bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear pulse evolution in seeded free-electron laser amplifiers and in free-electron laser cascades
Authors: Giannessi L. , Musumeci P. , Spampinati S.
Published: August 2005

The advances in laser technology have made available very short and intense laser pulses which can be used to seed a high-gain single-pass free-electron laser (FEL) amplifier. With these seed pulses, a regime of the FEL interaction where the radiation evolution is simultaneously dominated by nonlinear effects (saturation) and time-dependent effects (slippage) can be explored. This regime is characterized by the propagation of a solitary wavelike pulse where the power of the optical wave grows quadratically with time, its pulse length decreases and the spectral bandwidth increases. We analyze the interplay between the field and particle dynamics of this propagation regime which was studied before and termed super-radiance. Furthermore we analyze the properties of the strong higher-order harmonic emission from this wave and its behavior when propagating in a cascade FEL. The super-radiant pulse is indeed capable of passing through the stages of a cascade FEL and to regenerate itself at the wavelength of the higher-order harmonic. The optical pulse obtained is shorter than a cooperation length and is strongly chirped in frequency, thus allowing further longitudinal compression down to the attosecond time scale.
Pulsed-laser-deposited p-type ZnO films with phosphorus doping
Authors: Vaithianathan Veeramuthu , Lee Byung-Teak , Kim Sang Sub
Published: August 2005

We report the preparation of p-type ZnO thin films on Al2O3(0001) substrates with phosphorus doping by pulsed laser deposition using Zn3P2 as the dopant source material. The results of the Hall effect measurements taken at room temperature indicate that the 3-mol% phosphorus-doped ZnO films thermally annealed at temperatures between 600 and 800°C under an O2 atmosphere exhibit p-type behavior with a hole concentration of 5.1×1014−1.5×1017cm−3, a hole mobility of 2.38−39.3cm2∕Vs, and a resistivity of 17−330Ωcm. The low-temperature (15K) photoluminescence results reveal that the peak related to the neutral-acceptor bound exciton (A0,X) emission at 3.358eV is only observed in the films showing p-type behavior. Our results not only demonstrate that there is a narrow temperature window for rapid thermal annealing in which phosphorus-doped p-type ZnO films can be obtained, but also suggest that the use of Zn3P2 can provide an effective approach to the preparation of p-type ZnO films.
Thermal response of Ru electrodes in contact with SiO2 and Hf-based high-k gate dielectrics
Authors: Wen H.-C. , Lysaght P. , Alshareef H. N. , Huffman C. , Harris H. R. , Choi K. , Senzaki Y. , Luan H. , Majhi P. , Lee B. H. , Campin M. J. , Foran B. , Lian G. D. , Kwong D.-L.
Published: August 2005

A systematic experimental evaluation of the thermal stability of Ru metal gate electrodes in direct contact with SiO2 and Hf-based dielectric layers was performed and correlated with electrical device measurements. The distinctly different interfacial reactions in the Ru∕SiO2, Ru∕HfO2, and Ru∕HfSiOx film systems were observed through cross-sectional high-resolution transmission electron microscopy, high angle annular dark field scanning transmission electron microscopy with electron-energy-loss spectra, and energy dispersive x-ray spectra analysis. Ru interacted with SiO2, but remained stable on HfO2 at 1000°C. The onset of Ru∕SiO2 interfacial interactions is identified via silicon substrate pitting possibly from Ru diffusion into the dielectric in samples exposed to a 900°C∕10-s anneal. The dependence of capacitor device degradation with decreasing SiO2 thickness suggests Ru diffuses through SiO2, followed by an abrupt, rapid, nonuniform interaction of ruthenium silicide as Ru contacts the Si substrate. Local interdiffusion detected on Ru∕HfSiOx samples may be due to phase separation of HfSiOx into HfO2 grains within a SiO2 matrix, suggesting that SiO2 provides a diffusion pathway for Ru. Detailed evidence consistent with a dual reaction mechanism for the Ru∕SiO2 system at 1000°C is presented.
Hard x-ray holographic microscopy using refractive prism and Fresnel zone plate objective
Authors: Suzuki Yoshio , Takeuchi Akihisa
Published: August 2005

An optics for hard x-ray holographic microscopy has been developed and preliminary experiments have been done at SPring-8 undulator beamline 20XU. The optical system consists of an x-ray objective lens (Fresnel zone plate) and a wave front-division-type interferometer with prism optics. The illuminating x-ray beam is coherent with parallel radiation, and the spatially coherent area is much larger than the aperture of the objective lens. The refractive prism is placed behind the back focal plane of the objective lens in order to configure the wavefront-dividing interferometer. Half of the illuminating radiation is used for illuminating an object, and the other half is used for forming a reference wave. The magnified image of the object is generated at an image plane, and the reference wave is superimposed on the magnified image of the object. The recorded interferogram includes both amplitude and phase information of the object. The spatial resolution is determined by the numerical aperture of the objective lens. Therefore, in principle, this method enables holographic imaging at nanometer scale to be carried out in the hard x-ray region.
Apparatus to measure high-temperature thermal conductivity and thermoelectric power of small specimens
Authors: Dasgupta T. , Umarji A. M.
Published: August 2005

A thermal conductivity apparatus based on the parallel heat-flow technique has been fabricated to measure the thermal conductivity of small specimens. The steady-state method is used to measure samples of 1×1×10mm3 dimension in the temperature range of room temperature–700 K. The details of instrument fabrication, the method of calibration, and typical measurements on test samples are described. The apparatus can also be used to measure the Seebeck coefficient in the same temperature range. As an example we report the thermal properties of CrSi2, which is a potential candidate for high-temperature thermoelectric applications.
High spatial resolution Hall sensor array for edge plasma magnetic field measurements
Authors: Liu Yuhong , Maurer David A. , Navratil Gerald A. , Rivera Nicholas
Published: August 2005

A one-dimensional, high-spatial resolution, 20-element Hall sensor array has been developed to directly measure the edge plasma perpendicular magnetic field and its fluctuations as a function of radius with 4-mm resolution. The array employs new small-area, high-sensitivity indium antimonide (InSb) Hall probes in combination with a high-density seven-layer printed circuit board to provide for connections to supply Hall current, record the measured Hall voltage output signals, and mitigate inductive pickup. A combination of bench and in situ measurements is described that provides absolute calibration of the diagnostic array in the presence of a strong transverse magnetic field component that is approximately 1000 times greater than the perpendicular fluctuating field needed to be resolved by the diagnostic. The Hall probes calibrated using this method are capable of magnetic field measurements with a sensitivity of 7V∕T over the frequency band from 0 to 20 kHz.
The effect of TiO2 doping on the structure and magnetic and magnetotransport properties of La0.75Sr0.25MnO3 composite
Authors: Kameli P. , Salamati H. , Eshraghi M. , Mohammadizadeh M. R.
Published: August 2005

The effect of TiO2 doping on the structure and magnetic and magnetotransport properties of La0.75Sr0.25MnO3 (LSMO)∕xTiO2 has been investigated. These studies show that at low doping level (x⩽2) TiO2 mainly goes into the grain-boundary region, but at high doping level (x⩾3), some part of the TiO2 goes into the perovskite lattice substituting Mn in LSMO and the remainder segregates as a separate phase at the grain boundaries. Results also show that the TiO2 doping has an important effect on a low-field magnetoresistance. In the magnetic field of 8000Oe and at 77K a magnetoresistance value of ∼20% was observed for the composite with a TiO2 doping level of x=2.
Controlled rotation of sound-trapped small particles by an acoustic needle
Authors: Hu Junhui , Tay Chiaolin , Cai Yanmin , Du Jinlong
Published: August 2005

We show that an acoustic needle, mechanically driven by an ultrasonic transducer in air, can rotate sound-trapped small particles around its tip in water. The rotation is very stable when sound field around the tip is appropriate. For an acoustic needle at a given location in a sound field, the revolution speed of trapped particles can be controlled by the acoustic pressure near the tip or by driving voltage and frequency of the ultrasonic transducer. For Flying Color seeds, a revolution speed larger than 300rpm can be obtained.
β
-phase-domain-free α-MnAs thin films on GaAs(001) by postgrowth annealing
Authors: Song J. H. , Cui Y. , Lee J. J. , Ketterson J. B.
Published: August 2005

Postgrowth annealing effects on a heteroepitaxial MnAs thin film grown on a GaAs(001) substrate have been investigated. The β-MnAs phase domains of an as-grown sample, observed as dark stripes in the surface topography at room temperature, disappear completely after postgrowth annealing. In support of this finding, the paramagnetic contribution to the magnetic hysteresis loop arising from the β-MnAs phase domains is also not observed at 300K. We attribute the origin of these effects to relaxation of the elastic strain in the MnAs thin film.
Effective intermediate layers for highly efficient stacked organic light-emitting devices
Authors: Sun J. X. , Zhu X. L. , Peng H. J. , Wong M. , Kwok H. S.
Published: August 2005

Effective intermediate electrode layers comprising of LiF(1nm)∕Ca(25nm)∕Ag(15nm) or LiF(1nm)∕Al(3nm)∕Au(15nm) were studied in stacked organic light-emitting devices (OLEDs). Stacked OLEDs with two identical emissive units consisting of NPB∕Alq3: C545T/BCP exhibited superior luminous efficiency-current density characteristics over conventional single-unit devices. At 20mA∕cm2, the luminous efficiency of the stacked OLEDs using the intermediate layers of LiF∕Ca∕Ag and LiF∕Al∕Au were about 19.6cd∕A and 17.5cd∕A, respectively, almost doubling that of the corresponding control devices, as expected.
Fabrication and characterization of freestanding GaAs∕AlGaAs core-shell nanowires and AlGaAs nanotubes by using selective-area metalorganic vapor phase epitaxy
Authors: Noborisaka J. , Motohisa J. , Hara S. , Fukui T.
Published: August 2005

We fabricated GaAs∕AlGaAs core-shell nanowires by using selective-area metalorganic vapor phase epitaxy. First, GaAs nanowires were selectively grown on partially masked GaAs (111)B substrates; then AlGaAs was grown to form freestanding heterostructured nanowires. Investigation of nanowire diameter as a function of AlGaAs growth time suggested that the AlGaAs was grown on the sidewalls of the GaAs nanowires, forming GaAs∕AlGaAs core-shell structures. Microphotoluminescence measurements of GaAs and GaAs∕AlGaAs core-shell nanowires reveal an enhancement of photoluminescence intensity in GaAs∕AlGaAs core-shell structures. Based on these core-shell nanowires, AlGaAs nanotubes were formed by using anisotropic dry etching and wet chemical preferential etching to confirm the formation of a core-shell structure and to explore a new class of materials.
Large exchange bias and high stability of CoFe∕CrPt films with L10 CrPt as the pinning layer
Authors: Dai B. , Cai J. W. , Lai W. Y. , An Y. K. , Mai Z. H. , Shen F. , Liu Y. Z. , Zhang Z.
Published: August 2005

We have studied an antiferromagnetic L10 CrPt film as a pinning layer. dc magnetron sputtered [Pt∕Cr] multilayers on a Co0.9Fe0.1 layer exhibit no exchange bias. After being annealed at 350 °C for 5 h in a vacuum, the equiatomic [Pt∕Cr] multilayer stack is transformed into a uniform CrPt alloy film with L10 phase, which pins the adjacent 120 Å CoFe layer with a pinning field of ∼70Oe and a coercivity of only 28 Oe. The hysteresis loop of this exchange biased system is almost square and the interdiffusion between the CrPt and the CoFe layers is rather small. The equivalent interface exchange energy ΔE, 0.12erg∕cm2, is comparable to the typical value of FeMn biasing system. However, the blocking temperature, at which the exchange bias disappears, is as high as 600 °C, 150 °C higher than the highest value ever reported. Since it possesses extremely good thermal stability, large exchange bias, little interdiffusion, and high corrosion resistance, the antiferromagnetic CrPt film is proposed to serve as a pinning layer for magnetoresistive devices.
Super-elastic titanium alloy with unstable plastic deformation
Authors: Hao Y. L. , Li S. J. , Sun S. Y. , Zheng C. Y. , Hu Q. M. , Yang R.
Published: August 2005

Here we report a non-toxic β-type titanium alloy exhibiting unstable elastic and plastic deformation behavior. Elastic instability leads to remarkable elastic softening, i.e., the decrease of incipient Young’s modulus with slight pre-straining. In spite of partial recovery during room-temperature aging, a stable modulus of 33GPa matching that of human bone can be maintained. Plastic instability causes highly-localized deformation which is very effective in grain refinement but contributes little to strength. We thus obtain soft nanostructured metallic materials (NMMs): The flow stress increases by only ∼5.5% as coarse grains are reduced to below 50nm, in contrast with several times increase for previously-reported NMMs.
Determination of the folding transition states of barnase by using ΦI-value-restrained simulations validated by double mutant ΦIJ-values
Authors: Salvatella Xavier , Dobson Christopher M. , Fersht Alan R. , Vendruscolo Michele
Published: August 2005

The protein barnase folds from the denatured state into its native conformation via a high-energy intermediate. Using ΦI-values determined experimentally from single-point mutations as restraints in all-atom molecular dynamics simulations, we have determined ensembles of structures corresponding to the transition states for the formation of the folding intermediate and its conversion into the native state. We have also introduced a stringent validation of the approach used to calculate such structures by predicting interaction ΦIJ-values determined experimentally from a series of double-mutant cycles. The ensembles that we have obtained illustrate the heterogeneity in the nucleation-condensation process by which barnase folds. Obligatory steps of this process include the sequential formation of two folding nuclei, which correspond to the two main hydrophobic cores of the protein. Nonobligatory steps include the elongation of the strand β1 and the formation of the helix α2. The results confirm that the use of experimental observables such as ΦI-values as restraints in molecular dynamics simulations is a powerful general strategy to characterize the relatively heterogeneous structural ensembles that populate nonnative regions of the energy landscapes of proteins.
Diagnosing breast cancer by using Raman spectroscopy
Authors: Haka Abigail S. , Shafer-Peltier Karen E. , Fitzmaurice Maryann , Crowe Joseph , Dasari Ramachandra R. , Feld Michael S.
Published: August 2005

We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from
ex vivo
samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical/morphological makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied
in vivo
to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed.
Herbivores cause a rapid increase in hereditary symbiosis and alter plant community composition
Authors: Clay Keith , Holah Jenny , Rudgers Jennifer A.
Published: August 2005

Microbial symbioses are ubiquitous in nature. Hereditary symbionts warrant particular attention because of their direct effects on the evolutionary potential of their hosts. In plants, hereditary fungal endophytes can increase the competitive ability, drought tolerance, and herbivore resistance of their host, although it is unclear whether or how these ecological benefits may alter the dynamics of the endophyte symbiosis over time. Here, we demonstrate that herbivores alter the dynamics of a hereditary symbiont under field conditions. Also, we show that changes in symbiont frequency were accompanied by shifts in the overall structure of the plant community. Replicated 25-m2plots were enriched with seed of the introduced grass,Lolium arundinaceumat an initial frequency of 50% infection by the systemic, seed-transmitted endophyteNeotyphodium coenophialum. Over 54 months, there was a significantly greater increase in endophyte-infection frequency in the presence of herbivores (30% increase) than where mammalian and insect herbivory were experimentally reduced by fencing and insecticide application (12% increase). Under ambient mammalian herbivory, the above-ground biomass of nonhost plant species was reduced compared with the mammal-exclusion treatment, and plant composition shifted toward greater relative biomass of infected, tall fescue grass. These results demonstrate that herbivores can drive plant–microbe dynamics and, in doing so, modify plant community structure directly and indirectly.
Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection
Authors: Matsuyama Shutoku , Ujike Makoto , Morikawa Shigeru , Tashiro Masato , Taguchi Fumihiro
Published: August 2005

A unique coronavirus severe acute respiratory syndrome-coronavirus (SARS-CoV) was revealed to be a causative agent of a life-threatening SARS. Although this virus grows in a variety of tissues that express its receptor, the mechanism of the severe respiratory illness caused by this virus is not well understood. Here, we report a possible mechanism for the extensive damage seen in the major target organs for this disease. A recent study of the cell entry mechanism of SARS-CoV reveals that it takes an endosomal pathway. We found that proteases such as trypsin and thermolysin enabled SARS-CoV adsorbed onto the cell surface to enter cells directly from that site. This finding shows that SARS-CoV has the potential to take two distinct pathways for cell entry, depending on the presence of proteases in the environment. Moreover, the protease-mediated entry facilitated a 100- to 1,000-fold higher efficient infection than did the endosomal pathway used in the absence of proteases. These results suggest that the proteases produced in the lungs by inflammatory cells are responsible for high multiplication of SARS-CoV, which results in severe lung tissue damage. Likewise, elastase, a major protease produced in the lungs during inflammation, also enhanced SARS-CoV infection in cultured cells.
RPE65 is the isomerohydrolase in the retinoid visual cycle
Authors: Moiseyev Gennadiy , Chen Ying , Takahashi Yusuke , Wu Bill X. , Ma Jian-xing
Published: August 2005

RPE65 is an abundant protein in the retinal pigment epithelium. Mutations in RPE65 are associated with inherited retinal dystrophies. Although it is known that RPE65 is critical for regeneration of 11-
cis
retinol in the visual cycle, the function of RPE65 is elusive. Here we show that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting
all-trans
retinyl ester to 11-
cis
retinol in the visual cycle. The initial rate for the reaction is 2.9 pmol/min per mg of RPE65 expressed in 293A cells. The isomerohydrolase activity of RPE65 requires coexpression of lecithin retinol acyltransferase in the same cell to provide its substrate. This enzymatic activity is linearly dependent on the expression levels of RPE65. This study demonstrates that RPE65 is the long-sought isomerohydrolase and fills a major gap in our understanding of the visual cycle. Identification of the function of RPE65 will contribute to the understanding of the pathogenesis for retinal dystrophies associated with RPE65 mutations.
Circadian modulation of complex learning in diurnal and nocturnal
Aplysia
Authors: Lyons Lisa C. , Rawashdeh Oliver , Katzoff Ayelet , Susswein Abraham J. , Eskin Arnold
Published: August 2005

Understanding modulation of memory, as well as the mechanisms underlying memory formation, has become a key issue in neuroscience research. Previously, we found that the formation of long-term, but not short-term, memory for a nonassociative form of learning, sensitization, was modulated by the circadian clock in the diurnal
Aplysia californica
. To define the scope of circadian modulation of memory, we examined an associative operant learning paradigm, learning that food is inedible (LFI). Significantly greater long-term memory of LFI occurred when
A. californica
were trained and tested during the subjective day, compared with animals trained and tested in the subjective night. In contrast, animals displayed similar levels of short-term memory for LFI when trained in either the subjective day or night. Circadian modulation of long-term memory for LFI was dependent on the time of training, rather than the time of testing. To broaden our investigation of circadian modulation of memory, we extended our studies to a nocturnal species,
Aplysia fasciata
. Contrary to the significant memory observed during the day with the diurnal
A. californica
,
A. fasciata
showed no long-term memory for LFI when trained during the day. However,
A. fasciata
demonstrated significant long-term memory when trained and tested during the night. Thus, the circadian clock modulates memory formation in phase with the animals' activity period. The results from our studies of circadian modulation of long-term sensitization and LFI suggest that circadian modulation of memory formation may be a general phenomenon with potentially widespread implications for many types of long-term learning.
Mechanism of peptide bond synthesis on the ribosome
Authors: Trobro Stefan , Åqvist Johan
Published: August 2005

With the emergence of atomic-resolution crystal structures of bacterial ribosomal subunits, major advances in eliciting structure–function relationships of the translation process are underway. Nevertheless, the detailed mechanism of peptide bond synthesis that occurs on the large ribosomal subunit remains unknown. Separate x-ray structures of aminoacyl-tRNA and peptidyl-tRNA analogues bound to the ribosomal A- and P-sites, however, allow for structural modeling of the active complex in catalysis. Here, we combine available structural data to construct such a model of the peptidyl transfer reaction center with bound substrates. Molecular dynamics and free energy perturbation simulations then are used in combination with an empirical valence bond description of the reaction energy surface to examine possible catalytic mechanisms. Already, simulations of the reactant and tetrahedral intermediate states reveal a stable, preorganized H-bond network poised for catalysis. The most favorable mechanism is found not to involve any general acid–base catalysis by ribosomal groups but an intrareactant proton shuttling via the P-site adenine O2′ oxygen, which follows the attack of the A-site α-amino group on the P-site ester. The calculated rate enhancement for this mechanism is ≈10
5
, and the catalytic effect is found to be entirely of entropic origin, in accordance with recent experimental data, and is associated with the reduction of solvent reorganization energy rather than with substrate alignment or proximity. This mechanism also explains the inability of 2′-deoxyadenine P-site substrates to promote peptidyl transfer. The observed H-bond network suggests an important structural role of several universally conserved rRNA residues.
Site-specific genomic targeting inDrosophila
Authors: Horn Carsten , Handler Alfred M.
Published: August 2005

Transcriptional regulation of transgenes depends upon genomic localization in higher eukaryotes. For the applied use of transgenic organisms as producers of pharmaceutically relevant proteins or as pest population control agents, a method to make transgene expression predictable is highly desirable. A targeting method that allows precise cassette replacement comprising solely genes of interest (without extraneous donor vector sequences) would be highly advantageous for insects and other multicellular organisms. In this report, we describe a method for transgene targeting to predefined chromosomal sites inDrosophilaby using a transposon vector that, once integrated in the germ line, acts as an acceptor site for donor vectors. To make recombinational insertions irreversible, a FLP recombinase-mediated cassette exchange strategy was used, and to enhance donor-target pairing, a homing sequence from thelinottelocus was used. Site-specific recombinants were screened by interconvertible eye fluorescence marker phenotypes yielding, on average, targeted insertions at a frequency of 23%. The cassette exchange system provides for repetitive integrations into the same locus, allowing comparative analysis of true transgenic alleles. Furthermore, this method was used to stabilize a targeted transgene by the postintegration excision of putatively mobile transposon sequences. The genomic targeting and stabilization strategy described forDrosophilashould be applicable to other insects, specifically for the goals of optimizing heterologous protein expression and enhancing ecological safety of transgenic strains intended for release in biocontrol programs.
Loss and gain of chromosome 5 controls growth of
Candida albicans
on sorbose due to dispersed redundant negative regulators
Authors: Kabir M. Anaul , Ahmad Ausaf , Greenberg Jay R. , Wang Ying-Kai , Rustchenko Elena
Published: August 2005

A reversible decrease or increase of
Candida albicans
chromosome copy number was found to be a prevalent means of survival of this opportunistic pathogen, under conditions that kill cells or inhibit their propagation. The utilization of a secondary carbon source,
l
-sorbose, by reversible loss of chromosome 5, serves as a model system. We have determined that an ≈209-kbp portion of the right arm of chromosome 5 contains at least five spatially separated, functionally redundant regions that control utilization of
l
-sorbose. The regions bear no structural similarity among themselves, and four of them contain sequences that bear no similarity with any known sequence. We identified a regulatory gene in region A that encodes a helix-loop-helix protein. Most important, the multiple redundant regulators scattered along chromosome 5 explain, in a simple, elegant way, why the loss of the entire homologue is usually required for growth on sorbose. Thus, an entire chromosome acts as a single regulatory unit, a feature not previously considered. Our finding appears to be a paradigm for the control of other phenotypes in
C. albicans
that also depend on chromosome loss, thus implying that
C. albicans
genes are not distributed randomly among different chromosomes.
Direct NMR observation of a substrate protein bound to the chaperonin GroEL
Authors: Horst Reto , Bertelsen Eric B. , Fiaux Jocelyne , Wider Gerhard , Horwich Arthur L. , Wüthrich Kurt
Published: August 2005

The reaction cycle and the major structural states of the molecular chaperone GroEL and its cochaperone, GroES, are well characterized. In contrast, very little is known about the nonnative states of the substrate polypeptide acted on by the chaperonin machinery. In this study, we investigated the substrate protein human dihydrofolate reductase (hDHFR) while bound to GroEL or to a single-ring analog, SR1, by NMR spectroscopy in solution under conditions where hDHFR was efficiently recovered as a folded, enzymatically active protein from the stable complexes upon addition of ATP and GroES. By using the NMR techniques of transverse relaxation-optimized spectroscopy (TROSY), cross-correlated relaxation-induced polarization transfer (CRIPT), and cross-correlated relaxation-enhanced polarization transfer (CRINEPT), bound hDHFR could be observed directly. Measurements of the buildup of hDHFR NMR signals by different magnetization transfer mechanisms were used to characterize the dynamic properties of the NMR-observable parts of the bound substrate. The NMR data suggest that the bound state includes random coil conformations devoid of stable native-like tertiary contacts and that the bound hDHFR might best be described as a dynamic ensemble of randomly structured conformers.
Tactile form and location processing in the human brain
Authors: Van Boven Robert W. , Ingeholm John E. , Beauchamp Michael S. , Bikle Philip C. , Ungerleider Leslie G.
Published: August 2005

To elucidate the neural basis of the recognition of tactile form and location, we used functional MRI while subjects discriminated gratings delivered to the fingertip of either the right or left hand. Subjects were required to selectively attend to either grating orientation or grating location under identical stimulus conditions. Independent of the hand that was stimulated, grating orientation discrimination selectively activated the left intraparietal sulcus, whereas grating location discrimination selectively activated the right temporoparietal junction. Hence, hemispheric dominance appears to be an organizing principle for cortical processing of tactile form and location.
Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett Syndrome
Authors: Dani Vardhan S. , Chang Qiang , Maffei Arianna , Turrigiano Gina G. , Jaenisch Rudolf , Nelson Sacha B.
Published: August 2005

Rett Syndrome (RTT) is a devastating neurological disorder that is caused by mutations in the
MECP2
gene.
Mecp2
-mutant mice have been used as a model system to study the disease mechanism. Our previous work has suggested that MeCP2 malfunction in neurons is the primary cause of RTT in the mouse. However, the neurophysiological consequences of MeCP2 malfunction remain obscure. Using whole-cell patch-clamp recordings in cortical slices, we show that spontaneous activity of pyramidal neurons is reduced in
Mecp2
-mutant mice. This decrease is not caused by a change in the intrinsic properties of the recorded neurons. Instead, the balance between cortical excitation and inhibition is shifted to favor inhibition over excitation. Moreover, analysis of the miniature excitatory postsynaptic currents (mEPSCs)/inhibitory postsynaptic currents (mIPSCs) in the
Mecp2
-mutant cortex reveals a reduction in mEPSC amplitudes, without significant change in the average mIPSC amplitude or frequency. These findings provide the first detailed electrophysiological analysis of
Mecp2
-mutant mice and provide a framework for understanding the pathophysiology of the disease and tools for studying the underlying disease mechanisms.
Effects of seasonal climate forecasts and participatory workshops among subsistence farmers in Zimbabwe
Authors: Patt Anthony , Suarez Pablo , Gwata Chiedza
Published: August 2005

Improvements in the ability to model El Niño and other large-scale interannual climate variations have allowed for the development of seasonal climate forecasts, predicting rainfall and temperature anomalies for many places around the world. These forecasts have allowed developing countries to predict shortfalls in grain yields, with benefits for food security. Several countries communicate the forecasts to subsistence farmers, which could allow them to mitigate the effects of drought on their harvests by adapting their cropping decisions accordingly. However, it has not been demonstrated that subsistence farmers benefit from having access to the forecasts. Here we present evidence of subsistence farmers using the forecasts over multiple years to make different decisions and significantly improving their harvests when they do so. In a controlled study, farmers in Zimbabwe who reported adapting their farming methods to seasonal climate forecasts significantly improved their harvests over baseline amounts. Moreover, farmers who had attended a brief workshop and learned more about the forecasts were significantly more likely to use the forecasts than were farmers who learned of the forecasts through nonparticipatory channels.
The end-product method of measuring whole-body protein turnover: a review of published results and a comparison with those obtained by leucine infusion
Authors: Duggleby S. L. , Waterlow J. C.
Published: August 2005

The present review summarizes the results of all published papers on whole-body protein turnover in man measured by [15N]glycine and the end-product method using both urea and ammonia. It begins with a short account of the underlying assumptions and the justification for the use of [15N]glycine. The results are then compared with those of a large sample of measurements by the ‘gold standard’ precursor method with continuous infusion of [13C]leucine. The pros and cons of the two methods are compared and it is suggested that there is a place for further work by the less invasive end-product method, particularly for population studies of the genetic, environmental and functional determinants of whole-body rates of protein synthesis.
High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial
Authors: Trebble Timothy M. , Stroud Mike A. , Wootton Stephen A. , Calder Philip C. , Fine David R. , Mullee Mark A. , Moniz Caje , Arden Nigel K.
Published: August 2005

Crohn's disease is associated with altered bone turnover that may be influenced by nutritional status, the systemic inflammatory response, cytokine production by circulating (peripheral blood) mononuclear cells (PBMC) and antioxidant micronutrient intake. High-dose fish oil is associated with reductions in disease relapse and inflammatory markers, and modulates PBMC function. The effect of fish oil plus antioxidants on bone turnover and PBMC function (the production of interferon-γ and prostaglandin E2) in Crohn's disease was investigated in a randomised-controlled trial. Patients with currently or recently raised biochemical markers of inflammation (C-reactive protein ≧6·9 mg/l or erythrocyte sedimentation rate ≧18 mm/h) received fish oil (providing 2·7 g/d EPA and DHA) and antioxidants (vitamins A, C and E, and Se) (n 31) or placebo (n 30) for 24 weeks. Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline (bone resorption) and serum osteocalcin (bone formation). Fish oil plus antioxidants were associated with increases in EPA, DHA Se in plasma (all P<0·01), and with a reduction in interferon-γ production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (r −0·33, P=0·009). There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio, or in nutritional status. Dietary supplementation in Crohn's disease with high intakes of EPA and DHA, as fish oil, plus antioxidants was associated with a modulated production of interferon-γ by PBMC but not altered indices of bone turnover.
Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats
Authors: Díez Nieves , Pérez Raquel , Hurtado Verónica , Santidrián Santiago
Published: August 2005

Diet is the most common cause of mild hyperhomocysteinaemia (HHcy), which occurs in approximately 5–7 % of the general population. Since HHcy causes endothelial damage by oxidative stress in different organs, the present study was designed to examine whether HHcy might be involved in renal oxidative stress. Twenty-five male Wistar rats were randomly divided into two groups: one (n13) was fedad libituma folate-free diet (FF) and the other (n12) was fed the same diet supplemented with folic acid (control, CO). After 8 weeks the animals were killed and kidneys removed. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in plasma and kidney homogenates. Renal tissue sections were analysed by indirect immunostaining with the primary antibody against oxidatively modified LDL receptor (LOX-1). A marked HHcy was confirmed in the FF group. As compared with CO animals, MDA levels in plasma and kidney homogenate were significantly higher in FF rats (P<0·05). Similarly, renal GPx and SOD activities were significantly higher in the FF group (P<0·001). No differences were found in LOX-1 immunohistochemical expression, which in the two groups was displayed in tubular cells. The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1.
Effect of copper supplementation on indices of copper status and certain CVD risk markers in young healthy women
Authors: Bügel Susanne , Harper Angela , Rock Edmond , O'Connor Jacqueline M. , Bonham Maxine P. , Strain J. J.
Published: August 2005

Western diets containing suboptimal Cu concentrations could be widespread. A link between marginal Cu deficiency and CVD has been suggested. The objective of the present study was to investigate the effect of Cu supplementation on both Cu status and CVD risk factors in healthy young women. Sixteen women with a mean age of 24 (sd 2) years participated in a randomised crossover study of three 4-week periods with 3-week washouts between periods. During each intervention period, subjects received 0, 3 or 6 mg elemental Cu/d as CuSO4in addition to their habitual diet. Blood samples were taken to assess the effect of supplementation on putative markers of Cu status. The content of plasma lipids, lipoprotein (a), apo and certain haemostatic factors, as putative indices of CVD, was also analysed. Daily supplementation with 3 mg Cu significantly increased (P<0·05) serum Cu concentration and the activity of erythrocyte superoxide dismutase, although there was no further significant increase after an intake of 6 mg Cu/d. The concentration of the fibrinolytic factor plasminogen activator inhibitor type 1 was significantly reduced (P<0·05) by about 30% after supplementation with 6 mg Cu/d. No other marker of Cu status or CVD risk factor was affected by Cu supplementation. The results indicate that supplementation with 3 or 6 mg Cu/d may improve Cu status in these healthy young women. Increased Cu intake could reduce the risk of CVD and atherosclerosis in man by promoting improved fibrinolytic capacity.
Is religious fasting related to iron status in Greek Orthodox Christians?
Authors: Sarri Katerina O. , Kafatos Anthony G. , Higgins Siobhan
Published: August 2005

The Orthodox Christian diet is unique in regularly interchanging from an omnivore to a vegetarian-type diet, and no study to date has focused on the impact of this on Fe status. Thirty-five Greek Orthodox Christian strict fasters (n17 male,n18 female; mean age 43·6±13·2 years) and twenty-four controls (n11 male,n13 female; mean age 39·8±7·6 years) were studied before (pre) and near completion (end) of the Christmas fasting (CF) period (40 d), during which meat and dairy products are prohibited. Fe status was assessed using standard haematological parameters, and Fe deficiency was determined via serum ferritin levels (<12 ng/ml) and the tri-index model. While fasters had marginally poorer pre haematological indicators, values were well above the cut-off levels, suggesting that intermittent fasting for a mean of 22·5±15·5 years did not have any substantial adverse effects on Fe status. During the CF period the changes in Fe status indices were more beneficial for fasters than for control subjects. In particular, fasters increased their ferritin levels (P=0·02) and decreased their total Fe-binding capacity (P<0·001). Compared with males, the effect of CF was more pronounced in female fasters. No subjects were detected with Fe deficiency at the end of the CF period. End dietary Fe and fibre intake were significantly higher in the fasters as compared with the control group (P=0·038 andP=0·001, respectively). Adherence to the Orthodox Christian dietary guidelines does not have a major impact on Fe status and is not associated with a significantly greater degree of Fe deficiency.
Effect of potassium salts in rats adapted to an acidogenic high-sulfur amino acid diet
Authors: Sabboh Houda , Horcajada Marie-Noëlle , Coxam Véronique , Tressol Jean-Claude , Besson Catherine , Rémésy Christian , Demigné Christian
Published: August 2005

Low-grade metabolic acidosis, consecutive to excessive catabolism of sulfur amino acids and a high dietary Na:K ratio, is a common feature of Western food habits. This metabolic alteration may exert various adverse physiological effects, especially on bone, muscle and kidneys. To assess the actual effects of various K salts, a model of the Westernised diet has been developed in rats: slight protein excess (20 % casein); cations provided as non-alkalinising salts; high Na:K ratio. This diet resulted in acidic urine (pH 5·5) together with a high rate of divalent cation excretion in urine, especially Mg. Compared with controls, K supplementation as KCl accentuated Ca excretion, whereas potassium bicarbonate or malate reduced Mg and Ca excretion and alkalinised urine pH (up to 8). In parallel, citraturia was strongly increased, together with 2-ketoglutarate excretion, by potassium bicarbonate or malate in the diet. Basal sulfate excretion, in the range of 1 mmol/d, was slightly enhanced in rats fed the potassium malate diet. The present model of low-grade metabolic acidosis indicates that potassium malate may be as effective as KHCO3 to counteract urine acidification, to limit divalent cation excretion and to ensure high citrate concentration in urine.
The optimal diet for women with polycystic ovary syndrome?
Authors: Marsh Kate , Brand-Miller Jennie
Published: August 2005

An optimal diet is one that not only prevents nutrient deficiencies by providing sufficient nutrients and energy for human growth and reproduction, but that also promotes health and longevity and reduces the risk of diet-related chronic diseases. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known, but such a diet must not only assist short term with weight management, symptoms and fertility, but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. With insulin resistance and compensatory hyperinsulinaemia now recognised as a key factor in the pathogenesis of PCOS, it has become clear that reducing insulin levels and improving insulin sensitivity are an essential part of management. Diet plays a significant role in the regulation of blood glucose and insulin levels, yet research into the dietary management of PCOS is lacking and most studies have focused on energy restriction rather than dietary composition per se. On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended. Because PCOS carries significant metabolic risks, more research is clearly needed.
Modification of skin composition by conjugated linoleic acid alone or with combination of other fatty acids in mice
Authors: Oikawa Daichi , Nakanishi Tomonori , Nakamura Yoshi-nori , Yamamoto Takaya , Yamaguchi Atsuko , Shiba Nobuya , Iwamoto Hisao , Tachibana Tetsuya , Furuse Mitsuhiro
Published: August 2005

The effects of conjugated linoleic acid (CLA), γ-linolenic acid (GLA), linoleic acid (LA), and their combinations, on skin composition in mice were investigated. Mice (8 weeks old) were orally administered with either LA, GLA, CLA, LA + GLA, LA + CLA, or CLA + GLA for 4 weeks. Then, the skin was analysed for triacylglycerol content, fatty acid composition and collagen content. Additionally, thicknesses of the dermis layer and subcutaneous tissue layer, and the size and number of adipocytes were measured histologically. The skin fatty acid composition was modified depending upon the fatty acid composition of supplemented oils. In each oil-alone group, skin triacylglycerol content was the highest in LA, followed by GLA and CLA treatments. Combinations with CLA had a similar triacylglycerol content compared with the CLA-alone group. No significant changes in collagen content were observed among any treatments. The effects on subcutaneous thickness were similar to the results obtained in the triacylglycerol contents, where groups supplemented with CLA alone or other fatty acids had significantly thinner subcutaneous tissue compared with the LA-alone group. However, no significant difference was detected in the thickness of the dermis layers. The number of adipocytes was highest in the LA + GLA group and tended to be reduced by CLA with or without the other fatty acids. These results suggest that CLA alone or in combination with other fatty acids strongly modifies skin composition in mice.
No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers
Authors: Chango Abalo , Fillon-Emery Nathalie , Mircher Clotilde , Bléhaut Henri , Lambert Daniel , Herbeth Bernard , James S. Jill , Réthoré Marie-Odile , Nicolas Jean Pierre
Published: August 2005

The cause of the non-disjunction leading to trisomy 21 remains unclear. Recent evidence has suggested that 5, 10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21. The purpose of the present study was to analyse these findings among the French population and to investigate whether common polymorphisms in genes of the folate and homocysteine pathway, including the MTHFR 677C>T, MTHFR 1298A>C, the methionine synthase (MTR) 2756A>G, the cystathionine β-synthase (CBS) 844Ins68 and the reduced folate carrier (RFC-1) 80G>A polymorphisms, contribute to the risk of trisomy 21. The risk was studied by analysing independent and combined genotypes in 119 case mothers and 119 control mothers. The MTHFR 677T, MTHFR 1298C, MTR2756G, MTRR66G, CBSIns68+ and the RFC-1 80G allele frequencies were not significantly different among French case mothers, compared with control mothers. The risk of having a child with trisomy 21 did not appear to be linked to polymorphisms in genes associated with folate and homocysteine metabolism.