bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Obesity and Correlations With Lifestyle and Dietary Factors in Chinese Men
Authors: Lee Sang‐Ah , Wen Wanqing , Xu Wang Hong , Zheng Wei , Li Honglan , Yang Gong , Xiang Yong‐Bing , Shu Xiao‐Ou
Published: March 2008

Objective: To estimate the age‐adjusted prevalence of general and centralized obesity among Chinese men living in urban Shanghai.

Methods and Procedures: A cross‐sectional study was conducted in 61,582 Chinese men aged 40–75. BMI (kg/m2) was used to measure overweight (23 ≤ BMI < 27.4) and obesity (BMI ≥ 27.5) based on the World Health Organization (WHO) recommended criteria for Asians. Waist‐to‐hip ratio (WHR) was used to measure moderate (75th ≤ WHR < 90th percentile) and severe (WHR ≥ 90th percentile) centralized obesity.

Results: The average BMI and WHR were 23.7 kg/m2 and 0.90, respectively. The prevalence of overweight was 48.6% and obesity was 10.5%. The prevalence of general and centralized obesity was higher in men with high income or who were retired, tea drinkers, or nonusers of ginseng than their counterparts. Men with high education had a higher prevalence of overweight and centralized obesity, but had a lower prevalence of obesity and severe centralized obesity compared to those with less education. Current smokers or alcohol drinkers had a lower prevalence of general obesity but higher prevalence of centralized obesity than nonsmokers or nondrinkers of alcohol. Ex‐smokers and ex‐alcohol drinkers had a higher prevalence of general and centralized obesity compared to nonsmokers and nondrinkers of alcohol. Prevalence of obesity was associated with high energy intake and less daily physical activity.

Discussion: The prevalence of obesity among Chinese men in urban Shanghai was lower than that observed in Western countries but higher than that in other Asian countries, and the prevalence of general and centralized obesity differed by demographic, lifestyle, and dietary factors.
Effect of Peroxisome Proliferator‐activated Receptor‐α Ligands in the Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue
Authors: Toyoda Takuya , Kamei Yasutomi , Kato Hirotsugu , Sugita Satoshi , Takeya Motohiro , Suganami Takayoshi , Ogawa Yoshihiro
Published: March 2008

Objective: This study was designed to examine the effect of peroxisome proliferator‐activated receptor‐α (PPAR‐α) ligands on the inflammatory changes induced by the interaction between adipocytes and macrophages in obese adipose tissue.

Methods and Procedures: PPAR‐α ligands (Wy‐14,643 and fenofibrate) were added to 3T3‐L1 adipocytes, RAW264 macrophages, or co‐culture of 3T3‐L1 adipocytes and RAW264 macrophages in vitro, and monocyte chemoattractant protein‐1 (MCP‐1) and tumor necrosis factor‐α (TNF‐α) mRNA expression and secretion were examined. PPAR‐α ligands were administered to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR‐α ligands was also evaluated in the adipose tissue explants and peritoneal macrophages obtained from PPAR‐α‐deficient mice.

Results: In the co‐culture of 3T3‐L1 adipocytes and RAW264 macrophages, PPAR‐α ligands reduced MCP‐1 and TNF‐α mRNA expression and secretion in vitro relative to vehicle‐treated group. The anti‐inflammatory effect of Wy‐14,643 was observed in adipocytes treated with macrophage‐conditioned media or mouse recombinant TNF‐α and in macrophages treated with adipocyte‐conditioned media or palmitate. Systemic administration of PPAR‐α ligands inhibited the inflammatory changes in adipose tissue from ob/ob mice. Wy‐14,643 also exerted an anti‐inflammatory effect in the adipose tissue explants but not in peritoneal macrophages obtained from PPAR‐α‐deficient mice.

Discussion: This study provides evidence for the anti‐inflammatory effect of PPAR‐α ligands in the interaction between adipocytes and macrophages in obese adipose tissue, thereby improving the dysregulation of adipocytokine production and obesity‐related metabolic syndrome.
Theoretical analysis of a palladium-based one-dimensional metallo-dielectric photonic band gap structure for applications to H2 sensors
Authors: Vincenti Maria Antonietta , Trevisi Simona , De Sario Marco , Petruzzelli Vincenzo , D’Orazio Antonella , Prudenzano Francesco , Cioffi Nicola , de Ceglia Domenico , Scalora Michael
Published: March 2008

In this paper we report a numerical study of a palladium-based metallo-dielectric photonic band gap structure for the purpose of detecting H2. In particular, and as an example, we will explore applications to the diagnosis of lactose malabsorption, more commonly known as lactose intolerance condition. This pathology occurs as a result of an incomplete absorption or digestion of different substances, causing an increased spontaneous emission of H2 in human breath. Palladium is considered in order to exploit its well known ability to absorb hydrogen spontaneously. The proposed structure is particularly able to detect the lactose malabsorption level of the patient with relatively high sensitivity and rapidity.
Effect of pole tip geometry on remnant field
Authors: Shen Xiao , Victora R. H.
Published: March 2008

When the coil current of a magnetic write head is turned off, magnetization in the head will try to relax to an equilibrium state that is energetically favored. For a 1:1 aspect ratio single pole type writer with cross track flares and a large throat height, the remnant field is large owing to the shape anisotropy of the pole tip. Reducing the flare height will reduce the remnant field. A pole tip design with both cross track and down track flares is proposed. The cross track throat height is large but the down track throat height is small. This design reduces the remnant field dramatically and produces both a high write field and a square shaped footprint.
Stimulated echoes and two-dimensional nuclear magnetic resonance spectra for solids with simple line shapes
Authors: Geil Burkhard , Diezemann Gregor , Böhmer Roland
Published: March 2008

Nuclear magnetic resonance (NMR) experiments on ion conductors often yield rather unstructured spectra, which are hard to interpret if the relation between the actual translational motion of the mobile species and the changes of the NMR frequencies is not known. In order to facilitate a general analysis of experiments on solids with such spectra, different models for the stochastic evolution of the NMR frequencies are considered. The treated models involve random frequency jumps, diffusive evolutions, or approximately fixed frequency jumps. Two-dimensional nuclear magnetic resonance spectra as well as stimulated-echo functions for the study of slow and ultraslow translational dynamics are calculated for Gaussian equilibrium line shapes. The results are compared with corresponding ones from rotational models and with experimental data.
Calculation of electric dipole (hyper)polarizabilities by long-range-correction scheme in density functional theory: A systematic assessment for polydiacetylene and polybutatriene oligomers
Authors: Kirtman Bernard , Bonness Sean , Ramirez-Solis Alejandro , Champagne Benoit , Matsumoto Hironori , Sekino Hideo
Published: March 2008

The long-range correction (LC) for treating electron exchange in density functional theory, combined with the Becke–Lee–Yang–Parr (BLYP) exchange-correlation functional, was used to determine (hyper)polarizabilities of polydiacetylene/polybutatriene oligomers. In comparison with coupled-cluster calculations including single and double excitations as well as a perturbative treatment of triple excitations, our values indicate that the tendency of conventional functionals to result in a catastrophic overshoot for these properties is alleviated but not eliminated. No clear-cut preference for LC-BLYP over Hartree–Fock values is obtained. This analysis is consistent with the calculations of Sekino et al. [J. Chem. Phys. 126, 014107 (2007)] on polyacetylene and molecular hydrogen oligomers. Thus, the performance of LC-BLYP with regard to (hyper)polarizabilities of quasilinear conjugated systems is now well characterized.
High brightness and high polarization electron source using transmission photocathode with GaAs-GaAsP superlattice layers
Authors: Yamamoto Naoto , Nakanishi Tsutomu , Mano Atsushi , Nakagawa Yasuhide , Okumi Shoji , Yamamoto Masahiro , Konomi Taro , Jin Xiuguang , Ujihara Toru , Takeda Yoshikazu , Ohshima Takashi , Saka Takashi , Kato Toshihiro , Horinaka Hiromichi , Yasue Tsuneo , Koshikawa Takanori , Kuwahara Makoto
Published: March 2008

In order to produce a high brightness and high spin polarization electron beam, a pointlike emission mechanism is required for the photocathode of a GaAs polarized electron source. For this purpose, the laser spot size on the photocathode must be minimized, which is realized by changing the direction of the injection laser light from the front side to the back side of the photocathode. Based on this concept, a 20kV gun was constructed with a transmission photocathode including an active layer of a GaAs–GaAsP superlattice layer. This system produces a laser spot diameter as small as 1.3μm for 760–810nm laser wavelength. The brightness of the polarized electron beam was ∼2.0×107Acm−2sr−1, which corresponds to a reduced brightness of ∼1.0×107Am−2sr−1V−1. The peak polarization of 77% was achieved up to now. A charge density lifetime of 1.8×108Ccm−2 was observed for an extracted current of 3μA.
Spectroscopy and implosion dynamics of low wire number nested arrays on the 1MA COBRA generator
Authors: Safronova A. S. , Kantsyrev V. L. , Esaulov A. A. , Ouart N. D. , Yilmaz M. F. , Williamson K. M. , Shrestha I. , Osborne G. C. , Greenly J. B. , Chandler K. M. , McBride R. D. , Chalenski D. A. , Hammer D. A. , Kusse B. R. , LePell P. D.
Published: March 2008

Low wire number nested array Z-pinch experiments have been carried out with wires made of aluminum, stainless steel (uniform), and combinations of these two materials (mixed) on the 1MA COBRA generator at Cornell University [J. D. Douglass, J. B. Greenly, D. A. Hammer et al., in Proceedings of the 15th IEEE International Pulsed Power Conference (IEEE, Piscataway, NJ, 2005)]. The outer array consisted of eight wires, whereas the inner array had four or eight wires. The 10μm Al wires were alloy 5056 and the 6.25μm stainless steel wires were alloy SS304. The diagnostic suite included fast-x-ray and extreme ultraviolet (EUV) detectors, a time-gated x-ray pinhole camera, x-ray spectrometers, and laser shadow imaging. The main focus was made on the spectroscopic study of plasma evolution after the main x-ray burst though the data from photoconducting detector (PCD) and EUV signals over the whole period of current, and in addition laser shadowgraphy images before the main x-ray burst were analyzed. Modeling of the time-gated spectra recorded after the main x-ray burst indicates that the electron temperature Te either follows the PCD signals and peaks at times of the second (and the third if present) x-ray burst or has the higher value at the first frame (closest to the main x-ray burst), then slightly changes and increases at the last frame, which coincides with the second maximum of the current. It was also found that the values of Te never drop below 150eV, and the EUV signal remains intense even when the PCD signal is almost zero.
Dispersion relation of high-frequency plasma oscillations in Hall thrusters
Authors: Lazurenko A. , Coduti G. , Mazouffre S. , Bonhomme G.
Published: March 2008

The dispersion relation of high-frequency plasma oscillations (>1MHz) in a Hall thruster is estimated from two point probe measurements. The probes are located outside the accelerating channel nearby the channel exit. The probe orientation allows us to investigate the evolution of azimuthal and axial wave numbers with the oscillation frequency. The azimuthal dispersion relation is nearly linear. The axial dispersion relation depends upon the probe position, which translates into a varying slope. The observed features of the two dispersion relations can be explained in terms of spatial structure of the high-frequency plasma instabilities.
Real time observation of the field driven periodic transformation of domain walls in Permalloy nanowires at the Larmor frequency and its first harmonic
Authors: Hayashi Masamitsu , Thomas Luc , Rettner Charles , Moriya Rai , Parkin Stuart S. P.
Published: March 2008

We have observed two different field driven precessional propagation modes of a magnetic domain wall in permalloy nanowires using time resolved resistance measurements. The resistance of the nanowire oscillates at the Larmor precession frequency and at its first harmonic, corresponding to periodic transformations of the propagating domain wall between a transverse wall and either one of a vortex or an antivortex wall or both of these.
Electronic excited-state energies from a linear response theory based on the ground-state two-electron reduced density matrix
Authors: Greenman Loren , Mazziotti David A.
Published: March 2008

Ground-state two-particle reduced density matrices (2-RDMs) are used to calculate excited-state energy spectra. Solving the Schrödinger equation for excited states dominated by single excitations from the ground-state wavefunction requires the ground-state 2- and 3-RDMs. The excited states, however, can be obtained without a knowledge of the ground-state 3-RDM by two methods: (i) cumulant expansion methods which build the 3-RDM from the 2-RDM, and (ii) double commutator methods which eliminate the 3-RDM. Previous work [Mazziotti, Phys. Rev. A 68, 052501 (2003)] examined the accuracy of excited states extracted from ground-state 2-RDMs, which were calculated by full configuration interaction or the variational 2-RDM method. In this work we employ (i) advances in semidefinite programming to treat the excited states of water and hydrogen fluoride and chains of hydrogen atoms, and (ii) the addition of partial three-particle N-representability conditions to compute more accurate ground-state 2-RDMs. With the hydrogen chains we examine the metal-to-insulator transition as measured by the band gap (the difference between the ground-state and the first excited-state energies), which is difficult for excited-state methods to capture.
Energy and energy gradient matrix elements with N-particle explicitly correlated complex Gaussian basis functions with L=1
Authors: Bubin Sergiy , Adamowicz Ludwik
Published: March 2008

In this work we consider explicitly correlated complex Gaussian basis functions for expanding the wave function of an N-particle system with the L=1 total orbital angular momentum. We derive analytical expressions for various matrix elements with these basis functions including the overlap, kinetic energy, and potential energy (Coulomb interaction) matrix elements, as well as matrix elements of other quantities. The derivatives of the overlap, kinetic, and potential energy integrals with respect to the Gaussian exponential parameters are also derived and used to calculate the energy gradient. All the derivations are performed using the formalism of the matrix differential calculus that facilitates a way of expressing the integrals in an elegant matrix form, which is convenient for the theoretical analysis and the computer implementation. The new method is tested in calculations of two systems: the lowest P state of the beryllium atom and the bound P state of the positronium molecule (with the negative parity). Both calculations yielded new, lowest-to-date, variational upper bounds, while the number of basis functions used was significantly smaller than in previous studies. It was possible to accomplish this due to the use of the analytic energy gradient in the minimization of the variational energy.
Field localization inside a lossy dielectric slab by means of cantor dielectric multilayers
Authors: Chiadini Francesco , Scaglione Antonio , Fiumara Vincenzo , Gallina Ilaria
Published: March 2008

A Cantor multilayer is an electromagnetic band-gap structure consisting of a stack of alternating high-/low-permittivity dielectric layers whose optical lengths follow the fractal Cantor construction. The deepest stop band is bounded by two narrow transmission peaks centered at frequencies where a strong field localization occurs inside the structure. This phenomenon also occurs if a lossy dielectric slab is inserted at the midpoint of the multilayer as a defect layer and can be conveniently used to make the field intensity inside the slab significantly stronger than the intensity of the field incident on the Cantor structure.
Effect of cluster size of chalcogenide glass nanocolloidal solutions on the surface morphology of spin-coated amorphous films
Authors: Kohoutek T. , Wagner T. , Frumar M. , Chrissanthopoulos A. , Kostadinova O. , Yannopoulos S. N.
Published: March 2008

Amorphous chalcogenide thin film deposition can be achieved by a spin-coating technique from proper solutions of the corresponding glass. Films produced in this way exhibit certain grain texture, which is presumably related to the cluster size in solution. This paper deals with the search of such a correlation between grain size of surface morphology of as-deposited spin-coated As33S67 chalcogenide thin films and cluster size of the glass in butylamine solutions. Optical absorption spectroscopy and dynamic light scattering were employed to study optical properties and cluster size distributions in the solutions at various glass concentrations. Atomic force microscopy is used to study the surface morphology of the surface of as-deposited and thermally stabilized spin-coated films. Dynamic light scattering revealed a concentration dependence of cluster size in solution. Spectral-dependence dynamic light scattering studies showed an interesting athermal photoaggregation effect in the liquid state.
A velocity map ion imaging study of difluorobenzene-water complexes: Binding energies and recoil distributions
Authors: Bellm Susan M. , Moulds Rebecca J. , van Leeuwen Matthew P. , Lawrance Warren D.
Published: March 2008

The binding energies of the p-, m-, and o-difluorobenzene-H2O complexes have been measured by velocity map ion imaging to be 922±10, 945±10, and 891±4cm−1, respectively. The lack of variation provides circumstantial evidence for water binding to the three isomers via the same interaction, viz. an in-plane O–H⋯F hydrogen bond to one of the fluorine atoms on the ring, with a second, weaker interaction of the water O atom with an ortho hydrogen, as determined previously for the p-difluorobenzene-H2O complex [Kang et al., J. Phys. Chem. A 109, 767 (2005)]. The ground state binding energies for the difluorobenzene-H2O complexes are ∼5%–11% larger than that for benzene-H2O, where binding occurs to the π electrons out-of-plane. However, in the S1 state the binding energies of the o- and p-difluorobenzene-H2O complexes are smaller than the benzene-H2O value, raising an interesting question about whether the geometry at the global energy minimum remains in-plane in the excited electronic states of these two complexes. Recoil energy distributions for dissociation of p-difluorobenzene-H2O have been measured from the 31¯, 52¯, and 3151¯ levels of the excited electronic state. These levels are 490, 880, and 1304cm−1, respectively, above the dissociation threshold. Within the experimental uncertainty, the recoil energy distributions are the same for dissociation from these three states, with average recoil energies of ∼100cm−1. These recoil energies are 60% larger than was observed for the dissociation of p-difluorobenzene-Ar, which is a substantially smaller increase than the 400% seen in a comparable study of dissociation within the triplet state for pyrazine-Ar, -H2O complexes. The majority of the available energy is partitioned into vibration and rotation of the fragments.
Piezoelectric properties and hardening behavior of K5.4Cu1.3Ta10O29-doped K0.5Na0.5NbO3 ceramics
Authors: Lin Dunmin , Kwok K. W. , Chan H. L. W.
Published: March 2008

Lead-free piezoelectric ceramics K0.5Na0.5NbO3+xmol% K5.4Cu1.3Ta10O29 have been prepared by a conventional ceramic fabrication technique. All the ceramics possess a perovskite structure with orthorhombic symmetry. Our results reveal that the addition of K5.4Cu1.3Ta10O29 is effective in improving the densification of the ceramics. Besides, after the addition of K5.4Cu1.3Ta10O29, the Curie temperature and the tetragonal-orthorhombic phase transition temperature decrease and the P-E loop becomes constricted, in particular, for the ceramic with x=0.75. Based on the symmetry-conforming principle of point defects, it is suggested that defect dipoles are formed by the acceptor dopant ions Cu2+ and O2− vacancies along the polarization direction. As a result of the low migration rate of defects, the defect dipoles remain in the original orientation during the P-E loop measurement and thus provide restoring forces to reverse the switched polarizations. Similarly, the defect dipoles do not response along with the polarization in the normal piezoelectric activities and thus provide “pinning” to the deformed polarization, making the ceramics become “hardened.” For the ceramic with x=0.75, the mechanical quality factor Qm becomes maximum at a value of 1530, while the other piezoelectric properties remain reasonably high: piezoelectric coefficient d33=90pC∕N, planar and thickness mode electromechanical coupling factors kP=41 and kt=46%.
Efficient simple structure red phosphorescent organic light emitting devices with narrow band-gap fluorescent host
Authors: Park Tae Jin , Jeon Woo Sik , Park Jung Joo , Kim Sun Young , Lee Yong Kyun , Jang Jin , Kwon Jang Hyuk , Pode Ramchandra
Published: March 2008

Using a narrow band-gap fluorescent host material, bis(10-hydroxybenzo[h] quinolinato)beryllium complex, efficient red phosphorescent organic light emitting diodes (PHOLEDs) comprising two layers have been reported. Significantly low driving voltage of 4.5V to reach a luminance of 1000cd∕m2 is reported in this simple structure PHOLEDs. The current and power efficiencies of bilayered red PHOLED are 9.66cd∕A and 6.90lm∕W, respectively, promising for low power display and lighting applications.
Facility for fast neutron irradiation tests of electronics at the ISIS spallation neutron source
Authors: Andreani C. , Pietropaolo A. , Salsano A. , Gorini G. , Tardocchi M. , Paccagnella A. , Gerardin S. , Frost C. D. , Ansell S. , Platt S. P.
Published: March 2008

The VESUVIO beam line at the ISIS spallation neutron source was set up for neutron irradiation tests in the neutron energy range above 10MeV. The neutron flux and energy spectrum were shown, in benchmark activation measurements, to provide a neutron spectrum similar to the ambient one at sea level, but with an enhancement in intensity of a factor of 107. Such conditions are suitable for accelerated testing of electronic components, as was demonstrated here by measurements of soft error rates in recent technology field programable gate arrays.
Arrayed electrowetting microwells
Authors: Zhou K. , Heikenfeld J.
Published: March 2008

Colored oils and aqueous solutions have been electromechanically pumped in and out of arrayed microwells. The microwells comprised pyramidal pits in Si substrates that were coated with an aluminum electrode and a hydrophobic dielectric. These substrates were then suspended between volumes of water and oil. When colored oil was placed behind the substrate, surface tension forces caused the oil to completely fill the microwells and provide brilliant red coloration to the array. With application of ∼30–50V, electrowetting drove the colored oil behind the substrate and the reflection was made dominantly white.
Phase separation behavior of Ge2Sb2Te5 line structure during electrical stress biasing
Authors: Nam Sung-Wook , Kim Cheolkyu , Kwon Min-Ho , Lee Hyo-Sung , Wi Jung-Sub , Lee Dongbok , Lee Tae-Yon , Khang Yoonho , Kim Ki-Bum
Published: March 2008

We report the breakdown behavior of a patterned Ge2Sb2Te5 multiline structure during the voltage-driven electric stress biasing. Scanning Auger microscope analysis shows that the breakdown process accompanies with a phase separation of Ge2Sb2Te5 into an Sb, Te-rich phase and a Ge-rich phase. The phase separation is explained by the incongruent melting of Ge2Sb2Te5 based on the pseudobinary phase diagram between Sb2Te3 and GeTe. It is claimed that this phase separation behavior by incongruent melting provides one of the plausible mechanisms of the device failure in a phase change memory.
Giant anisotropy of second harmonic generation for a single ZnSe nanowire
Authors: Barzda V. , Cisek R. , Spencer T. L. , Philipose U. , Ruda H. E. , Shik A.
Published: March 2008

The effect of second harmonic generation was experimentally investigated in ZnSe nanowires grown by the vapor-liquid-solid method. The effect dramatically depended on the angle between the nanowire axis and the linear polarization of the excitation light. The magnitude of the effect was 20 times stronger for the parallel polarization in comparison with the perpendicular one. The results were theoretically explained in terms of a large difference in dielectric constants between the nanowire and the environment, resulting in a strong orientation-dependent optical electric field in the nanowire.
Transcriptional control of noise in gene expression
Authors: Sánchez Álvaro , Kondev Jané
Published: March 2008

Cis
-regulatory control of transcription is the dominant form of regulation of gene expression. Recent experimental results suggest that, in addition to the mean expression level, cell-to-cell variability might also be transcriptionally regulated. Here, we develop a stochastic model of transcriptional regulation that allows us to calculate closed-form analytical expressions for the mean and variance of the protein and mRNA distributions for an arbitrarily complex
cis
-regulatory motif. Our model allows us to investigate how noise may be transcriptionally regulated independently from the mean expression. We show that our approach is in excellent agreement with stochastic simulations and experiment, and leads to an experimentally testable formula for the noise in gene expression as a function of inducer-molecule concentrations.
A two-step nucleotide-flipping mechanism enables kinetic discrimination of DNA lesions by AGT
Authors: Hu Jie , Ma Ao , Dinner Aaron R.
Published: March 2008

O
6
-alkylguanine-DNA alkyltransferase (AGT) repairs damage to the human genome by flipping guanine and thymine bases into its active site for irreversible transfer of alkyl lesions to Cys-145, but how the protein identifies its targets has remained unknown. Understanding molecular recognition in this system, which can serve as a paradigm for the many nucleotide-flipping proteins that regulate genes and repair DNA in all kingdoms of life, is particularly important given that inhibitors are in clinical trials as anticancer therapeutics. Computational approaches introduced recently for harvesting and statistically characterizing trajectories of molecularly rare events now enable us to elucidate a pathway for nucleotide flipping by AGT and the forces that promote it. In contrast to previously proposed flipping mechanisms, we observe a two-step process that promotes a kinetic, rather than a thermodynamic, gate-keeping strategy for lesion discrimination. Connection is made to recent single-molecule studies of DNA-repair proteins sliding on DNA to understand how they sense subtle chemical differences between bases efficiently.
Genome-wide analysis for discovery of rice microRNAs reveals natural antisense microRNAs (nat-miRNAs)
Authors: Lu Cheng , Jeong Dong-Hoon , Kulkarni Karthik , Pillay Manoj , Nobuta Kan , German Rana , Thatcher Shawn R. , Maher Christopher , Zhang Lifang , Ware Doreen , Liu Bin , Cao Xiaofeng , Meyers Blake C. , Green Pamela J.
Published: March 2008

Small RNAs (21–24 nt) are involved in gene regulation through translation inhibition, mRNA cleavage, or directing chromatin modifications. In rice, currently ≈240 microRNAs (miRNAs) have been annotated. We sequenced more than four million small RNAs from rice and identified another 24 miRNA genes. Among these, we found a unique class of miRNAs that derive from natural
cis
-antisense transcript pairs. This configuration generates miRNAs that can perfectly match their targets. We provide evidence that the miRNAs function by inducing mRNA cleavage in the middle of their complementary site. Their production requires Dicer-like 1 (DCL1) activity, which is essential for canonical miRNA biogenesis. All of the natural antisense miRNAs (nat-miRNAs) identified in this study have large introns in their precursors that appear critical for nat-miRNA evolution and for the formation of functional miRNA loci. These findings suggest that other natural
cis
-antisense loci with similar exon–intron arrangements could be another source of miRNA genes.
Structural basis of GM1 ganglioside recognition by simian virus 40
Authors: Neu Ursula , Woellner Karin , Gauglitz Guenter , Stehle Thilo
Published: March 2008

Simian virus 40 (SV40) has been a paradigm for understanding attachment and entry of nonenveloped viruses, viral DNA replication, and virus assembly, as well as for endocytosis pathways associated with caveolin and cholesterol. We find by glycan array screening that SV40 recognizes its ganglioside receptor GM1 with a quite narrow specificity, but isothermal titration calorimetry shows that individual binding sites have a relatively low affinity, with a millimolar dissociation constant. The high-resolution crystal structure of recombinantly produced SV40 capsid protein, VP1, in complex with the carbohydrate portion of GM1, reveals that the receptor is bound in a shallow solvent-exposed groove at the outer surface of the capsid. Through a complex network of interactions, VP1 recognizes a conformation of GM1 that is the dominant one in solution. Analysis of contacts provides a structural basis for the observed specificity and suggests binding mechanisms for additional physiologically relevant GM1 variants. Comparison with murine Polyomavirus (Polyoma) receptor complexes reveals that SV40 uses a different mechanism of sialic acid binding, which has implications for receptor binding of human polyomaviruses. The SV40–GM1 complex reveals a parallel to cholera toxin, which uses a similar cell entry pathway and binds GM1 in the same conformation.
Incremental parameter evaluation from incomplete data with application to the population pharmacology of anticoagulants
Authors: Vlad Marcel O. , Dan Corlan Alexandru , Morán Federico , Oefner Peter , Ross John
Published: March 2008

We develop a method for parameter evaluation from incomplete data. Improved estimates of the desired parameters are evaluated step by step, from experiment to experiment by using both Bayesian and informational methods. We make dynamical, improved predictions while the experiments are still going on and keep and interpret information about local fluctuations, which is lost on applying global techniques. The input of information in small packets leads to semi-analytic methods for data processing. An evolution criterion for parameter evaluation, similar to Fisher's theorem of population selection, is derived. We develop direct processing methods, which can be applied to low dimensional systems, semi-analytic methods based on direct or double logarithmic phase expansions, steepest descent approaches, variation and perturbation methods. The techniques are illustrated by developing a method of long-term planning of treatments with oral anticoagulants based on limited clinical data. The efficiency of treatment by oral anticoagulants depends strongly on various anthropometric and genotypic factors, which lead to large variations of the clinical response. We use the clinical data, which accumulates from medical consultations, for extracting improved, incremental information about the statistical properties of the kinetic and anthropometric parameters for a given patient, which in turn is used for making repeated, improved clinical predictions as the treatment proceeds.
Cytosine methylation profiling of cancer cell lines
Authors: Ehrich Mathias , Turner Julia , Gibbs Peter , Lipton Lara , Giovanneti Mara , Cantor Charles , van den Boom Dirk
Published: March 2008

DNA-methylation changes in human cancer are complex and vary between the different types of cancer. Capturing this epigenetic variability in an atlas of DNA-methylation changes will be beneficial for basic research as well as translational medicine. Hypothesis-free approaches that interrogate methylation patterns genome-wide have already generated promising results. However, these methods are still limited by their quantitative accuracy and the number of CpG sites that can be assessed individually. Here, we use a unique approach to measure quantitative methylation patterns in a set of >400 candidate genes. In this high-resolution study, we employed a cell-line model consisting of 59 cancer cell lines provided by the National Cancer Institute and six healthy control tissues for discovery of methylation differences in cancer-related genes. To assess the effect of cell culturing, we validated the results from colon cancer cell lines by using clinical colon cancer specimens. Our results show that a large proportion of genes (78 of 400 genes) are epigenetically altered in cancer. Although most genes show methylation changes in only one tumor type (35 genes), we also found a set of genes that changed in many different forms of cancer (seven genes). This dataset can easily be expanded to develop a more comprehensive and ultimately complete map of quantitative methylation changes. Our methylation data also provide an ideal starting point for further translational research where the results can be combined with existing large-scale datasets to develop an approach that integrates epigenetic, transcriptional, and mutational findings.
Thrombin Induces Fibroblast CCL2/JE Production and Release via Coupling of PAR1to Gαqand Cooperation between ERK1/2 and Rho Kinase Signaling Pathways
Authors: Deng Xiaoling , Mercer Paul F. , Scotton Chris J. , Gilchrist Annette , Chambers Rachel C.
Published: March 2008

Uncontrolled activation of the coagulation cascade after tissue injury has been implicated in both inflammation and tissue fibrosis. Thrombin exerts pluripotent cellular effects via its high-affinity receptor, proteinase-activated receptor-1 (PAR1) and signaling via Gαi/o, Gαq, or Gα12/13. Activation of PAR1on fibroblasts, a key effector cell in fibrosis, results in the induction of several mediators, including the potent monocyte and fibrocyte chemoattractant CCL2. The aim of this study was to identify the G protein and signaling pathway involved in PAR1-mediated CCL2 production and release. Using a novel PAR1antagonist that blocks the interaction between PAR1and Gαq, we report for the first time that PAR1coupling to Gαqis essential for thrombin-induced CCL2 gene expression and protein release in murine lung fibroblasts. We further demonstrate that these effects are mediated via the cooperation between ERK1/2 and Rho kinase signaling pathways: a calcium-independent protein kinase C (PKC), c-Raf, and ERK1/2 pathway was found to mediate PAR1-induced CCL2 gene transcription, whereas a phospholipase C, calcium-dependent PKC, and Rho kinase pathway influences CCL2 protein release. We propose that targeting the interaction between PAR1and Gαqmay allow us to selectively interfere with PAR1proinflammatory and profibrotic signaling, while preserving the essential role of other PAR1-mediated cellular responses.
Deficiency of Zonula Occludens-1 Causes Embryonic Lethal Phenotype Associated with Defected Yolk Sac Angiogenesis and Apoptosis of Embryonic Cells
Authors: Katsuno Tatsuya , Umeda Kazuaki , Matsui Takeshi , Hata Masaki , Tamura Atsushi , Itoh Masahiko , Takeuchi Kosei , Fujimori Toshihiko , Nabeshima Yo-ichi , Noda Tetsuo , Tsukita Shoichiro , Tsukita Sachiko
Published: March 2008

Zonula occludens (ZO)-1/2/3 are the members of the TJ-MAGUK family of membrane-associated guanylate kinases associated with tight junctions. To investigate the role of ZO-1 (encoded by Tjp1) in vivo, ZO-1 knockout (Tjp1−/−) mice were generated by gene targeting. Although heterozygous mice showed normal development and fertility, delayed growth and development were evident from E8.5 onward in Tjp1−/−embryos, and no viable Tjp1−/−embryos were observed beyond E11.5. Tjp1−/−embryos exhibited massive apoptosis in the notochord, neural tube area, and allantois at embryonic day (E)9.5. In the yolk sac, the ZO-1 deficiency induced defects in vascular development, with impaired formation of vascular trees, along with defective chorioallantoic fusion. Immunostaining of wild-type embryos at E8.5 for ZO-1/2/3 revealed that ZO-1/2 were expressed in almost all embryonic cells, showing tight junction-localizing patterns, with or without ZO-3, which was confined to the epithelial cells. ZO-1 deficiency depleted ZO-1-expression without influence on ZO-2/3 expression. In Tjp1+/+yolk sac extraembryonic mesoderm, ZO-1 was dominant without ZO-2/3 expression. Thus, ZO-1 deficiency resulted in mesoderms with no ZO-1/2/3, associated with mislocalization of endothelial junctional adhesion molecules. As a result, angiogenesis was defected in Tjp1−/−yolk sac, although differentiation of endothelial cells seemed to be normal. In conclusion, ZO-1 may be functionally important for cell remodeling and tissue organization in both the embryonic and extraembryonic regions, thus playing an essential role in embryonic development.
The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian Cells
Authors: Gandre-Babbe Shilpa , van der Bliek Alexander M.
Published: March 2008

Few components of the mitochondrial fission machinery are known, even though mitochondrial fission is a complex process of vital importance for cell growth and survival. Here, we describe a novel protein that controls mitochondrial fission. This protein was identified in a small interfering RNA (siRNA) screen using Drosophila cells. The human homologue of this protein was named Mitochondrial fission factor (Mff). Mitochondria of cells transfected with Mff siRNA form a closed network similar to the mitochondrial networks formed when cells are transfected with siRNA for two established fission proteins, Drp1 and Fis1. Like Drp1 and Fis1 siRNA, Mff siRNA also inhibits fission induced by loss of mitochondrial membrane potential, it delays cytochrome c release from mitochondria and further progression of apoptosis, and it inhibits peroxisomal fission. Mff and Fis1 are both tail anchored in the mitochondrial outer membrane, but other parts of these proteins are very different and they exist in separate 200-kDa complexes, suggesting that they play different roles in the fission process. We conclude that Mff is a novel component of a conserved membrane fission pathway used for constitutive and induced fission of mitochondria and peroxisomes.
Variant-specific [PSI+] Infection Is Transmitted by Sup35 Polymers within [PSI+] Aggregates with Heterogeneous Protein Composition
Authors: Bagriantsev Sviatoslav N. , Gracheva Elena O. , Richmond Janet E. , Liebman Susan W.
Published: March 2008

The [PSI+] prion is the aggregated self-propagating form of the Sup35 protein from the yeast Saccharomyces cerevisiae. Aggregates of Sup35 in [PSI+] cells exist in different heritable conformations, called “variants,” and they are composed of detergent-resistant Sup35 polymers, which may be closely associated with themselves, other proteins, or both. Here, we report that disassembly of the aggregates into individual Sup35 polymers and non-Sup35 components increases their infectivity while retaining their variant specificity, showing that variant-specific [PSI+] infection can be transmitted by Sup35 polymers alone. Morphological analysis revealed that Sup35 isolated from [PSI+] yeast has the appearance of short barrels, and bundles, which seem to be composed of barrels. We show that the major components of two different variants of [PSI+] are interacting infectious Sup35 polymers and Ssa1/2. Using a candidate approach, we detected Hsp104, Ssb1/2, Sis1, Sse1, Ydj1, and Sla2 among minor components of the aggregates. We demonstrate that Ssa1/2 efficiently binds to the prion domain of Sup35 in [PSI+] cells, but that it interacts poorly with the nonaggregated Sup35 found in [psi−] cells. Hsp104, Sis1, and Sse1 interact preferentially with the prion versus nonprion form of Sup35, whereas Sla2 and Ssb1/2 interact with both forms of Sup35 with similar efficiency.
A suite of Perl modules for handling microarray data
Authors: Morris James A. , Gayther Simon A. , Jacobs Ian J. , Jones Christopher
Published: March 2008

Summary: We describe PerlMAT, a Perl microarray toolkit providing easy to use object-oriented methods for the simplified manipulation, management and analysis of microarray data. The toolkit provides objects for the encapsulation of microarray spots and reporters, several common microarray data file formats and GAL files. In addition, an analysis object provides methods for data processing, and an image object enables the visualisation of microarray data. This important addition to the Perl developer's library will facilitate more widespread use of Perl for microarray application development within the bioinformatics community. The coherent interface and well-documented code enables rapid analysis by even inexperienced Perl developers.

Availability: Software is available at http://sourceforge.net/projects/perlmat

Contact:  james.morris@ucl.ac.uk
An analytical pipeline for genomic representations used for cytosine methylation studies
Authors: Thompson Reid F. , Reimers Mark , Khulan Batbayar , Gissot Mathieu , Richmond Todd A. , Chen Quan , Zheng Xin , Kim Kami , Greally John M.
Published: March 2008

Motivation: Representations of the genome can be generated by the selection of a subpopulation of restriction fragments using ligation-mediated PCR. Such representations form the basis for a number of high-throughput assays, including the HELP assay to study cytosine methylation. We find that HELP data analysis is complicated not only by PCR amplification heterogeneity but also by a complex and variable distribution of cytosine methylation. To address this, we created an analytical pipeline and novel normalization approach that improves concordance between microarray-derived data and single locus validation results, demonstrating the value of the analytical approach. A major influence on the PCR amplification is the size of the restriction fragment, requiring a quantile normalization approach that reduces the influence of fragment length on signal intensity. Here we describe all of the components of the pipeline, which can also be applied to data derived from other assays based on genomic representations.

Contact:  jgreally@aecom.yu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Disappearing bodies and ghost vortices
Authors: Eames I
Published: March 2008

In many dispersed multiphase flows bubbles, droplets, and particles move and disappear due to a phase change. Practical examples include vapour bubbles condensing in subcooled liquids, fuel droplets evaporating in a hot gas and ice crystals melting in water. After these ‘bodies’ have disappeared, they leave behind a remnant ‘ghost’ vortex as an expression of momentum conservation.

A general framework is developed to analyse why and how a ghost vortex is generated. A study of these processes is incomplete without a detailed discussion of the concept of momentum for unbounded flows. We show how momentum can be defined unambiguously for unbounded flows and show its connection with other expressions, particularly that of Lighthill. We apply our analysis to interpret new observations of condensing vapour bubbles and discuss droplet evaporation. We show that the use of integral invariants, widely applied in turbulence, introduces a new perspective to dispersed multiphase flows.
Learning strategy selection in the water maze and hippocampal CREB phosphorylation differ in two inbred strains of mice
Authors: Sung Jin-Young , Goo June-Seo , Lee Dong-Eun , Jin Da-Qing , Bizon Jennifer L. , Gallagher Michela , Han Jung-Soo
Published: March 2008

Learning strategy selection was assessed in two different inbred strains of mice, C57BL/6 and DBA/2, which are used for developing genetically modified mouse models. Male mice received a training protocol in a water maze using alternating blocks of visible and hidden platform trials, during which mice escaped to a single location. After training, mice were required to choose between the spatial location where the platform had been during training (a place strategy) and a visible platform presented in a new location (a cued/response strategy). Both strains of mice had similar escape performance on the visible and hidden platform trials during training. However, in the strategy preference test, C57BL/6 mice selected a place strategy significantly more often than DBA/2 mice. Because much evidence implicates the hippocampus and striatum as important neural substrates for spatial/place and cued/response learning, respectively, the engagement of the hippocampus was then assessed after either place or cue training by determining levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) in these two mouse strains. Results revealed that hippocampal CREB levels in both strains of mice were significantly increased after place in comparison to cued training. However, the relation of hippocampal pCREB levels to training was strain dependent; pCREB was significantly higher in C57BL/6 mice than in DBA/2 mice after place training, while hippocampal pCREB levels did not differ between strains after cued training. These findings indicate that pCREB, specifically associated with place/spatial training, is closely tied to differences in spatial/place strategy preference between C57BL/6 and DBA/2 mice.
Aging affects acquisition and reversal of reward-based associative learning
Authors: Weiler Julia A. , Bellebaum Christian , Daum Irene
Published: March 2008

Reward-based associative learning is mediated by a distributed network of brain regions that are dependent on the dopaminergic system. Age-related changes in key regions of this system, the striatum and the prefrontal cortex, may adversely affect the ability to use reward information for the guidance of behavior. The present study investigated the effects of healthy aging on different components of reward learning, such as acquisition, reversal, effects of reward magnitude, and transfer of learning. A group of 30 young (mean age = 24.2 yr) and a group of 30 older subjects (mean age = 64.1 yr) completed two probabilistic reward-based stimulus association learning tasks. Older subjects showed poorer overall acquisition and impaired reversal learning, as well as deficits in transfer learning. When only those subjects who showed evidence of significant learning were considered, younger subjects showed equivalently fast learning irrespective of reward magnitude, while learning curves in older subjects were steeper for high compared to low reward magnitudes. Acquired equivalence learning, which requires generalization across stimuli and transfer of learned contingencies to new stimuli, was mildly impaired in older subjects.