bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronized and configurable source of electrical pulses for x-ray pump-probe experiments
Authors: Strachan J. P. , Chembrolu V. , Yu X. W. , Tyliszczak T. , Acremann Y.
Published: May 2007

A method is described for the generation of software tunable patterns of nanosecond electrical pulses. The bipolar, high repetition rate (up to 250MHz), fast rise time (<30ps), square pulses are suitable for applications such as the excitation sequence in dynamic pump-probe experiments. Synchronization with the time structure of a synchrotron facility is possible as well as fine control of the relative delay in steps of 10ps. The pulse generator described here is used to excite magnetic nanostructures with current pulses. Having an excitation system which can match the high repetition rate of a synchrotron allows for utilization of the full x-ray flux and is needed in experiments which require a large photon flux. The fast rise times allow for picosecond time resolution in pump-probe experiments. All pulse pattern parameters are configurable by software.
Surface excess free energy of simple fluids confined in cylindrical pores by isothermal-isobaric Monte Carlo: Influence of pore size
Authors: Puibasset Joël
Published: May 2007

Confined fluid properties are mainly determined by interfacial phenomena characterized by surface quantities. Based on a simple model of Lennard-Jones particles confined in a cylindrical pore, this study introduces a grand potential surface quantity to quantify the difference in the thermodynamic pressure between the bulk and the confined fluids. The usual surface tension γ defined as this grand potential difference for the same chemical potential in both confined and bulk states is generally strongly dependent on both the chemical potential and temperature. It is proposed here to introduce another surface quantity ζ which measures the thermodynamic pressure difference between confined and bulk states for identical densities. It is shown that this quantity is much less dependent on confined fluid density or chemical potential. It is actually constant along the gaslike and liquidlike adsorption/desorption branches for an irreversible isotherm (hysteresis), with a different value for each branch. For reversible supercritical isotherms, ζ is shown to remain constant in the low and high density parts of the isotherm. This independence on chemical potential (or equivalently fluid density) is believed to be of great interest for practical applications when one desires to calculate thermodynamic quantities such as the usual surface tension γ or the thermodynamic pressure of a confined fluid for any given chemical potential and temperature. Such calculations are required to determine fundamental properties such as metastability or coexistence. The effects of temperature, fluid/substrate interaction strength, and pore size are studied.
Design and performance of a curved-crystal x-ray emission spectrometer
Authors: Hudson A. C. , Stolte W. C. , Lindle D. W. , Guillemin R.
Published: May 2007

A curved-crystal x-ray emission spectrometer has been designed and built to measure 2–5keV x-ray fluorescence resulting from a core-level excitation of gas phase species. The spectrometer can rotate 180°, allowing detection of emitted x rays with variable polarization angles, and is capable of collecting spectra over a wide energy range (20eV wide with 0.5eV resolution at the Cl K edge) simultaneously. In addition, the entire experimental chamber can be rotated about the incident-radiation axis by nearly 360° while maintaining vacuum, permitting measurements of angular distributions of emitted x rays.
High-resolution characterization of ultrashallow junctions by measuring in vacuum with scanning spreading resistance microscopy
Authors: Zhang L. , Ohuchi K. , Adachi K. , Ishimaru K. , Takayanagi M. , Nishiyama A.
Published: May 2007

The spatial resolution of scanning spreading resistance microscopy has been limited by using conventional probes when measuring in air. Sufficient electric contact of a probe-sample has been difficult to obtain in air due to the existence of moisture/contamination. Two-dimensional carrier profiling of nanoscale silicon devices is performed in a vacuum with conventional probes, and a high spatial resolution is obtained. Ultrashallow junctions down to 10nm are measured accurately with high reproducibility. Experimental results show that a good electric contact between probe and sample is important for obtaining high spatial resolution.
Proposition to build a digitally controlled biphase sinusoidal generator
Authors: Bayard Jean
Published: May 2007

We propose a new method to build a biphase sinusoidal generator which provides two signals: v1=Vmsin (ωt) and v2=Vmsin (ωt+φ), where Vm, ω, and φ are digitally controlled. Measurements on a prototype confirm the analytical calculations. The article relates especially to the phase control.
Feedforward correction of nonlinearities in piezoelectric scanner constructions and its experimental verification
Authors: Graffel B. , Müller F. , Müller A.-D. , Hietschold M.
Published: May 2007

Piezoelectrical actuators widely used in scanning devices for highly resolved displacement generation exhibit a number of known nonlinear effects as hysteresis and creep. This article describes an attempt to minimize those nonlinearities by recognizing the relation between scan range and voltage magnitude in a scanner specific function. In addition, by utilizing a strain gauge sensor system, a forward displacement correction is realized. The mathematical procedure behind the hysteresis correction is described in detail. The dependence of the higher order correction factors on parameters such as scan speed, scan range, or center position is studied carefully to extract their influence on the result. Finally, integral nonlinearities of about 1% are proven in experiments with an atomic force microscope.
Demonstration of unpinned GaAs surface and surface inversion with gate dielectric made of Si3N4
Authors: Li W. P. , Wang X. W. , Liu Y. X. , Shim S. I. , Ma T. P.
Published: May 2007

The authors have measured the electrical properties of metal insulator semiconductor capacitors of GaAs, with ex situ jet-vapor-deposited Si3N4 as a gate dielectric. Unpinning of GaAs surface was demonstrated by ac conductance and capacitance-voltage (C-V) measurement; GaAs surface inversion has been demonstrated by quasistatic C-V and hysteresis C-V measurements. Hydrogen plasma predeposition treatment at 200°C has been shown to reduce interface-state density. The lowest interface-state density that the authors measured was 9×1011∕cm2∕eV at 0.57eV above EV for p-type GaAs, and the smallest hysteresis window was 100mV.
Periodic versus aperiodic: Enhancing the sensitivity of porous silicon based optical sensors
Authors: Moretti Luigi , Rea Ilaria , De Stefano Luca , Rendina Ivo
Published: May 2007

The authors have compared the sensitivities of resonant optical biochemical sensors, based on both periodic and aperiodic porous silicon structures, such as the Bragg and the Thue-Morse multilayer. The shifts of the reflectivity spectra of these devices on exposure to several chemical compounds have been measured: the aperiodic multilayer is more sensitive than the periodic one. Adopting a simple theoretical model of the optical response of devices, they inferred that the aperiodic structure provide a higher filling capability with respect to the periodic one, due to the lower number of interfaces.
Enhancement of room-temperature hole conductivity in narrow and strained Ge quantum well by double-side modulation doping
Authors: Myronov M. , Shiraki Y. , Mouri T. , Itoh K. M.
Published: May 2007

The room-temperature two-dimensional hole gas (2DHG) conductivity as high as 649.3μS is obtained by implementation of double-side modulation doping (DS-MOD) of an 8nm thick strained Ge quantum well in a SiGe heterostructure. This conductivity is about three times higher than that of the conventional SiGe heterostructure with single-side modulation doping (SS-MOD). While the low-temperature (T=3K) mobility with DS-MOD is two times higher than that with SS-MOD, the room-temperature mobility of the two is practically the same, suggesting that phonon scattering is the dominant limiting mechanism at the device operating temperatures.
Shot noise spectroscopy of electronic spin flips in quantum dots
Authors: Gorelik L. Y. , Kulinich S. I. , Shekhter R. I. , Jonson M. , Vinokur V. M.
Published: May 2007

Spin decoherence and spin flips crucially affect the tunneling transport of spin-polarized electrons through a quantum dot connected to magnetic leads. Here, the authors show that the low-frequency shot noise in such structures diverges as the spin relaxation rate for electrons on the dot goes to zero, reaching giant super-Poissonian values for realistic spin-flip rates. It is also shown that combined measurements of the average current and the shot noise as a function of bias voltage and external magnetic field offer a spectroscopic tool for studying electronic spin relaxation rates in this system.
Polarization switching and fatigue in Pb(Zr0.52Ti0.48)O3 films sandwiched by oxide electrodes with different carrier types
Authors: Chen Feng , Liu Q. Z. , Wang H. F. , Zhang F. H. , Wu Wenbin
Published: May 2007

By using highly conductive p-type La0.7Sr0.3MnO3 (LSMO) and n-type La0.07Sr0.93SnO3 (LSSO) as electrodes, all-oxide Pb(Zr0.52Ti0.48)O3 (PZT) capacitors, LSMO/PZT/LSMO, LSSO/PZT/LSSO, LSSO/PZT/LSMO, and LSMO/PZT/LSSO, have been grown epitaxially on (001)SrTiO3 substrates, and their structure, switching, fatigue, and optical properties were investigated. Strikingly, contrary to the LSMO/PZT/LSMO capacitors, those having the n-type electrode show poor fatigue resistance especially at lower driving frequencies, which was further confirmed by using another n-type oxide electrode, SrTi0.9Sb0.1O3. The results suggest that with a depletion layer at the PZT/LSSO interface, charge accumulation and injection during switching may be responsible for the fatigue.
Liquid core photonic crystal fiber sensor based on surface enhanced Raman scattering
Authors: Zhang Yi , Shi Chao , Gu Claire , Seballos Leo , Zhang Jin Z.
Published: May 2007

This letter reports on a hollow core photonic crystal fiber that is modified to allow for filling of only the core with a liquid and its use for detection of surface enhanced Raman scattering from molecules in solution with silver nanoparticles. Both experimental demonstration and theoretical simulation are presented and discussed. The developed sensor is tested in the detection of rhodamine 6G, human insulin, and tryptophan with good sensitivity (10−4–10−5M) due to enhanced interaction volume.
Array feature size influences nucleic acid surface capture in DNA microarrays
Authors: Dandy David S. , Wu Peng , Grainger David W.
Published: May 2007

Analyte affinity capture by surface-immobilized diagnostic agents is a routinely used assay format for profiling numerous medically and technologically important target analytes. These assays suffer from numerous performance limitations, including sensitivity and rapidity. Assay miniaturization is advocated to improve surface-capture performance, specifically exploiting the inverse relationship between analyte flux and capture feature size under mass transfer-limiting capture conditions that characterize many such assay formats. Reduced capture feature sizes, e.g., microarrays, are proposed to overcome mass transfer limitations, yet this is difficult to achieve across several size scales. This study validates certain advantages advocated for capture spot miniaturization using a rationale to understand surface capture miniaturization strategies. Experimentally derived immobilized ligand and target capture densities as a function of microspot size for DNA oligomers immobilized on model gold substrates are compared directly with theoretical analysis, validating the hypothesis that miniaturization yields many practical assay advantages. Specifically, results show that transitions from assay mass transfer limiting to kinetically limiting conditions as feature size decreases identify an optimal microspot size range for a specific bioassay system. Analytical advantages realized from such assay miniaturization are more uniform target-spot coverage and substantially increased rate of capture (hybridization), increasing assay signal and rapidity.
A silent chemokine receptor regulates steady-state leukocyte homing
in vivo
Authors: Heinzel Kornelia , Benz Claudia , Bleul Conrad C.
Published: May 2007

The location of leukocytes in different microenvironments is intimately connected to their function and, in the case of leukocyte precursors, to the executed differentiation and maturation program. Leukocyte migration within lymphoid organs has been shown to be mediated by constitutively expressed chemokines, but how the bioavailability of these homeostatic chemokines is regulated remains unknown. Here, we report
in vivo
evidence for the role of a nonsignaling chemokine receptor in the migration of leukocytes under physiological, i.e., noninflammatory, conditions. We have studied the
in vivo
role of the silent chemokine receptor CCX-CKR1 by both loss- and gain-of-function approaches. CCX-CKR1 binds the constitutively expressed chemokines CC chemokine ligand (CCL)19, CCL21, and CCL25. We find that CCX-CKR1 is involved in the steady-state homing of CD11c
+
MHCII
high
dendritic cells to skin-draining lymph nodes, and it affects the homing of embryonic thymic precursors to the thymic anlage. These observations indicate that the silent chemokine receptor CCX-CKR1, which is exclusively expressed by stroma cells, but not hematopoietic cells themselves, regulates homeostatic leukocyte migration by controlling the availability of chemokines in the extracellular space. This finding adds another level of complexity to our understanding of leukocyte homeostatic migration.
Indoor seismology by probing the Earth's interior by using sound velocity measurements at high pressures and temperatures
Authors: Li Baosheng , Liebermann Robert C.
Published: May 2007

The adiabatic bulk (
K

S

) and shear (
G
) moduli of mantle materials at high pressure and temperature can be obtained directly by measuring compressional and shear wave velocities in the laboratory with experimental techniques based on physical acoustics. We present the application of the current state-of-the-art experimental techniques by using ultrasonic interferometry in conjunction with synchrotron x radiation to study the elasticity of olivine and pyroxenes and their high-pressure phases. By using these updated thermoelasticity data for these phases, velocity and density profiles for a pyrolite model are constructed and compared with radial seismic models. We conclude that pyrolite provides an adequate explanation of the major seismic discontinuities at 410- and 660-km depths, the gradient in the transition zone, as well as the velocities in the lower mantle, if the uncertainties in the modeling and the variations in different seismic models are considered. The characteristics of the seismic scaling factors in response to thermal anomalies suggest that anticorrelations between bulk sound and shear wave velocities, as well as the large positive density anomalies observed in the lower mantle, cannot be explained fully without invoking chemical variations.
Evolutionary responses of discontinuous gas exchange in insects
Authors: White Craig R. , Blackburn Tim M. , Terblanche John S. , Marais Elrike , Gibernau Marc , Chown Steven L.
Published: May 2007

The discontinuous gas-exchange cycles (DGCs) observed in many quiescent insects have been a cause of debate for decades, but no consensus on their evolutionary origin or adaptive significance has been achieved. Nevertheless, three main adaptive hypotheses have emerged: (i) the hygric hypothesis suggests that DGCs reduce respiratory water loss; (ii) the chthonic hypothesis suggests that DGCs facilitate gas exchange during environmental hypoxia, hypercapnia, or both; and (iii) the oxidative-damage hypothesis suggests that DGCs minimize oxidative tissue damage. However, most work conducted to date has been based on single-species investigations or nonphylogenetic comparative analyses of few species, despite calls for a strong-inference, phylogenetic approach. Here, we adopt such an approach by using 76 measurements of 40 wild-caught species to examine macrophysiological variation in DGC duration in insects. Potential patterns of trait variation are first identified on the basis of the explicita prioripredictions of each hypothesis, and the best phylogenetic generalized least-squares fit of the candidate models to the data is selected on the basis of Akaike's information criterion. We find a significant positive relationship between DGC duration and habitat temperature and an important interaction between habitat temperature and precipitation. This result supports the hygric hypothesis. We conclude that the DGCs of insects reduce respiratory water loss while ensuring adequate gas exchange.
Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate
AKAP10
in heart rhythm regulation
Authors: Tingley Whittemore G. , Pawlikowska Ludmila , Zaroff Jonathan G. , Kim Taeryn , Nguyen Trieu , Young Stephen G. , Vranizan Karen , Kwok Pui-Yan , Whooley Mary A. , Conklin Bruce R.
Published: May 2007

Sudden cardiac death due to abnormal heart rhythm kills 400,000–460,000 Americans each year. To identify genes that regulate heart rhythm, we are developing a screen that uses mouse embryonic stem cells (mESCs) with gene disruptions that can be differentiated into cardiac cells for phenotyping. Here, we show that the heterozygous disruption of the
Akap10
(D-AKAP2) gene that disrupts the final 51 aa increases the contractile response of cultured cardiac cells to cholinergic signals. In both heterozygous and homozygous mutant mice derived from these mESCs, the same
Akap10
disruption increases the cardiac response to cholinergic signals, suggesting a dominant interfering effect of the
Akap10
mutant allele. The mutant mice have cardiac arrhythmias and die prematurely. We also found that a common variant of
AKAP10
in humans (646V, 40% of alleles) was associated with increased basal heart rate and decreased heart rate variability (markers of low cholinergic/vagus nerve sensitivity). These markers predict an increased risk of sudden cardiac death. Although the molecular mechanism remains unknown, our findings in mutant mESCs, mice, and a common human
AKAP10
SNP all suggest a role for AKAP10 in heart rhythm control. Our stem cell-based screen may provide a means of identifying other genes that control heart rhythm.
Evidence for mutation showers
Authors: Wang Jicheng , Gonzalez Kelly D. , Scaringe William A. , Tsai Kimberly , Liu Ning , Gu Dongqing , Li Wenyan , Hill Kathleen A. , Sommer Steve S.
Published: May 2007

Mutants in the Big Blue transgenic mouse system show spontaneous clustered multiple mutations with unexpectedly high frequency, consistent with chronocoordinate events. We tested the prediction that the multiple mutations seen within the
lacI
mutation target sometimes occur in the context of chronocoordinate multiple mutations spanning multiple kilobases (mutation showers). Additional sequencing of mutants was performed in regions immediately flanking the
lacI
region (total of 10.7 kb). Nineteen additional mutations were found outside the
lacI
region (“ectomutations”) from 10 mutants containing two or more
lacI
mutations, whereas only one ectomutation was found in 130 mutants with a single mutation (
P
< 0.0001). The mutation showers had an average of approximately one mutation per 3 kb. Four mutants showed closely spaced double mutations in the new sequence, and analysis of the spacing between these mutations revealed significant clustering (
P
= 0.0098). To determine the extent of the mutation showers, regions (8.5 kb total) remote from the
lacI
region (≈16–17 kb away) were sequenced. Only two additional ectomutations were found in these remote regions, consistent with mutation showers that generally do not extend more than ≈30 kb. We conclude that mutation showers exist and that they constitute at least 0.2% and possibly 1% or more of mutational events observed in this system. The existence of mutation showers has implications for oncogenesis and evolution, raising the possibilities of “cancer in an instant” and “introns as sponges to reduce the deleterious impact of mutation showers.”
A cell nanoinjector based on carbon nanotubes
Authors: Chen Xing , Kis Andras , Zettl A. , Bertozzi Carolyn R.
Published: May 2007

Technologies for introducing molecules into living cells are vital for probing the physical properties and biochemical interactions that govern the cell's behavior. Here, we report the development of a nanoscale cell injection system (termed the nanoinjector) that uses carbon nanotubes to deliver cargo into cells. A single multiwalled carbon nanotube attached to an atomic force microscope (AFM) tip was functionalized with cargo via a disulfide-based linker. Penetration of cell membranes with this “nanoneedle” was controlled by the AFM. The following reductive cleavage of the disulfide bonds within the cell's interior resulted in the release of cargo inside the cells, after which the nanoneedle was retracted by AFM control. The capability of the nanoinjector was demonstrated by injection of protein-coated quantum dots into live human cells. Single-particle tracking was used to characterize the diffusion dynamics of injected quantum dots in the cytosol. This technique causes no discernible membrane or cell damage, and can deliver a discrete number of molecules to the cell's interior without the requirement of a carrier solvent.
Nucleation of protein fibrillation by nanoparticles
Authors: Linse Sara , Cabaleiro-Lago Celia , Xue Wei-Feng , Lynch Iseult , Lindman Stina , Thulin Eva , Radford Sheena E. , Dawson Kenneth A.
Published: May 2007

Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human β
2
-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and β
2
-microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surface-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials.
The missing step of the
l
-galactose pathway of ascorbate biosynthesis in plants, an
l
-galactose guanyltransferase, increases leaf ascorbate content
Authors: Laing William A. , Wright Michele A. , Cooney Janine , Bulley Sean M.
Published: May 2007

The gene for one postulated enzyme that converts GDP-
l
-galactose to
l
-galactose-1-phosphate is unknown in the
l
-galactose pathway of ascorbic acid biosynthesis and a possible candidate identified through map-based cloning is the uncharacterized gene At4g26850. We identified a putative function for At4g26850 using PSI-Blast and motif searching to show it was a member of the histidine triad superfamily, which includes
d
-galactose uridyltransferase. We cloned and expressed this
Arabidopsis
gene and the homologous gene from
Actinidia chinensis
in
Escherichia coli
and assayed the expressed protein for activities related to converting GDP-
l
-galactose to
l
-galactose-1-P. The expressed protein is best described as a GDP-
l
-galactose-hexose-1-phosphate guanyltransferase (EC 2.7.7.), catalyzing the transfer of GMP from GDP-
l
-galactose to a hexose-1-P, most likely
d
-mannose-1-phosphate
in vivo
. Transient expression of this
A. chinensis
gene in tobacco leaves resulted in a >3-fold increase in leaf ascorbate as well as a 50-fold increase in GDP-
l
-galactose-
d
-mannose-1-phosphate guanyltransferase activity.
Simple sequence repeats in prokaryotic genomes
Authors: Mrázek Jan , Guo Xiangxue , Shah Apurva
Published: May 2007

Simple sequence repeats (SSRs) in DNA sequences are composed of tandem iterations of short oligonucleotides and may have functional and/or structural properties that distinguish them from general DNA sequences. They are variable in length because of slip-strand mutations and may also affect local structure of the DNA molecule or the encoded proteins. Long SSRs (LSSRs) are common in eukaryotes but rare in most prokaryotes. In pathogens, SSRs can enhance antigenic variance of the pathogen population in a strategy that counteracts the host immune response. We analyze representations of SSRs in >300 prokaryotic genomes and report significant differences among different prokaryotes as well as among different types of SSRs. LSSRs composed of short oligonucleotides (1–4 bp length, designated LSSR
1–4
) are often found in host-adapted pathogens with reduced genomes that are not known to readily survive in a natural environment outside the host. In contrast, LSSRs composed of longer oligonucleotides (5–11 bp length, designated LSSR
5–11
) are found mostly in nonpathogens and opportunistic pathogens with large genomes. Comparisons among SSRs of different lengths suggest that LSSR
1–4
are likely maintained by selection. This is consistent with the established role of some LSSR
1–4
in enhancing antigenic variance. By contrast, abundance of LSSR
5–11
in some genomes may reflect the SSRs' general tendency to expand rather than their specific role in the organisms' physiology. Differences among genomes in terms of SSR representations and their possible interpretations are discussed.
A kinematic description of the trajectories of
Listeria monocytogenes
propelled by actin comet tails
Authors: Shenoy V. B. , Tambe D. T. , Prasad A. , Theriot J. A.
Published: May 2007

The bacterial pathogen
Listeria monocytogenes
propels itself in the cytoplasm of the infected cells by forming a filamentous comet tail assembled by the polymerization of the cytoskeletal protein actin. Although a great deal is known about the molecular processes that lead to actin-based movement, most macroscale aspects of motion, including the nature of the trajectories traced out by the motile bacteria, are not well understood. Here, we present 2D trajectories of
Listeria
moving between a glass-slide and coverslip in a
Xenopus
frog egg extract motility assay. We observe that the bacteria move in a number of fascinating geometrical trajectories, including winding S curves, translating figure eights, small- and large-amplitude sine curves, serpentine shapes, circles, and a variety of spirals. We then develop a dynamic model that provides a unified description of these seemingly unrelated trajectories. A key ingredient of the model is a torque (not included in any microscopic models of which we are aware) that arises from the rotation of the propulsive force about the body axis of the bacterium. We show that a large variety of trajectories with a rich mathematical structure are obtained by varying the rate at which the propulsive force moves about the long axis. The trajectories of bacteria executing both steady and saltatory motion are found to be in excellent agreement with the predictions of our dynamic model. When the constraints that lead to planar motion are removed, our model predicts motion along regular helical trajectories, observed in recent experiments.
Mapping the elusive neonicotinoid binding site
Authors: Tomizawa Motohiro , Talley Todd T. , Maltby David , Durkin Kathleen A. , Medzihradszky Katalin F. , Burlingame Alma L. , Taylor Palmer , Casida John E.
Published: May 2007

Two types of structurally similar nicotinic agonists have very different biological and physicochemical properties. Neonicotinoids, important insecticides including imidacloprid and thiacloprid, are nonprotonated and selective for insects and their nicotinic receptors, whereas nicotinoids such as nicotine and epibatidine are cationic and selective for mammalian systems. We discovered that a mollusk acetylcholine binding protein (AChBP), as a structural surrogate for the extracellular ligand-binding domain of the nicotinic receptor, is similarly sensitive to neonicotinoids and nicotinoids. It therefore seemed possible that the proposed very different interactions of the neonicotinoids and nicotinoids might be examined with a single AChBP by using optimized azidochloropyridinyl photoaffinity probes. Two azidoneonicotinoids with a nitro or cyano group were compared with the corresponding desnitro or descyano azidonicotinoids. The four photoactivated nitrene probes modified AChBP with up to one agonist for each subunit based on analysis of the intact derivatized protein. Identical modification sites were observed by collision-induced dissociation analysis for the neonicotinoids and nicotinoids with similar labeling frequency of Tyr-195 of loop C and Met-116 of loop E at the subunit interface. The nitro- or cyano-substituted guanidine/amidine planes of the neonicotinoids provide a unique electronic conjugation system to interact with loop C Tyr-188. The neonicotinoid nitro oxygen and cyano nitrogen contact loop C Cys-190/Ser-189, whereas the cationic head of the corresponding nicotinoids is inverted for hydrogen-bonding and cation-π contact with Trp-147 and Tyr-93. These structural models based on AChBP directly map the elusive neonicotinoid binding site and further describe the molecular determinants of agonists on nicotinic receptors.
Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling
Authors: Kawagoe Tatsukata , Sato Shintaro , Jung Andreas , Yamamoto Masahiro , Matsui Kosuke , Kato Hiroki , Uematsu Satoshi , Takeuchi Osamu , Akira Shizuo
Published: May 2007

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.
Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells
Authors: Zhang Xiaoming , Deriaud Edith , Jiao Xinan , Braun Deborah , Leclerc Claude , Lo-Man Richard
Published: May 2007

Newborns and infants are highly susceptible to viral and bacterial infections, but the underlying mechanism remains poorly understood. We show that neonatal B cells effectively control the production of proinflammatory cytokines by both neonatal plasmacytoid and conventional dendritic cells, in an interleukin (IL) 10–dependent manner, after Toll-like receptor (TLR) 9 triggering. This antiinflammatory property of neonatal B cells may extend to other TLR agonists (Pam3CSK4, lipopolysaccharide, and R848) and viruses. In the absence of B cells or of CD5+ B cell subsets, neonatal mice developed stronger inflammatory responses and became lethally susceptible to CpG challenge after galactosamine sensitization, whereas wild-type (WT) mice were resistant. Paradoxically, interferon (IFN)-α/β enhanced the inflammatory response to CpG challenge in adult mice, whereas they helped to control neonatal acute inflammation by stimulating the secretion of IL-10 by neonatal B cells. Finally, WT neonatal B cells rescued IL-10−/− neonates from a lethal CpG challenge, whereas IFN-α/β receptor–deficient B cells did not. Our results show that type I IFNs support a negative regulatory role of neonatal B cells on TLR-mediated inflammation, with important implications for neonatal inflammation and infection.
CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response
Authors: Peixoto António , Evaristo César , Munitic Ivana , Monteiro Marta , Charbit Alain , Rocha Benedita , Veiga-Fernandes Henrique
Published: May 2007

To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Different mRNAs were induced at very different time points of the response, were transcribed during different time periods, and could decline or persist independently of the antigen load. Consequently, distinct gene coexpression patterns/different cell types were generated at the various phases of the immune responses. During primary stimulation, inflammatory molecules were induced and down-regulated shortly after activation, generating early cells that only mediated inflammation. Cytotoxic T cells were generated at the peak of the primary response, when individual cells simultaneously expressed multiple killer molecules, whereas memory cells lost killer capacity because they no longer coexpressed killer genes. Surprisingly, during secondary responses gene transcription became permanent. Secondary cells recovered after antigen elimination were more efficient killers than cytotoxic T cells present at the peak of the primary response. Thus, primary responses produced two transient effector types. However, after boosting, CD8 T cells differentiate into long-lived killer cells that persist in vivo in the absence of antigen.
Cytomegalovirus exploits IL-10–mediated immune regulation in the salivary glands
Authors: Humphreys Ian R. , de Trez Carl , Kinkade April , Benedict Chris A. , Croft Michael , Ware Carl F.
Published: May 2007

The salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. Despite control of viral infection by strong T cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. Here, we show that T cell immunity in the salivary glands is limited by the induction of CD4 T cells expressing the regulatory cytokine interleukin (IL)-10. Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced viral load in the salivary glands, but not in the spleen. The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumulation of CD4 T cells expressing interferon γ, suggesting that IL-10R signaling limits effector T cell differentiation. Consistent with this, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced effector T cell differentiation and increased the number of interferon γ–producing T cells, thus limiting virus replication in the salivary glands. Collectively, the results indicate that modulating effector T cell differentiation can counteract pathogen exploitation of the mucosa, thus limiting persistent virus replication and transmission.
Interleukin-12: A master regulator
Authors: Bashyam Hema
Published: May 2007

Early resistance to pathogens requires a swift response from NK cells. In 1989, Giorgio Trinchieri identified an NK growth factor and activator, later called interleukin-12 (IL-12). This discovery helped reveal the regulatory link between innate and adaptive immunity.
ChromatinDB: a database of genome-wide histone modification patterns forSaccharomyces cerevisiae
Authors: O’Connor Timothy R. , Wyrick John J.
Published: May 2007

Summary: Covalent modifications to histone proteins play a critical role in regulating gene transcription. Previous studies have used chromatin immunoprecipitation (ChIP) based microarray assays to profile genomic regions that are enriched or depleted for a particular histone modification. Such studies have been conducted extensively in the yeast Saccharomyces cerevisiae, but currently no comprehensive data repositories or analysis tools are available for these data sets. For this reason, we have developed the ChromatinDB database, which contains genome-wide ChIP data for 22 different histones or histone modifications in S.cerevisiae. ChromatinDB provides novel tools to facilitate the visualization and statistical analysis of chromatin features for user-selected gene sets.

Availability:  http://www.bioinformatics2.wsu.edu/ChromatinDB

Contact:  jwyrick@wsu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
CRCView: a web server for analyzing and visualizing microarray gene expression data using model-based clustering
Authors: Xiang Zuoshuang , Qin Zhaohui S. , He Yongqun
Published: May 2007

Summary: CRCView is a user-friendly point-and-click web server for analyzing and visualizing microarray gene expression data using a Dirichlet process mixture model-based clustering algorithm. CRCView is designed to clustering genes based on their expression profiles. It allows flexible input data format, rich graphical illustration as well as integrated GO term based annotation/interpretation of clustering results.

Availability:  http://helab.bioinformatics.med.umich.edu/crcview/

Contact:  yongqunh@umich.edu
Bioinformatics software for biologists in the genomics era
Authors: Kumar Sudhir , Dudley Joel
Published: May 2007

Motivation: The genome sequencing revolution is approaching a landmark figure of 1000 completely sequenced genomes. Coupled with fast-declining, per-base sequencing costs, this influx of DNA sequence data has encouraged laboratory scientists to engage large datasets in comparative sequence analyses for making evolutionary, functional and translational inferences. However, the majority of the scientists at the forefront of experimental research are not bioinformaticians, so a gap exists between the user-friendly software needed and the scripting/programming infrastructure often employed for the analysis of large numbers of genes, long genomic segments and groups of sequences. We see an urgent need for the expansion of the fundamental paradigms under which biologist-friendly software tools are designed and developed to fulfill the needs of biologists to analyze large datasets by using sophisticated computational methods. We argue that the design principles need to be sensitive to the reality that comparatively small teams of biologists have historically developed some of the most popular biological software packages in molecular evolutionary analysis. Furthermore, biological intuitiveness and investigator empowerment need to take precedence over the current supposition that biologists should re-tool and become programmers when analyzing genome scale datasets.

Contact:  s.kumar@asu.edu
Management Considerations for Differentiated Thyroid Carcinoma Presenting as a Metastasis to the Skull Base
Authors: Mydlarz Wojciech K. , Wu Julie , Aygun Nafi , Olivi Alessandro , Carey John P. , Westra William H. , Tufano Ralph P.
Published: May 2007

Objectives/Hypothesis: To characterize the salient features of skull base metastasis from differentiated thyroid carcinoma, discuss the diagnostic and treatment strategies, and propose rational management guidelines for such tumors.

Study Design: Case report.

Methods: Review of English literature from MEDLINE with the addition of our case.

Results: Skull base metastasis from differentiated thyroid carcinoma is rare, with only 20 cases reported to date, including our case report. On the basis of a review of all reported cases, both follicular and papillary thyroid cancers can metastasize to the skull base. Our case is unique because the lesion extends locally into the cavernous sinus and beyond. Histopathologic diagnosis is limited by the remote location of lesions. Most tumors are highly vascular, and there is potential for significant morbidity and mortality associated with surgical resection. The overall survival ranges from less than one year to 10+ years from the discovery of the metastasis and is similar in both tumor subtypes. There is no clear consensus on the management strategy for skull base metastasis from differentiated thyroid carcinoma. Interestingly, surgical resection of both the primary and metastatic lesions yields similar survival when compared with resection of the primary tumor alone.

Conclusions: Distant metastasis from differentiated thyroid carcinoma needs to be considered in the differential diagnosis of destructive skull base lesions, regardless of the patient's age. Histopathologic tissue diagnosis should always be attempted, followed by total thyroidectomy, radioiodine, or external beam radiation, and chronic thyroid‐stimulating hormone suppression. Surgical resection of the metastatic lesion should only be performed in carefully selected cases because it is associated with significant morbidity.
Algorithm for Reconstruction After Endoscopic Pituitary and Skull Base Surgery
Authors: Tabaee Abtin , Anand Vijay K. , Brown Seth M. , Lin Jerry W. , Schwartz Theodore H.
Published: May 2007

Introduction: The expanding role of endoscopic skull base surgery necessitates a thorough understanding of the indications, techniques, and limitations of the various approaches to reconstruction. The technique and outcomes of endoscopic skull base reconstruction remain incompletely described in the literature.

Study Design and Methods: Patients undergoing endoscopic skull base surgery underwent an algorithmic approach to reconstruction based on tumor location, defect size, and presence of intraoperative cerebrospinal fluid (CSF) leak. A prospective database was reviewed to determine the overall efficacy of reconstruction and to identify risk factors for postoperative CSF leak.

Results: The diagnosis in the 127 patients in this series included pituitary tumor in 70 (55%) patients, encephalocele in 16 (12.6%) patients, meningioma in 11 (8.7%) patients, craniopharyngioma in 9 (7.1%) patients, and chordoma in 6 (4.7%) patients. Successful reconstruction was initially achieved in 91.3% of patients. Eleven (8.7%) patients experienced postoperative CSF leak, 10 of which resolved with lumbar drainage alone. One (0.8%) patient required revision surgery. Correlation between postoperative CSF leak and study variables revealed a statistically significant longer duration of surgery (243 vs. 178 min, P = .008) and hospitalization (12.1 vs. 4.5 days, P < .0001) and a trend toward larger tumors (mean, 3.2 vs. 2.3 cm; P = .058) in patients experiencing postoperative CSF leak.

Conclusion: The algorithm for reconstruction after endoscopic surgery presented in this study is associated with excellent overall efficacy. A greater understanding of risk factors for postoperative CSF leak is imperative to achieve optimal results.
Spectrum of bone marrow findings in patients with angioimmunoblastic T‐cell lymphoma
Authors: Grogg Karen L. , Morice William G. , Macon William R.
Published: May 2007

Bone marrow (BM) biopsy is often performed early in the evaluation of patients with angioimmunoblastic T‐cell lymphoma (AITL), and may be the first diagnostic tissue sample; yet the BM histopathology associated with this disease has not been well described. In this study, BM specimens from 13 patients with AITL were reviewed. Seven (54%) were involved by AITL, which was characterised by paratrabecular and interstitial polymorphous infiltrates containing cytologically atypical lymphocytes, histiocytes and eosinophils. The neoplastic cells were positive for CD10 and CXCL13 by immunohistochemistry in a subset of cases. As in lymph nodes, the lymphomatous infiltrate in some BMs contained numerous small or scattered large B cells, resembling either benign lymphoid aggregates or T cell rich large B cell lymphoma, respectively. Secondary haematological changes were frequent and presented independent of BM involvement by AITL; these included trilineage haematopoietic hyperplasia and plasmacytosis. When BM biopsy preceded the diagnosis of AITL, these secondary changes were misinterpreted as chronic myeloproliferative disease (n = 2), or plasma cell dyscrasia (n = 2). In two cases, these changes obscured the presence of BM involvement by AITL. The spectrum of BM findings in AITL patients is important to recognise for early and accurate diagnosis in this disease.
Increased risk for invasive pneumococcal diseases in children with acute lymphoblastic leukaemia
Authors: Meisel Roland , Toschke André Michael , Heiligensetzer Cora , Dilloo Dagmar , Laws Hans‐Jürgen , Von Kries Rüdiger ,   the Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED) Study Group
Published: May 2007

Asplenia and other conditions of immunodeficiency are established risk factors for invasive pneumococcal disease (IPD). There are no current data available on the risk of IPD in children with acute lymphoblatic leukaemia (ALL), the most common type of childhood malignancy. This study combined data from a nation‐wide surveillance for IPD and the German childhood cancer registry, and showed that children with ALL carry a more than 10‐fold higher risk for IPD than the general paediatric population. As a substantial proportion of IPD occurs during maintenance chemotherapy, children with ALL may represent candidates for the evaluation of prophylactic interventions including vaccination.
MDR1 polymorphism influences the outcome of multiple myeloma patients
Authors: Buda Gabriele , Maggini Valentina , Galimberti Sara , Martino Alessandro , Giuliani Nicola , Morabito Fortunato , Genestreti Giovenzio , Iacopino Pasquale , Rizzoli Vittorio , Barale Roberto , Rossi Anna M. , Petrini Mario
Published: May 2007

The multidrug resistance gene (MDR1) has been reported to be an additional prognostic factor in acute myeloid leukaemia patients. This study evaluated the prognostic role of MDR1 in the outcome of 115 multiple myeloma patients treated with DAV (dexamethasone, doxorubicin [adryamicin] and vincristine) regimen followed by autologous transplantation. In particular, when investigating the C3435T polymorphism, a prognostic value of MDR1 genotypes for overall survival (OS) was observed. Our data suggested a longer OS for patients with C/T and T/T genotypes (log‐rank test, P = 0·02) compared with patients with C/C genotype.