involvement, including mEF exposure to MMC, density of feeder cells, and different wash steps during the preparation of feeder cells. These variables are critical to the subsequent planting of hESCs because remnants of MMC would be unsafe with respect to long‐term culture of hESCs The novel data here evaluates the remnant amounts of MMC in a hESCs culture system using HPLC/MS/MS. The ultimate objective of this study is the control of MMC within a safe range.