bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory effect in Sm C* phase of electroclinic liquid crystals
Authors: Choudhary A. , Kaur S. , Singh G. , Prakash J. , Thakur A. K. , Biradar A. M.
Published: April 2007

Dielectric, textural, and electro-optical investigations have been carried out on a material exhibiting de Vries smectic A phase transition in sample cells of various thicknesses. Thickness independent memory effect has been observed in this special class of ferroelectric liquid crystals (FLCs) known as de Vries electroclinic liquid crystals. Unlike the FLC materials, surface anchoring energy does not play a role in the memory effect due to the fact that pitch is around 2 micron and basic assumption of SSFLC effect is not valid. The conversion of short-range azimuthal (Φ) ordering of molecules in Sm C* phase into a long-range azimuthal ordering under the influence of field could be one of the possible explanations. The transformation of molecular ordering in Sm C* phase under field may be mediated by dipolar interaction and viscoelastic properties.
Molecular dynamics simulations of stretched gold nanowires: The relative utility of different semiempirical potentials
Authors: Pu Qing , Leng Yongsheng , Tsetseris Leonidas , Park Harold S. , Pantelides Sokrates T. , Cummings Peter T.
Published: April 2007

The mechanical elongation of a finite gold nanowire has been studied by molecular dynamics simulations using different semiempirical potentials for transition metals. These potentials have been widely used to study the mechanical properties of finite metal clusters. Combining with density functional theory calculations along several atomic-configuration trajectories predicted by different semiempirical potentials, the authors conclude that the second-moment approximation of the tight-binding scheme (TB-SMA) potential is the most suitable one to describe the energetics of finite Au clusters. They find that for the selected geometries of Au wires studied in this work, the ductile elongation of Au nanowires along the [001] direction predicted by the TB-SMA potential is largely independent of temperature in the range of 0.01–298K. The elongation leads to the formation of monatomic chains, as has been observed experimentally. The calculated force-versus-elongation curve is remarkably consistent with available experimental results.
Chiral separation on a model adsorbent with periodic surface heterogeneity
Authors: Szabelski Paweł , Sholl David S.
Published: April 2007

Optimization of enantioselectivity in heterogeneous catalysis and chiral chromatography is a challenging task for the production of enantiopure chemicals. Enantioselective adsorbents usually consist of a surface with chiral receptors being either chiral molecules linked to the surface or chiral pockets formed by molecular templating of the surface. In both cases, the enantioselectivity is controlled mainly by the strength of the receptor-enantiomer interaction, such that one-to-one correspondence is usually preserved. The authors use Monte Carlo calculations to show that this steric requirement is not a necessary condition for the effective separation of chiral molecules. In particular, they propose a way in which a chiral surface can be constructed by a suitable spatial distribution of active sites for which the classical concept of a chiral receptor is no longer useful. Their calculations indicate that the effectiveness of the separation is affected mainly by the difference in shape of the adsorption energy distribution functions corresponding to the enantiomers.
Competition effects in diffusion-controlled bulk reactions between ions
Authors: Traytak S. D. , Barzykin A. V. , Tachiya M.
Published: April 2007

A numerical solution for competitive diffusion into two static charged sinks is presented and compared against an approximate analytical solution. It is shown that for an attractive Coulomb potential the correction to the total diffusive flux of ionic reactants due to diffusion interaction between sinks may be ignored for large enough values of the Onsager length and thus the reaction rate can be described by the classical Debye formula. On the other hand, for repulsive potentials the competition becomes more profound than in the case of uncharged sinks. However, this effect is of little interest because of a small value of the diffusive flux on the reaction surface.
Alternatives to the electron density for describing Coulomb systems
Authors: Ayers Paul W. , Nagy Agnes
Published: April 2007

Stimulated by the difficulty of deriving effective kinetic energy functionals of the electron density, the authors consider using the local kinetic energy as the fundamental descriptor for molecular systems. In this ansatz, the electron density must be expressed as a functional of the local kinetic energy. There are similar results for other quantities, including the local temperature and the Kohn-Sham potential. One potential advantage of these approaches—and especially the approach based on the local temperature—is the chemical relevance of the fundamental descriptor.
Shear-strain-induced chemical reactivity of layered molecular crystals
Authors: Kuklja Maija M. , Rashkeev Sergey N.
Published: April 2007

A density-functional theory study of shear related dissociation of two molecular crystals, diamino-dinitroethylene (FOX-7) and triamino-trinitrobenzine (TATB), is presented. A detailed explanation is proposed for the fact that FOX-7 is more sensitive than TATB while their sensitivities to initiation of chemistry have been expected to be comparable. The authors suggest that shear plays a crucial role in the dissociation of molecules in organic energetic crystals and may be imperative in providing specific recommendations on ways for materials design.
Calibration of atomic force microscope cantilevers using piezolevers
Authors: Aksu Saltuk B. , Turner Joseph A.
Published: April 2007

The atomic force microscope (AFM) can provide qualitative information by numerous imaging modes, but it can also provide quantitative information when calibrated cantilevers are used. In this article a new technique is demonstrated to calibrate AFM cantilevers using a reference piezolever. Experiments are performed on 13 different commercially available cantilevers. The stiff cantilevers, whose stiffness is more than 0.4 N/m, are compared to the stiffness values measured using nanoindentation. The experimental data collected by the piezolever method is in good agreement with the nanoindentation data. Calibration with a piezolever is fast, easy, and nondestructive and a commercially available AFM is enough to perform the experiments. In addition, the AFM laser must not be calibrated. Calibration is reported here for cantilevers whose stiffness lies between 0.08 and 6.02 N/m.
Microwave-assisted magnetization switching of Ni80Fe20 in magnetic tunnel junctions
Authors: Moriyama T. , Cao R. , Xiao John Q. , Lu J. , Wang X. R. , Wen Q. , Zhang H. W.
Published: April 2007

Microwave-assisted magnetization switching was investigated using Fe30Co70∕AlOx∕Ni80Fe20 magnetic tunnel junctions incorporated with a coplanar waveguide. Coercivity field of Ni80Fe20 layer was dramatically reduced in a small amplitude microwave. The authors eliminated the thermal effect in coercivity reduction by comparing two types of measurements which are with and without spin precession in the presence of microwave. It was found that the coercivity reduction depends on both frequency and power of the microwave. The numerical simulation based on Landau-Lifshitz-Gilbert equation reproduced the trend of the experimental data. The results indicate that microwave can be an efficient means to switch the magnetization of a thin film.
Phosphorus doping and hydrogen passivation of donors and defects in silicon nanowires synthesized by laser ablation
Authors: Fukata N. , Chen J. , Sekiguchi T. , Matsushita S. , Oshima T. , Uchida N. , Murakami K. , Tsurui T. , Ito S.
Published: April 2007

Phosphorus (P) doping was performed during the synthesis of silicon nanowires (SiNWs) by laser ablation. At least three types of signals were observed by electron spin resonance (ESR) at 4.2K. Phosphorus doping into substitutional sites of crystalline Si in SiNWs was demonstrated by the detection of an ESR signal with a g value of 1.998, which corresponds to conduction electrons in crystalline Si, and by an energy-dispersive x-ray spectroscopy spectrum of the PKα line. The ESR results also revealed the presence of defects. These defects were partially passivated by hydrogen and oxygen atoms.
Nonlinear extension of the x-ray diffraction enhanced imaging
Authors: Maksimenko Anton
Published: April 2007

Diffraction enhanced imaging is the analyzer-based x-ray imaging technique which allows extraction of the refraction and absorption contrasts from two images taken on the opposite sides of the rocking curve of the analyzer. It is widely used in different fields of science. However, the information provided by the method is qualitative rather than quantitative. This happens because either side of the rocking curve is approximated as a line. One can overcome this problem of considering the rocking curve instead of the approximation. This letter is dedicated to the implementation of this idea and includes theoretical background and experimental validation.
Simple technique for obtaining photoacoustic spectra corrected for the spectral variation of the source in single scan
Authors: Sathiyamoorthy K. , Vijayan C. , Kothiyal M. P.
Published: April 2007

A simple technique is presented to obtain normalized photoacoustic (PA) spectra corrected for the spectral variation of the source in a single scan. The input light beam is passed through the center of a dual slot chopper, which splits it into two chopped output beams at two different frequencies at a fixed ratio. The beams fall on the sample and the reference kept side-by-side in the same sample chamber. The PA signals are detected by a microphone and processed by two lock-in amplifiers tuned at two different frequencies. The technique is tested by recording the PA spectra of standard samples.
Electron and hole mobilities in polymorphs of benzene and naphthalene: Role of intermolecular interactions
Authors: Datta Ayan , Mohakud Sasmita , Pati Swapan K.
Published: April 2007

The hole and electron mobilities of the polymorphs of benzene and naphthalene crystals are estimated through quantum chemical calculations. The reorganization energy (λ) and the charge-transfer matrix elements (Hmn) calculated for the two molecules reveal that these crystals can be used for dual applications, for both hole and electron conductance. The electron mobilities are five to eight times more than the hole mobilities for benzene while for naphthalene, the hole mobilities are almost an order magnitude more than the electron mobilities. The transfer matrices for both hole and electron conductance decrease monotonically with increase in the intermolecular distances. Calculations for various unique stacked dimers as determined from the radial distribution functions in both the crystals for the two molecules show strong dependence on the orientations of the rings and for similar intermolecular separations; Hmnhole is larger than Hmnelectron. The crystal mobilities are calculated from the weighted average over all the unique pair of molecules. The overall preference in a crystal for hole or electron mobility depends on the mutual competition of λhole∕λelectron and Hmnhole∕Hmnelectron. From our microscopic understanding of essential parameters, specific dimers are identified from the crystalline solids of the two polymorphs and experimental strategies are suggested to enrich such pairs in aggregates for enhancing mobilities for these organic solids.
Third-order scattering model for the diffuse backscattering intensity patterns of polarized light from a turbid medium
Authors: Deng Yong , Lu Qiang , Luo Qingming , Zeng Shaoqun
Published: April 2007

The authors develop a third-order scattering approximation model for characterizing the diffuse backscattering intensity patterns of polarized light from turbid media. Phase function is applied to select optimum scattering paths of three successive scattering events. Bouger’s law and the theory of incoherent scattering of light by spheres are used to form the analytical expressions. Comparisons of the calculations of the second-order model and the experimental measurements show that the third-order model can also describe the spatial characteristics of polarized patterns; moreover, it is more accurate and sensitive than the second-order model in revealing the polarized patterns dependent on scattering coefficients.
Surface enhanced Raman scattering of nanoporous gold: Smaller pore sizes stronger enhancements
Authors: Qian L. H. , Yan X. Q. , Fujita T. , Inoue A. , Chen M. W.
Published: April 2007

The authors report the surface enhanced Raman scattering (SERS) of nanoporous gold with nanopore sizes ranging from 5to700nm. Their comprehensive investigations prove that the strongest SERS enhancement of nanoporous gold takes place from the samples with an ultrafine nanopore size of ∼5–10nm. Both the enhancement factor and detection limit of the ultrafine nanoporous substrate are one to two orders of magnitude better than those of coarsened nonporous gold with smooth surfaces. Moreover, careful microstructure characterization reveals that the anomalous SERS enhancement of the annealed nanoporous gold arises from roughsurfaces with characteristic surface irregularities.
Mn
3
Ga
, a compensated ferrimagnet with high Curie temperature and low magnetic moment for spin torque transfer applications
Authors: Balke Benjamin , Fecher Gerhard H. , Winterlik Jürgen , Felser Claudia
Published: April 2007

This work reports about the electronic, magnetic, and structural properties of the binary compound Mn3Ga. The tetragonal DO22 phase of Mn3Ga was successfully synthesized and investigated. It has been found that the material is hard magnetic with an energy product of Hc×Br=52.5kJm−3 and an average saturation magnetization of about 0.25μB∕at. at 5K. The saturation magnetization indicates a ferrimagnetic order with partially compensating moments at the Mn atoms on crystallographically different sites. The Curie temperature is above 730K where the onset of decomposition is observed. The electronic structure calculations indicate a nearly half-metallic ferrimagnetic order with 88% spin polarization at the Fermi energy.
Explosive field emission and plasma expansion of carbon nanotube cathodes
Authors: Liao Qingliang , Zhang Yue , Huang Yunhua , Qi Junjie , Gao Zhanjun , Xia Liansheng , Zhang Huang
Published: April 2007

High intensity electron emission cathodes based on carbon nanotube films have been successfully fabricated. An investigation of the explosive field emission properties of the carbon nanotube cathode in a double-pulse mode was presented and a high emission current density of 309A∕cm2 was obtained. The time-and-space resolution of the electron-beam flow from the cathode was investigated. The formation of the cathode plasma layer was proven and the plasma expanded at a velocity of ∼7.8cm∕μs toward the anode. The formation of cathode plasma has no preferential position and the local enhancement of electron beams is random.
Theoretical study on the sound absorption of electrolytic solutions. I. Theoretical formulation
Authors: Yamaguchi T. , Matsuoka T. , Koda S.
Published: April 2007

A theory is formulated that describes the sound absorption of electrolytic solutions due to the relative motion of ions, including the formation of ion pairs. The theory is based on the Kubo-Green formula for the bulk viscosity. The time correlation function of the pressure is projected onto the bilinear product of the density modes of ions. The time development of the product of density modes is described by the diffusive limit of the generalized Langevin equation, and approximate expressions for the three- and four-body correlation functions required are given with the hypernetted-chain integral equation theory. Calculations on the aqueous solutions of model electrolytes are performed. It is demonstrated that the theory describes both the activated barrier crossing between contact and solvent-separated ion pairs and the Coulombic correlation between ions.
Advanced temperature compensation for piezoresistive sensors based on crystallographic orientation
Authors: Chui B. W. , Aeschimann L. , Akiyama T. , Staufer U. , de Rooij N. F. , Lee J. , Goericke F. , King W. P. , Vettiger P.
Published: April 2007

We describe a highly effective method of reducing thermal sensitivity in piezoresistive sensors, in particular silicon cantilevers, by taking advantage of the dependence of the piezoresistive coefficient of silicon on crystallographic orientation. Two similar strain-sensing elements are used, positioned at 45 degrees to each other: One is set along a crystalline axis associated with a maximum piezoresistive coefficient to produce the displacement signal, while the other is set along an axis of the vanishing coefficient to produce the reference signal. Unlike other approaches, both sensing elements are coupled to the same cantilever body, maximizing thermal equilibration. Measurements show at least one order of magnitude improvement in thermal disturbance rejection over conventional approaches using uncoupled resistors.
Approaches to rationalising selection of test environments for on-farm lentil variety trials in Mediterranean rainfed cropping systems
Authors: Sarker A. , Singh M. , El-Ashkar F. , Erskine W. , De-Pauw E.
Published: April 2007

This study focused on various approaches to rationalising the selection of test environments using on-farm trial data from 5 lentil (Lens culiniaris Medikus subsp. culinaris) genotypes. It was conducted over 3 years in 30 environments across 16 locations in Syria. There was maximum discrimination in the ratio of between-cluster to within-cluster variances, based on genotype yield responses to the environments. Four clusters represented the test locations, reflecting a gradient in the levels of yield and seasonal rainfall. We observed significant genotypic differences and genotype × environment interactions. Genotype × cluster interaction accounted for a substantial portion of the genotype × environment interaction. This supported a reduction in the number of test locations to evaluate genotype and environment interaction. Temporal interactions were either low or insignificant. The improved lines produced stable and significantly higher yields than the local cultivar. The structure of the clusters formed indicated the presence of research stations in each cluster. We recommend that locations for future on-farm testing should include one research location and a farmer field in each cluster (or the mega-zone) so formed. Climatic variables or geographical nearness cannot replace the role of genotype response when rationalising test locations.
Effect of lamb age and electrical stimulation on the colour stability of fresh lamb meat
Authors: Jacob R. H. , D'Antuono M. F. , Smith G. M. , Pethick D. W. , Warner R. D.
Published: April 2007

The aim of this experiment was to compare the effects of electrical stimulation and lamb age on the retail colour stability of lamb meat. Poll Dorset Merino crossbred lambs that were 5 months (‘suckers’, SU) and 12 months (‘carryovers’, CO) finished on the same green annual pasture were slaughtered at a commercial abattoir. Half of the carcasses in each age group (10) were either electrically stimulated (ES) or not stimulated (NES) post-dressing with a commercial high voltage electrical stimulation system. Luminescence (L), hue angle (indication of redness), chroma (intensity), and oxy/met (a measure of browning) values were measured at 0 h (0 days), 21 h (0.86 days), 93 h (3.88 days), and 166 h (6.91 days) after meat had been cut 1 day after slaughter, over wrapped, and put under simulated retail display conditions. Three muscles, m. longissimus thoracis et lumborum (LL), m. gluteus medias (GM), and m. rectus femoris (RF), were measured in this way. A linear mixed model was used to fit a repeated-measurements model to the light measurements of L, hue angle, chroma, and oxy/met. Oxy/met rate of change was compared by fitting splines to predict the time required for oxy/met to reach an arbitrary benchmark value of 3.
Colour and rate of colour change during display were affected by both age class and electrical stimulation but these effects depended on the muscle. The LL was the darkest (lowest L) and reddest (lowest hue angle), whilst RF was the most stable in colour (lowest rate of change for oxy/met) of the 3 muscles tested. Age class had a greater effect on oxy/met rate of change for the LL and GM compared with RF. Oxy/met of LL changed more rapidly for CO than SU lambs. ES increased the time for oxy/met to reach 3 in RF and GM for SU only but did so for both age groups in LL. ES decreased this time in RF and GM for CO. CO meat contained a higher concentration of myoglobin than SU meat. Negative effects of electrical stimulation on colour stability are more likely to occur in older lambs and in the GM and RF rather than in the LL.
Estimating crop area using seasonal time series of Enhanced Vegetation Index from MODIS satellite imagery
Authors: Potgieter A. B. , Apan A. , Dunn P. , Hammer G.
Published: April 2007

Cereal grain is one of the main export commodities of Australian agriculture. Over the past decade, crop yield forecasts for wheat and sorghum have shown appreciable utility for industry planning at shire, state, and national scales. There is now an increasing drive from industry for more accurate and cost-effective crop production forecasts. In order to generate production estimates, accurate crop area estimates are needed by the end of the cropping season. Multivariate methods for analysing remotely sensed Enhanced Vegetation Index (EVI) from 16-day Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery within the cropping period (i.e. April–November) were investigated to estimate crop area for wheat, barley, chickpea, and total winter cropped area for a case study region in NE Australia. Each pixel classification method was trained on ground truth data collected from the study region. Three approaches to pixel classification were examined: (i) cluster analysis of trajectories of EVI values from consecutive multi-date imagery during the crop growth period; (ii) harmonic analysis of the time series (HANTS) of the EVI values; and (iii) principal component analysis (PCA) of the time series of EVI values. Images classified using these three approaches were compared with each other, and with a classification based on the single MODIS image taken at peak EVI. Imagery for the 2003 and 2004 seasons was used to assess the ability of the methods to determine wheat, barley, chickpea, and total cropped area estimates. The accuracy at pixel scale was determined by the percent correct classification metric by contrasting all pixel scale samples with independent pixel observations. At a shire level, aggregated total crop area estimates were compared with surveyed estimates. All multi-temporal methods showed significant overall capability to estimate total winter crop area. There was high accuracy at pixel scale (>98% correct classification) for identifying overall winter cropping. However, discrimination among crops was less accurate. Although the use of single-date EVI data produced high accuracy for estimates of wheat area at shire scale, the result contradicted the poor pixel-scale accuracy associated with this approach, due to fortuitous compensating errors. Further studies are needed to extrapolate the multi-temporal approaches to other geographical areas and to improve the lead time for deriving cropped-area estimates before harvest.
Impact of subsoil water use on wheat yield
Authors: Kirkegaard J. A. , Lilley J. M. , Howe G. N. , Graham J. M.
Published: April 2007

Water stored deep in the soil profile is generally considered valuable to crop yield because it becomes available during grain filling, but the value of subsoil water for grain yield has not been isolated and quantified in the field. We used rainout shelters with irrigation to control the water supply to wheat crops that had different amounts of subsoil water available to isolate and quantify the efficiency with which the subsoil water was converted to grain yield. Under moderate post-anthesis stress, 10.5 mm of additional subsoil water used in the 1.35–1.85 m layer after anthesis increased grain yield by 0.62 t/ha, representing an efficiency of 59 kg/ha.mm. The additional yield resulted from a period of higher assimilation 12–27 days after anthesis and was related to an increase in grain size rather than other yield components. Under more severe stress with earlier onset, extra water use below 1.25 m was accompanied by additional water use in upper soil layers and it was more difficult to isolate and quantify the benefit of deep water to grain yield. The additional water used from all layers from the time the stress was imposed was converted to grain at 30–40 kg/ha.mm, but this increased to 60 kg/ha.mm for water used after anthesis. The high efficiency for subsoil water use is 3 times that typically expected for total seasonal water use, and twice that previously estimated for total post-anthesis water use in a similar environment. The results demonstrate that relatively small amounts of subsoil water can be highly valuable to grain yield.
Evaluation of annual pasture legumes in northern New South Wales. 2. Trifolium and Medicago spp. and other legumes
Authors: Lodge G. M. , Harden S.
Published: April 2007

Two studies to evaluate annual pasture legumes were sown in replicated plots near Tamworth, New South Wales. In the first (experiment 1), 24 entries were sown in 1995 and in a second study (experiment 2) 33 entries were sown in 1996. Green herbage mass (kg DM/ha) was assessed in the year of sowing (spring) and thereafter four times per year until spring 2000. Limited data were also collected to estimate maturity grading, seed yield and seedling regeneration.
For each experiment, green herbage mass data were examined using cubic smoothing splines and at the end of each study, green herbage mass values predicted from the model were used to assess the significance (P = 0.05) of differences between cultivars or lines. In spring 2000 (experiment 1), Trifolium subterraneum var. brachycalycinum cv. Clare had the highest rank of the cultivars and lines, and T. michelianum cv. Paradana the lowest (previously cultivated site). For the native pasture site, CPI 70056B subterranean clover had the highest rank and Ornithopus compressus cv. Paros the lowest.
In experiment 2, Clare had the highest rank in spring 2000 and T. resupinatum cv. Bolta had the lowest ranking. Long-term green herbage mass appeared to be strongly influenced by maturity grading, but other factors may have affected the performance of annual Medicago spp., O. compressus, T. resupinatum, and T. michelianum. Results from the current study and previous reported research indicated that T. subterraneum var. subterraneum cvv. York (evaluated as CPI 89846B) and Junee and T. subterraneum var. brachycalycinum cv. Clare performed best in northern New South Wales.
Root penetration rate - a benchmark to identify soil and plant limitations to rooting depth in wheat
Authors: Kirkegaard J. A. , Lilley J. M.
Published: April 2007

Data on wheat rooting depth was compiled from 36 agronomic experiments conducted in southern NSW from 1990 to 2004. Rooting depth was measured by direct soil coring and observation of roots using core-break or root washing techniques. Maximum rooting depth varied from 80 to 180 cm and was influenced by the depth of soil wetting, soil type and the duration of the vegetative phase (sowing to anthesis) as determined by interactions of sowing date, variety and seasonal conditions. The root penetration rate (RPR cm/day), defined as (maximum root depth measured at or after anthesis) / (days from sowing to anthesis), emerged as a simple but unifying parameter which could be used to estimate the potential rooting depth of wheat on different soils. RPR, expressed on a thermal time basis, was highly correlated with that expressed on a simpler time basis (r = 0.92). Incomplete wetting of the soil profile reduced maximum rooting depth and RPR in 12 of the 36 crops studied, and root penetration in the subsoil was clearly restricted in soil layers with less than 45 to 50% plant available water. Soil type influenced the RPR. The average RPR for wheat was 1.13 ± 0.04 cm/day on Red Kandosols (n = 11), 1.01 ± 0.07 cm/day on a Red Sodosol (n = 3) and 0.79 ± 0.03 cm/day on Red Chromosols (n = 10). The RPR was relatively constant across cultivars and sowing dates within these soil types, although there was some evidence for a reduction in RPR with later sowing independent of time or thermal time. We suggest that the RPR (cm/day) established for wheat on various soil types provides a useful tool for wheat growers to estimate the rooting depth and available water and nutrients in-season. It also provides a benchmark to indicate potential subsoil limitations to crop growth, and for researchers investigating opportunities to increase the maximum rooting depth of wheat through management or breeding.
Discovery of a small molecule antagonist of the parathyroid hormone receptor by using an N-terminal parathyroid hormone peptide probe
Authors: Carter Percy H. , Liu Rui-Qin , Foster William R. , Tamasi Joseph A. , Tebben Andrew J. , Favata Margaret , Staal Ada , Cvijic Mary Ellen , French Michele H. , Dell Vanessa , Apanovitch Donald , Lei Ming , Zhao Qihong , Cunningham Mark , Decicco Carl P. , Trzaskos James M. , Feyen Jean H. M.
Published: April 2007

Once-daily s.c. administration of either human parathyroid hormone (PTH)-(1–84) or recombinant human PTH-(1–34) provides for dramatic increases in bone mass in women with postmenopausal osteoporosis. We initiated a program to discover orally bioavailable small molecule equivalents of these peptides. A traditional high-throughput screening approach using cAMP activation of the PTH/PTH-related peptide receptor (PPR) as a readout failed to provide any lead compounds. Accordingly, we designed a new screen for this receptor that used a modified N-terminal fragment of PTH as a probe for small molecule binding to the transmembrane region of the PPR, driven by the assumption that the pharmacological properties (agonist/antagonist) of compounds that bound to this putative signaling domain of the PPR could be altered by chemical modification. We developed DPC-AJ1951, a 14 amino acid peptide that acts as a potent agonist of the PPR, and characterized its activity in
ex vivo
and
in vivo
assays of bone resorption. In addition, we studied its ability to initiate gene transcription by using microarray technology. Together, these experiments indicated that the highly modified 14 amino acid peptide induces qualitatively similar biological responses to those produced by PTH-(1–34), albeit with lower potency relative to the parent peptide. Encouraged by these data, we performed a screen of a small compound collection by using DPC-AJ1951 as the ligand. These studies led to the identification of the benzoxazepinone SW106, a previously unrecognized small molecule antagonist for the PPR. The binding of SW106 to the PPR was rationalized by using a homology receptor model.
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig
Authors: Radhakrishnan Arun , Ikeda Yukio , Kwon Hyock Joo , Brown Michael S. , Goldstein Joseph L.
Published: April 2007

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins
Authors: Sun Li-Ping , Seemann Joachim , Goldstein Joseph L. , Brown Michael S.
Published: April 2007

Two classes of sterols, cholesterol and oxysterols, block export of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi by preventing the binding of COPII-coated proteins to a hexapeptide sorting signal (MELADL) in Scap, the SREBP-escort protein. Here, we show that anti-MELADL blocks COPII binding
in vitro
, and microinjection of Fab anti-MELADL blocks Scap·SREBP movement in cells. Cholesterol and oxysterols block COPII binding to MELADL by binding to different intracellular receptors, cholesterol to Scap and oxysterols to Insig. Cysteine labeling shows that both binding events produce a conformational change near the MELADL sequence, abrogating COPII binding but not anti-MELADL binding. Mutagenesis experiments raise the possibility that the distance of MELADL from the ER membrane is crucial for COPII binding, and we speculate that sterols and Insig block SREBP transport by altering the location of MELADL with respect to the membrane, rendering it inaccessible to COPII proteins.
Smallpox subunit vaccine produced
in planta
confers protection in mice
Authors: Golovkin Maxim , Spitsin Sergei , Andrianov Vyacheslav , Smirnov Yuriy , Xiao Yuhong , Pogrebnyak Natalia , Markley Karen , Brodzik Robert , Gleba Yuri , Isaacs Stuart N. , Koprowski Hilary
Published: April 2007

We report here the
in planta
production of the recombinant vaccinia virus B5 antigenic domain (pB5), an attractive component of a subunit vaccine against smallpox. The antigenic domain was expressed by using efficient transient and constitutive plant expression systems and tested by various immunization routes in two animal models. Whereas oral administration in mice or the minipig with collard-derived insoluble pB5 did not generate an anti-B5 immune response, intranasal administration of soluble pB5 led to a rise of B5-specific immunoglobulins, and parenteral immunization led to a strong anti-B5 immune response in both mice and the minipig. Mice immunized i.m. with pB5 generated an antibody response that reduced virus spread
in vitro
and conferred protection from challenge with a lethal dose of vaccinia virus. These results indicate the feasibility of producing safe and inexpensive subunit vaccines by using plant production systems.
Plc1p Is Required for SAGA Recruitment and Derepression of Sko1p-regulated Genes
Authors: Guha Nilanjan , Desai Parima , Vancura Ales
Published: April 2007

In Saccharomyces cerevisiae, many osmotically inducible genes are regulated by the Sko1p-Ssn6p-Tup1p complex. On osmotic shock, the MAP kinase Hog1p associates with this complex, phosphorylates Sko1p, and converts it into an activator that subsequently recruits Swi/Snf and SAGA complexes. We have found that phospholipase C (Plc1p encoded by PLC1) is required for derepression of Sko1p-Ssn6p-Tup1p–controlled osmoinducible genes upon osmotic shock. Although plc1Δ mutation affects the assembly of the preinitiation complex after osmotic shock, it does not affect the recruitment of Hog1p and Swi/Snf complex at these promoters. However, Plc1p facilitates osmotic shock–induced recruitment of the SAGA complex. Like plc1Δ cells, SAGA mutants are osmosensitive and display compromised expression of osmotically inducible genes. The reduced binding of SAGA to Sko1p-Ssn6p-Tup1p–repressed promoters in plc1Δ cells does not correlate with reduced histone acetylation. However, SAGA functions at these promoters to facilitate recruitment of the TATA-binding protein. The results thus provide evidence that Plc1p and inositol polyphosphates affect derepression of Sko1p-Ssn6p-Tup1p–controlled genes by a mechanism that involves recruitment of the SAGA complex and TATA-binding protein.
Rab1b Interacts with GBF1 and Modulates both ARF1 Dynamics and COPI Association
Authors: Monetta Pablo , Slavin Ileana , Romero Nahuel , Alvarez Cecilia
Published: April 2007

Assembly of the cytosolic coat protein I (COPI) complex at the ER–Golgi interface is directed by the ADP ribosylation factor1 (Arf1) and its guanine nucleotide exchange factor (GBF1). Rab1b GTPase modulates COPI recruitment, but the molecular mechanism underlying this action remains unclear. Our data reveal that in vivo expression of the GTP-restricted Rab1b mutant (Rab1Q67L) increased the association of GBF1 and COPI to peripheral structures localized at the ER exit sites (ERES) interface. Active Rab1b also stabilized Arf1 on Golgi membranes. Furthermore, we characterized GBF1 as a new Rab1b effector, and showed that its N-terminal domain was involved in this interaction. Rab1b small interfering RNA oligonucleotide assays suggested that Rab1b was required for GBF1 membrane association. To further understand how Rab1b functions in ER-to-Golgi transport, we analyzed GFP-Rab1b dynamics in HeLa cells. Time-lapse microscopy indicated that the majority of the Rab1b-labeled punctuated structures are relatively short-lived with limited-range movements. FRAP of Golgi GFP-Rab1bwt showed rapid recovery (t1/2120 s) with minimal dependence on microtubules. Our data support a model where Rab1b-GTP induces GBF1 recruitment at the ERES interface and at the Golgi complex where it is required for COPII/COPI exchange or COPI vesicle formation, respectively.
Cell Polarity Development and Protein Trafficking in Hepatocytes Lacking E-Cadherin/β-Catenin–based Adherens Junctions
Authors: Théard Delphine , Steiner Magdalena , Kalicharan Dharamdajal , Hoekstra Dick , van IJzendoorn Sven C.D.
Published: April 2007

Using a mutant hepatocyte cell line in which E-cadherin and β-catenin are completely depleted from the cell surface, and, consequently, fail to form adherens junctions, we have investigated adherens junction requirement for apical–basolateral polarity development and polarized membrane trafficking. It is shown that these hepatocytes retain the capacity to form functional tight junctions, develop full apical–basolateral cell polarity, and assemble a subapical cortical F-actin network, although with a noted delay and a defect in subsequent apical lumen remodeling. Interestingly, whereas hepatocytes typically target the plasma membrane protein dipeptidyl peptidase IV first to the basolateral surface, followed by its transcytosis to the apical domain, hepatocytes lacking E-cadherin–based adherens junctions target dipeptidyl peptidase IV directly to the apical surface. Basolateral surface-directed transport of other proteins or lipids tested was not visibly affected in hepatocytes lacking E-cadherin–based adherens junctions. Together, our data show that E-cadherin/β-catenin–based adherens junctions are dispensable for tight junction formation and apical lumen biogenesis but not for apical lumen remodeling. In addition, we suggest a possible requirement for E-cadherin/β-catenin–based adherens junctions with regard to the indirect apical trafficking of specific proteins in hepatocytes.
Multiple Interactions Drive Adaptor-Mediated Recruitment of the Ubiquitin Ligase Rsp5 to Membrane Proteins In Vivo and In Vitro
Authors: Sullivan James A. , Lewis Michael J. , Nikko Elina , Pelham Hugh R.B.
Published: April 2007

Recognition of membrane proteins by the Nedd4/Rsp5 ubiquitin ligase family is a critical step in their targeting to the multivesicular body pathway. Some substrates contain “PY” motifs (PPxY), which bind to WW domains in the ligase. Others lack PY motifs and instead rely on adaptors that recruit the ligase to them. To investigate the mechanism of adaptor-mediated ubiquitination, we have characterized the interactions between the adaptor Bsd2, the ubiquitin ligase Rsp5, and the membrane proteins Cps1, Tre1, and Smf1 from Saccharomyces cerevisiae. We have reconstituted adaptor-mediated modification of Cps1 and Tre1 in vitro, and we show that two PY motifs in Bsd2 and two WW domains (WW2 and WW3) in Rsp5 are crucial for this. The binding of a weak noncanonical DMAPSY motif in Bsd2 to WW3 is an absolute requirement for Bsd2 adaptor function. We show that sorting of the manganese transporter Smf1, which requires both Bsd2 and Tre1, depends upon two PY motifs in Bsd2 and one motif in Tre1 but only two WW domains in Rsp5. We suggest that sequential assembly of first a Bsd2/Rsp5 complex, then a Tre1/Bsd2/Rsp5 complex followed by a rearrangement of PY–WW interactions is required for the ubiquitination of Smf1.
Supramolecular self-assembly codes for functional structures
Authors: Palmer Liam C , Velichko Yuri S , Olvera de la Cruz Monica , Stupp Samuel I
Published: April 2007

Small-molecule self-assembly has proven to be a rich field for the controlled synthesis of supramolecular objects with the size scale of polymers and interesting properties. Using several recent examples from our laboratory, we discuss the development of chemical structure codes for supramolecular self-assembly objects with defined shapes. The resulting materials formed by these objects are promising for electronic functions and biological functions for regenerative medicine.
Hole-vibronic coupling in oligothiophenes: impact of backbone torsional flexibility on relaxation energies
Authors: da Silva Filho Demetrio A , Coropceanu Veaceslav , Fichou Denis , Gruhn Nadine E , Bill Tonja G , Gierschner Johannes , Cornil Jérôme , Brédas Jean-Luc
Published: April 2007

Density functional theory calculations together with highly resolved gas-phase ultraviolet photoelectron spectroscopy have been applied to oligothiophene chains with up to eight thiophene rings. One of the important parameters governing the charge transport properties in the condensed phase is the amount of energy relaxation upon ionization. Here, we investigate the impact on this parameter of the backbone flexibility present in oligothiophenes as a result of inter-ring torsional motions. With respect to oligoacenes that are characterized by a coplanar and rigid backbone, the torsional flexibility in oligothiophenes adds to the relaxation energy and leads to the broadening of the first ionization peak, making its analysis more complex.
Multilevel structure in behaviour and in the brain: a model of Fuster's hierarchy
Authors: Botvinick Matthew M
Published: April 2007

A basic question, intimately tied to the problem of action selection, is that of how actions are assembled into organized sequences. Theories of routine sequential behaviour have long acknowledged that it must rely not only on environmental cues but also on some internal representation of temporal or task context. It is assumed, in most theories, that such internal representations must be organized into a strict hierarchy, mirroring the hierarchical structure of naturalistic sequential behaviour. This article reviews an alternative computational account, which asserts that the representations underlying naturalistic sequential behaviour need not, and arguably cannot, assume a strictly hierarchical form. One apparent liability of this theory is that it seems to contradict neuroscientific evidence indicating that different levels of sequential structure in behaviour are represented at different levels in a hierarchy of cortical areas. New simulations, reported here, show not only that the original computational account can be reconciled with this alignment between behavioural and neural organization, but also that it gives rise to a novel explanation for how this alignment might develop through learning.
Biologically constrained action selection improves cognitive control in a model of the Stroop task
Authors: Stafford Tom , Gurney Kevin N
Published: April 2007

The Stroop task is a paradigmatic psychological task for investigating stimulus conflict and the effect this has on response selection. The model of Cohen
et al.
(Cohen
et al
. 1990
Psychol. Rev.
97
, 332–361) has hitherto provided the best account of performance in the Stroop task, but there remains certain key data that it fails to match. We show that this failure is due to the mechanism used to perform final response selection—one based on the diffusion model of choice behaviour (Ratcliff 1978
Psychol. Rev.
85
, 59–108). We adapt the model to use a selection mechanism which is based on the putative human locus of final response selection, the basal ganglia/thalamo-cortical complex (Redgrave
et al.
1999
Neuroscience
89
, 1009–1023). This improves the match to the core human data and, additionally, makes it possible for the model to accommodate, in a principled way, additional mechanisms of cognitive control that enable better fits to the data. This work prompts a critique of the diffusion model as a mechanism of response selection, and the features that any response mechanism must possess to provide adaptive action selection. We conclude that the consideration of biologically constrained solutions to the action selection problem is vital to the understanding and improvement of cognitive models of response selection.
Action selection and refinement in subcortical loops through basal ganglia and cerebellum
Authors: Houk J.C , Bastianen C , Fansler D , Fishbach A , Fraser D , Reber P.J , Roy S.A , Simo L.S
Published: April 2007

Subcortical loops through the basal ganglia and the cerebellum form computationally powerful distributed processing modules (DPMs). This paper relates the computational features of a DPM's loop through the basal ganglia to experimental results for two kinds of natural action selection. First, functional imaging during a serial order recall task was used to study human brain activity during the selection of sequential actions from working memory. Second, microelectrode recordings from monkeys trained in a step-tracking task were used to study the natural selection of corrective submovements. Our DPM-based model assisted in the interpretation of puzzling data from both of these experiments. We come to posit that the many loops through the basal ganglia each regulate the embodiment of pattern formation in a given area of cerebral cortex. This operation serves to instantiate different kinds of action (or thought) mediated by different areas of cerebral cortex. We then use our findings to formulate a model of the aetiology of schizophrenia.
An agent-based model of group decision making in baboons
Authors: Sellers W.I , Hill R.A , Logan B.S
Published: April 2007

We present an agent-based model of the key activities of a troop of chacma baboons (Papio hamadryas ursinus) based on the data collected at De Hoop Nature Reserve in South Africa. We analyse the predictions of the model in terms of how well it is able to duplicate the observed activity patterns of the animals and the relationship between the parameters that control the agent's decision procedure and the model's predictions. At the current stage of model development, we are able to show that across a wide range of decision parameter values, the baboons are able to achieve their energetic and social time requirements. The simulation results also show that decisions concerning movement (group action selection) have the greatest influence on the outcomes. Those cases where the model's predictions fail to agree with the observed activity patterns have highlighted key elements that were missing from the field data, and that would need to be collected in subsequent fieldwork. Based on our experience, we believe group decision making is a fertile field for future research, and agent-based modelling offers considerable scope for understanding group action selection.