bluuebunny/crossref_metadata_2025 huggingface dataset:
Boundary effects on electrophoresis of colloidal cylinders
Authors: Keh Huan J. , Horng Kuo D. , Kuo Jimmy
Published: April 2006

An exact analytical study is presented for the electrophoresis of an infinite insulating cylinder in the proximity of an infinite plane wall parallel to its axis. The electric field is exerted perpendicular to the particle axis in two fundamental cases: normal to a conducting plane and parallel to a non-conducting wall. The electrical double layers adjacent to solid surfaces are assumed to be thin with respect to the particle radius and the gap thickness between surfaces. The two-dimensional electrostatic and hydrodynamic governing equations are solved in the quasi-steady limit using bipolar coordinates and the typical electric-field-line, equipotential-line and streamline patterns are exhibited. Corrections to Smoluchowski's equation for the electrophoretic velocities of the particle are determined in simple closed forms as a function of λ, the ratio of particle radius to distance of the particle axis from the wall. Interestingly, the electrophoretic mobility of the cylinder in the direction parallel to a dielectric plane increases monotonically as the particle approaches the wall and becomes infinity when the particle touches the wall. For the motion of a cylinder normal to a conducting plane, the presence of the wall causes a reduction in the electrophoretic velocity, which goes to zero as λ → 1. It is found that boundary effects on the electrophoresis of a cylinder are much stronger than for a sphere at the same value of λ. The boundary effects on the particle mobility and on the fluid flow pattern in electrophoresis differ significantly from those of the corresponding sedimentation problem with which comparisons are made.
Linear-eddy modelling of turbulent transport. Part 6. Microstructure of diffusive scalar mixing fields
Authors: Kerstein Alan R.
Published: April 2006

The linear-eddy approach for modelling molecular mixing in turbulent flow involves stochastic simulation on a one-dimensional domain with sufficient resolution to include all physically relevant lengthscales. In each realization, molecular diffusion is implemented deterministically, punctuated by a sequence of instantaneous, statistically independent ‘rearrangement events’ (measure-preserving maps) representing turbulent stirring. These events emulate the effect of compressive strain on the scalar field. An inertial-range similarity law is incorporated.

The model reproduces key features of scalar power spectra, including dependences of spectra! amplitudes and transition wavenumbers on Reynolds and Schmidt numbers. Computed scaling exponents governing scalar power spectra, higher-order fluctuation statistics such as structure functions, and the spatial distribution of scalar level crossings are close to measured exponents. It is inferred that the characterization of stirring as a sequence of independent events (the model analogue of eddies) leads to a useful representation of mixing-field microstructure.
Onset of three-dimensionality, equilibria, and early transition in flow over a backward-facing step
Authors: Kaiktsis Lambros , Karniadakis George Em , Orszag Steven A.
Published: April 2006

A numerical study of three-dimensional equilibria and transition to turbulence in flow over a backward-facing step is performed using direct numerical solution of the incompressible Navier-Stokes equations. The numerical method is a high-order-accurate mixed spectral/spectral-element method with efficient viscous outflow boundary conditions. The appearance of three-dimensionality in nominally two-dimensional geometries is investigated at representative Reynolds numbers ranging from the onset of three-dimensional bifurcation to later transitional stages. Strongly three-dimensional regions are identified through standard correlation coefficients and new three-dimensionality indices, as well as through instantaneous and time-average streamline patterns and vorticity contours. Our results indicate that onset of three-dimensionality occurs at the boundaries between the primary and secondary recirculating zones with the main channel flow, the latter being the most stable flow component. There is. therefore, strong secondary instability in the shear layers, mainly due to the one emanating from the step corner.

The flow further downstream is excited through the action of the upstream shear layers acquiring a wavy form closely resembling Tollmien–Schlichting waves both spatially and temporally with a characteristic frequency f1; upstream, at the shear layer another incommensurate frequency, f2, is present. The two-frequency flow locks-in to a single frequency if external excitations are imposed at the inflow at a frequency close to f1 or f2; the smaller amplitude excitations, however, may cause a strong quasi-periodic response. Such excitations may significantly increase or decrease (by more than 20%) the length of the primary separation zone XR at lock-in or quasi-periodic states. The equilibrium states resulting from the secondary instability at supercritical Reynolds numbers produce a flow modulated in the spanwise direction, with corresponding variations in the reattachment location XR. While three-dimensionality explains partially the discrepancy between numerical predictions and experimental results on XR at higher Reynolds number Re, the main source of discrepancy is attributed to the inflow conditions, and in particular to external disturbances superimposed on the mean flow, the latter being the main reason also for the somewhat earlier transition found in laboratory experiments.
Temporal interactions in direction-selective complex cells of area 18 and the posteromedial lateral suprasylvian cortex (PMLS) of the cat
Authors: VAJDA ILDIKÓ , BORGHUIS BART G. , VAN DE GRIND WIM A. , LANKHEET MARTIN J.M.
Published: April 2006

Temporal interactions in direction-sensitive complex cells in area 18 and the posteromedial lateral suprasylvian cortex (PMLS) were studied using a reverse correlation method. Reverse correlograms to combinations of two temporally separated motion directions were examined and compared in the two areas. A comparison to the first-order reverse correlograms allowed us to identify nonlinear suppression or facilitation due to pairwise combinations of motion directions. Results for area 18 and PMLS were very different. Area 18 showed a single type of nonlinear behavior: similar directions facilitated and opposite directions suppressed spike probability. This effect was most pronounced for motion steps that followed each other immediately and decreased with increasing delay between steps. In PMLS, the picture was much more diverse. Some cells exhibited nonlinear interactions, that were opposite to those in area 18 (facilitation for opposite directions and suppression for similar ones), while the majority did not show a systematic interaction profile. We conclude that nonlinear second-order reverse correlation characteristics reveal different functional properties, despite similarities in the first-order reverse correlation profiles. Directional interactions in time revealed optimal integration of similar directions in area 18, but motion opponency—at least in some cells—in PMLS.
Reforming Family Transfers in Southern Europe: Is there a Role for Universal Child Benefits?
Authors: Matsaganis Manos , O'Donoghue Cathal , Levy Horacio , Coromaldi Manuela , Mercader-Prats Magda , Rodrigues Carlos Farinha , Toso Stefano , Tsakloglou Panos
Published: April 2006

The drive to reduce child poverty is of particular interest in southern Europe, where public assistance to low-income families with children is often meagre or not available at all. The paper examines the effect of income transfers to families in Greece, Italy, Spain and Portugal using a benefit-tax model. The distributional impact of actual programmes is shown to be weak, hence the scope for reform great. As an illustration, the European benefit-tax model EUROMOD is used to simulate universal child benefits equivalent to those in Britain, Denmark and Sweden. The anti-poverty effect of such benefits is found to be in proportion to their fiscal cost.
Some Useful Sources
Authors: Brannan Tessa
Published: April 2006

www.interactweb.org.uk

An alliance of practitioners, researchers, writers and policy makers committed to putting effective deliberative, participatory and co-operative approaches at the heart of debate, decision making and action in the UK. The website contains a list of publications on participation and partnership, case studies, discussion papers and information about current initiatives.
Vitamins A and E Status in an Urban Lebanese Population: A Case Study at Dar Al-Fatwa Area, Beirut
Authors: Obeid Omar A. , Al-Ghali Rola M. , Al-Ghali Rola M. , Hwalla Nahla
Published: April 2006

Vitamin A and E status are widely studied in various populations because of their association with several diseases. Fasting plasma vitamin A and E status of 857 Lebanese adults residing in Dar Al-Fatwa, Beirut were assessed using high performance liquid chromatography (HPLC). Mean retinol and alpha-tocopherol concentrations were 59.8 ± 29 µg/dL and 1.0 ± 0.5 mg/dL, respectively in which only 0.2% were retinol-deficient, while 0.7% were alpha-tocopherol-deficient. Vitamin A and E correlated positively with plasma concentrations of total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides. Vitamin E, but not vitamin A, correlated positively with blood pressure and glucose. A good status of vitamins A and E was found among the studied Lebanese sample and the elevation in vitamin A and E levels was associated with unfavorable lipid profile.
Ressourcen - ein Grundbegriff der Entwicklungspsychologie und Entwicklungspsychopathologie?
Authors: Petermann Franz , Schmidt Martin H.
Published: April 2006

Zusammenfassung. Der Einbezug von Ressourcen in Diagnostik und Therapie bildet in der Behandlung von Kindern eine besondere Herausforderung. Die Begriffe “Ressource“, “Resilienz“, “Schutz- und Kompensationsfaktor“ werden geklärt. Für die Erschließung von Entwicklungspotenzialen ist die Unterscheidung in Individual- und Umfeldressourcen hilfreich. Ansätze einer ressourcenorientierten Diagnostik, Klassifikation und Therapie werden skizziert. Als ressourcenorientiert wird eine Intervention definiert, die neben der Symptomreduzierung auch der Kompetenzentwicklung eine entscheidende Rolle einräumt.
North Anatolian Fault in the Gulf of Izmit (Turkey): Rapid vertical motion in response to minor bends of a nonvertical continental transform
Authors: Cormier Marie‐Helene , Seeber Leonardo , McHugh Cecilia M. G. , Polonia Alina , Çagatay Namik , Emre Ömer , Gasperini Luca , Görür Naci , Bortoluzzi Giovanni , Bonatti Enrico , Ryan William B. F. , Newman Kori R.
Published: April 2006

The catastrophic rupture of the North Anatolian Fault east of the Marmara Sea on 17 August 1999 highlighted a need for mapping the underwater extension of that continental transform. A new bathymetric map of Izmit Gulf indicates that the fault follows the axis of the gulf with a few minor bends. Submerged shorelines and shelf breaks that formed during the Last Glacial Maximum provide markers to quantify vertical deformation. Variable tilting of these horizons reveals that vertical deformation is highest just south of the fault. A correlation between vertical deformation of the southern fault block and distance to fault bends can be accounted for by a fault dipping steeply to the south. Hence subsidence (uplift) of the southern, hanging wall block would be expected where the fault strikes at a slightly transtensional (transpressional) orientation to relative plate motion. Subsidence reaches about 8 mm/yr west of the town of Golcuk and might be accommodated in 1–2 m subsidence events during large earthquakes. That scenario is compatible with the tsunami runups and the coseismic subsidence of the southern shore that occurred in 1999. Seafloor morphology also suggests that earthquakes are accompanied by widespread gas and fluid release. The periphery of the deepest basin displays a hummocky texture diagnostic of sediment fluidization, and mud volcanoes occur west of Hersek peninsula that might be activated by earthquakes. Finally, the backscatter imagery reveals a series of lineaments midway through the gulf that are interpreted as products of the 1999 surface rupture. The seafloor is undisturbed farther west, suggesting that surface slip decreased to an insignificant level beyond Hersek. Possibly, the stress shadow from the 10 July 1894 earthquake, which was felt strongly along the western Izmit Gulf, contributed to arrest the 1999 surface rupture.
Intermolecular intersystem crossing in single-molecule spectroscopy: Terrylene in anthracene crystal
Authors: Nicolet A. , Kol’chenko M. A. , Kozankiewicz B. , Orrit M.
Published: April 2006

We present a spectroscopic study of terrylene in anthracene crystals at the ensemble and single-molecule levels. In this matrix, single-molecule fluorescence is reduced by three orders of magnitude. Correlation measurements allow us to identify a new relaxation channel, matrix-enhanced intersystem crossing. This process starts with a singlet-to-triplet energy transfer from guest to host, after which the triplet exciton is transferred back to the guest. The intermolecular intersystem crossing is expected whenever the lowest triplet state of the host is located between the lowest singlet S1 and lowest triplet T1 excited states of the guest. It must be considered when searching for new host-guest systems for single-molecule spectroscopy.
A minimal model for stabilization of biomolecules by hydrocarbon cross-linking
Authors: Hamacher K. , Hübsch A. , McCammon J. A.
Published: April 2006

Programmed cell death regulating protein motifs play an essential role in the development of an organism, its immune response, and disease-related cellular mechanisms. Among those motifs the BH3 domain of the BCL-2 family is found to be of crucial importance. Recent experiments showed how the isolated, otherwise unstructured BH3 peptide can be modified by a hydrocarbon linkage to regain function. We parametrized a reduced, dynamic model for the stability effects of such covalent cross-linking and confirmed that the model reproduces the reinforcement of the structural stability of the BH3 motif by cross-linking. We show that an analytically solvable model for thermostability around the native state is not capable of reproducing the stabilization effect. This points to the crucial importance of the peptide dynamics and the fluctuations neglected in the analytic model for the cross-linking system to function properly. This conclusion is supported by a thorough analysis of a simulated Gō model. The resulting model is suitable for rational design of generic cross-linking systems in silicio.
Binding energies in benzene dimers: Nonlocal density functional calculations
Authors: Puzder Aaron , Dion Maxime , Langreth David C.
Published: April 2006

The interaction energy and minimum energy structure for different geometries of the benzene dimer have been calculated using the recently developed nonlocal correlation energy functional for calculating dispersion interactions. The comparison of this straightforward and relatively quick density functional based method with recent calculations provides a promising first step to elucidate how the former, quicker method might be exploited in larger more complicated biological, organic, aromatic, and even infinite systems such as molecules physisorbed on surfaces and van der Waals crystals.
On the analysis of Liquid Crystal NMR dipolar coupling data via mixed a priori-maximum entropy methods
Authors: Celebre Giorgio , Cinacchi Giorgio
Published: April 2006

In this Letter, a general expression is derived for the conformational distribution function of a molecule dissolved in an anisotropic condensed fluid medium by combining an a priori model with the maximum entropy principle applied to treatment of liquid crystalline-NMR data. The recently proposed additive potential maximum entropy (APME) method is recovered as a special case, when the AP is chosen as the a priori model and the orientational order is low.
Optimal transition paths of stochastic chemical kinetic systems
Authors: Liu Di
Published: April 2006

We present a new framework for finding the optimal transition paths of metastable stochastic chemical kinetic systems with large system sizes. The optimal transition paths are identified, in terms of reaction advancement coordinates, to be the most probable paths according to large deviation theory for the limiting dynamics governed by stochastic differential equations. Dynamical equations for the optimal transition paths are obtained using the variational principle. A multiscale minimum action method is proposed as a numerical scheme to solve the optimal transition paths. Applications to the toggle switch model are presented.
Subnanosecond Pockels cell switching using avalanche transistors
Authors: Bishop A. I. , Barker P. F.
Published: April 2006

Achieving subnanosecond optical switching using a Pockels cell requires an electrically optimized cell design and a compatible fast driver. We report on the design and operation of a high voltage, high speed switching circuit which is capable of achieving an optical switching time of 238ps when used in conjunction with a 6mm aperture Pockels cell. The driver uses a Marx-configured avalanche-transistor design to deliver up to 4kV pulses into a 50Ω load with approximately 12ps jitter and an output pulse length of 7ns. The Pockels cell is a commercially available unit. The observed optical switching time and the jitter in timing of the output pulse are the best currently reported in the literature. We also demonstrate the production of rectangular optical pulses of approximately 3.6ns duration by reflecting the electrical pulse using a mismatched termination.
Molecular dynamics simulations studies of nanoparticles in an isotropic liquid crystal matrix: Single particle behavior and pairwise interactions
Authors: Tian Pu , Smith Grant D. , Glaser Matthew
Published: April 2006

We report results of molecular dynamics simulation studies of the behavior of spherical nanoparticles (NPs) in a dense isotropic nematogen matrix comprised of soft spherocylinders (SSCs). The SSCs exhibit a tendency for frustrated planar anchoring at the NP surface that results in a long-range (compared to the size of the NPs and SSCs) reduction in local orientational ordering and increased fluctuations in local orientational ordering compared to the pure isotropic phase of the SSCs. The potential of mean force between two nanoparticles exhibits a novel long-range repulsive tail separated from short-range molecular packing peaks by a shallow local minimum in free energy. The long-range repulsion is caused by NP-induced ordering fluctuations while the shallow minimum results from increased local ordering within the confinement region in between two NPs. The influence of the NPs on local orientational order in the nematogen matrix and the nematogen-induced interaction between NPs are found to depend strongly on the size of the NPs.
Metal-enhanced chemiluminescence: Radiating plasmons generated from chemically induced electronic excited states
Authors: Chowdhury Mustafa H. , Aslan Kadir , Malyn Stuart N. , Lakowicz Joseph R. , Geddes Chris D.
Published: April 2006

In this letter, we report the observation of metal-enhanced chemiluminescence. Silver Island films, in close proximity to chemiluminescence species, can significantly enhance luminescence intensities; a 20-fold increase in chemiluminescence intensity was observed as compared to an identical control sample containing no silver. This suggests the use of silver nanostructures in the chemiluminescence-based immunoassays used in the biosciences today, to improve signal and therefore analyte detectability. In addition, this finding suggests that surface plasmons can be directly excited by chemically induced electronically excited luminophores, a significant finding toward our understanding of fluorophore-metal interactions and the generation of surface plasmons.
Contrasting characteristics of pulsed and sinusoidal cold atmospheric plasma jets
Authors: Walsh J. L. , Shi J. J. , Kong M. G.
Published: April 2006

Pulsed excitation of cold atmospheric plasmas is commonly believed to offer valuable benefits compared to the mainstream sinusoidal excitation. However, direct comparison of pulsed and sinusoidal atmospheric plasmas remains few, if any, thus casting an uncertainty of whether pulsed excitation facilitates any significant advantage. In this letter, we report a comparison study of pulsed and sinusoidal cold atmospheric plasma jets through electrical characterization, gas temperature measurement, and optical detection of reactive plasma species. An example of pulsed excitation is shown to reduce the electrical energy consumption by a factor of 12 for producing the same amount of oxygen atoms.
Mechanism of nanoelectronic switch based on telescoping carbon nanotubes
Authors: Yan Qimin , Zhou Gang , Hao Shaogang , Wu Jian , Duan Wenhui
Published: April 2006

From ab initio calculations, a nanoelectronic switch is proposed based on telescoping double-walled carbon nanotubes (TDWCNTs), which can be conveniently turned on or off via the relative motion of tubes along the tube axis. It is found that the quantum conductance of switch periodically oscillates with the overlapping length of the two shells of the TDWCNT, which is mainly attributed to the variation of coupling effect between π electronic states of the two shells. The switching of TDWCNTs is determined by the distributions of delocalized frontier molecular orbitals of this system.
High-strength sputter-deposited Cu foils with preferred orientation of nanoscale growth twins
Authors: Zhang X. , Wang H. , Chen X. H. , Lu L. , Lu K. , Hoagland R. G. , Misra A.
Published: April 2006

Bulk Cu foils have been synthesized via magnetron sputtering with an average twin spacing of 5nm. Twin interfaces are of {111} type and normal to the growth direction. Growth twins with such high twin density and preferred orientation have never been observed in elemental metals. These Cu foils exhibited tensile strengths of 1.2GPa, a factor of 3 higher than that reported earlier for nanocrystalline Cu, average uniform elongation of 1%–2%, and ductile dimple fracture surfaces. This work provides a route for the synthesis of ultrahigh-strength, ductile pure metals via control of twin spacing and twin orientation in vapor-deposited materials.
Fabrication of buried channel waveguides in photosensitive glass using proton beam writing
Authors: Bettiol A. A. , Venugopal Rao S. , Teo E. J. , van Kan J. A. , Watt Frank
Published: April 2006

We report our results on the fabrication and characterization of buried, channel optical waveguides in photosensitive Foturan™ glass using a high energy proton beam. Waveguides were fabricated with varying fluence, and the propagation loss and refractive index change were measured. Near-field mode data measured at 632.8nm showed that waveguiding could be achieved for all fluences ranging from 1014to1016protons∕cm2. The maximum positive refractive index change of 1.6×10−3 was measured for the highest fluence. The waveguide propagation losses measured using the scattering technique were estimated to be in the range of 8.3–12.9dB∕cm, increasing with proton fluence.
Molecular-level mechanisms of nanoparticle detachment in laser-induced plasma shock waves
Authors: Zhou Dong , Cetinkaya Cetin
Published: April 2006

Detachment and detachment mechanisms of nanoparticles from flat surfaces subjected to shock waves are investigated by employing molecular gas dynamic simulations using the direct simulation Monte Carlo method and experimental transient pressure data. Two mechanisms for nanoparticle detachment based on rolling moment resistance of the adhesion bond and the elastic restitution effect are introduced. As a result of present simulations, it is computationally demonstrated that the pulsed laser-induced shock waves can generate sufficient rolling moments to detach sub-100-nm particles and initiate removal. The transient moment exerted on a 60nm polystyrene latex particle on a silicon substrate is presented and discussed.
Targeting AMAP1 and cortactin binding bearing an atypical src homology 3/proline interface for prevention of breast cancer invasion and metastasis
Authors: Hashimoto Shigeru , Hirose Mayumi , Hashimoto Ari , Morishige Masaki , Yamada Atsuko , Hosaka Harumi , Akagi Ken-ichi , Ogawa Eiji , Oneyama Chitose , Agatsuma Tsutomu , Okada Masato , Kobayashi Hidenori , Wada Hiromi , Nakano Hirofumi , Ikegami Takahisa , Nakagawa Atsushi , Sabe Hisataka
Published: April 2006

Invasive potentials of carcinomas greatly contribute to their metastasis, which is a major threat in most cancers. We have recently shown that Arf6 plays a pivotal role in breast cancer invasive activities and identified AMAP1 as an effector of GTP-Arf6 in invasion. Expression of AMAP1 correlates well with invasive phenotypes of primary tumors of the human breast. We also have shown that AMAP1 functions by forming a trimeric protein complex with cortactin and paxillin. In this complex, AMAP1 binds to the src homology 3 (SH3) domain of cortactin via its proline-rich peptide, SKKRPPPPPPGHKRT. SH3 domains are known to bind generally to the proline-rich ligands with a one-to-one stoichiometry. We found that AMAP1/cortactin binding is very atypical in its stoichiometry and interface structure, in which one AMAP1 proline-rich peptide binds to two cortactin SH3 domains simultaneously. We made a cell-permeable peptide derived from the AMAP1 peptide, and we show that this peptide specifically blocks AMAP1/cortactin binding, but not other canonical SH3/proline bindings, and effectively inhibits breast cancer invasion and metastasis. Moreover, this peptide was found to block invasion of other types of cancers, such as glioblastomas and lung carcinomas. We also found that a small-molecule compound, UCS15A, which was previously judged as a weak inhibitor against canonical SH3/proline bindings, effectively inhibits AMAP1/cortactin binding and breast cancer invasion and metastasis. Together with fine structural analysis, we propose that the AMAP1/cortactin complex, which is not detected in normal mammary epithelial cells, is an excellent drug target for cancer therapeutics.
Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A
Streptococcus
Authors: Beres Stephen B. , Richter Ellen W. , Nagiec Michal J. , Sumby Paul , Porcella Stephen F. , DeLeo Frank R. , Musser James M.
Published: April 2006

In recent years we have studied the relationship between strain genotypes and patient phenotypes in group A
Streptococcus
(GAS), a model human bacterial pathogen that causes extensive morbidity and mortality worldwide. We have concentrated our efforts on serotype M3 organisms because these strains are common causes of pharyngeal and invasive infections, produce unusually severe invasive infections, and can exhibit epidemic behavior. Our studies have been hindered by the lack of genome-scale phylogenies of multiple GAS strains and whole-genome sequences of multiple serotype M3 strains recovered from individuals with defined clinical phenotypes. To remove some of these impediments, we sequenced to closure the genome of four additional GAS strains and conducted comparative genomic resequencing of 12 contemporary serotype M3 strains representing distinct genotypes and phenotypes. Serotype M3 strains are a single phylogenetic lineage. Strains from asymptomatic throat carriers were significantly less virulent for mice than sterile-site isolates and evolved to a less virulent phenotype by multiple genetic pathways. Strain persistence or extinction between epidemics was strongly associated with presence or absence, respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A serotype M3 clone significantly underrepresented among necrotizing fasciitis cases has a unique frameshift mutation that truncates MtsR, a transcriptional regulator controlling expression of genes encoding iron-acquisition proteins. Expression microarray analysis of this clone confirmed significant alteration in expression of genes encoding iron metabolism proteins. Our analysis provided unprecedented detail about the molecular anatomy of bacterial strain genotype-patient phenotype relationships.
A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus
Authors: Scimone M. Lucila , Aifantis Iannis , Apostolou Irina , von Boehmer Harald , von Andrian Ulrich H.
Published: April 2006

Homing of bone marrow (BM)-derived progenitors to the thymus is essential for T cell development. We have previously reported that two subpopulations of common lymphoid progenitors, CLP-1 and CLP-2, coexist in the BM and give rise to lymphocytes. We demonstrate that CLP-2 migrate to the thymus more efficiently than any other BM-derived progenitors. Short-term adoptive transfer experiments revealed that CLP-2 homing involves P-selectin/P-selectin glycoprotein ligand 1 interactions, pertussis toxin-sensitive chemoattractant signaling by CC chemokine ligand 25 through CC chemokine receptor 9, and binding of the integrins α4β1 and αLβ2 to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Preferential thymus-tropism of CLP-2 correlated with higher chemokine receptor 9 expression than on other BM progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade.
Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria
Authors: Deng Han-Xiang , Shi Yong , Furukawa Yoshiaki , Zhai Hong , Fu Ronggen , Liu Erdong , Gorrie George H. , Khan Mohammad S. , Hung Wu-Yen , Bigio Eileen H. , Lukas Thomas , Dal Canto Mauro C. , O'Halloran Thomas V. , Siddique Teepu
Published: April 2006

Twenty percent of the familial form of amyotrophic lateral sclerosis (ALS) is caused by mutations in the Cu, Zn-superoxide dismutase gene (
SOD1
) through the gain of a toxic function. The nature of this toxic function of mutant SOD1 has remained largely unknown. Here we show that WT SOD1 not only hastens onset of the ALS phenotype but can also convert an unaffected phenotype to an ALS phenotype in mutant SOD1 transgenic mouse models. Further analyses of the single- and double-transgenic mice revealed that conversion of mutant SOD1 from a soluble form to an aggregated and detergent-insoluble form was associated with development of the ALS phenotype in transgenic mice. Conversion of WT SOD1 from a soluble form to an aggregated and insoluble form also correlates with exacerbation of the disease or conversion to a disease phenotype in double-transgenic mice. This conversion, observed in the mitochondrial fraction of the spinal cord, involved formation of insoluble SOD1 dimers and multimers that are crosslinked through intermolecular disulfide bonds via oxidation of cysteine residues in SOD1. Our data thus show a molecular mechanism by which SOD1, an important protein in cellular defense against free radicals, is converted to aggregated and apparently ALS-associated toxic dimers and multimers by redox processes. These findings provide evidence of direct links among oxidation, protein aggregation, mitochondrial damage, and SOD1-mediated ALS, with possible applications to the aging process and other late-onset neurodegenerative disorders. Importantly, rational therapy based on these observations can now be developed and tested.
A genetic variant at the fatty acid-binding protein
aP2
locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease
Authors: Tuncman G. , Erbay E. , Hom X. , De Vivo I. , Campos H. , Rimm E. B. , Hotamisligil G. S.
Published: April 2006

Obesity and the associated pathologies including dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular disease constitute a major threat to global human health. Yet, the genetic factors that differentially predispose individuals to this cluster of pathologies are unclear. The fatty acid-binding protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and macrophages. Mice with aP2 deficiency are partially resistant to obesity-induced insulin resistance and type 2 diabetes, have lower circulating triglycerides, and exhibit marked protection against atherosclerosis. Here, we demonstrate a functionally significant genetic variation at the
aP2
locus in humans that results in decreased adipose tissue
aP2
expression due to alteration of the CAAT box/enhancer-binding protein binding and reduced transcriptional activity of the
aP2
promoter. In population genetic studies with 7,899 participants, individuals that carry this T-87C polymorphism had lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes compared with subjects homozygous for the WT allele. Taken together, our results indicate that reduction in aP2 activity in humans generate a metabolically favorable phenotype that is similar to aP2 deficiency in experimental models.
Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy
Authors: Reits Eric A. , Hodge James W. , Herberts Carla A. , Groothuis Tom A. , Chakraborty Mala , K.Wansley Elizabeth , Camphausen Kevin , Luiten Rosalie M. , de Ru Arnold H. , Neijssen Joost , Griekspoor Alexander , Mesman Elly , Verreck Frank A. , Spits Hergen , Schlom Jeffrey , van Veelen Peter , Neefjes Jacques J.
Published: April 2006

Radiotherapy is one of the most successful cancer therapies. Here the effect of irradiation on antigen presentation by MHC class I molecules was studied. Cell surface expression of MHC class I molecules was increased for many days in a radiation dose-dependent manner as a consequence of three responses. Initially, enhanced degradation of existing proteins occurred which resulted in an increased intracellular peptide pool. Subsequently, enhanced translation due to activation of the mammalian target of rapamycin pathway resulted in increased peptide production, antigen presentation, as well as cytotoxic T lymphocyte recognition of irradiated cells. In addition, novel proteins were made in response to γ-irradiation, resulting in new peptides presented by MHC class I molecules, which were recognized by cytotoxic T cells. We show that immunotherapy is successful in eradicating a murine colon adenocarcinoma only when preceded by radiotherapy of the tumor tissue. Our findings indicate that directed radiotherapy can improve the efficacy of tumor immunotherapy.
Evaluation of Cytotoxic Effects of Dichloromethane Extract of Guduchi (Tinospora cordifolia Miers ex Hook F & THOMS) on Cultured HeLa Cells
Authors: Jagetia Ganesh Chandra , Rao Shaival Kamalaksha
Published: April 2006

Extracts of Tinospora cordifolia (TCE) have been shown to possess anti‐tumor properties, but the mechanism of the anti‐tumor function of TCE is poorly understood. This investigation elucidates the possible mechanism underlying the cytotoxic effects of dichlormethane extracts of TCE, after selecting optimal duration and concentration for treatment. HeLa cells were exposed to various concentrations of TCE, which has resulted in a concentration‐dependent decline in the clonogenicity, glutathione‐S‐transferase (GST) activity and a concentration‐dependent increase in lipid peroxidation (TBARS) with a peak at 4 h and lactate dehydrogenase (LDH) release with a peak at 2 h. Our results suggest that the cytotoxic effect of TCE may be due to lipid peroxidation and release of LDH and decline in GST.
Humor and Laughter May Influence Health: II. Complementary Therapies and Humor in a Clinical Population
Authors: Bennett Mary Payne , Lengacher Cecile
Published: April 2006

Our results support a connection between sense of humor and self‐reported physical health, however, it is difficult to determine the relationship to any specific disease process. Whereas relationships between sense of humor and self‐reported measures of physical well‐being appear to be supported, more research is required to determine interrelationships between sense of humor and well‐being.
Electroencephalographic Approximate Entropy Changes in Healthy Volunteers during Remifentanil Infusion
Authors: Noh Gyu-Jeong , Kim Kye-Min , Jeong Yong-Bo , Jeong Seong-Wook , Yoon Hee-Suk , Jeong Sung-Moon , Kang Sung-Hong , Linares Olinto , Kern Steven E.
Published: April 2006

Background

The aim of this study was to investigate the independent effect of remifentanil on the approximate entropy (ApEn) in frontoparietal montages. The authors investigated which montages were relevant to assess the remifentanil effect on the electroencephalogram. Spectral edge frequency and the canonical univariate parameter were used as comparators.

Methods

Twenty-eight healthy volunteers were enrolled. With recording of the electroencephalogram at the F3, F4, Cz, P3, and P4 montages, remifentanil was infused at the rate of 1-8 mug . kg . min for 15-20 min. The relation between remifentanil concentration and the electroencephalographic parameters were tested by Spearman correlation. Signal-to-noise ratio, artifact robustness, coefficient of variation of the median baseline and maximal electroencephalographic effects, and ratio of average maximal electroencephalographic effect to interindividual baseline variability were measured. The performance of ApEn as an index of remifentanil effect site concentrations was tested by prediction probability.

Results

Approximate entropy showed significant correlation (R = -0.6465, P < 0.0001) with remifentanil concentration. It provided comparable signal-to-noise ratio, artifact robustness, and ratio of average maximal electroencephalographic effect to interindividual baseline variability to 95% spectral edge frequency. The coefficients of variation of the median baseline and maximal electroencephalo graphic effects were smallest in ApEn. Parietal montages showed higher ratios of average maximal electroencephalographic effect to interindividual baseline variability for all electroencephalographic parameters and lower coefficients of variation of the baseline values for ApEn and 95% spectral edge frequency than frontal montages. The prediction probability of ApEn was 0.7730.

Conclusions

Approximate entropy derived from a parietal montage is appropriate for the assessment of the remifentanil effect on the electroencephalogram.
A Genetic Analysis of Opioid-induced Hyperalgesia in Mice
Authors: Liang De-Yong , Liao Guochun , Wang Jianmei , Usuka Jonathan , Guo YingYing , Peltz Gary , Clark J David
Published: April 2006

Background

Opioid-induced hyperalgesia (OIH) is a syndrome of increased sensitivity to noxious stimuli, seen after both the acute and chronic administration of opioids, that has been observed in humans and rodent models. This syndrome may reduce the clinical utility of opioids in treating acute and chronic pain.

Methods

In these studies, the authors measured the propensity of 15 strains of inbred mice to develop mechanical manifestations of OIH. These data were subjected to in silico genetic analysis, which resulted in the association of haplotypic blocks within or near several known genes. Both pharmacologic agents and transgenic mice were used to confirm the functional association of the most strongly linked gene with OIH.

Results

Both baseline mechanical nociceptive thresholds and the percentage changes in these thresholds after 4 days of morphine treatment were found to be highly strain dependent. The haplotypic blocks most strongly associated with the mechanical OIH data were located within the beta2 adrenergic receptor gene (beta2-AR). Using the selective beta2-AR antagonist butoxamine, the authors observed a dose-dependent reversal of OIH. Furthermore, deletion of the beta2-AR gene sharply reduced the mechanical allodynia present after morphine treatment in the wild-type mouse strain. Analysis of the associated beta2-AR haplotypic block identified single nucleotide polymorphisms potentially explaining in part the strain specific differences in OIH.

Conclusions

Genetic variants of the beta2-AR gene seem to explain some part of the differences between various strains of mice to develop OIH. The association of this gene with OIH suggests specific pharmacologic strategies for reducing the impact of OIH on patients consuming opioids.
Variability of the 13C‐Acetate Breath Test for Gastric Emptying of Liquids in Healthy Children
Authors: Hauser B. , De Schepper J. , Caveliers V. , Salvatore S. , Salvatoni A. , Vandenplas Y.
Published: April 2006

Purpose:

Scintigraphy is considered as the “gold standard” for measuring gastric emptying (GE). The 13C‐acetate breath test (13C‐ABT) offers an attractive alternative to measure GE of liquids as it is nonradioactive. The aim of this study was to assess the variability of the 13C‐ABT for GE of liquids in healthy children using nondispersive infrared spectrometry (NDIRS).

Methods:

The 13C‐ABT was repeated at least 2 times in 21 healthy children (6 girls and 15 boys), aged between 6.2 and 16.4 years, 2 to 7 days apart. After an overnight fast, a standardized milk drink, labeled with 50 or 100 mg 13C‐acetate according to weight, was administered. Breath samples were taken before feeding, at 5‐minute intervals for the first 40 minutes and at 10‐minute intervals for the following 140 minutes after feeding. Breath samples were analyzed using NDIRS, and 13C recovery was used to calculate values for gastric half‐emptying time (t1/2), time of peak 13C exhalation, or gastric lag phase (tlag) and gastric emptying coefficient (GEC). Intraindividual variabilities of the parameters t1/2, tlag, and GEC were expressed as coefficient of intrasubject variation (CV).

Results:

The median CV of t1/2 was 8.3% (CV range, 1.6%‐16.2%; t1/2 interindividual range, 65‐112 minutes; and t1/2 intraindividual range, 4‐33 minutes). The median CV of tlag was 16.6% (CV range, 2.0%‐26.6%; tlag interindividual range, 31‐76 minutes; and tlag intraindividual range, 1‐35 minutes). The median CV of GEC was 4.3% (CV range, 0.8%‐15.7%; GEC interindividual range, 3.81‐4.89; GEC intraindividual range, 0.08‐1.31). The CVs of t1/2, tlag, and GEC were independent of age, sex, weight, height, and measured values of t1/2, tlag, and GEC.

Conclusions:

The 13C‐ABT using NDIRS is an easy, noninvasive, and nonradioactive procedure with a large intraindividual variation for measuring GE of liquids in healthy children, but comparable to the variation reported with other techniques.
Effects of osmotic pressure in the extracellular matrix on tissue deformation
Authors: Lu Y , Parker K.H , Wang W
Published: April 2006

In soft tissues, large molecules such as proteoglycans trapped in the extracellular matrix (ECM) generate high levels of osmotic pressure to counter-balance external pressures. The semi-permeable matrix and fixed negative charges on these molecules serve to promote the swelling of tissues when there is an imbalance of molecular concentrations. Structural molecules, such as collagen fibres, form a network of stretch-resistant matrix, which prevents tissue from over-swelling and keeps tissue integrity. However, collagen makes little contribution to load bearing; the osmotic pressure in the ECM is the main contributor balancing external pressures. Although there have been a number of studies on tissue deformation, there is no rigorous analysis focusing on the contribution of the osmotic pressure in the ECM on the viscoelastic behaviour of soft tissues. Furthermore, most previous works were carried out based on the assumption of infinitesimal deformation, whereas tissue deformation is finite under physiological conditions. In the current study, a simplified mathematical model is proposed. Analytic solutions for solute distribution in the ECM and the free-moving boundary were derived by solving integro-differential equations under constant and dynamic loading conditions. Osmotic pressure in the ECM is found to contribute significantly to the viscoelastic characteristics of soft tissues during their deformation.
Pleomorphic hyalinizing angiectatic tumor of soft parts: case report and literature review
Authors: El‐Tal Abd‐El‐Kader , Mehregan Darius
Published: April 2006

Abstract:  Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a rare soft tissue neoplasm. Few cases have been reported in the literature thus far. PHAT is a spindle cell neoplasm with a prominent vascular component which displays some features of both neurilemoma and malignant fibrous histiocytoma. Lesions typically occur on the lower extremities of adults, however, lesions in other anatomic locations have been described. In this paper, we report a 60 years old female with PHAT of the right foot and review the current literature.
Immunization status of children under 7 years in the Vikas Nagar area, North India
Authors: Elliott C. , Farmer K.
Published: April 2006

Background  Immunization has played a major part in reducing childhood morbidity and mortality worldwide. Knowledge of vaccine coverage and reasons for poor uptake are essential for the achievement of herd immunity.

Method  An observational study was carried out in September 2003, in 10 villages in the Vikas Nagar area around Herbertpur Christian Hospital in Uttaranchal, North India. We aimed to assess vaccination rates and potential socio‐cultural, economic and religious influences on vaccine uptake. A total of 470 families were visited and details of immunization status of the oldest child under 7 years in each household were taken. Age range of children included was 9 months to 6 years.

Results  The overall primary immunization rate was 77.2%, children receiving the first booster was 73.1% and children receiving the second booster was 58.4%. The most common vaccinations to be missed were the diphtheria, pertussis, tetanus at 18 months and diphtheria, tetanus at 5 years. Measles was the most frequently omitted vaccination in the primary course (19.4%). Poor education was the most frequent reason given by parents for failure to vaccinate. Immunization rates did not differ according to gender of the child. A lower immunization rate was found in Muslim families (65.4% primary) compared with Hindu (85.2%). Parental literacy had a beneficial effect such that up to 20% more children were immunized.

Conclusion  These results highlight the potential importance of literacy, and religious or cultural influences on the success of the Expanded Programme of Immunization, and will have important implications for areas with similar cultural demographics.
HBV genes induce cytotoxic T‐lymphocyte response upon adeno‐associated virus (AAV) vector delivery into dendritic cells
Authors: You H. , Liu Y. , Cong M. , Ping W. , You C. , Zhang D. , Mehta J. L. , Hermonat P. L.
Published: April 2006

Summary.  Hepatitis B virus (HBV) has been an increasing problem throughout the world and remains difficult to treat. But immunotherapeutic approaches offer new, effective treatments. Three recombinant adeno‐associated virus (AAV) type 2 vectors, carrying one of the HBV S, C or X gene, were used to load (transduce) professional antigen‐presenting dendritic cells (DC) for the purpose of stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction efficiency. Most importantly, all three AAV‐loaded DC stimulated rapid, antigen‐specific and major histocompatibility complex (MHC)‐restricted CTL. In vitro, these CTL killed (30–50%) synthetic antigen‐positive autologous targets as well as HepG2 liver cell targets. In comparing the three antigens, it was found that AAV/HBV‐C‐derived CTL consistently had the highest killing efficiency. CTL derived from AAV/HBV‐C‐loaded DC also showed significantly higher killing of targets than that from bacterially generated C‐protein‐loaded DC. Further studies showed that AAV/HBV‐C‐derived CTL had higher interferon (IFN)‐gamma. These data suggest that AAV/HBV antigen gene‐loading of DC may be useful for immunotherapeutic protocols against HBV infection and that the HBV C antigen may be the most useful for this purpose.