bluuebunny/crossref_metadata_2025 huggingface dataset:
Subwavelength plastic wire terahertz time-domain spectroscopy
Authors: You Borwen , Lu Ja-Yu , Liu Tze-An , Peng Jin-Long , Pan Ci-Ling
Published: February 2010

This work demonstrates the feasibility of a terahertz time-domain spectrometer based on a subwavelength-diameter plastic wire (SPW) for sensing applications. The dispersion property of the SPW is experimentally and theoretically studied. The SPW exhibits a low and controllable waveguide dispersion, which can be engineered by changing the core diameter, the core index, and the cladding index of the wire. Two white powders, tryptophan and polyethylene, deposited on the bottom of the wire can be successfully distinguished based on the waveguide dispersion of SPW. The SPW would be a promising candidate for combination with biochips for sensing minute molecules.
Atomically-thin crystalline films and ribbons of bismuth telluride
Authors: Teweldebrhan Desalegne , Goyal Vivek , Rahman Muhammad , Balandin Alexander A.
Published: February 2010

The authors report on “graphene-like” exfoliation of the large-area crystalline films and ribbons of bismuth telluride with the thicknesses of a few atoms. It is demonstrated that Bi2Te3 crystal can be mechanically separated into its building blocks—Te–Bi–Te–Bi–Te atomic fivefolds—with the thickness of ∼1 nm and even further—to subunits with smaller thicknesses. The atomically-thin films can be structured into suspended crystalline ribbons providing quantum confinement in two dimensions. The quasi two-dimensional crystals of bismuth telluride revealed high electrical conductivity and low thermal conductivity. The proposed atomic-layer engineering of bismuth telluride opens up a principally new route for drastic enhancement of the thermoelectric figure of merit.
Nuclear magnetic resonance measurement and lattice-Boltzmann simulation of the nonlocal dispersion tensor
Authors: Hunter M. W. , Jackson A. N. , Callaghan P. T.
Published: February 2010

The nonlocal dispersion tensor DNL provides a fundamental description of velocity correlations and displacement information in a dispersive system. It is shown that pulsed gradient spin echo nuclear magnetic resonance can be used to measure this tensor, and we present here the first measurement of DNL in a complex flow by this or any other methods. These measurements are complemented by simulations based on a lattice-Boltzmann calculation of the fluid flow. For dispersive flow in a random bead pack of monosized spheres, six nonzero, independent components remain. These components have been measured at three times less than τv, the time to flow one bead diameter. It is shown here that the various elements of DNL provide insights regarding the dispersive flow, which are extremely sensitive to the details of local correlations.
Propagation of ultrashort laser pulses in optically ionized gases
Authors: Morozov A. , Luo Y. , Suckewer S. , Gordon D. F. , Sprangle P.
Published: February 2010

Propagation of 800 nm, 120 fs laser pulses with intensities of 4×1016 W/cm2 in supersonic gas jets of N2 and H2 is studied using a shear-type interferometer. The plasma density distribution resulting from photoionization is resolved in space and time with simultaneously measured initial neutral density distribution. A distinct difference in laser beam propagation distance is observed when comparing propagation in jets of H2 and N2. This is interpreted in terms of ionization induced refraction, which is stronger when electrons are produced from states of higher ionization potential. Three dimensional particle-in-cell simulations, based on directly solving the Maxwell–Lorentz system of equations, show the roles played by the forward Raman and ionization scattering instabilities, which further affect the propagation distance.
Cyclodextrins: Promising candidate media for high-capacity hydrogen adsorption
Authors: Zhu Haiyan , Liu Yongning , Chen Yuanzhen , Wen Zhenyi
Published: February 2010

Cyclodextrins (CDs) found with inexpensive starch are in a particular hollow and truncated cone-type configuration. First-principles calculations indicate that a single α-CD can adsorb up to 48 hydrogen molecules by the influence of the oxygen structures in the α-CD’s hydroxyl (-OH) and epoxy functional groups; while the result additionally shows that the gravimetric storage capacity can reach to 9.8 wt %. These results are helpful for developing high-capacity hydrogen-storage materials.
Fluid epitaxialization effect on velocity dependence of dynamic contact angle in molecular scale
Authors: Ito Takahiro , Hirata Yosuke , Kukita Yutaka
Published: February 2010

Molecular dynamics simulations were used to investigate the effect of epitaxial ordering of the fluid molecules on the microscopic dynamic contact angle. The simulations were performed in a Couette-flow-like geometry where two immiscible fluids were confined between two parallel walls moving in opposite directions. The extent of ordering was varied by changing the number density of the wall particles. As the ordering becomes more evident, the change in the dynamic contact angle tends to be more sensitive to the increase in the relative velocity of the contact line to the wall. Stress components around the contact line is evaluated in order to examine the stress balance among the hydrodynamic stresses (viscous stress and pressure), the deviation of Young’s stress from the static equilibrium condition, and the fluid-wall shear stress induced by the relative motion between them. It is shown that the magnitude of the shear stress on the fluid-wall surface is the primary contribution to the sensitivity of the dynamic contact angle and that the sensitivity is intensified by the fluid ordering near the wall surface.
Energy harvesting using a modified rectangular cymbal transducer based on 0.71Pb(Mg1/3Nb2/3)O3–0.29PbTiO3 single crystal
Authors: Ren Bo , Or Siu Wing , Zhao Xiangyong , Luo Haosu
Published: February 2010

In this paper, we presented a modified rectangular cymbal transducer used as the vibration energy harvesting device based on 0.71Pb(Mg1/3Nb2/3)O3–0.29PbTiO3 single crystal. The vibration modes of the device were analyzed and the electrical properties were studied systematically. Under a cyclic force of 0.55 N (peak value), a high peak voltage of 45.7 V and maximum power of 14 mW were measured at 500 Hz with a proof mass of 17.0 g. The power density of the transducer is more than three times as high as that of the Pb(ZrxTi1−x)O3 (PZT) ceramic cymbal transducer. The results demonstrate the potential of the device in energy harvesting applied to low-power portable electronics and wireless sensors.
Revealing microstructural inhomogeneities with dark-field neutron imaging
Authors: Hilger A. , Kardjilov N. , Kandemir T. , Manke I. , Banhart J. , Penumadu D. , Manescu A. , Strobl M.
Published: February 2010

Dark-field neutron tomography was applied to obtain three-dimensional volumetric data representing the distribution of micrometer and submicrometer sized structures in bulk samples. This is a size range that complements the range of direct spatial resolution. A phase grating setup implemented in a conventional imaging instrument enables corresponding tomographic investigations on reasonable time scales. Different samples were investigated and demonstrate the applicability of the method for the investigation of structural materials. Local variations in the small-angle scattering in BiSn, AlSi, and aluminum samples were mapped and the results are discussed with respect to the contrast formation of the method.
The role of rare earth elements in the structures of FeB-based glass forming liquid alloys
Authors: Pan S. P. , Qin J. Y. , Gu T. K.
Published: February 2010

The structures of liquid Fe72RE6B22 (RE=Sc, Er, Ho, Dy, Y, Sm, Gd, Nd, and Ce) alloys were investigated by ab initio molecular dynamics simulation. The results show that the chemical affinity of Fe-RE and RE-B may influence the glass forming ability more than the atomic size of RE atom in these alloys. As expected, the ⟨0,3,6,0⟩ polyhedron dominates around B atoms and is significantly enriched by adding RE elements to the liquid Fe78B22 alloy. The good glass formers do not correspond to the larger percentages but to more RE atoms in the shell of ⟨0,3,6,0⟩ polyhedron. These features suggest that the effect of the chemical composition of ⟨0,3,6,0⟩ polyhedron on the glass forming ability may be larger than that of its quantity in these alloys.
Tunneling magnetoresistance in Fe/MgO granular multilayers
Authors: García-García A. , Vovk A. , Pardo J. A. , Štrichovanec P. , Algarabel P. A. , Magén C. , De Teresa J. M. , Morellón L. , Ibarra M. R.
Published: February 2010

We have investigated the transport and magnetotransport properties in Fe/MgO multilayers around the Fe percolation threshold as a function of the temperature and the nominal thickness of iron layer (t). Electrical resistivity measurements allowed us to disclose the charge transport mechanisms involved, which are closely related to the degree of discontinuity in the Fe layers. The samples with Fe thickness below percolation threshold (t∼0.8 nm) exhibit isotropic magnetoresistance (MR), which can be understood considering spin-polarized electron tunneling between nanometer-sized, superparamagnetic Fe grains. The MR ratio increases with decreasing temperature from ∼3% at room temperature to ∼10% at 30 K. The temperature dependence of MR can be explained satisfactorily in terms of a modified Mitani’s model.
Acoustic band gaps in phononic crystal strip waveguides
Authors: Hsu Feng-Chia , Lee Chiung-I , Hsu Jin-Chen , Huang Tsun-Che , Wang Chin-Hung , Chang Pin
Published: February 2010

We study the elastic wave propagation in phononic-crystal strip waveguides cut from a silicon phononic-crystal plate with square-lattice vacuum holes through analyzing the band structure and transmission spectra. We show the influence of different cutting ways is crucial to the band-gap formation, and four types of native strip modes are deserved to be fully taken into account. The results show that though there is no band gap existing in the phononic-crystal plates with a low filling fraction, band gaps are created in their corresponding cut strip waveguide because the derivative traction-free boundaries strongly modulate the shear-horizontal bands.
First-principles study of ultrathin (2×2) Gd nanowires encapsulated in carbon nanotubes
Authors: Parq Jae-Hyeon , Yu Jaejun , Kim Gunn
Published: February 2010

Using density-functional calculations, we investigate the structural and magnetic properties of ultrathin Gd and Gd-carbide nanowires (NWs) encapsulated in narrow carbon nanotubes (CNTs). The equilibrium geometry of an encapsulated (2×2) Gd-NW is markedly different from that of bulk Gd crystals. The charge-density analysis shows pronounced spin-dependent electron transfer in the encapsulated Gd-NW in comparison with that of Gd-carbide NWs. We conclude that Gd-CNT hybridization is primarily responsible for both the structural difference and electron transfer in the encapsulated Gd-NW.
Mass density of individual cobalt nanowires
Authors: Philippe L. , Cousin B. , Wang Zhao , Zhang D. F. , Michler J.
Published: February 2010

The mass density of nanowires is determined using in situ resonance frequency experiments combined with quasistatic nanotensile tests. Our results reveal an average mass density of 7.36 g/cm3, which is below the theoretical density of bulk cobalt. The results are discussed in terms of the measurement accuracy and the microstructure of the nanowires.
ZnO nanowires array p-n homojunction and its application as a visible-blind ultraviolet photodetector
Authors: Leung Y. H. , He Z. B. , Luo L. B. , Tsang C. H. A. , Wong N. B. , Zhang W. J. , Lee S. T.
Published: February 2010

We demonstrated a simple and low-cost fabrication of ZnO p-n homojunction. The junction consists of n-type ZnO nanowires array by a hydrothermal method covered with p-type Al, N co-doped ZnO film by a sol-gel method. The junction exhibits good rectification characteristics, with reverse leakage current and rectification ratio of ∼5 μA and ∼150 at bias of 3 V, respectively. The junction is operated as a photodetector when light radiation is shined on the glass-side of the device. The photodetector shows a peak responsivity at 384 nm with UV-visible responsivity ratio (R384 nm/R550 nm) of ∼70 at an operating bias of −3 V.
Variational geminal-augmented multireference self-consistent field theory: Two-electron systems
Authors: Varganov Sergey A. , Martínez Todd J.
Published: February 2010

We introduce a geminal-augmented multiconfigurational self-consistent field method for describing electron correlation effects. The approach is based on variational optimization of a MCSCF-type wave function augmented by a single geminal. This wave function is able to account for some dynamic correlation without explicit excitations to virtual molecular orbitals. Test calculations on two-electron systems demonstrate the ability of the proposed method to describe ionic and covalent electronic states in a balanced way, i.e., including the effects of both static and dynamic correlation simultaneously. Extension of the theory to larger systems will potentially provide an alternative to standard multireference methods.
Neutral atoms are entangled in hyperfine states via Rydberg blockade
Authors: Miller Johanna
Published: February 2010

An interaction between highly excited atoms can be used to engineer a superposition of low-energy quantum states, as two research groups now demonstrate.
Assessing the Applicability and Effectiveness of 3D Visualisation in Environmental Impact Assessment
Authors: Lai Poh C , Kwong Kim-Hung , Mak Ann S H
Published: February 2010

Computerised 3D models are more intuitive and rich in landscape detail. They are considered an essential visualisation method for the presentation of environmental data with spatial contents. The 3D technology has been increasingly applied in environmental impact assessment (EIA) and urban planning to view and better appreciate human impacts on the environment. Their uses are not restricted to the professionals. Because of their great likeness to the natural world, 3D representations have also been employed to convey information to the general population through public hearings, workshops, and the Internet. The use of 3D visualisation in EIA applications is not without problems, particularly for those without the necessary skills in computer operations and map comprehension. This paper is an assessment of the applicability and effectiveness of 3D visualisation in EIA. First we illustrate different scenarios of 3D portrayals in environmental management. This is followed by a discussion about the problems and concerns of using 3D visualisation in presenting environmental data. These issues are examined in greater detail to highlight various technical considerations and types of data suitable (or not suitable) for the implementation of 3D models. A reference is made to the potential incorporation of feedback mechanisms in a 3D system intended for public participation.
Omnipresent Sprawl? A Review of Urban Simulation Models with Respect to Urban Shrinkage
Authors: Schwarz Nina , Haase Dagmar , Seppelt Ralf
Published: February 2010

Simulation models on urban land-use change help in understanding urban systems and assist in urban planning. One of the challenges of simulating urban regions in Europe as well as in North America or Japan is urban shrinkage, where deindustrialisation, massive population losses, and ageing cause unforeseen (or unexpected) commercial and housing vacancies in cities. In order to set up a conceptual framework for model improvement to assist such challenges, we review recent urban land-use-change simulation models, using four different modelling approaches: system dynamics, linked transport — urban models, cellular automata, and agent-based modelling. The focus of the review is to assess the causalities and feedback mechanisms that were implemented in these models. The results show that simulation models are very heterogeneous in implemented mechanisms leading to urban land-use dynamics. No single model fulfils all of the criteria required to model urban shrinkage in a spatially explicit way. However, system-dynamic models that are documented in the literature can serve as a good starting point for spatially nonexplicit simulation, and one example was found for linked transport — urban models which encompasses aspects of urban shrinkage. The potential of cellular automata is unclear as spatially explicit data on vacancies to feed this class of models is usually not available. Agent-based models appear to be the most promising approach for spatially explicit modelling of urban shrinkage.
Transport and signaling through the phosphate-binding site of the yeast Pho84 phosphate transceptor
Authors: Popova Yulia , Thayumanavan Palvannan , Lonati Elena , Agrochão Margarida , Thevelein Johan M.
Published: February 2010

A novel concept in eukaryotic signal transduction is the use of nutrient transporters and closely related proteins as nutrient sensors. The action mechanism of these “transceptors” is unclear. The Pho84 phosphate transceptor in yeast transports phosphate and mediates rapid phosphate activation of the protein kinase A (PKA) pathway during growth induction. We have now identified several phosphate-containing compounds that act as nontransported signaling agonists of Pho84. This indicates that signaling does not require complete transport of the substrate. For the nontransported agonist glycerol-3-phosphate (Gly3P), we show that it is transported by two other carriers, Git1 and Pho91, without triggering signaling. Gly3P is a competitive inhibitor of transport through Pho84, indicating direct interaction with its phosphate-binding site. We also identified phosphonoacetic acid as a competitive inhibitor of transport without agonist function for signaling. This indicates that binding of a compound into the phosphate-binding site of Pho84 is not enough to trigger signaling. Apparently, signaling requires a specific conformational change that may be part of, but does not require, the complete transport cycle. Using Substituted Cysteine Accessibility Method (SCAM) we identified Phe
160
in TMD IV and Val
392
in TMD VIII as residues exposed with their side chain into the phosphate-binding site of Pho84. Inhibition of both transport and signaling by covalent modification of Pho84
F160C
or Pho84
V392C
showed that the same binding site is used for transport of phosphate and for signaling with both phosphate and Gly3P. Our results provide to the best of our knowledge the first insight into the molecular mechanism of a phosphate transceptor.
Mass spectrometry imaging of mating
Tetrahymena
show that changes in cell morphology regulate lipid domain formation
Authors: Kurczy Michael E. , Piehowski Paul D. , Van Bell Craig T. , Heien Michael L. , Winograd Nicolas , Ewing Andrew G.
Published: February 2010

Mass spectrometry imaging has been used here to suggest that changes in membrane structure drive lipid domain formation in mating single-cell organisms. Chemical studies of lipid bilayers in both living and model systems have revealed that chemical composition is coupled to localized membrane structure. However, it is not clear if the lipids that compose the membrane actively modify membrane structure or if structural changes cause heterogeneity in the surface chemistry of the lipid bilayer. We report that time-of-flight secondary ion mass spectrometry images of mating
Tetrahymena thermophila
acquired at various stages during mating demonstrate that lipid domain formation, identified as a decrease in the lamellar lipid phosphatidylcholine, follows rather than precedes structural changes in the membrane. Domains are formed in response to structural changes that occur during cell-to-cell conjugation. This observation has wide implications in all membrane processes.
Histone modification levels are predictive for gene expression
Authors: Karlić Rosa , Chung Ho-Ryun , Lasserre Julia , Vlahoviček Kristian , Vingron Martin
Published: February 2010

Histones are frequently decorated with covalent modifications. These histone modifications are thought to be involved in various chromatin-dependent processes including transcription. To elucidate the relationship between histone modifications and transcription, we derived quantitative models to predict the expression level of genes from histone modification levels. We found that histone modification levels and gene expression are very well correlated. Moreover, we show that only a small number of histone modifications are necessary to accurately predict gene expression. We show that different sets of histone modifications are necessary to predict gene expression driven by high CpG content promoters (HCPs) or low CpG content promoters (LCPs). Quantitative models involving H3K4me3 and H3K79me1 are the most predictive of the expression levels in LCPs, whereas HCPs require H3K27ac and H4K20me1. Finally, we show that the connections between histone modifications and gene expression seem to be general, as we were able to predict gene expression levels of one cell type using a model trained on another one.
Ordered ferrimagnetic form of ferrihydrite reveals links among structure, composition, and magnetism
Authors: Michel F. Marc , Barrón Vidal , Torrent José , Morales María P. , Serna Carlos J. , Boily Jean-François , Liu Qingsong , Ambrosini Andrea , Cismasu A. Cristina , Brown Gordon E.
Published: February 2010

The natural nanomineral ferrihydrite is an important component of many environmental and soil systems and has been implicated as the inorganic core of ferritin in biological systems. Knowledge of its basic structure, composition, and extent of structural disorder is essential for understanding its reactivity, stability, and magnetic behavior, as well as changes in these properties during aging. Here we investigate compositional, structural, and magnetic changes that occur upon aging of “2-line” ferrihydrite in the presence of adsorbed citrate at elevated temperature. Whereas aging under these conditions ultimately results in the formation of hematite, analysis of the atomic pair distribution function and complementary physicochemical and magnetic data indicate formation of an intermediate ferrihydrite phase of larger particle size with few defects, more structural relaxation and electron spin ordering, and pronounced ferrimagnetism relative to its disordered ferrihydrite precursor. Our results represent an important conceptual advance in understanding the nature of structural disorder in ferrihydrite and its relation to the magnetic structure and also serve to validate a controversial, recently proposed structural model for this phase. In addition, the pathway we identify for forming ferrimagnetic ferrihydrite potentially explains the magnetic enhancement that typically precedes formation of hematite in aerobic soil and weathering environments. Such magnetic enhancement has been attributed to the formation of poorly understood, nano-sized ferrimagnets from a ferrihydrite precursor. Whereas elevated temperatures drive the transformation on timescales feasible for laboratory studies, our results also suggest that ferrimagnetic ferrihydrite could form naturally at ambient temperature given sufficient time.
Targeting of SMAD5 links microRNA-155 to the TGF-β pathway and lymphomagenesis
Authors: Rai Deepak , Kim Sang-Woo , McKeller Morgan R. , Dahia Patricia L. M. , Aguiar Ricardo C. T.
Published: February 2010

The mechanisms by which microRNA dysfunction contributes to the pathogenesis of diffuse large B cell lymphoma (DLBCL) are not well established. The identification of the genes and pathways directly targeted by these small regulatory RNAs is a critical step to advance this field. Using unbiased genome-wide approaches in DLBCL, we discovered that the oncogenic microRNA-155 (miR-155) directly targets the bone morphogenetic protein (BMP)-responsive transcriptional factor SMAD5. Surprisingly, we found that in DLBCL a noncanonical signaling module linking TGF-β1 signals to SMAD5 is also active. In agreement with these data, miR-155 overexpression rendered DLBCLs resistant to the growth-inhibitory effects of both TGF-β1 and BMPs, via defective induction of p21 and impaired cell cycle arrest. In confirmatory experiments, RNAi-based SMAD5 knockdown recapitulated in vitro and in vivo the effects miR-155 overexpression. Furthermore, in primary DLBCLs, miR-155 overexpression inhibited SMAD5 expression and disrupted its activity, as defined by individual and global analyses of its transcriptional targets. Together, our data helped explain miR-155 function, highlighted a hitherto unappreciated role of SMAD5 in lymphoma biology, and defined a unique mechanism used by cancer cells to escape TGF-β’s growth-inhibitory effects.
Fundamental signatures of short- and long-range electron transfer for the blue copper protein azurin at Au/SAM junctions
Authors: Khoshtariya Dimitri E. , Dolidze Tina D. , Shushanyan Mikhael , Davis Kathryn L. , Waldeck David H. , van Eldik Rudi
Published: February 2010

The blue copper protein from
Pseudomonas aeruginosa
, azurin, immobilized at gold electrodes through hydrophobic interaction with alkanethiol self-assembled monolayers (SAMs) of the general type [-S - (CH
2
)

n

 - CH
3
] (
n
 = 4, 10, and 15) was employed to gain detailed insight into the physical mechanisms of short- and long-range biomolecular electron transfer (ET). Fast scan cyclic voltammetry and a Marcus equation analysis were used to determine unimolecular standard rate constants and reorganization free energies for variable
n
, temperature (2–55 °C), and pressure (5–150 MPa) conditions. A novel global fitting procedure was found to account for the reduced ET rate constant over almost five orders of magnitude (covering different
n
, temperature, and pressure) and revealed that electron exchange is a direct ET process and not conformationally gated. All the ET data, addressing SAMs with thickness variable over
ca.
12 Å, could be described by using a single reorganization energy (0.3 eV), however, the values for the enthalpies and volumes of activation were found to vary with
n
. These data and their comparison with theory show how to discriminate between the fundamental signatures of short- and long-range biomolecular ET that are theoretically anticipated for the adiabatic and nonadiabatic ET mechanisms, respectively.
Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic
Authors: Wu Joseph T. , Lee Cheuk Kwong , Cowling Benjamin J. , Yuen Kwok Yung
Published: February 2010

Treatment strategies for severe cases of pandemic influenza have focused on antiviral therapies. In contrast, passive immunotherapy with convalescent blood products has received limited attention. We consider the hypothesis that a passive-immunotherapy program that collects plasma from a small percentage of recovered adults can harvest sufficient convalescent plasma to treat a substantial percentage of severe cases during a pandemic. We use a mathematical model to estimate the demand and supply of passive immunotherapy during an influenza pandemic in Hong Kong. If >5% of 20- to 55-year-old individuals recovered from symptomatic infection donate their plasma (donor percentage > 5%), >67% of severe cases can be offered convalescent plasma transfusion (treatment coverage > 67%) in a moderately severe epidemic (
R
0
< 1.4 with 0.5% of symptomatic cases becoming severe). A donor percentage of 5% is comparable to the average blood donation rate of 38.1 donations per 1,000 people in developed countries. Increasing the donor percentage above 15% does not significantly boost the convalescent plasma supply because supply is constrained by plasmapheresis capacity during most stages of the epidemic. The demand–supply balance depends on the natural history and transmission dynamics of the disease via the epidemic growth rate only. Compared to other major cities, Hong Kong has a low plasmapheresis capacity. Therefore, the proposed passive-immunotherapy program is a logistically feasible mitigation option for many developed countries. As such, passive immunotherapy deserves more consideration by clinical researchers regarding its safety and efficacy as a treatment for severe cases of pandemic influenza.
Determining the distribution of probes between different subcellular locations through automated unmixing of subcellular patterns
Authors: Peng Tao , Bonamy Ghislain M. C. , Glory-Afshar Estelle , Rines Daniel R. , Chanda Sumit K. , Murphy Robert F.
Published: February 2010

Many proteins or other biological macromolecules are localized to more than one subcellular structure. The fraction of a protein in different cellular compartments is often measured by colocalization with organelle-specific fluorescent markers, requiring availability of fluorescent probes for each compartment and acquisition of images for each in conjunction with the macromolecule of interest. Alternatively, tailored algorithms allow finding particular regions in images and quantifying the amount of fluorescence they contain. Unfortunately, this approach requires extensive hand-tuning of algorithms and is often cell type-dependent. Here we describe a machine-learning approach for estimating the amount of fluorescent signal in different subcellular compartments without hand tuning, requiring only the acquisition of separate training images of markers for each compartment. In testing on images of cells stained with mixtures of probes for different organelles, we achieved a 93% correlation between estimated and expected amounts of probes in each compartment. We also demonstrated that the method can be used to quantify drug-dependent protein translocations. The method enables automated and unbiased determination of the distributions of protein across cellular compartments, and will significantly improve imaging-based high-throughput assays and facilitate proteome-scale localization efforts.
Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome
Authors: Miao Edward A. , Mao Dat P. , Yudkovsky Natalya , Bonneau Richard , Lorang Cynthia G. , Warren Sarah E. , Leaf Irina A. , Aderem Alan
Published: February 2010

The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the cytokines IL-1β and IL-18, whereas certain NLRs trigger their subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type III secretion systems (T3SS) to deliver virulence factors to the cytosol of host cells, where they modulate cell physiology to favor the pathogen. We show here that NLRC4/Ipaf detects the basal body rod component of the T3SS apparatus (rod protein) from
S. typhimurium
(PrgJ),
Burkholderia pseudomallei
(BsaK),
Escherichia coli
(EprJ and EscI),
Shigella flexneri
(MxiI), and
Pseudomonas aeruginosa
(PscI). These rod proteins share a sequence motif that is essential for detection by NLRC4; a similar motif is found in flagellin that is also detected by NLRC4.
S. typhimurium
has two T3SS:
Salmonella
pathogenicity island-1 (SPI1), which encodes the rod protein PrgJ, and SPI2, which encodes the rod protein SsaI. Although PrgJ is detected by NLRC4, SsaI is not, and this evasion is required for virulence in mice. The detection of a conserved component of the T3SS apparatus enables innate immune responses to virulent bacteria through a single pathway, a strategy that is divergent from that used by plants in which multiple NB-LRR proteins are used to detect T3SS effectors or their effects on cells. Furthermore, the specific detection of the virulence machinery permits the discrimination between pathogenic and nonpathogenic bacteria.
Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex
Authors: Pernigo Stefano , Fukuzawa Atsushi , Bertz Morten , Holt Mark , Rief Matthias , Steiner Roberto A. , Gautel Mathias
Published: February 2010

In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin form a ternary complex that is crucial for the function of the M-band as a mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10, which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to hereditary muscle diseases. The M10 domain is unusual not only in that it is a frequent target of disease-linked mutations, but also in that it is the only currently known muscle Ig-domain that interacts with two ligands—obscurin and obsl1—in different sarcomeric subregions. Using x-ray crystallography, we show the structural basis for titin M10 interaction with obsl1 in a novel antiparallel Ig-Ig architecture and unravel the molecular basis of titin-M10 linked myopathies. The severity of these pathologies correlates with the disruption of the titin-obsl1/obscurin complex. Conserved signature residues at the interface account for differences in affinity that direct the cellular sorting in cardiomyocytes. By engineering the interface signature residues of obsl1 to obscurin, and vice versa, their affinity for titin can be modulated similar to the native proteins. In single-molecule force-spectroscopy experiments, both complexes yield at forces of around 30 pN, much lower than those observed for the mechanically stable Z-disk complex of titin and telethonin, suggesting why even moderate weakening of the obsl1/obscurin-titin links has severe consequences for normal muscle functions.
Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice
Authors: Lai Huafang , Engle Michael , Fuchs Anja , Keller Thomas , Johnson Syd , Gorlatov Sergey , Diamond Michael S. , Chen Qiang
Published: February 2010

Over the past decade, West Nile virus (WNV) has spread to all 48 of the lower United States as well as to parts of Canada, Mexico, the Caribbean, and South America, with outbreaks of neuroinvasive disease occurring annually. At present, no therapeutic or vaccine is available for human use. Epidemics of WNV and other emerging infectious disease threats demand cost-efficient and scalable production technologies that can rapidly transfer effective therapeutics into the clinical setting. We have previously reported that Hu-E16, a humanized anti-WNV mAb, binds to a highly conserved epitope on the envelope protein, blocks viral fusion, and shows promising postexposure therapeutic activity. Herein, we generated a plant-derived Hu-E16 mAb that can be rapidly scaled up for commercial production. Plant Hu-E16 was expressed at high levels within 8 days of infiltration in
Nicotiana benthamiana
plants and retained high-affinity binding and potent neutralizing activity in vitro against WNV. A single dose of plant Hu-E16 protected mice against WNV-induced mortality even 4 days after infection at rates that were indistinguishable from mammalian-cell-produced Hu-E16. This study demonstrates the efficacy of a plant-produced mAb against a potentially lethal infection several days after exposure in an animal challenge model and provides a proof of principle for the development of plant-derived mAbs as therapy against emerging infectious diseases.
Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis
Authors: Li Shijie , Brown Michael S. , Goldstein Joseph L.
Published: February 2010

The livers of insulin-resistant, diabetic mice manifest selective insulin resistance, suggesting a bifurcation in the insulin signaling pathway: Insulin loses its ability to block glucose production (i.e., it fails to suppress
PEPCK
and other genes of gluconeogenesis), yet it retains its ability to stimulate fatty acid synthesis (i.e., continued enhancement of genes of lipogenesis). Enhanced lipogenesis is accompanied by an insulin-stimulated increase in the mRNA encoding SREBP-1c, a transcription factor that activates the entire lipogenic program. Here, we report a branch point in the insulin signaling pathway that may account for selective insulin resistance. Exposure of rat hepatocytes to insulin produced a 25-fold increase in SREBP-1c mRNA and a 95% decrease in PEPCK mRNA. Insulin-mediated changes in both mRNAs were blocked by inhibitors of PI3K and Akt, indicating that these kinases are required for both pathways. In contrast, subnanomolar concentrations of rapamycin, an inhibitor of the mTORC1 kinase, blocked insulin induction of
SREBP-1c
, but had no effect on insulin suppression of
PEPCK
. We observed a similar selective effect of rapamycin in livers of rats and mice that experienced an insulin surge in response to a fasting-refeeding protocol. A specific inhibitor of S6 kinase, a downstream target of mTORC1, did not block insulin induction of
SREBP-1c
, suggesting a downstream pathway distinct from S6 kinase. These results establish mTORC1 as an essential component in the insulin-regulated pathway for hepatic lipogenesis but not gluconeogenesis, and may help to resolve the paradox of selective insulin resistance in livers of diabetic rodents.
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome
Authors: Rucci Francesca , Notarangelo Luigi D. , Fazeli Alex , Patrizi Laura , Hickernell Thomas , Paganini Tiziana , Coakley Kristen M. , Detre Cynthia , Keszei Marton , Walter Jolan E. , Feldman Lauren , Cheng Hwei-Ling , Poliani Pietro Luigi , Wang Jing H. , Balter Barbara B. , Recher Mike , Andersson Emma-Maria , Zha Shan , Giliani Silvia , Terhorst Cox , Alt Frederick W. , Yan Catherine T.
Published: February 2010

DNA ligase IV (LIG4) is an essential component of the nonhomologous end-joining (NHEJ) repair pathway and plays a key role in V(D)J recombination. Hypomorphic
LIG4
mutations in humans are associated with increased cellular radiosensitivity, microcephaly, facial dysmorphisms, growth retardation, developmental delay, and a variable degree of immunodeficiency. We have generated a knock-in mouse model with a homozygous Lig4 R278H mutation that corresponds to the first
LIG4
mutation reported in humans. The phenotype of homozygous mutant mice
Lig4
R278H/R278H
(
Lig4
R/R
) includes growth retardation, a decreased life span, a severe cellular sensitivity to ionizing radiation, and a very severe, but incomplete block in T and B cell development. Peripheral T lymphocytes show an activated and anergic phenotype, reduced viability, and a restricted repertoire, reminiscent of human leaky SCID. Genomic instability is associated with a high rate of thymic tumor development. Finally,
Lig4
R/R
mice spontaneously produce low-affinity antibodies that include autoreactive specificities, but are unable to mount high-affinity antibody responses. These findings highlight the importance of LIG4 in lymphocyte development and function, and in genomic stability maintenance, and provide a model for the complex phenotype of LIG4 syndrome in humans.
Structure and structural transition of chiral domains in oligo(p-phenylenevinylene) assembly investigated by scanning tunneling microscopy
Authors: Chen Qing , Chen Ting , Wang Dong , Liu Hui-Biao , Li Yu-Liang , Wan Li-Jun
Published: February 2010

OPV3-CHO molecules are employed to prepare assembly on highly oriented pyrolytic graphite, and the so-prepared assembly is investigated by scanning tunneling microscopy. In the assembly chiral domains are observed with various structures such as linear and windmill. The chiral structural formation, stability, transition, and possible unification are intensively studied. After thermal annealing, linear structure was the only structure. To achieve a unified assembly with a single structure, an efficient method is proposed by coadsorption of OPV3-CHO with selected molecules. For example, an assembly with side-by-side helix structure is formed by a simple coadsorption of OPV3-CHO with alkyl bromide (C

n

H

2
n
+1

Br,
n
 = 15–18). The experiments by cocrystallization of OPV3-CHO/C

n

H

2
n
+1

X
(
X
 = Cl, Br, and I) show the important role of halogen bonding in formation of the uniform structure. The results are significant in understanding the intermolecular noncovalent interactions that dominate the surface structure and chirality.
Phospholipase Cγ1 is essential for T cell development, activation, and tolerance
Authors: Fu Guoping , Chen Yuhong , Yu Mei , Podd Andy , Schuman James , He Yinghong , Di Lie , Yassai Maryam , Haribhai Dipica , North Paula E. , Gorski Jack , Williams Calvin B. , Wang Demin , Wen Renren
Published: February 2010

Phospholipase Cγ1 (PLCγ1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLCγ1 in T cell biology, we generated and examined mice with T cell–specific deletion of PLCγ1. We demonstrate that PLCγ1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-κB. Importantly, PLCγ1 deficiency impairs the development and function of FoxP3+ regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCγ1 is essential for T cell development, activation, and tolerance.
Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines
Authors: Kisand Kai , Bøe Wolff Anette S. , Podkrajšek Katarina Trebušak , Tserel Liina , Link Maire , Kisand Kalle V. , Ersvaer Elisabeth , Perheentupa Jaakko , Erichsen Martina Moter , Bratanic Nina , Meloni Antonella , Cetani Filomena , Perniola Roberto , Ergun-Longmire Berrin , Maclaren Noel , Krohn Kai J. E. , Pura Mikuláš , Schalke Berthold , Ströbel Philipp , Leite Maria Isabel , Battelino Tadej , Husebye Eystein S. , Peterson Pärt , Willcox Nick , Meager Anthony
Published: February 2010

Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.
The Locus Lookup tool at MaizeGDB: identification of genomic regions in maize by integrating sequence information with physical and genetic maps
Authors: Andorf Carson M. , Lawrence Carolyn J. , Harper Lisa C. , Schaeffer Mary L. , Campbell Darwin A. , Sen Taner Z.
Published: February 2010

Summary: Methods to automatically integrate sequence information with physical and genetic maps are scarce. The Locus Lookup tool enables researchers to define windows of genomic sequence likely to contain loci of interest where only genetic or physical mapping associations are reported. Using the Locus Lookup tool, researchers will be able to locate specific genes more efficiently that will ultimately help them develop a better maize plant. With the availability of the well-documented source code, the tool can be easily adapted to other biological systems.

Availability: The Locus Lookup tool is available on the web at http://maizegdb.org/cgi-bin/locus_lookup.cgi. It is implemented in PHP, Oracle and Apache, with all major browsers supported. Source code is freely available for download at http://ftp.maizegdb.org/open_source/locus_lookup/.

Contact:  taner.sen@ars.usda.gov
Acupuncture May Stimulate Anticancer Immunity via Activation of Natural Killer Cells
Authors: Johnston Michael Francis , Ortiz Sánchez Elizabeth , Vujanovic Nikola L. , Li Wenhui
Published: February 2010

This article presents the hypothesis that acupuncture enhances anticancer immune functions by stimulating natural killer (NK) cells. It provides background information on acupuncture, summarizes the current scientific understanding of the mechanisms through which NK cells act to eliminate cancer cells, and reviews evidence that acupuncture is associated with increases in NK cell quantity and function in both animals and humans. The key contribution of this article involves the use of cellular immunology and molecular biological theory to interpret and synthesize evidence from disparate animal and human studies in formulating the ‘acupuncture immuno‐enhancement hypothesis’: clinicians may use acupuncture to promote the induction and secretion of NK‐cell activating cytokines that engage specific NK cell receptors that endogenously enhance anticancer immune function.
Evolution of acidocalcisomes and their role in polyphosphate storage and osmoregulation in eukaryotic microbes
Authors: Docampo Roberto , Ulrich Paul , Moreno Silvia N. J.
Published: February 2010

Acidocalcisomes are acidic electron-dense organelles, rich in polyphosphate (poly P) complexed with calcium and other cations. While its matrix contains enzymes related to poly P metabolism, the membrane of the acidocalcisomes has a number of pumps (Ca2+-ATPase, V-H+-ATPase, H+-PPase), exchangers (Na+/H+, Ca2+/H+), and at least one channel (aquaporin). Acidocalcisomes are present in both prokaryotes and eukaryotes and are an important storage of cations and phosphorus. They also play an important role in osmoregulation and interact with the contractile vacuole complex in a number of eukaryotic microbes. Acidocalcisomes resemble lysosome-related organelles (LRO) from mammalian cells in many of their properties. They share similar morphological characteristics, acidic properties, phosphorus contents and a system for targeting of their membrane proteins through adaptor complex-3 (AP-3). Storage of phosphate and cations may represent the ancestral physiological function of acidocalcisomes, with cation and pH homeostasis and osmoregulatory functions derived following the divergence of prokaryotes and eukaryotes.
Diversity and reductive evolution of mitochondria among microbial eukaryotes
Authors: Hjort Karin , Goldberg Alina V. , Tsaousis Anastasios D. , Hirt Robert P. , Embley T. Martin
Published: February 2010

All extant eukaryotes are now considered to possess mitochondria in one form or another. Many parasites or anaerobic protists have highly reduced versions of mitochondria, which have generally lost their genome and the capacity to generate ATP through oxidative phosphorylation. These organelles have been called hydrogenosomes, when they make hydrogen, or remnant mitochondria or mitosomes when their functions were cryptic. More recently, organelles with features blurring the distinction between mitochondria, hydrogenosomes and mitosomes have been identified. These organelles have retained a mitochondrial genome and include the mitochondrial-like organelle ofBlastocystisand the hydrogenosome of the anaerobic ciliateNyctotherus. Studying eukaryotic diversity from the perspective of their mitochondrial variants has yielded important insights into eukaryote molecular cell biology and evolution. These investigations are contributing to understanding the essential functions of mitochondria, defined in the broadest sense, and the limits to which reductive evolution can proceed while maintaining a viable organelle.