bluuebunny/crossref_metadata_2025 huggingface dataset:
Ordering of ErAs nanoparticles embedded in epitaxial InGaAs layers
Authors: Klenov Dmitri O. , Zide Joshua M. O. , LeBeau James M. , Gossard Arthur C. , Stemmer Susanne
Published: March 2007

The authors report on the microstructures of semimetallic ErAs nanoparticles embedded in epitaxial InGaAs layers by codeposition of Er. The size of the particles (1–3nm) was approximately independent of the amount of deposited Er. At large ErAs concentrations (>3at.%), the particles showed a strong tendency to order on the {114} planes of the semiconductor matrix. The ordering was only observed along one of the ⟨110⟩ directions, likely reflecting the strong anisotropy in surface diffusion.
Enhanced photocatalytic activity of Ag microgrid connected TiO2 nanocrystalline films
Authors: Pan Feng , Zhang Junying , Zhang Weiwei , Wang Tianmin , Cai Chao
Published: March 2007

One reason for the high degree of photogenerated carrier recombination was found to be the charge accumulation caused by the uneven reaction area on the photocatalyst surface. The authors connected TiO2 nanoparticles with conducting Ag microgrid. Obvious photocatalytic activity improvement (81%) over the pure TiO2 was observed, which is attributed to the electron-hole pairs separation by the metal-semiconductor contact and the large specific area of metal grid, which increased the O2 absorption and transported the electrons to the sites needed for the deoxidize reactions. This structure lowers the electron accumulation on the particles and improves the utilization ratio of the photoexcited carriers.
Velcro® nonlinear mechanics
Authors: Pugno Nicola Maria
Published: March 2007

In this letter a Velcro® nonlinear mechanics is presented. In particular, a calculation of the “elastic strength” of hooks with friction is derived. The author quantifies, as the intuition and Velcro® material suggest, that hooks (and loops) allow reversible strong attachment, finding elastic plastic or hyperelastic nonlinear behaviors, as a function of the competition between friction and finite displacements. Thus, the author presents here a Velcro® nonlinear mechanics to design and optimize hooked systems.
Self-assembling of ABC linear triblock copolymers in nanocylindrical tubes
Authors: Feng Jie , Ruckenstein Eli
Published: March 2007

By employing Monte Carlo simulations for various tube diameters and preferences of the tube surface for the A, B, and C segments, the morphologies of A5B5C5, A5B10C5, and A5B5C10 triblock copolymer melts confined in nanocylindrical tubes were examined. The interaction parameters between different segments were considered constant εAB=εAC=εBC=0.3kBT, the tube diameter was changed from d=9×lattice parameter to d=33×lattice parameter, and the preferences of the tube surface for the segments A, B, and C (−εAS,−εBS, and −εCS) were varied between 0.05kBT and kBT. ABCCBA alternately stacked disks were generated in most tubes when the preference of the tube surface for any of the segments was weak, and the morphologies tended to transform into curved lamellae in tubes with large diameters when the preference for one of the segments was high. Numerous novel morphologies, such as ABC double helixes, AB single helix+C double helixes, AB double helixes+C quadruple helixes, plate morphologies with fins, dendrites, etc., which were located in the phase diagram between the stacked disks and the curved lamellar structures, were identified. Additionally, the orientation parameters indicating the alignments of the polymer chains were calculated and correlated with the morphologies.
State-to-state inelastic scattering of OH by HI: A comparison with OH–HCl and OH–HBr
Authors: Moise A. , Parker D. H. , ter Meulen J. J.
Published: March 2007

Relative state-to-state cross sections and steric asymmetries have been measured for the scattering process: OH(XΠ3∕22,v=0,J=3∕2,MJ=3∕2,f)+HI(Σ1,v=0,J<4)→OH(XΠ2,v=0,Ω=1∕2,J=1∕2–5∕2andΩ=3∕2,J=3∕2–9∕2,e∕f)+HI, at 690cm−1 collision energy. Comparison with the previously studied systems OH–HCl and OH–HBr reveals relevant features of the potential energy surfaces of these molecular systems. Some measured differences concerning the internal energy distribution after collision and the propensities for the impact with one or the other side of the OH molecule in scattering by HCl, HBr, and HI molecules are discussed.
Compact optical fiber sensor smart node
Authors: Lloyd Seth W. , Newman Jason A. , Wilding Daniel R. , Selfridge Richard H. , Schultz Stephen M.
Published: March 2007

We present a new optical fiber sensor interrogator specifically designed for an embedded instrumentation system. The proposed system consists of a super luminescent diode as a broadband source, a high speed tunable micro-electro-mechanical system (MEMS) filter, photodetector, and an integrated microprocessor for data aggregation, processing, and communication. The entire system is integrated together in a compact package to create a fiber “smart” sensor. The system is capable of interrogating a variety of multiplexed fiber sensors, processing the data, and communicating the results digitally. As an example, the system has been calibrated with an array of fiber Bragg grating sensors.
Reduced conductivity in the terahertz skin-depth layer of metals
Authors: Laman N. , Grischkowsky D.
Published: March 2007

The terahertz conductivities of plates of Cu and Al were measured to remain the same at 295 and 77K using waveguide terahertz time domain spectroscopy (THz-TDS). This result was true for a variety of commercial alloys and surface preparations. Consequently, carrier scattering by lattice defects within the 100nm THz skin depth is much larger than scattering by phonons at room temperature. However, an exception was found to be the THz skin-depth layer of an evaporated 300nm Al film in contact with a polished Si surface. For this interface Al layer, the conductivity increased by a factor of 4 when cooled to 77K.
Frequency-agile terahertz-wave spectrometer for high-resolution gas sensing
Authors: Guo Ruixiang , Akiyama Koichi , Minamide Hiroaki , Ito Hiromasa
Published: March 2007

A tabletop, frequency-agile terahertz-wave spectrometer was developed based on an injection-seeded terahertz-wave parametric generator. High-resolution (<100MHz) spectra of polar gases can be measured in a wide frequency region (0.6–2.4THz) within a short time (several minutes) with this spectrometer. To demonstrate the potential of this system, the authors performed real-time detection of the absorption line due to rotational transitions of the water molecule and determined their pressure-broadening coefficient.
Comparison of metal-oxide-semiconductor capacitors on c- and m-plane gallium nitride
Authors: Matocha Kevin , Tilak Vinayak , Dunne Greg
Published: March 2007

The properties of the SiO2∕GaN interface were characterized using metal-oxide-semiconductor capacitors on polar c-plane (0001) and nonpolar m-plane (0 1 -1 0) GaN crystal faces. GaN m-plane samples show the absence of pyroelectric polarization effects. Additionally, capacitance-voltage hysteresis is less on m-plane compared to c-plane GaN surfaces, suggesting a lower interface-state density at the m-plane GaN∕SiO2 interface.
Mid-infrared imaging with a solid immersion lens and broadband laser source
Authors: Michaels Chris A.
Published: March 2007

The application of hemispherical solid immersion lenses (SILs) is an approach to increasing the spatial resolution attainable with infrared (IR) microscopy. A hemispherical SIL forms an image for which the effective numerical aperture and magnification are increased by a factor of the SIL material index of refraction. A microscope designed for exploration of IR SIL imaging based on a hemispherical ZnSe SIL, an InSb focal plane array detector, and a broadband IR laser source is described. The imaging characteristics of this system are reported, including the spatial resolution improvement achieved in the imaging of organic test samples.
Self-organized patterning of molecularly thin liquid polymer films utilizing molecular flow induced by ultraviolet irradiation
Authors: Zhang Hedong , Mitsuya Yasunaga , Fukuoka Natsuko , Imamura Masashi , Fukuzawa Kenji
Published: March 2007

A self-organized patterning method for molecularly thin liquid polymer films on solid surfaces has been demonstrated. In contrast to conventional methods that prepattern solid surfaces and then use the patterns as templates for polymer films, this method utilizes self-organization of polymers induced by ultraviolet (UV) radiation through a mask, thereby directly patterning the polymer films and omitting the prepatterning process. Such UV irradiation locally modified the interaction between polymer films and solid surfaces. As a result, molecular flow occurred at the boundary between the irradiated and nonirradiated areas, leading to three-dimensional surface structures.
Characterization of the texture of silicide films using electron backscattered diffraction
Authors: De Keyser K. , Detavernier C. , Van Meirhaeghe R. L.
Published: March 2007

Electron backscattered diffraction (EBSD) was used to characterize the texture of NiSi films. The various texture components (i.e., the types of preferred orientation, e.g., axiotaxy or epitaxy) could be identified, and their volume fraction could be quantified. Moreover, the spatial distribution of texture components could be studied in blanket films. Orientation imaging microscopy using EBSD is a promising technique to study the texture of silicide or germanide films both on blanket and patterned substrates.
Improved transport properties of Al2O3∕AlGaN∕GaN metal-oxide-semiconductor heterostructure field-effect transistor
Authors: Kordoš P. , Gregušová D. , Stoklas R. , Čičo K. , Novák J.
Published: March 2007

The authors report on improved transport properties of Al2O3∕AlGaN∕GaN metal-oxide-semiconductor heterostructure field-effect transistors (MOSHFETs). It is found that the drift mobility in the MOSHFET structures with 4nm thick Al2O3 gate oxide is significantly higher than that in HFETs. The zero-bias mobilities are 1950 and 1630cm2∕Vs for the MOSHFET and HFET, respectively. An ∼40% increase of the saturation drain current in the MOSHFETs compared to the HFETs seems to be larger than expected from the passivation effects. The MOSHFET devices show a higher transconductance (with peak values of ∼115mS∕mm) than the HFETs (∼70mS∕mm). Analysis of the device performance indicates a decrease of the parasitic series resistance together with an enhancement of the effective velocity of the channel electrons in the MOSHFET devices.
Ion beam irradiated channel waveguides in Er3+-doped tellurite glass
Authors: Berneschi S. , Nunzi Conti G. , Bányász I. , Watterich A. , Khanh N. Q. , Fried M. , Pászti F. , Brenci M. , Pelli S. , Righini G. C.
Published: March 2007

Erbium-doped tellurite glasses are of great interest for the fabrication of active integrated circuits because of their unique properties in terms of bandwidth and rare earth solubility. The fabrication of multimode channel waveguides in a glass of this family, namely, a sodium-tungsten-tellurite glass, is demonstrated using a high-energy ion beam irradiation technique. Nitrogen ions with dose of 1.0×1016ions∕cm2 and 1.5MeV energy were used for this aim. The waveguiding effect was investigated using the end-fire coupling technique.
Corrected Article: “Experimental study of liquid metal channel flow under the influence of a nonuniform magnetic field” [Phys. Fluids 18, 065108 (2006)]
Authors: Andreev O. , Kolesnikov Yu. , Thess A.
Published: March 2007

We present an experimental study of a liquid metal flow in a rectangular channel under the influence of an inhomogeneous magnetic field. This is a fundamental problem of liquid metal magnetohydrodynamics that is relevant to the technique of electromagnetic braking in the process of continuous casting of steel as well as for Lorentz force velocimetry. Based on local velocity and electric potential measurements we identify three distinct flow regions; namely (i) a turbulence suppression region, (ii) a vortical region, and (iii) a wall jet region. It is shown that in region (i) the applied inhomogeneous magnetic field brakes the incoming flow in its central part and transforms the velocity profile, which is initially flat, into an M-shaped form. In the central part of the flow, the intensity of the velocity fluctuations is found to decrease strongly. In region (ii) where the magnetic field is strongest, the flow is characterized by large-scale vortical structures which are time dependent for certain values of the control parameters. In region (iii), downstream of the magnetic system, two sidewall boundary layers are observed which generate velocity fluctuations with intensity up to 25% of the mean flow. These boundary layers bear close resemblance to wall jets known from ordinary hydrodynamics. Our experimental data provide a comprehensive database against which numerical simulations and turbulence models can be tested.
Local Taxation and the Relationship between Incomes and Property Values
Authors: Davies Rhys , Orton Michael , Bosworth Derek
Published: March 2007

The authors' concern is with the relationship between household income and property value, within the context of the debate about the fairness of council tax—the property-based system of local taxation in England. Although located within this particular debate, the fundamental issue of the relationship between household income and property value is of relevance to systems of property taxation the world over. Although the empirical literature to date makes reference to the links between property values and income levels in the context of debates about the fairness of council tax, the relationship between the two has not been empirically tested. The authors provide evidence of this relationship and show that, although there is a strong positive relationship between property values and income amongst higher income households, there is evidence of a ‘U-shaped’ relationship among lower income households. In addition, there is very strong evidence, that the elasticity of property prices with respect to income is not constant, but follows a bell-shaped distribution which is skewed to the right.
Globalization, Cultural Economy, and Not-So-Global Cities: The New Zealand Designer Fashion Industry
Authors: Larner Wendy , Molloy Maureen , Goodrum Alison
Published: March 2007

Research on so-called ‘global cities’ dominates the existing literature on globalization, fashion, and cities. In this we paper analyze the recent rise of a designer fashion industry in Auckland, New Zealand. The designer fashion industry has emerged as an unlikely success story as the New Zealand economy has globalized. Together with other creative industries, designer fashion is seen as an industry that can revamp New Zealand's international image and in doing so foster additional foreign investment. As the industry has succeeded, Auckland has disproportionately benefited, with sustained industry agglomeration and increasing infrastructural development in this city. However, the symbolic benefits of the designer fashion industry have proved more elusive. We show that the New Zealand designer fashion industry borrows symbolic capital from the global cities of designer fashion. We argue that this borrowing of symbolic capital underlines the need to think more carefully about the geographical specificity of the material, political, and symbolic processes associated with globalization and the cultural economy.
‘May I Have Your Attention’: Airport Geographies of Spectatorship, Position, and (im)Mobility
Authors: Adey Peter
Published: March 2007

This paper is concerned with the immobilities which airports induce and force to occur by positioning passengers through various and perhaps unconscious technological arrangements and performances of spectatorship. Through a conceptual reworking of spectatorship, these processes are explored through examples which range from the first airports, which functioned as city destinations from which to watch aircraft, to the carefully structured terminals of today. The airport is rethought as a space not merely to travel through but one which is designed to hold people in specific spaces. The paper also discusses the rationale behind these occurrences as they do not happen by random but are dictated by the forces of airline and airport regulation and economics.
Scat contents of the spotted-tailed quoll Dasyurus maculatus in the New England gorges, north-eastern New South Wales
Authors: Jarman Peter J. , Allen Lee R. , Boschma Dennis J. , Green Stuart W.
Published: March 2007

In 1313 scats of the spotted-tailed quoll Dasyurus maculatus, collected over 5 years from the gorge country of north-eastern New South Wales, the most frequent and abundant items were derived from mammals and a restricted set of insect orders. These quolls also ate river-associated items: waterbirds, eels, crayfish, aquatic molluscs and even frogs. Macropods contributed most of the mammal items, with possums, gliders and rodents also being common. Some food, particularly from macropods and lagomorphs, had been scavenged (as shown by fly larvae). The most frequent invertebrates were three orders of generally large insects Coleoptera, Hemiptera and Orthoptera, which were most frequent in summer and almost absent in winter scats. Monthly mean numbers of rodent and small dasyurid items per scat were inversely related to these large insects in scats. The numbers of reptile items were inversely related to the numbers of mammal (especially arboreal and small terrestrial mammal) items per scat, thus types of items interacted in their occurrences in monthly scat samples. Frequencies of most vertebrate items showed no seasonal, but much year-to-year, variation. This quoll population ate four main types of items, each requiring different skills to obtain: they hunted arboreal marsupials (possibly up trees), terrestrial small mammals and reptiles (on the ground), and seasonally available large insects (on trees or the ground), and scavenged carcases, mostly of large mammals but also birds and fishes (wherever they could find them).
Microhabitat separation and niche overlap among five assemblages of tropical skinks
Authors: Goodman Brett A.
Published: March 2007

The niche axes of microhabitat use, activity and size for 21 skink species from five assemblages (Alligator Creek, Cairns, Chillagoe, Cooktown and Mt Bartle Frere) in the biodiverse tropics of north-east Queensland were examined. Species within the same assemblage separated predominantly along two structural microhabitat gradients; one that ranged from microhabitats dominated by large rocks to leaf litter and total ground cover, and a second defined by increasing leaf litter, ground cover, undergrowth, proximity to vegetation and increased canopy cover. All species used available microhabitats non-randomly, with species from the same ecotype (arboreal, generalist, litter-dwelling, rock-using) clustering in multivariate ecological space. Despite evidence of within-assemblage niche overlap, null-model comparisons revealed that only one assemblage (Chillagoe) had greater niche overlap than would be expected by chance. Assemblages with more species occupied smaller niche space, indicating species packing. However, species with more diverse niches were less evenly packed. While most species overlapped in activity time and body size, differences among species from the same ecotype were observed. Despite subtle differences in temporal activity and body size, differences in structural microhabitat use appears to be the dominant niche axis allowing the coexistence of species within these assemblages of tropical skinks.
Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA
Authors: Heidel Jeremy D. , Yu Zhongping , Liu Joanna Yi-Ching , Rele Shyam M. , Liang Yongchao , Zeidan Ryan K. , Kornbrust Douglas J. , Davis Mark E.
Published: March 2007

The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis of complement factors does not reveal any changes that are clearly attributable to dosing with the nanoparticle formulation. Detection of increased IL-6 levels in all animals at 27 mg siRNA/kg and increased IFN-γ in one animal indicate that this high dose level produces a mild immune response. Overall, no clinical signs of toxicity clearly attributable to treatment are observed. The multiple administrations spanning a period of 17–18 days enable assessment of antibody formation against the human Tf component of the formulation. Low titers of anti-Tf antibodies are detected, but this response is not associated with any manifestations of a hypersensitivity reaction upon readministration of the targeted nanoparticle. Taken together, the data presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely be administered to non-human primates.
Domain-enhanced analysis of microarray data using GO annotations
Authors: Liu Jiajun , Hughes-Oliver Jacqueline M. , Menius J. Alan
Published: March 2007

Motivation: New biological systems technologies give scientists the ability to measure thousands of bio-molecules including genes, proteins, lipids and metabolites. We use domain knowledge, e.g. the Gene Ontology, to guide analysis of such data. By focusing on domain-aggregated results at, say the molecular function level, increased interpretability is available to biological scientists beyond what is possible if results are presented at the gene level.

Results: We use a ‘top–down’ approach to perform domain aggregation by first combining gene expressions before testing for differentially expressed patterns. This is in contrast to the more standard ‘bottom–up’ approach, where genes are first tested individually then aggregated by domain knowledge. The benefits are greater sensitivity for detecting signals. Our method, domain-enhanced analysis (DEA) is assessed and compared to other methods using simulation studies and analysis of two publicly available leukemia data sets.

Availability: Our DEA method uses functions available in R (http://www.r-project.org/) and SAS (http://www.sas.com/). The two experimental data sets used in our analysis are available in R as Bioconductor packages, ‘ALL’ and ‘golubEsets’ (http://www.bioconductor.org/).

Contact:  jliu6@stat.ncsu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
The impact of function perturbations in Boolean networks
Authors: Xiao Yufei , Dougherty Edward R.
Published: March 2007

Motivation: A network is said to be robust relative to a certain network characteristic if a small change in network structure does not significantly affect the characteristic. From the perspective of network stability, robustness is desirable; however, from the perspective of intervention to exert influence on network behavior, it is undesirable. For Boolean networks, there are two fundamental types of robustness. One type pertains to perturbing the state of the network and the other to perturbing the rule-based structure.

Results: This article explores the impact of function perturbations in Boolean networks from two aspects: (1) analysis: predict the impact on network state transitions and attractors via analytical approaches or identify a perturbation by observing its consequences; (2) synthesis: preserve or modify the network characteristics, especially attractors, by introducing a judicious change to the functions. The results are applied to achieve intervention that structurally alters the network to achieve a more favorable steady-state distribution and to identify the function perturbation that has led to altered observed behavior. The intervention procedure is applied to a WNT5A network to reduce the risk of metastasis in melanoma, and the identification procedure is applied to a Drosophila melanogaster segmentation polarity gene network to identify regulatory function perturbation.

Contact:  edward@ece.tamu.edu
UniRef: comprehensive and non-redundant UniProt reference clusters
Authors: Suzek Baris E. , Huang Hongzhan , McGarvey Peter , Mazumder Raja , Wu Cathy H.
Published: March 2007

Motivation: Redundant protein sequences in biological databases hinder sequence similarity searches and make interpretation of search results difficult. Clustering of protein sequence space based on sequence similarity helps organize all sequences into manageable datasets and reduces sampling bias and overrepresentation of sequences.

Results: The UniRef (UniProt Reference Clusters) provide clustered sets of sequences from the UniProt Knowledgebase (UniProtKB) and selected UniProt Archive records to obtain complete coverage of sequence space at several resolutions while hiding redundant sequences. Currently covering >4 million source sequences, the UniRef100 database combines identical sequences and subfragments from any source organism into a single UniRef entry. UniRef90 and UniRef50 are built by clustering UniRef100 sequences at the 90 or 50% sequence identity levels. UniRef100, UniRef90 and UniRef50 yield a database size reduction of ∼10, 40 and 70%, respectively, from the source sequence set. The reduced redundancy increases the speed of similarity searches and improves detection of distant relationships. UniRef entries contain summary cluster and membership information, including the sequence of a representative protein, member count and common taxonomy of the cluster, the accession numbers of all the merged entries and links to rich functional annotation in UniProtKB to facilitate biological discovery. UniRef has already been applied to broad research areas ranging from genome annotation to proteomics data analysis.

Availability: UniRef is updated biweekly and is available for online search and retrieval at http://www.uniprot.org, as well as for download at ftp://ftp.uniprot.org/pub/databases/uniprot/uniref

Contact:  bes23@georgetown.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Inherent chaperone‐like activity of aspartic proteases reveals a distant evolutionary relation to double‐ψ barrel domains of AAA‐ATPases
Authors: Hulko Michael , Lupas Andrei N. , Martin Jörg
Published: March 2007

Chaperones and proteases share the ability to interact with unfolded proteins. Here we show that enzymatically inactive forms of the aspartic proteases HIV‐1 protease and pepsin have inherent chaperone‐like activity and can prevent the aggregation of denatured substrate proteins. In contrast to proteolysis, which requires dimeric enzymes, chaperone‐like activity could be observed also with monomeric domains. The involvement of the active site cleft in the chaperone‐like function was demonstrated by the inhibitory effect of peptide substrate inhibitors. The high structural similarity between aspartic proteases and the N‐terminal double‐ψ barrels of Cdc48‐like proteins, which are involved in the unfolding and dissociation of proteins, suggests that they share a common ancestor. The latent chaperone‐like activity in aspartic proteases can be seen as a relic that has further evolved to serve substrate binding in the context of proteolytic activity.
A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation
Authors: Olsen Ole H. , Rand Kasper D. , Østergaard Henrik , Persson Egon
Published: March 2007

Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF‐bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation loop 3 (residues 365–374{216–225}) of the so‐called activation domain and the 170‐loop (residues 313–322{170A–175}) succeeding the TF‐binding helix. The latter finding is corroborated by experiments demonstrating rapid deglycosylation of Asn322 in free FVIIa by PNGase F but almost complete protection in the presence of TF or an active‐site inhibitor. Based on MD simulations, a key switch of the TF‐induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S1 and S3 substrate pockets, the activation pocket, and N‐terminal insertion.
A filamentous molecular chaperone of the prefoldin family from the deep‐sea hyperthermophile Methanocaldococcus jannaschii
Authors: Whitehead Timothy A. , Boonyaratanakornkit Boonchai B. , Höllrigl Volker , Clark Douglas S.
Published: March 2007

Prefoldin is a molecular chaperone found in the domains eukarya and archaea that acts in conjunction with Group II chaperonin to correctly fold other nascent proteins. Previously, our group identified a putative single subunit of prefoldin, γ PFD, that was up‐regulated in response to heat stress in the hyperthermophilic archaeon Methanocaldococcus jannaschii. In order to characterize this protein, we subcloned and expressed it and the other two prefoldin subunits from M. jannaschii, α and β PFD, into Eschericia coli and characterized the proteins. Whereas α and β PFD readily assembled into the expected hexamer, γ PFD would not assemble with either protein. Instead, γ PFD forms long filaments of defined dimensions measuring 8.5 nm × 1.7–3.5 nm and lengths exceeding 1 μm. Filamentous γ PFD acts as a molecular chaperone through in vitro assays, in a manner comparable to PFD. A possible molecular model for filament assembly is discussed.
Computational design and biochemical characterization of maize nonspecific lipid transfer protein variants for biosensor applications
Authors: Choi Eun Jung , Mao Jessica , Mayo Stephen L.
Published: March 2007

Lipid transfer proteins (LTPs) are a family of proteins that bind and transfer lipids. Utilizing the maize LTP, we have successfully engineered fluorescent reagentless biosensors for the natural ligand of LTPs; this was achieved by using computational protein design to remove a disulfide bridge and attaching a thio‐reactive fluorophore. Conformational change induced by ligand titration is thought to affect the fluorescence of the fluorophore, allowing detection of ligand binding. Fluorescence measurements show that our LTP variants have affinity to palmitate that is consistent with wild‐type LTP. These molecules have the potential to be utilized as scaffolds to design hydrophobic ligand biosensors or to serve as drug carriers.
The S2 subsites of cathepsins K and L and their contribution to collagen degradation
Authors: Lecaille Fabien , Chowdhury Shafinaz , Purisima Enrico , Brömme Dieter , Lalmanach Gilles
Published: March 2007

The exchange of residues 67 and 205 of the S2 pocket of human cysteine cathepsins K and L induces a permutation of their substrate specificity toward fluorogenic peptide substrates. While the cathepsin L‐like cathepsin K (Tyr67Leu/Leu205Ala) mutant has a marked preference for Phe, the Leu67Tyr/Ala205Leu cathepsin L variant shows an effective cathepsin K‐like preference for Leu and Pro. A similar turnaround of inhibition was observed by using specific inhibitors of cathepsin K [1‐(N‐Benzyloxycarbonyl‐leucyl)‐5‐(N‐Boc‐phenylalanyl‐leucyl)carbohydrazide] and cathepsin L [N‐(4‐biphenylacetyl)‐S‐methylcysteine‐(D)‐Arg‐Phe‐β‐phenethylamide]. Molecular modeling studies indicated that mutations alter the character of both S2 and S3 subsites, while docking calculations were consistent with kinetics data. The cathepsin K‐like cathepsin L was unable to mimic the collagen‐degrading activity of cathepsin K against collagens I and II, DQ‐collagens I and IV, and elastin‐Congo Red. In summary, double mutations of the S2 pocket of cathepsins K (Y67L/L205A) and L (L67Y/A205L) induce a switch of their enzymatic specificity toward small selective inhibitors and peptidyl substrates, confirming the key role of residues 67 and 205. However, mutations in the S2 subsite pocket of cathepsin L alone without engineering of binding sites to chondroitin sulfate are not sufficient to generate a cathepsin K‐like collagenase, emphasizing the pivotal role of the complex formation between glycosaminoglycans and cathepsin K for its unique collagenolytic activity.
Structure‐based mutagenesis of the substrate‐recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3
Authors: Bouyain Samuel , Leahy Daniel J.
Published: March 2007

The E3 ubiquitin ligase neuregulin receptor degrading protein 1 (Nrdp1) mediates the ligand‐independent degradation of the epidermal growth factor receptor family member ErbB3/HER3. By regulating cellular levels of ErbB3, Nrdp1 influences ErbB3‐mediated signaling, which is essential for normal vertebrate development. Nrdp1 belongs to the tripartite or RBCC (RING, B‐box, coiled‐coil) family of ubiquitin ligases in which the RING domain is responsible for ubiquitin ligation and a variable C‐terminal region mediates substrate recognition. We report here the 1.95 Å crystal structure of the C‐terminal domain of Nrdp1 and show that this domain is sufficient to mediate ErbB3 binding. Furthermore, we have used site‐directed mutagenesis to map regions of the Nrdp1 surface that are important for interacting with ErbB3 and mediating its degradation in transfected cells. The ErbB3‐binding site localizes to a region of Nrdp1 that is conserved from invertebrates to vertebrates, in contrast to ErbB3, which is only found in vertebrates. This observation suggests that Nrdp1 uses a common binding site to recognize its targets in different species.
Interleukin‐1 alpha genotype and outcome of unrelated donor haematopoietic stem cell transplantation for chronic myeloid leukaemia
Authors: Mehta Parinda A. , Eapen Mary , Klein John P. , Gandham Sharavi , Elliott James , Zamzow Tiffany , Combs Michelle , Aplenc Richard , MacMillan Margaret L. , Weisdorf Daniel J. , Petersdorf Effie , Davies Stella M.
Published: March 2007

Interleukin‐1 alpha (IL‐1α) is a pro‐inflammatory cytokine that is implicated in the initiation/maintenance of graft‐versus‐host disease (GVHD) and the immune response to infection. A cytosine (C) to thymine (T) transition at position −889 is believed to influence gene transcription. A previous single institution study showed that the presence of at least oneIL1AT allele in the donor was associated with improved survival after unrelated donor haematopoietic stem cell transplant and lower transplant‐related mortality if the donor and recipient each possessed theIL1AT allele. The present study sought to confirm these results in a larger homogeneous population. Thus the study population included 426 patients older than 18 years with chronic myeloid leukaemia (CML), transplanted in first chronic phase and receiving a total body irradiation and cyclophosphamide preparative regimen. Donor recipient pairs were categorised into four groups according to the presence or absence of anIL1AT allele in the donor and recipient. There were no significant differences in patient, donor and transplant characteristics between the groups. We did not observe an association with IL‐1αgenotype in donor and/or recipient and transplant‐outcome. These data suggest that the outcome of unrelated donor transplant for CML is not influenced by IL‐1αgenotype.
Mothers' knowledge of young child development in a developing country
Authors: Ertem I. O. , Atay G. , Dogan D. G. , Bayhan A. , Bingoler B. E. , Gok C. G. , Ozbas S. , Haznedaroglu D. , Isikli S.
Published: March 2007

Background  Although interventions on child development target supporting mothers' relationships with their children, little is known about maternal knowledge of child development in developing countries. The purpose of this study was to determine maternal knowledge about child development in Turkey.

Methods  The Caregiver Knowledge of Child Development Inventory (CKCDI) developed for this study consisted of questions on when children begin to demonstrate developmental skills and when caregivers should provide opportunities for developmental stimulation.

Results  In total, 1200 mothers of children aged ≤3 years chosen by random population‐based sampling were administered the CKCDI in their homes. Of the 1055 mothers with complete data (88%), 64% had at most secondary school education and 11% were employed. The median CKCDI questionnaire score was 19 (highest possible score 40). Mothers believed that most developmental skills and activities should occur at later than normative ages and most mothers did not know that sight (52%), vocalization (79%), social smiling (59%) and overall brain development (68%) begins in the early months of life. In a linear regression model with CKCDI score as the dependent and age of child, number of children, maternal and paternal age and education as the independent variables, higher maternal education and lower number of children were found to be independent predictors of higher CKCDI scores (P < 0.001).

Conclusions  These results illustrate the degree to which caregivers from Turkey may be lacking information on early childhood development and that caregiver knowledge needs to be further investigated so that culture‐specific and effective interventions can be planned.
Fathering and adolescents' psychological adjustment: the role of fathers' involvement, residence and biology status
Authors: Flouri E.
Published: March 2007

Background  Studies on fathering and child mental health are now increasingly looking for specificity in children's psychological adjustment, indicating whether the impact of fathering is diagnostically specific or non‐specific.

Methods  Data from 435 fathers of secondary school‐aged children in Britain were used to explore the association between resident biological fathers', non‐resident biological fathers' and stepfathers' involvement and children's total difficulties, prosocial behaviour, emotional symptoms, conduct problems, hyperactivity and peer problems (all measured with the Strengths and Difficulties Questionnaire) in adolescence.

Results  After controlling for child‐, father‐ and family‐related factors, fathers' involvement was negatively associated with children's total difficulties and hyperactivity, was positively associated with children's prosocial behaviour, and was unrelated with children's emotional symptoms, conduct problems and peer problems. There was no non‐resident biological father effect. Compared with resident biological fathers, stepfathers reported more total difficulties, conduct problems and hyperactivity in their children even after adjusting for involvement.

Conclusions  Whether this reflects stepfathers' low tolerance levels or biological fathers' complacency, as sociobiologists would argue, or whether this is due to pre‐existing predispositions of children in families which separate and restructure, to the effects of these multiple family changes or to the high exposure of children in restructured families to parental risk factors, is, given the data available and the study design, unclear. However, this study showed that, compared with their peers in biological father families, adolescents in stepfather families are perceived to be at higher risk of behaviour problems, and that father involvement is related to specific aspects of child adjustment.
Long‐term effects of growth hormone (GH) on bone mineral status and bone turnover markers in patients with isolated GH deficiency and multiple pituitary hormone deficiency
Authors: Gonc E. Nazli , Kandemir Nurgun
Published: March 2007

Objective  This study was designed to assess the long‐term effects of growth hormone (GH) replacement therapy on bone mass and bone turnover markers in children with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD).

Materials and methods  Fifty children (35 IGHD, 15 MPHD) receiving GH replacement therapy were enrolled in the study. The patients were followed for 38·6 ± 15·7 months (1–5 years). Bone mineral density (BMD) of the lumbar region and bone turnover markers [PTH, osteocalcin, bone‐specific alkaline phosphatase (boneALP), and the carboxyterminal propeptide of type‐1 collagen (CPP‐I)] were assessed annually.

Results  The height standard deviation score (SDS) of patients with IGHD and MPHD at diagnosis was statistically significant (P = 0·012), and the change in height SDS during 3 years (Δheight SDS3 years) was statistically similar between these two groups (P = 0·651). The BMD z‐scores of the two groups were comparable at the start of GH therapy (P = 0·083), and then increased in both groups similarly during 5 years of GH replacement therapy (F = 0·349, P = 0·567). When the BMD z‐scores during 5 years of GH therapy were analysed in the IGHD and MPHD groups separately, it was found that the BMD z‐score increased significantly in IGHD (P < 0·001) but the increase was not significant in MPHD (P = 0·140). Multiple regression analysis showed that the change in BMD z‐score during 3 years of GH therapy (ΔBMD z‐score3 years) was predicted by the BMD z‐score and height SDS at the start of GH therapy and by Δheight SDS3 years in the IGHD group (t = −2·582, P = 0·02; t = 2·322, P = 0·034 and t = 2·908, P = 0·01, respectively). Age and BMD z‐score and height SDS at diagnosis were found to have predictive values for the ΔBMD z‐score3 years (t = −3·652, P = 0·022; t = −4·073, P = 0·015 and t = 3·389, P = 0·028, respectively) in the MPHD group. The changes in boneALP, osteocalcin, CPP‐1 and PTH levels during the therapy were statistically similar between the IGHD and MPHD groups.

Conclusion  BMD increased during GH therapy in the IGHD and MPHD groups. GH had a positive effect on bone mass in the short as well as the long term. Early diagnosis and treatment could improve peak bone mass in patients with MPHD. The time and dose of sex steroids for pubertal induction and progression, which mimics physiological secretion, might also contribute to bone accretion in patients with MPHD.
Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings
Authors: Sapio Maria Rosaria , Posca Daniela , Raggioli Angelo , Guerra Anna , Marotta Vincenzo , Deandrea Maurilio , Motta Manuela , Limone Paolo Piero , Troncone Giancarlo , Caleo Alessia , Rossi Guido , Fenzi Gianfranco , Vitale Mario
Published: March 2007

Background  Fine‐needle aspiration biopsy (FNAB) is the primary means to distinguish benign from malignant nodules and select patients for surgery. However, adjunctive diagnostic tests are needed because in 20–40% of cases the FNAB result is uncertain.

Objective  We investigated whether a search for the oncogenes RET/PTC, TRK and BRAFV600E in thyroid aspirates could refine an uncertain diagnosis.

Patients and methods  A total of 132 thyroid aspirates, including colloid nodules, inadequate samplings, indeterminate and suspicious for malignancy were analysed by reverse transcription polymerase chain reaction (RT‐PCR) and mutant allele‐specific amplification techniques for the presence of oncogenes.

Results  No oncogenes were detected in 48 colloid nodules, 46 inadequate and 19 indeterminate FNABs, then confirmed to be benign at histology. No oncogenes were detected in one follicular thyroid cancer (FTC) with indeterminate cytology. Five out of six papillary thyroid cancers (83%) with FNAB suspicious for malignancy were correctly diagnosed by the presence of oncogenes. Among these, four (67%) contained the BRAF mutation and one (17%) contained RET/PTC‐3. On final analysis, no false‐positive results were reported in 131 samples and five out of seven carcinomas (71%) were correctly diagnosed. The finding of oncogenes in FNAB specimens suspicious for malignancy guided the extent of surgical resection, changing the surgery from diagnostic to therapeutic in five cases.

Conclusions  Detection of RET/PTC, TRK and BRAFV600E in FNAB specimens is proposed as a diagnostic adjunctive tool in the evaluation of thyroid nodules with suspicious cytological findings.
Independent association between insulin‐like growth factor‐I and dehydroepiandrosterone sulphate in women in middle adulthood
Authors: Kasayama Soji , Morita Shinya , Otsuki Michio , Asanuma Nobuyuki , Saito Hiroshi , Mukai Mikio , Koga Masafumi
Published: March 2007

Objective  The age‐related decrease in circulating dehydroepiandrosterone sulphate (DHEAS) and insulin‐like growth factor (IGF)‐I levels is suggested to be involved in various age‐related changes. As both hormones are regulated differently, by ACTH and GH, respectively, reasons for the almost parallel changes of their circulating levels during ageing remain unknown. The objectives of this study were to verify variables that influence serum IGF‐I as well as DHEAS levels in subjects in middle adulthood.

Subjects and methods  We determined serum DHEAS and IGF‐I levels in 362 Japanese subjects aged 30–65 years (225 men and 137 women) undergoing health examinations, who had no hepatic disease, renal disease, malignant disease, diabetes mellitus, or asthma. Variables influencing DHEAS and IGF‐I were analysed.

Results  DHEAS as well as IGF‐I levels were higher in men than in women. DHEAS was positively associated with IGF‐I and negatively with age, in both men and women. By multivariate regression analysis, age was negatively associated with DHEAS in both men and women. IGF‐I was found to be independently associated with DHEAS in women. Age was the only negative independent factor for IGF‐I in both men and women, while DHEAS was the only positive independent factor in women.

Conclusions  The present study demonstrates that DHEAS and IGF‐I levels are associated with each other, independent of age, in women in middle adulthood.