bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Cu/Co bilayer gate electrodes using selective chemical vapor deposition and soft lithographic patterning
Authors: Yang H. J. , Lee J. , Kim S. , Ko Y. K. , Shin H. J. , Lee J. G. , Kim C. , Sung M. M. , Bang H. J. , Cho B. S. , Bae Y. H. , Lee J. H. , Kim D. H. , Jeong C. O. , Kim S. Y. , Lim S. K.
Published: December 2006

A templated Cu/Co bilayer gate electrode was fabricated using the combined method of consecutive and selective chemical vapor deposition (CVD), and octadecyltrichlorosilane (OTS) microcontact printing techniques. Soft lithographically patterned self-assembled monolayers (SAMs) can direct the growth of Co occurring at the low temperatures 50–90 °C and serve as a template for the consecutive and selective growth of Cu, thereby forming stable and high quality Cu/Co bilayer gate electrodes on a glass substrate. This simple process provides fewer process steps and higher performance than other conventional processes, and can be applied to the fabrication of large area and high resolution thin film transistor liquid crystal displays.
Correlation between micropipes on SiC substrate and dc characteristics of AlGaN∕GaN high-electron mobility transistors
Authors: Bang Hyungjin , Mitani Takeshi , Nakashima Shinichi , Sazawa Hiroyuki , Hirata Koji , Kosaki Masayoshi , Okumura Hajime
Published: December 2006

We report the influence of the size of hollow cores that extend from micropipes in SiC substrates on the dc characteristics of AlGaN∕GaN high-electron mobility transistors (HEMTs) fabricated on the substrates. Significant deterioration of the dc characteristics of HEMTs fabricated in the vicinity of hollow cores with a diameter of 5μm was observed, while no major deterioration was observed for HEMTs fabricated around hollow cores whose diameters were 1.5 and 3μm. A clear correlation between the size of hollow cores and free carrier densities at the peripheries of the cores was observed using micro-Raman imaging. The high densities of free carriers around relatively large hollow cores were suggested to be the cause of deterioration of the dc characteristics of HEMTs fabricated in the vicinity of the hollow cores. The device deterioration length with respect to the hollow core size was empirically deduced, and the effective decrease in the wafer yield was estimated as well.
Effects of interlayer exchange coupling on transport properties of Co∕Pd metallic multilayers with perpendicular magnetic anisotropy
Authors: Chihaya H. , Kamiko M. , Yamamoto R.
Published: December 2006

Ru-mediated interlayer exchange coupling (IEC) was introduced in Co∕Pd(111) metallic multilayers with perpendicular magnetic anisotropy. The magnetic and electronic transport properties were investigated. The magnetically controlled Co∕Pd(111) multilayers exhibited unique resistivity changes. This is quite common in perpendicular antiferromagnetically (AF) coupled systems where the AF coupled multilayer stacks switch separately during field reversal. However, we found that even within the stacks, the individual ferromagnetic layers switch separately, such that the AF configurations are present during reversal even within the same multilayer stack. On considering the magnetic reversal and transport properties of the Co∕Pd multilayers, the IEC was found to cause antiferromagnetic alignment inside a multilayer stack that was sandwiched between two Ru layers. This phenomenon is mainly due to the thicker Pd films between the Co layers that allow more decoupling of individual Co layers than those employed in most of the previous studies.
Highly sensitive and ultrafast light modulation with a vanadyloxophthalocyanine-doped composite polymer guided wave mode device
Authors: Matsumoto Ryuji , Nagamura Toshihiko
Published: December 2006

We propose a guided wave mode (GWM) device with prism coupling, which is composed of a low-refractive-index polymer layer and a vanadyloxophthalocyanine-doped polymer layer. Reflectance dips due to the GWM were observed at specific incident angles depending on the wavelength and the thickness of each layer. The reflectance at the GWM can be controlled by the real part (n) and/or the imaginary part (k) of the complex refractive index of the waveguide layer. The k dependence of reflectance showing a minimum of almost zero at a certain value defined as kc was confirmed in the visible to near infrared region. The kc value varies linearly with the intensity of the evanescent wave. Highly sensitive and ultrafast control of reflection in the GWM geometry was demonstrated by the photoinduced complex refractive-index change upon femtosecond laser excitation of vanadyloxophthalocyanine.
Controlled formation of individually seeded, electrically addressable silicon nanowire arrays for device integration
Authors: Chang Ying-Lan , Yi Sung Soo , Chow Edmond , Girolami Grant , Young Yim , Liu Maozi , Albuschies Jörg , Amano Jun
Published: December 2006

The formation of large-scale arrays of individually seeded, electrically addressable Si nanowires with controlled dimension, placement, and orientation is demonstrated. Electron beam evaporated gold nanoparticles were used for nanowire synthesis. By controlling the lithography and metal deposition conditions, nanowire arrays with narrow size distributions have been achieved. Low-energy postgrowth ion beam treatment has been utilized to control the orientation of Si nanowires. This process also leads to the attachment of nanowires on the substrate. Fabrication of planar devices with robust metal contact formation becomes feasible. The method enables efficient and economical integration of nanowires into device architectures for various applications.
Electrical characterization of Fermi level pinning in metal/3,4,9,10 perylenetetracarboxylic dianhydride interfaces
Authors: Agrawal Ruchi , Ghosh Subhasis
Published: December 2006

Systematic studies of current injection from different metal electrodes to metal/3,4,9,10 perylenetetracarboxylic dianhydride (PTCDA) interfaces have been carried out. It has been observed that the barrier for carrier injection cannot be explained by simple vacuum alignment scheme. Moreover, injection barrier is almost independent of metal work function. These observations are explained by the changes of barrier height due to interface dipole barrier which compensate for the difference of work function of PTCDA and metals, leading to metal independent injection barrier and Fermi level pinning at metal/PTCDA interfaces.
Influence of paramagnetic defects on multicolored luminescence from nanocrystalline silicon
Authors: Sato Keisuke , Hirakuri Kenji
Published: December 2006

We report on the correlation between paramagnetic defects and the luminescent properties of nanocrystalline silicon (nc-Si) using electron spin resonance (ESR) and photoluminescence measurements. Nanocrystalline silicon having particle sizes from 1.9to3.0nm exhibited continuous luminescence from blue to red wavelengths. However, the density of nc-Si decreased as the luminescent color was shifted towards blue. Red/green/blue luminescent nc-Si contained three kinds of ESR centers, two nonradiative recombination centers (an a center and a Pb center), and a radiative recombination center (a Pce′ center). The a, Pb, and Pce′ centers originate from a Si dangling bond in nc-Si, a Si dangling bond in the nc-Si/silicon dioxide (SiO2) interface region, and electrons trapped in localized states close to the conduction band edge in the vicinity of the nc-Si surface, respectively. The spin densities of the Pb and Pce′ centers increased with the blueshift of the luminescent color. Increasing the spin density of the Pb center and reducing the density of nc-Si led to a reduction in the intensity from the red to the blue luminescence. These results indicate that this reduction in intensity as the emission was shifted towards blue was due to the presence of many Pb centers in a single particle and the generation of a little density of nc-Si.
Frequency stabilization of transverse Zeeman He–Ne laser by means of model predictive control
Authors: Lin Dejiao , Dai Gaoliang , Yin Chunyong , Jiang Xiangqian
Published: December 2006

A model predictive control (MPC) technique is proposed for the frequency stabilization of transverse Zeeman He–Ne laser. The beat frequency locking method is applied as the criterion of frequency stabilization. When heated by the voltage output of the feedback electronic circuit, the copper wire twisted around the laser tube is applied to maintain the length of the laser cavity and stabilize the frequency of the laser. Four steps for MPC design, i.e., model setup, output prediction, selection of reference path, and calculation of control quality, have been introduced. By this means, a single-chip microprocessor (80C196) generates a pulse width modulation wave that is transferred into a heating signal. The calibration result shows that the frequency stability of our proposed transverse Zeeman laser reaches 5.5×10−11 by means of the MPC method.
Quartet states of the acetylene cation: Electronic structure calculations and spin-orbit coupling terms
Authors: Hochlaf M. , Taylor S. , Eland J. H. D.
Published: December 2006

Highly correlated ab initio methods have been used to generate one-dimensional cuts of the six-dimensional potential energy surfaces of the quartet and lowest doublet states for the HCCH+ ion along the CH, CC, and cis and trans bending coordinates. Transition dipole moments and spin-orbit matrix elements are deduced. For the lowest 1Σu+4 state, the calculations predict a possible photon emission through the 1Πg4←1Σu+4 transition competing with internal conversion and predissociation processes. The potential surfaces are used together with spin-orbit matrix elements to discuss the metastability and the predissociation processes forming the C2H∕C2H++H+∕H products. Multistep spin-orbit induced predissociation pathways are suggested.
Color-variable organic light-emitting device by external light irradiation
Authors: Sakaguchi Koichi , Oosawa Takeru , Chikamatsu Masayuki , Yoshida Yuji , Azumi Reiko , Yase Kiyoshi
Published: December 2006

The authors demonstrate a color-variable organic light-emitting device by external light irradiation, where an organic photoelectric conversion layer out of titanyl phthalocyanine is inserted between blue- and green-emitting layers. By near-infrared (780nm) laser irradiation, the emission color is varied from blue to green. The color coordinate in Commission Internationale de l’Eclairage chromaticity is varied from (0.201, 0.193) to (0.302, 0.445). The color change mechanism can be interpreted by the change in carrier balance caused by the photocarrier generation in the device, resulting in the change in charge recombination site.
Microheaters fabricated from a conducting composite
Authors: Liu Liyu , Peng Suili , Niu Xize , Wen Weijia
Published: December 2006

The authors report the fabrication of microheaters based on a conducting composite of silver microparticles embedded in polydimethylsioxane (PDMS). Experimental results show that the microheaters exhibit good performance in temperature rise and decay characteristics, with localized heating at targeted spatial domains. A unique feature of the microheater here is its excellent integration capability with biocompatible PDMS and other polymer materials, with potential microchip applications for bioprocessing and chemical reactions.
Multispectral pixel performance using a one-dimensional photonic crystal design
Authors: Sun X. C. , Hu J. J. , Hong C. Y. , Viens J. F. , Duan X. M. , Das R. , Agarwal A. M. , Kimerling L. C.
Published: December 2006

A photodetector pixel using a photonic crystal structure incorporating photoconductive layers has been realized. The fabricated device exploits mode discrimination and resonant cavity enhancement to provide simultaneous multispectral detection capability, high quantum efficiency, and dramatically suppressed shot noise. Detectivities as high as 2.6×1010 and 2.0×1010cmHz1∕2W−1 at the two preselected wavelengths, 632 and 728nm, were achieved, respectively.
Application of atomic magnetometry in magnetic particle detection
Authors: Xu S. , Donaldson M. H. , Pines A. , Rochester S. M. , Budker D. , Yashchuk V. V.
Published: December 2006

The authors demonstrate the detection of magnetic particles carried by water in a continuous flow using an atomic magnetic gradiometer. Studies on three types of magnetic particles are presented: a single cobalt particle (diameter ∼150μm, multidomain), a suspension of superparamagnetic magnetite particles (diameter ∼1μm), and ferromagnetic cobalt nanoparticles (diameter ∼10nm). Estimated detection limits are 20μm diameter for a single cobalt particle at a water flow rate of 30ml∕min, 5×103 magnetite particles at 160ml∕min, and 50pl for the ferromagnetic fluid of cobalt nanoparticles at 130ml∕min. Possible applications of their method are discussed.
Interaction induced shifts in O–H stretching frequency of water in halide-ion water clusters: A microscopic approach with a bond descriptor
Authors: Tanwar Akhilesh , Bagchi Biman , Pal Sourav
Published: December 2006

Based on conceptual density functional theory, two new descriptors, the normalized atom-condensed Fukui functions (NFFs) and bond deformation kernel (BDK), are proposed to describe the O–H stretching frequency shifts in water halide-ion clusters by including local polarizations in the system. NFF, along with BDK, can be successfully used to describe interactions between different atoms, especially in cases where polarizations are quite important.
Dissociation dynamics of positive-ion and negative-ion fragments of gaseous and condensed Si(CH3)2Cl2 via Si 2p, Cl 2p, and Cl 1s core-level excitations
Authors: Chen J. M. , Lu K. T. , Lee J. M. , Chen C. K. , Haw S. C.
Published: December 2006

The state-selective positive-ion and negative-ion dissociation pathways of gaseous and condensed Si(CH3)2Cl2 following Cl 2p, Cl 1s, and Si 2p core-level excitations have been characterized. The excitations to a specific antibonding state (15a1* state) of gaseous Si(CH3)2Cl2 at the Cl 2p, Cl 1s, and Si 2p edges produce significant enhancement of fragment ions. This ion enhancement at specific core-excited states correlates closely with the ion kinetic energy distribution. The results deduced from ion kinetic energy distribution are consistent with results of quantum-chemical calculations on Si(CH3)2Cl2 using the ADF package. The Cl− desorption yields for Si(CH3)2Cl2∕Si(100) at ∼90K are notably enhanced at the 15a1* resonance at both Cl 2p and Si 2p edges. The resonant enhancement of Cl− yield occurs through the formation of highly excited states of the adsorbed molecules. These results provide insight into the state-selective ionic fragmentation of molecules via core-level excitation.
Dominance of SOX9 function over RUNX2 during skeletogenesis
Authors: Zhou Guang , Zheng Qiping , Engin Feyza , Munivez Elda , Chen Yuqing , Sebald Eiman , Krakow Deborah , Lee Brendan
Published: December 2006

Mesenchymal stem cell-derived osteochondroprogenitors express two master transcription factors, SOX9 and RUNX2, during condensation of the skeletal anlagen. They are essential for chondrogenesis and osteogenesis, respectively, and their haploinsufficiency causes human skeletal dysplasias. We show that SOX9 directly interacts with RUNX2 and represses its activity via their evolutionarily conserved high-mobility-group and runt domains. Ectopic expression of full-length SOX9 or its RUNX2-interacting domain in mouse osteoblasts results in an osteodysplasia characterized by severe osteopenia and down-regulation of osteoblast differentiation markers. Thus, SOX9 can inhibit RUNX2 function
in vivo
even in established osteoblastic lineage. Finally, we demonstrate that this dominant inhibitory function of SOX9 is physiologically relevant in human campomelic dysplasia. In campomelic dysplasia, haploinsufficiency of
SOX9
results in up-regulation of the RUNX2 transcriptional target
COL10A1
as well as all three members of
RUNX
gene family. In summary, SOX9 is dominant over RUNX2 function in mesenchymal precursors that are destined for a chondrogenic lineage during endochondral ossification.
FHIT-proteasome degradation caused by mitogenic stimulation of the EGF receptor family in cancer cells
Authors: Bianchi Francesca , Magnifico Alessandra , Olgiati Clelia , Zanesi Nicola , Pekarsky Yuri , Tagliabue Elda , Croce Carlo Maria , Ménard Sylvie , Campiglio Manuela
Published: December 2006

The tumor suppressor gene
FHIT
is inactivated by genetic and epigenetic changes in the majority of common human cancers. The human Fhit protein undergoes phosphorylation on tyrosine residue 114 by Src and related kinases both
in vitro
and
in vivo
. Src is a key cytoplasmic tyrosine kinase downstream to several growth factor receptors, including those of the EGF receptor family, which are overexpressed and activated in about one-third of human breast and ovarian carcinomas. However, the biological significance of Fhit phosphorylation by Src has remained elusive. In the present study, we demonstrate that
FHIT
acts as a checkpoint in cell proliferation mediated by activated tyrosine kinase receptors that recruit Src. Activation of EGF receptor family members induced Fhit phosphorylation by Src and the subsequent proteasome degradation of the phosphorylated Fhit protein. Indeed, the use of the Fhit mutant Y114F, which carries a phenylalanine instead of a tyrosine at position 114, unable to be phosphorylated on tyrosine 114 by Src, prevents Fhit degradation. Moreover, Fhit protein reduction is transient and occurs in a specific temporal window. During the signaling pathway of activated tyrosine kinase receptors, the phosphorylation of Fhit induces its degradation and the subsequent reduction in Fhit protein levels allows the transmission of the mitogenic signal; immediately thereafter, Fhit protein levels are restored. Such a scenario would suggest a key role for Fhit in the balance of proliferation/survival/apoptosis signals.
Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5α
Authors: Newman Ruchi M. , Hall Laura , Connole Michelle , Chen Guo-Lin , Sato Shuji , Yuste Eloisa , Diehl William , Hunter Eric , Kaur Amitinder , Miller Gregory M. , Johnson Welkin E.
Published: December 2006

Retroviral restriction factor TRIM5α exhibits a high degree of sequence variation among primate species. It has been proposed that this diversity is the cumulative result of ancient, lineage-specific episodes of positive selection. Here, we describe the contribution of within-species variation to the evolution of TRIM5α. Sampling within two geographically distinct Old World monkey species revealed extensive polymorphism, including individual polymorphisms that predate speciation (shared polymorphism). In some instances, alleles were more closely related to orthologues of other species than to one another. Both silent and nonsynonymous changes clustered in two domains. Functional assays revealed consequences of polymorphism, including differential restriction of a small panel of retroviruses by very similar alleles. Together, these features indicate that the primate TRIM5α locus has evolved under balancing selection. Except for the MHC there are few, if any, examples of long-term balancing selection in primates. Our results suggest a complex evolutionary scenario, in which fixation of lineage-specific adaptations is superimposed on a subset of critical polymorphisms that predate speciation events and have been maintained by balancing selection for millions of years.
Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis
Authors: Zaragoza Carlos , Saura Marta , Padalko Elizaveta Y. , Lopez-Rivera Ester , Lizarbe Tania R. , Lamas Santiago , Lowenstein Charles J.
Published: December 2006

Apoptosis is an innate immune response to viral infection that limits viral replication. However, the mechanisms by which cells detect viral infection and activate apoptosis are not completely understood. We now show that during Coxsackievirus infection, the viral protease 3C
pro
cleaves inhibitor of κBα (IκBα). A proteolytic fragment of IκBα then forms a stable complex with NF-κB, translocates to the nucleus, and inhibits NF-κB transactivation, increasing apoptosis and decreasing viral replication. In contrast, cells with reduced IκBα expression are more susceptible to viral infection, with less apoptosis and more viral replication. IκBα thus acts as a sensor of viral infection. Cleavage of host proteins by pathogen proteases is a novel mechanism by which the host recognizes and responds to viral infection.
ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease
Authors: Ryu Hoon , Lee Junghee , Hagerty Sean W. , Soh Byoung Yul , McAlpin Sara E. , Cormier Kerry A. , Smith Karen M. , Ferrante Robert J.
Published: December 2006

Chromatin remodeling and transcription regulation are tightly controlled under physiological conditions. It has been suggested that altered chromatin modulation and transcription dysfunction may play a role in the pathogenesis of Huntington's disease (HD). Increased histone methylation, a well established mechanism of gene silencing, results in transcriptional repression. ERG-associated protein with SET domain (ESET), a histone H3 (K9) methyltransferase, mediates histone methylation. We show that ESET expression is markedly increased in HD patients and in transgenic R6/2 HD mice. Similarly, the protein level of trimethylated histone H3 (K9) was also elevated in HD patients and in R6/2 mice. We further demonstrate that both specificity protein 1 (Sp1) and specificity protein 3 (Sp3) act as transcriptional activators of the ESET promoter in neurons and that mithramycin, a clinically approved guanosine–cytosine-rich DNA binding antitumor antibiotic, interferes with the DNA binding of these Sp family transcription factors, suppressing basal ESET promoter activity in a dose dependent manner. The combined pharmacological treatment with mithramycin and cystamine down-regulates ESET gene expression and reduces hypertrimethylation of histone H3 (K9). This polytherapy significantly ameliorated the behavioral and neuropathological phenotype in the R6/2 mice and extended survival over 40%, well beyond any existing reported treatment in HD mice. Our data suggest that modulation of gene silencing mechanisms, through regulation of the ESET gene is important to neuronal survival and, as such, may be a promising treatment in HD patients.
Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors
Authors: Paoletti Andrew C. , Parmely Tari J. , Tomomori-Sato Chieri , Sato Shigeo , Zhu Dongxiao , Conaway Ronald C. , Conaway Joan Weliky , Florens Laurence , Washburn Michael P.
Published: December 2006

Components of multiprotein complexes are routinely determined by using proteomic approaches. However, this information lacks functional content except when new complex members are identified. To analyze quantitatively the abundance of proteins in human Mediator we used normalized spectral abundance factors generated from shotgun proteomics data sets. With this approach we define a common core of mammalian Mediator subunits shared by alternative forms that variably associate with the kinase module and RNA polymerase (pol) II. Although each version of affinity-purified Mediator contained some kinase module and RNA pol II, Mediator purified through F-Med26 contained the most RNA pol II and the least kinase module as demonstrated by the normalized spectral abundance factor approach. The distinct forms of Mediator were functionally characterized by using a transcriptional activity assay, where F-Med26 Mediator/RNA pol II was the most active. This method of protein complex visualization has important implications for the analysis of multiprotein complexes and assembly of protein interaction networks.
Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis
Authors: Zhou Dun , Srivastava Rajneesh , Nessler Stefan , Grummel Verena , Sommer Norbert , Brück Wolfgang , Hartung Hans-Peter , Stadelmann Christine , Hemmer Bernhard
Published: December 2006

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Although the cause of MS is still uncertain, many findings point toward an ongoing autoimmune response to myelin antigens. Because of its location on the outer surface of the myelin sheath and its pathogenicity in the experimental autoimmune encephalomyelitis model, myelin oligodendrocyte glycoprotein (MOG) is one of the potential disease-causing self antigens in MS. However, the role of MOG in the pathogenesis of MS has remained controversial. In this study we addressed the occurrence of autoantibodies to native MOG and its implication for demyelination and axonal loss in MS. We applied a high-sensitivity bioassay, which allowed detecting autoantibodies that bind to the extracellular part of native MOG. Antibodies, mostly IgG, were found in sera that bound with high affinity to strictly conformational epitopes of the extracellular domain of MOG. IgG but not IgM antibody titers to native MOG were significantly higher in MS patients compared with different control groups with the highest prevalence in primary progressive MS patients. Serum autoantibodies to native MOG induced death of MOG-expressing target cellsin vitro. Serum from MS patients with high anti-MOG antibody titers stained white matter myelin in rat brain and enhanced demyelination and axonal damage when transferred to autoimmune encephalomyelitis animals. Overall these findings suggest a pathogenic antibody response to native MOG in a subgroup of MS patients.
GABA and G
i/o
differentially control circadian rhythms and synchrony in clock neurons
Authors: Aton Sara J. , Huettner James E. , Straume Martin , Herzog Erik D.
Published: December 2006

Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms
in vivo
. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We recorded firing and clock-gene expression patterns while blocking candidate signaling pathways for at least 8 days. GABA
A
and GABA
B
antagonism increased circadian peak firing rates and rhythm precision of cultured SCN neurons, but G
i/o
did not impair synchrony or rhythmicity. In contrast, inhibiting G
i/o
with pertussis toxin abolished rhythms in most neurons and desynchronized the population, phenocopying the loss of vasoactive intestinal polypeptide (VIP). Daily VIP receptor agonist treatment restored synchrony and rhythmicity to
VIP
−/−
SCN cultures during continuous GABA receptor antagonism but not during G
i/o
blockade. Pertussis toxin did not affect circadian cycling of the liver, suggesting that G
i/o
plays a specialized role in maintaining SCN rhythmicity. We conclude that endogenous GABA controls the amplitude of SCN neuronal rhythms by reducing daytime firing, whereas G
i/o
signaling suppresses nighttime firing, and it is necessary for synchrony among SCN neurons. We propose that G
i/o
, not GABA activity, converges with VIP signaling to maintain and coordinate rhythms among SCN neurons.
Dynamics of global transcriptome in bovine matured oocytes and preimplantation embryos
Authors: Misirlioglu M. , Page G. P. , Sagirkaya H. , Kaya A. , Parrish J. J. , First N. L. , Memili E.
Published: December 2006

Global activation of the embryonic genome is the most critical event in early mammalian development. After fertilization, a rich supply of maternal proteins and RNAs support development whereas a number of zygotic and embryonic genes are expressed in a stage-specific manner leading to embryonic genome activation (EGA). However, the identities of embryonic genes expressed and the mechanism(s) of EGA are poorly defined in the bovine. Using the Affymetrix bovine-specific DNA microarray as the biggest available array at present, we analyzed gene expression at two key stages of bovine development, matured oocytes (MII) and 8-cell-stage embryos, constituting the ultimate reservoir for life and a stage during which EGA takes place, respectively. Key genes in regulation of transcription, chromatin-structure cell adhesion, and signal transduction were up-regulated at the 8-cell stage as compared with 8-cell embryos treated with α-amanitin and MII. Genes controlling DNA methylation and metabolism were up-regulated in MII. These changes in gene expression, related to transcriptional machinery, chromatin structure, and the other cellular functions occurring during several cleavage stages, are expected to result in a unique chromatin structure capable of maintaining totipotency during embryogenesis and leading to differentiation during postimplantation development. Dramatic reprogramming of gene expression at the onset of development also has implications for cell plasticity in somatic cell nuclear transfer, genomic imprinting, and cancer.
Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells
Authors: Tsai Meng-Yin , Yeh Shauh-Der , Wang Ruey-Sheng , Yeh Shuyuan , Zhang Caixia , Lin Hung-Yun , Tzeng Chii-Ruey , Chang Chawnshang
Published: December 2006

Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (G-AR−/y) with normal spermatogenesis. Sperm count and motility in epididymis from AR−/ymice are similar to that of WT (G-AR+/y) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100% of female pups sired by G-AR−/ymales younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data providein vivoevidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell–cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR−/ymice with two other testicular cell-specific AR−/ymice and total AR knockout male mice. The results provide clearin vivoevidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR−/ymice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.
Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes
Authors: Legname Giuseppe , Nguyen Hoang-Oanh B. , Peretz David , Cohen Fred E. , DeArmond Stephen J. , Prusiner Stanley B.
Published: December 2006

On passaging synthetic prions, two isolates emerged with incubation times differing by nearly 100 days. Using conformational-stability assays, we determined the guanidine hydrochloride (Gdn·HCl) concentration required to denature 50% of disease-causing prion protein (PrP
Sc
) molecules, denoted as the [Gdn·HCl]
1/2
value. For the two prion isolates enciphering shorter and longer incubation times, [Gdn·HCl]
1/2
values of 2.9 and 3.7 M, respectively, were found. Intrigued by this result, we measured the conformational stabilities of 30 prion isolates from synthetic and naturally occurring sources that had been passaged in mice. When the incubation times were plotted as a function of the [Gdn·HCl]
1/2
values, a linear relationship was found with a correlation coefficient of 0.93. These findings demonstrate that (
i
) less stable prions replicate more rapidly than do stable prions, and (
ii
) a continuum of PrP
Sc
structural states enciphers a multitude of incubation-time phenotypes. Our data argue that cellular machinery must exist for propagating a large number of different PrP
Sc
conformers, each of which enciphers a distinct biological phenotype as reflected by a specific incubation time. The biophysical explanation for the unprecedented plasticity of PrP
Sc
remains to be determined.
Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms
Authors: Laxman Sunil , Riechers Aaron , Sadilek Martin , Schwede Frank , Beavo Joseph A.
Published: December 2006

African sleeping sickness is a disease caused byTrypanosoma brucei.T. bruceiproliferate rapidly in the mammalian bloodstream as long, slender forms, but at higher population densities they transform into nondividing, short, stumpy forms. This is thought to be a mechanism adopted byT. bruceito establish a stable host–parasite relationship and to allow a transition into the insect stage of its life cycle. Earlier studies have suggested a role for cAMP in mediating this transformation. In this study, using membrane-permeable nucleotide analogs, we show that it is not the cAMP analogs themselves but rather the hydrolyzed products of membrane-permeable cAMP analogs that prevent proliferation ofT. brucei. The metabolic products are more potent than the cAMP analogs, and hydrolysis-resistant cAMP analogs are not antiproliferative. We further show that the antiproliferative effect of these membrane-permeable adenosine analogs is caused by transformation into forms resembling short, stumpy bloodstream forms. These data suggest that the slender-to-stumpy transformation ofT. bruceimay not be mediated directly by cAMP and also raise the possibility of using such adenosine analogs as antitrypanosomal drugs.
Wide-field subdiffraction imaging by accumulated binding of diffusing probes
Authors: Sharonov Alexey , Hochstrasser Robin M.
Published: December 2006

A method is introduced for subdiffraction imaging that accumulates points by collisional flux. It is based on targeting the surface of objects by fluorescent probes diffusing in the solution. Because the flux of probes at the object is essentially constant over long time periods, the examination of an almost unlimited number of individual probe molecules becomes possible. Each probe that hits the object and that becomes immobilized is located with high precision by replacing its point-spread function by a point at its centroid. Images of lipid bilayers, contours of these bilayers, and large unilamellar vesicles are shown. A spatial resolution of ≈25 nm is readily achieved. The ability of the method to effect rapid nanoscale imaging and spatial resolution below Rayleigh criterion and without the necessity for labeling with fluorescent probes is proven.
RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea
Authors: Yuan Jing , Palioura Sotiria , Salazar Juan Carlos , Su Dan , O'Donoghue Patrick , Hohn Michael J. , Cardoso Alexander Machado , Whitman William B. , Söll Dieter
Published: December 2006

The trace element selenium is found in proteins as selenocysteine (Sec), the 21st amino acid to participate in ribosome-mediated translation. The substrate for ribosomal protein synthesis is selenocysteinyl-tRNA
Sec
. Its biosynthesis from seryl-tRNA
Sec
has been established for bacteria, but the mechanism of conversion from Ser-tRNA
Sec
remained unresolved for archaea and eukarya. Here, we provide evidence for a different route present in these domains of life that requires the tRNA
Sec
-dependent conversion of
O
-phosphoserine (Sep) to Sec. In this two-step pathway,
O
-phosphoseryl-tRNA
Sec
kinase (PSTK) converts Ser-tRNA
Sec
to Sep-tRNA
Sec
. This misacylated tRNA is the obligatory precursor for a Sep-tRNA:Sec-tRNA synthase (SepSecS); this protein was previously annotated as SLA/LP. The human and archaeal SepSecS genes complement
in vivo
an
Escherichia coli
Sec synthase (SelA) deletion strain. Furthermore, purified recombinant SepSecS converts Sep-tRNA
Sec
into Sec-tRNA
Sec
in vitro
in the presence of sodium selenite and purified recombinant
E. coli
selenophosphate synthetase (SelD). Phylogenetic arguments suggest that Sec decoding was present in the last universal common ancestor. SepSecS and PSTK coevolved with the archaeal and eukaryotic lineages, but the history of PSTK is marked by several horizontal gene transfer events, including transfer to non-Sec-decoding Cyanobacteria and fungi.
MotifScorer: using a compendium of microarrays to identify regulatory motifs
Authors: Brilli Matteo , Fani Renato , Lió Pietro
Published: December 2006

Summary: We describe MotifScorer, a program for systematic genome-wide identification of transcription sites. The program uses a compendium of gene expression microarrays and implements state-of-art partial least squares (PLSs) based regression and stepwise regression procedures. Candidate motifs from the upstream sequences of groups of co-regulated genes are identified and assigned a score using genomic background models and available motif finding tools. The use of a large library of expression data allows statistical comparative analysis of the specificity of motifs identified in different conditions.

Availability: MotifScorer, which is written in Java and Matlab, manual and example files are available from the authors.

Contact:  pl219@cam.ac.uk
Visualization of genomic aberrations using Affymetrix SNP arrays
Authors: Müller André , Holzmann Karlheinz , Kestler Hans A.
Published: December 2006

Motivation: DNA copy number aberrations are frequently found in different types of cancer. Recent developments of microarray-based approaches have broadened the knowledge on number and structure of such aberrations. High-density single nucleotide polymorphism (SNP) microarrays provide an extremely high resolution with up to 500 000 SNPs per genome. Owing to the enormous amount of data the detection of common aberrations in large datasets is a great challenge. We describe a novel open source software tool—IdeogramBrowser—which was specifically designed for use with the Affymetrix SNP arrays. It provides an interactive karyotypic visualization of multiple aberration profiles and direct links to GeneCards. Visualization of consensus regions together with gene representation allows the explorative assessment of the data.

Availability: IdeogramBrowser and its source code are freely available under a creative commons license and can be obtained from .  IdeogramBrowser is a platform independent Java application.

Contact:  hans.kestler@uni-ulm.de
Evaluating Complex Healthcare Systems: A Critique of Four Approaches
Authors: Boon Heather , MacPherson Hugh , Fleishman Sue , Grimsgaard Sameline , Koithan Mary , Norheim Arne Johan , Walach Harald
Published: December 2006

The purpose of this paper is to bring clarity to the emerging conceptual and methodological literature that focuses on understanding and evaluating complex or ‘whole’ systems of healthcare. An international working group reviewed literature from interdisciplinary or interprofessional groups describing approaches to the evaluation of complex systems of healthcare. The following four key approaches were identified: a framework from the MRC (UK), whole systems research, whole medical systems research described by NCCAM (USA) and a model from NAFKAM (Norway). Main areas of congruence include acknowledgment of the inherent complexity of many healthcare interventions and the need to find new ways to evaluate these; the need to describe and understand the components of complex interventions in context (as they are actually practiced); the necessity of using mixed methods including randomized clinical trials (RCTs) (explanatory and pragmatic) and qualitative approaches; the perceived benefits of a multidisciplinary team approach to research; and the understanding that methodological developments in this field can be applied to both complementary and alternative medicine (CAM) as well as conventional therapies. In contrast, the approaches differ in the following ways: terminology used, the extent to which the approach attempts to be applicable to both CAM and conventional medical interventions; the prioritization of research questions (in order of what should be done first) especially with respect to how the ‘definitive’ RCT fits into the process of assessing complex healthcare systems; and the need for a staged approach. There appears to be a growing international understanding of the need for a new perspective on assessing complex healthcare systems.
Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate
Authors: Lippiello Louis
Published: December 2006

Clinical testing of the nutraceuticals glucosamine (glcN) and chondroitin sulfate (CS) has shown efficacy in providing relief from symptoms in osteoarthritic patients. In vitro and in vivo studies support existence of a synergistic relationship upregulating synthetic activity in chondrocytes. A combination of glcN and CS may also be useful as adjunct therapy in sports‐related injuries if similar upregulation of collagen synthesis is elicited in accessory ligament and tendon joint tissue. Collagen and non‐collagenous protein (NCP) synthesis in cultures of bovine tenocytes, ligament cells and chondrocytes exposed to glcN + CS were assayed by uptake of radiolabeled proline into collagenase‐sensitive material. Assay of radiolabel in hydroxyproline (a specific marker for collagen synthesis) following HPLC isolation confirmed the specificity of the metabolic effect. Synthesis of total collagenase‐sensitive material was maximally upregulated at physiologically obtainable doses of glcN + CS. Tissue response followed the sequence ligament cells (+69%) > chondrocytes (+56%) > tenocytes (+22%). Labeled hydroxyproline increased by 132% in ligament cells, 27% in tenocytes and 49% in epitendon cells after a 48 h exposure to 5 μg ml−1 glcN + 4 μg ml−1 CS. Low dose combinations of glcN and CS effectively stimulate in vitro collagen and NCP synthesis by ligament cells, tenocytes and chondrocytes. Hence, therapeutic use following accessory joint tissue trauma may help augment repair processes.
Anti‐Inflammatory Activity of the Methanol Extract of Moutan Cortex in LPS‐Activated Raw264.7 Cells
Authors: Chun Seung-Chul , Jee Seon Young , Lee Sang Gon , Park Sook Jahr , Lee Jong Rok , Kim Sang Chan
Published: December 2006

Moutan Cortex (MCE) has been used in traditional medicine to remove heat from the blood, promote blood circulation and alleviate blood stasis. This study was conducted to evaluate the effects of MCE on regulatory mechanisms of cytokines and nitric oxide (NO) involved in immunological activity of Raw264.7 cells. Cells were pretreated with methanolic extracts of MCE, and further cultured for an appropriate time after lipopolyssacharide (LPS) addition. During the entire experimental period, 0.1 and 0.3 mg ml−1 of MCE had no cytotoxicity. In these concentrations, MCE inhibited the production of NO and prostaglandin E2 (PGE2), the expression of inducible NO synthase (iNOS), cyclooxygenase‐2 (COX‐2) and phosphorylated inhibitor of κBα (p‐IκBα), and the activation of nuclear factor κB (NF‐κB). MCE also reduced the concentration of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) in the Raw264.7 cells that were activated by LPS. These results demonstrate that MCE has anti‐inflammatory effects through the inhibition of iNOS and COX‐2 expression by suppressing the phosphorylation of I‐κBα and the activation of NF‐κB.
Comparison of Pharmacopuncture, Aquapuncture and Acepromazine for Sedation of Horses
Authors: Luna Stelio P. L. , Angeli Ana L. , Ferreira Cristiane L. , Lettry Vivien , Scognamillo-Szabó Márcia
Published: December 2006

Pharmacopuncture, the injection of subclinical doses of drugs into acupoints reduces drug undesirable side effects, residues in animal consumption products and treatment costs in large animals. Acepromazine (Acp) produces several undesirable effects, such as hypotension. Previous studies with the injection of 1/10 of Acp dose in dog acupoints showed its advantage for sedation, minimizing undesirable effects. Eight horses were randomly submitted to four different treatment protocols according to a Latin Square double‐blind design: (i) 0.1 ml kg−1 of saline subcutaneously injected at the cervical region, (ii) 0.1 mg kg−1 of Acp injected subcutaneously at the cervical region, (iii) 0.01 ml kg−1 of saline injected into GV1 acupoint (aquapuncture) and (iv) 0.01 mg kg−1 of Acp injected into GV1 acupoint (pharmacopuncture). Heart rate, respiratory rate, head height and degree of sedation were measured before and at 30, 60 and 90 min after treatments. Signs of sedation were observed in all treated groups at 30 min and only in 1/10Acp‐GV1 at 60 min after the treatments. Only the group treated with 0.1 mg kg−1 of Acp s.c. had significantly lower values of head height at 30 min. Respiratory rate tended to reduce in all groups but was significantly lower only in horses treated with 0.1 mg kg−1 of Acp s.c. Heart rate remained unchanged in all groups. Acp‐pharmacopuncture on GV1 in horses produced a mild sedation when compared with the conventional dose of Acp. More investigations are necessary to determine the optimal dosage of Acp‐pharmacopuncture for sedation in horses.
Caustun's Contrafacta
Authors: Milsom John
Published: December 2006

The received view of the Tudor composer Thomas Caustun is of a minor and relatively uninteresting figure. That view is adjusted, however, by the discovery among his works of contrafacta of music by Nicolas Gombert, Philippe van Wilder, Rogier Pathie and Sebastiano Festa. This article considers the reasons why Caustun made these adaptations, and why they they were published under his name, rather than those of their true composers, in John Day's anthology of Protestant church music, Mornyng and Evenyng Prayer and Communion (London, 1565).
HIF1α delays premature senescence through the activation of MIF
Authors: Welford Scott M. , Bedogni Barbara , Gradin Katarina , Poellinger Lorenz , Broome Powell Marianne , Giaccia Amato J.
Published: December 2006

Premature senescence in vitro has been attributed to oxidative stress leading to a DNA damage response. In the absence of oxidative damage that occurs at atmospheric oxygen levels, proliferation of untransformed cells continues for extended periods of time. We have investigated the role of the hypoxia-inducible factor 1α (HIF1α) transcription factor in preventing senescence in aerobic and hypoxic conditions. Using embryonic fibroblasts from a conditional HIF1α knockout mouse, we found that loss of HIF1α under aerobic conditions significantly accelerated the onset of cellular senescence, and decreased proliferation under hypoxia. Furthermore, we identify the macrophage migration inhibitory factor (MIF) as a crucial effector of HIF1α that delays senescence. Inhibition of MIF phenocopies loss of HIF1α. Our findings highlight a novel role for HIF1α under aerobic conditions, and identify MIF as a target responsible for this function.