bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between proton dynamics and line edge roughness in chemically amplified resist for post-optical lithography
Authors: Saeki Akinori , Kozawa Takahiro , Tagawa Seiichi , Cao Heidi B.
Published: December 2006

In chemically amplified (CA) resists for electron beam (EB) and extreme ultraviolet (EUV) lithographies, acids (a pair of proton and counteranion) generated upon exposure are utilized for resist pattern formation. As protons and counteranions are separately generated during the exposure, they initially have different spatial distributions. In this work, the authors investigated the effects of proton dynamics during the recombination between protons and counteranions and subsequent acid diffusion during postexposure bake on the line edge roughness (LER) formation of the latent image. The proton dynamics and acid diffusion were simulated by a Monte Carlo technique based on diffusion under Coulomb potential induced by many-body charged species. Based on the results shown here, the correlation between the linewidth and LER as a function of exposure dose and the concentration of base additives are discussed in terms of proton and acid trajectories. The obtained aspects not only provide detailed insight into the nature of reaction mechanism in CA-EB (EUV) resist but also would be of help in the development of resists and the optimization of process conditions.
Extensions of molecular ruler technology for nanoscale patterning
Authors: Srinivasan C. , Anderson M. E. , Carter E. M. , Hohman J. N. , Bharadwaja S. S. N. , Trolier-McKinstry S. , Weiss P. S. , Horn M. W.
Published: December 2006

By combining optical lithography and chemical self-assembly, the authors circumvent the limitations of photolithography and provide a parallel, low-cost alternative to fabricate sub-50nm features. Self-assembled multilayers, composed of alternating layers of α,ω-mercaptoalkanoic acids and copper (II) ions (“molecular rulers”), are used as an organic sidewall spacer resist on initial lithographic structures enabling the precise, proximal placement of a secondary structure via lift-off. Here, the authors implemented a positive-tone bilayer resist for improved line-edge characteristics of the secondary structure and evaluated the lithographic and electrical performance of nanostructures fabricated using this approach. Additionally, they describe extensions of this technique by which planar nanojunctions were created, and the generated nanometer-scale pattern was transferred to the underlying substrate.
Electrostatic chuck fringe field simulation and its impact on electron beam extreme ultraviolet mask patterning
Authors: Ruan Junru , Hartley John
Published: December 2006

The use of electrostatic chucks in electron beam extreme ultraviolet (EUV) mask patterning has been proposed for distortion control. The high voltages used in electrostatic chucking have the potential to establish fringe field near the edge of the critical area between the mask and the bottom lens plane of the electron optics. This electrostatic field may deflect the trajectories of imaging electrons, and images near the edge of the patterned mask would be degraded. The authors developed three-dimensional (3D) models for the electrostatic chucks and EUV masks and obtained the fringe field information using first order finite element method in Munro’s electron beam software (MEBSSW Ltd., 14 Cornwall Gardens, London SW7 4AN, England). Using electron ray tracing in the field enabled them to compute the deflection and blur introduced on an otherwise perfect point image. To understand how fringe fields influence the image condition of electron optic system when writing on the edge of EUV mask critical area, they need to combine two-dimensional (2D) modeling of electron optic system and 3D modeling of the fringe field. Aberration coefficients for the electron optics are obtained in the 2D models and are used for setting up the initial ray conditions for a large number of electrons as they enter the space between the final lens and the writing plane. These rays are then traced in the fringe field, and the final positions of the electrons recorded and statistically counted. The current density profiles for the images are then plotted as the histogram of electron counts versus position coordinates on the image plane. Comparing the current density profiles of the image with and without fringe field, they are able to determine the displacement and CD uniformity error introduced by the fringe field effect.
Orientation dependence of linewidth variation in sub-50-nm Gaussian e-beam lithography and its correction
Authors: Lu M. , Tennant D. M. , Jacobsen C. J.
Published: December 2006

The width of tilted line patterns, such as are needed when drawing circular structures, is found to vary with the oblique angle when it falls into the sub-50-nm scale in Gaussian e-beam lithography. The authors’ analysis shows that this orientation dependence of linewidth variation originates from the nonuniformity of discrete primitive filling in Cartesian coordinates. Two correction schemes based on pattern segmentation are proposed. Test exposures of high resolution zone plate patterns show that both two schemes work well; a double-insert scheme is superior in terms of dose distribution uniformity.
Properties of zone plates used for lithography
Authors: Zheng R. , Jiang L. , Feldman M.
Published: December 2006

The applications of zone plates to lithography are well known: to pattern, to measure, and to align between levels. Recent work has shown that zone plates with low numerical apertures and as few as two zones can produce focused spots that are nearly diffraction limited and that have minimal side lobes. With x-ray lithography such zone plates can be used to pattern vias down to at least 30nm in diameter. In addition, the small size of these zone plates permits them to be arranged in densely packed arrays, attractive for direct write and metrology applications. In spite of the importance of their potential applications, the imaging properties of these zone plates are generally unrecognized, and sometimes quite surprising. This work models zone plates with seven or fewer zones, as a function of their phase shifts and transmissions. X-ray wavelengths are emphasized, but the simulation results are supported by experimental work on zone plate geometries scaled up in size to the visible region.
Novel absorber stack for minimizing shadow effect in extreme ultraviolet mask
Authors: Kim Tae Geun , Kim Byung Hun , Kang In-Yong , Chung Yong-Chae , Ahn Jinho , Lee Seung Yoon , Park In-Sung , Kim Chung Yong , Lee Nae-Eung
Published: December 2006

Finding an optimized absorber stack is becoming a more critical issue in the fabrication of extreme ultraviolet (EUV) mask since it is directly related to the performance of lithography such as pattern fidelity and productivity. Optical simulation, deposition, and measurement have been conducted to establish an optimized absorber stack including antireflection coating (ARC), absorber layer, and capping (or buffer) layer, which satisfies major requirements for EUV mask applications. TaN and the other absorber candidates do not show acceptable reflectivity value (lower than 5%) in deep ultraviolet (DUV) wavelength region (199 or 257nm) for pattern inspection. DUV reflectivity can be lowered by applying C and Al2O3 layers as top ARCs for 199 and 257nm wavelengths, respectively, while keeping the EUV reflectivity at 13.5nm less than 1%. ARC-covered TaN absorber stacks result in a reduction of printed CD variation owing to the mitigation of the shadow effect. However, long-term stability and fabricability of these stacks should be examined further.
Integrated aerial image sensor: Design, modeling, and assembly
Authors: Xue Jing , Moen Kurt , Spanos Costas J.
Published: December 2006

The subject of this article is a novel integrated aerial image sensor (IAIS) system suitable for integration within the surface of an autonomous test wafer. The IAIS could be used as a lithography processing monitor, affording a “wafer’s eye view” of the process, and therefore facilitating advanced process control and diagnostics without integrating (and dedicating) the sensor to the processing equipment. The main IAIS challenge is to retrieve nanometer-scale aerial image detail, while utilizing micrometer-scale photodetector pixels. To address this problem, the authors propose a design of an on-wafer aperture mask that, when combined with an appropriate periodic aerial image, will produce a low spatial frequency interference pattern. They demonstrate a design example aimed at the 65nm technology node through TEMPEST simulation. Also they detail the IAIS modeling techniques based on Abbe’s formulation [Archiv f. Mikroskopische Anat 9, 413 (1873)]. The performance of the IAIS under different lithography settings can be predicted accordingly. The intent is to create a library that captures the aerial image to detector image correspondence in order to facilitate rapid analysis. They also examine several approaches towards the integration of charge-coupled device chips with a near field aperture mask. Capillary force assisted alignment assembly techniques appear quite promising and are being discussed in detail.
Acid generation efficiency in a model system of chemically amplified extreme ultraviolet resist
Authors: Kozawa Takahiro , Tagawa Seiichi , Oizumi Hiroaki , Nishiyama Iwao
Published: December 2006

A highly sensitive extreme ultraviolet (EUV) resist is strongly needed to reduce the development costs of high power EUV sources. Although highly sensitive chemically amplified resists based on acid-catalyzed reactions have been used in mass production lines, the chain length of acid catalytic reactions must be suppressed within several nanometers to meet the resolution requirement below the 32nm technology node. Under such circumstances, the initial acid yield produced by EUV exposure is critical to the formation of ultrafine patterns. Using an acid sensitive dye, the authors evaluated the number of acid molecules generated by an EUV photon. The observed acid yield was well explained by the ionization model for acid generation originally proposed for chemically amplified electron beam resists.
Enhancing etch resistance of hydrogen silsesquioxane via postdevelop electron curing
Authors: Yang Joel K. W. , Anant Vikas , Berggren Karl K.
Published: December 2006

In this work, the authors enhanced the etch resistance of the negative-tone electron resist, hydrogen silsesquioxane (HSQ) to CF4 reactive ion etching (RIE) by curing HSQ after development. They fabricated superconducting nanowires that were 15nm wide by pattern transfer into a 6-nm-thick layer of NbN using cured HSQ as the etch mask. HSQ was cured using a postdevelop electron-beam exposure step prior to RIE in CF4 chemistry. This curing step was shown not to impact the resolution of the HSQ structures while increasing their etch resistance. The results of the authors demonstrate that the etch resistance of HSQ can be tuned after development, which is a desirable resist property of HSQ in addition to its high resolution and low line-edge roughness.
Phase shift mask interferometric birefringence monitor
Authors: McIntyre Gregory R. , Neureuther Andrew
Published: December 2006

A new type of birefringence monitor based on phase shift masks is proposed and initially characterized for optical lithography using simulation of the electromagnetic artifacts and of the images that result. Birefringence is important in steppers at 193nm due to its inherent existence in crystal structures. The technique developed in this article employs a set of crossed polarizers with one located in a pinhole within an opaque layer in the back side of the photomask and the other just above the image plane. The small amount of rotation due to birefringence in the projection optics will create a fairly small transmission in the presence of birefringence. The detection of the small amount of birefringence is greatly enhanced by providing a circularly polarized reference wave from a subresolution chromeless grating with which the birefringent component interferometrically interacts with. Simulation studies show a theoretical sensitivity of this technique of 1.3% of the clear field intensity per nanometer of birefringence, where the signal is dependent on fast axis orientation. Implementation of other variations of birefringence monitors is discussed using as a key enabler a chromeless grating of subresolution pitch in place of a rotating wave plate.
Characterization of hydrogen silsesquioxane as a Cl2∕BCl3 inductively coupled plasma etch mask for air-clad InP-based quantum well waveguide fabrication
Authors: Park D. , Stievater T. H. , Rabinovich W. S. , Green N. , Kanakaraju S. , Calhoun L. C.
Published: December 2006

Air-clad InGaAsP∕InGaAs quantum well waveguides have been fabricated by inductively coupled plasma (ICP) etching using hydrogen silsesquioxane (HSQ) as an etch mask. First, HSQ has been studied for its contrast and resolution in electron beam lithography by varying e-beam exposure conditions and developer concentrations. Second, its etch resistance has been investigated in a chlorine-based ICP along with UVN30, a commercially available negative tone e-beam resist. Then, the optimum conditions for the exposure and development of HSQ for a chlorine-based ICP etching of InP-based material have been explored in terms of etch resistance. InGaAsP∕InGaAs quantum well material was patterned with HSQ by electron beam lithography. The waveguide was formed by the Cl2∕BCl3 ICP etching of InGaAsP∕InGaAs quantum well material and subsequent HCl-based wet etching of InAlAs sacrificial layer. The optical properties of the released waveguides were investigated and the initial optical measurements show low waveguide loss.
Nanowire fin field effect transistors via UV-based nanoimprint lithography
Authors: Fuchs A. , Bender M. , Plachetka U. , Kock L. , Wahlbrink T. , Gottlob H. D. B. , Efavi J. K. , Moeller M. , Schmidt M. , Mollenhauer T. , Moormann C. , Lemme M. C. , Kurz H.
Published: December 2006

A triple step alignment process for UV nanoimprint lithography (UV-NIL) for the fabrication of nanoscale fin field effect transistors (FinFETs) is presented. An alignment accuracy is demonstrated between two functional layers of less than 20nm (3σ). The electrical characterization of the FinFETs fabricated by a full NIL process demonstrates the potential of UV-NIL for future nanoelectronic devices.
Impact of registration error of reticle on total overlay error budget
Authors: Lee Doo-Youl , Chun Yong-Jin , Yoon Je-Bum , Lee Sang-Hee , Lee Suk-Joo , Cho Han-Ku , Moon Joo-Tae
Published: December 2006

As the overlay specification decreases drastically, it is necessary to consider how the total overlay is influenced by each contributing factor. In particular, it is expected that the contribution on overlay error budget can be quantitatively analyzed in terms of the correlation among registration errors of the reticle. The reticle contribution of about 25% is assessed by the breakdown of the sources of overlay metrology uncertainty through the double exposure technique (DET) process. A positive correlation of around 0.7 mitigates the reticle contribution by 180%, compared to the uncorrelated case. In both DET and double patterning technique (DPT) processes, it is needed to positively correlate the registration errors among many reticles in order to decrease the reticle contribution. To maintain the gain of 180% due to positive correlation, the correlation coefficient requisite has to be increased it is difficult to achieve highly positive correlation among more than three reticles. From an integration point of view, three reticles used in DET and DPT generate three combinations of reticle sets. When the positive correlation between two reticle sets is determined to be 0.78, the other reticle set will statistically have a smaller correlation coefficient, 0.61<0.78. With an overlay specification of 12% of design rule and a reticle contribution of 25%, the specification for registration error was expected to be 7.7nm (4×) at the 45nm node and 5.5nm (4×) at the 32nm node in the uncorrelated case between two reticles. The positive correlation of around 0.7–0.78 helps to reduce the reticle specification by around 200% even in the DPT process.
Microelectrical noise detector for rapid, specific, and sensitive identification of bacteria
Authors: Seo Sungkyu , Kim Hyun Chul , Cheng Mosong , Ruan Xinchang , Ruan Wei
Published: December 2006

Recently, sensing of phase-triggered ion cascades (SEPTIC), a nanotechnology for rapid detection of live, pathogenic bacteria on the scale of minutes with unparalleled specificity, has drawn a lot of attention. SEPTIC utilizes a nanowell device, consisting of two metal electrodes with a gap between 5 and 200nm, to probe the ion effluxes from specific bacteria when they are infected by phages. Whether the effluxes occur can be identified by evaluating the power spectral density of the voltage noise in the nanowell. This article presents further development of SEPTIC, using E. coli, E. coli phage T7, and a control bacteria as analytes. A microwell, identical to a nanowell except that the gap is 4μm, proved capable of probing the ion efflux as well. When ion efflux occurred, abnormal pulses that were much higher than the noise level and lasted for 0.1–0.3s were observed in the voltage noise output from the microwell. These durations agree with the average duration of ion efflux. While in negative tests, observed abnormal pulses were much shorter than 0.1s. Also, positives showed 1∕f noise while negatives showed white noise in 1–10Hz. No false positives or negatives were observed. Given the size of microwell and the simplified detection electronics, the cost of SEPTIC is significantly reduced and the robustness is well improved, indicating very promising applications in clinical diagnosis and biodefense.
Influence of light polarization on UV stabilization of prepatterned resists
Authors: Wissen M. , Bogdanski N. , Moellenbeck S. , Helm P. , Scheer H.-C.
Published: December 2006

Details of a mix and match process of thermal nanoimprint lithography and UV lithography have been investigated, where the smaller patterns were defined by imprint, whereas the larger patterns were prepared by UV lithography within the same layer of negative tone resist. Stabilization of the prepatterned resist after imprint by UV curing within the open windows of a mask is different from stabilization under flood exposure. In addition to reflection at the substrate, which leads to a height dependent, vertically modulated exposure dose pattern, the pattern edges, due to diffraction effects, result in an additional lateral modulation of the exposure dose. Distinct local intensity minima and maxima develop within the resist. The intensity differences are particularly strong in the case of pattern widths in the wavelength dimension. Furthermore the direction of light polarization affects the exposure dose pattern. In the case of pattern widths well above the wavelength mainly an underexposure along the edges of the prepatterned layer remains, independent of the polarization direction. The authors found that, under exposure conditions best suited for UV lithography, the stabilization of a prepatterned layer remains incomplete. Full stabilization requires overexposure on the cost of resolution of the UV lithography and edge steepness of the lithographically defined patterns.
Electron beam induced deposition of low resistivity platinum from Pt(PF3)4
Authors: Barry John D. , Ervin Matthew , Molstad Jay , Wickenden Alma , Brintlinger Todd , Hoffman Patrik , Meingailis John
Published: December 2006

The authors have deposited Pt from Pt(PF3)4 using a focused 10keV electron beam (scanning electron microscopy) in an FEI 620 dual beam system and measured the resistivity and composition of the deposits. To measure resistivity, lines of Pt were deposited across four gold fingers and the cross-sectional area of the lines was measured by focused ion beam sectioning. The resistivity varies between about 30 and 650μΩcm and is orders of magnitude lower than the resistivity achieved by e-beam-induced deposition using the usual organometallic precursor, (methylcyclopentadienyl) trimethyl platinum. In general, the higher the beam current the lower the resistivity. They have used wavelength dispersive x-ray analysis to measure the composition of rectangles deposited with various beam currents. Typical at.% values of (Pt:P:F) are 81:17:2 and 58:32:10. Minimum linewidth that they have deposited is 80nm, and with a stationary beam of 2.8nA they have deposited a pillar of 135nm in diameter. They have also deposited Pt structures on freestanding carbon nanotubes and have used the deposits to contact nanofibers. Electron-beam-induced deposition of a “good” metal is particularly useful in geometries where standard lithography is awkward, such as making contacts to fibers or nanotubes randomly dispersed on a surface or freestanding.
Super-self-aligned back-gate∕double-gate planar transistors: Novel fabrication approach
Authors: Lin Hao , Liu Haitao , Kumar Arvind , Avci Uygar , Van Delden Jay S. , Tiwari Sandip
Published: December 2006

This work presents a reproducible, super-self-aligned approach for fabricating back-gate∕double-gate transistors with a thin silicon channel and thick doped source∕drain polysilicon access regions. Such a device structure can lead to ultimate electrostatic control of the channel without sacrificing source∕drain series resistance in a deeply scaled field effect transistor. The approach consists of a unique combination of silicon complementary-metal-oxide-semiconductor front-end processing techniques, along with wafer bonding, sidewall spacer formation (in oxide and nitride), solid-state junction diffusion, and multistage chemical mechanical polishing for wafer-level planarization. The authors further demonstrate the formation of a reliable contact at the source∕drain junction interface between doped polysilicon and the undoped silicon channel. In the design, through oxidation, the authors are able to introduce strain in the structure, as well as buried interconnects in a plane below the device. Both n-channel and p-channel devices have shown high drive currents, strong back-gate coupling, and high effective carrier mobility.
Mechanical property evaluation of Au-coated nanospring fabricated by combination of focused-ion-beam chemical vapor deposition and sputter coating
Authors: Nakamatsu Ken-ichiro , Kanda Kazuhiro , Haruyama Yuichi , Ichihashi Toshinari , Kaito Takashi , Matsui Shinji
Published: December 2006

Au-coated nanosprings were fabricated by a combination of focused-ion-beam chemical vapor deposition (FIB-CVD) and sputter coating. A Au thin layer was successfully coated onto nanosprings fabricated by FIB-CVD. To confirm the mechanical motion, the authors performed an optical microscopy observation in which the Au sputter-coated nanosprings were able to expand and contract mechanically, as flexibly as macroscale springs. The measured spring constants of the Au-coated nanosprings ranged from 0.27to16N∕m, depending on the coil-section diameter. In addition, through the quantitative measurement of the mechanical characteristic of the nanosprings, the authors estimated that Au-coated nanosprings had a sufficient mechanical strength, which is useful for application in nanoelectromechanical system with three dimensions.
Approach to variable frequency measurements of carbon nanotube transistors
Authors: Amlani Islamshah , Lewis Jonathan , Zhang Ruth , Nordquist Kevin , Rockwell Steve , Woodward Dan
Published: December 2006

An approach to variable frequency characterization of high impedance devices such as a carbon nanotube field-effect transistor is presented. A top-gated nanotube transistor is configured as a common source amplifier, and frequency response function of the device is measured. Evidence of signal amplification is observed in time domain as well as frequency domain up to a unity gain frequency of approximately 600kHz. The observed roll-off in frequency is solely due to the measurement setup.
Three-dimensional resist development simulation with discrete models
Authors: Schnattinger T. , Bär E. , Erdmann A.
Published: December 2006

Control and minimization of line-edge roughness (LER) is a crucial problem for further advancements in lithography. To simulate LER, a switch from continuous to discrete, molecular level resist models is required. This article presents a new algorithm for the discrete resist structure generation with nonoverlapping polymer distributions and a novel development simulation approach. The presented concept allows simultaneously the simulation of macroscopic profile dimensions as well as of microscopic roughness properties of the resist. Required microscopic dissolution times of the polymers are derived from the corresponding simulated local macroscopic development rates. By retaining all other resist parameters unchanged in the simulation, the isolated influence of varying the assumed polymer size, branching geometry, and dissolution time variations on LER is examined with this new method. Small, strongly tangled polymers lead to considerably lower LER values than bigger or less bended polymers. Compared to the investigated polymer size and geometry, the examined range of variances in the dissolution times has only a weak influence on LER.
Inhibition of
Plasmodium falciparum
Oocyst Production by Membrane-Permeant Cysteine Protease Inhibitor E64d
Authors: Eksi S. , Czesny B. , van Gemert G.-J. , Sauerwein R. W. , Eling W. , Williamson K. C.
Published: December 2006

During asexual intraerythrocytic growth,
Plasmodium falciparum
utilizes hemoglobin obtained from the host red blood cell (RBC) as a nutrient source. Papain-like cysteine proteases, falcipains 2 and 3, have been reported to be involved in hemoglobin digestion and are targets of current antimalarial drug development efforts. However, their expression during gametocytogenesis, which is required for malaria parasite transmission, has not been studied. Many of the available antimalarials do not inhibit development of sexual stage parasites, and therefore, the persistence of gametocytes after drug treatment allows continued transmission of the disease. In the work reported here, incubation of stage V gametocytes with membrane-permeant cysteine protease inhibitor E64d significantly inhibited oocyst production (80 to 100%). The same conditions inhibited processing of gametocyte-surface antigen Pfs230 during gametogenesis but did not alter the morphology of the food vacuole in gametocytes, inhibit emergence, or block male exflagellation. E64d reduced the level of oocyst production more effectively than that reported previously for falcipain 1-knockout parasites, suggesting that falcipains 2 and 3 may also be involved in malaria parasite transmission. However, in this study only falcipain 3 and not falcipain 2 was found to be expressed in stage V gametocytes. Interestingly, during gametocytogenesis falcipain 3 was transported into the red blood cell and by stage V was localized in vesicles along the RBC surface, consistent with a role during gamete emergence. The ability of a membrane-permeant cysteine protease inhibitor to significantly reduce malaria parasite transmission suggests that future drug design should include evaluation of gametogenesis and sporogonic development.
Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence ofAspergillus fumigatus
Authors: Simitsopoulou M. , Roilides E. , Likartsis C. , Ioannidis J. , Orfanou A. , Paliogianni F. , Walsh T. J.
Published: December 2006

We assessed the effect of voriconazole (VRC) on the expression and release of selected cytokines and chemokines in the THP-1 human monocytic cell line in response toAspergillus fumigatushyphal fragments (HF) by cDNA microarray analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay. Stimulation of THP-1 cells by HF alone caused a significant up-regulation ofCCL4(MIP1B) andCCL16, whileCCL2(MCP1) was down-regulated. By comparison, in the presence of VRC, a large number of genes such asCCL3(MIP1A),CCL4(MIP1B),CCL5(RANTES),CCL7(MCP3),CCL11(EOTAXIN),CCL15(MIP1Δ),CXCL6, andCXCL13were strongly up-regulated in THP-1 cells challenged by HF, whereasCCL20(MIP3A) andCCL21(MIP2) were down-regulated. Among five genes differentially expressed in THP-1 cells,IL12A,IL12B, andIL-16were down-regulated whereasIL-11andTGFB1were significantly up-regulated in the presence of VRC. The inflammation-related genesIFNγ,IL1R1, andTNFAwere also up-regulated in THP-1 cells exposed to HF only in the presence of VRC. RT-PCR of four selected genes validated the results of microarrays. The release of interleukin 1β (IL-1β) and IL-12 was significantly increased from monocytes stimulated either by HF alone (P< 0.05) or in the presence of VRC (P< 0.01 andP< 0.05, respectively). In contrast, tumor necrosis factor alpha release from monocytes was enhanced only in the presence of VRC (P< 0.01). The chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β were decreased under both conditions (P< 0.01). These results demonstrate that in the presence of VRC, HF induces a more pronounced profile of gene expression in THP-1 cells than HF alone, potentially leading to more-efficient host resistance toA. fumigatus.
Assessment of the Effect of Mefloquine on Artesunate Pharmacokinetics in Healthy Male Volunteers
Authors: Davis Timothy M. E. , England Michelle , Dunlop Anne-Marie , Page-Sharp Madhu , Cambon Nathalie , Keller Thomas G. , Heidecker János L. , Ilett Kenneth F.
Published: December 2006

The effect of mefloquine on artesunate pharmacokinetics was assessed in 20 volunteers given artesunate for 3 days, followed ≥21 days later by combination therapy for 3 days. The areas under the concentration-time curve from 0 h to infinity for dihydroartemisinin, the active metabolite of artesunate, were similar on day 3 of the two dosing periods (
P
= 0.12), implying no interaction.
Role of RpoS in Fine-Tuning the Synthesis of Vi Capsular Polysaccharide inSalmonella entericaSerotype Typhi
Authors: Santander Javier , Wanda Soo-Young , Nickerson Cheryl A. , Curtiss Roy
Published: December 2006

Regulation of the synthesis of Vi polysaccharide, a major virulence determinant inSalmonella entericaserotype Typhi, is under the control of two regulatory systems,ompR-envZandrscB-rscC, which respond to changes in osmolarity. Some serotype Typhi strains exhibit overexpression of Vi polysaccharide, which masks clinical detection of lipopolysaccharide O antigen. This variation in Vi polysaccharide and O antigen display (VW variation) has been observed since the initial studies of serotype Typhi. In this study, we report thatrpoSplays a role in this increased expression in Vi polysaccharide. We constructed a variety of isogenic serotype Typhi mutants that differed in their expression levels of RpoS and examined the role of therpoSproduct in synthesis of Vi polysaccharide under different osmolarity conditions. Vi polysaccharide synthesis was also examined in serotype Typhi mutants in which the native promoter of therpoSwas replaced by anaraCPBADcassette, so that the expression ofrpoSwas arabinose dependent. The RpoS−strains showed increased syntheses of Vi polysaccharide, which at low and medium osmolarities masked O antigen detection. In contrast, RpoS+strains showed lower syntheses of Vi polysaccharide, and an increased detection of O antigen was observed. During exponential growth, whenrpoSis unstable or present at low levels, serotype Typhi RpoS+strains overexpress the Vi polysaccharide at levels comparable to those for RpoS−strains. Our results show that RpoS is another regulator of Vi polysaccharide synthesis and contributes to VW variation in serotype Typhi, which has implications for the development of recombinant attenuatedSalmonellavaccines in humans.
Aspergillus fumigatusDoes Not Require Fatty Acid Metabolism via Isocitrate Lyase for Development of Invasive Aspergillosis
Authors: Schöbel Felicitas , Ibrahim-Granet Oumaïma , Avé Patrick , Latgé Jean-Paul , Brakhage Axel A. , Brock Matthias
Published: December 2006

Aspergillus fumigatusis the most prevalent airborne filamentous fungus causing invasive aspergillosis in immunocompromised individuals. Only a limited number of determinants directly associated with virulence are known, and the metabolic requirements of the fungus to grow inside a host have not yet been investigated. Previous studies on pathogenic microorganisms, i.e., the bacteriumMycobacterium tuberculosisand the yeastCandida albicans, have revealed an essential role for isocitrate lyase in pathogenicity. In this study, we generated an isocitrate lyase deletion strain to test whether this strain shows attenuation in virulence. Results have revealed that isocitrate lyase fromA. fumigatusis not required for the development of invasive aspergillosis. In a murine model of invasive aspergillosis, the wild-type strain, an isocitrate lyase deletion strain, and a complemented mutant strain were similarly effective in killing mice. Moreover, thin sections demonstrated invasive growth of all strains. Additionally, thin sections of lung tissue from patients with invasive aspergillosis stained with anti-isocitrate lyase antibodies remained negative. From these results, we cannot exclude the use of lipids or fatty acids as a carbon source forA. fumigatusduring invasive growth. Nevertheless, test results do imply that the glyoxylate cycle fromA. fumigatusis not required for the anaplerotic synthesis of oxaloacetate under infectious conditions. Therefore, an antifungal drug inhibiting fungal isocitrate lyases, postulated to act againstCandidainfections, is assumed to be ineffective againstA. fumigatus.
Induction of Host Chemotactic Response byEncephalitozoonspp
Authors: Fischer Jeffrey , West Jeffrey , Agochukwu Nnenaya , Suire Colby , Hale-Donze Hollie
Published: December 2006

Microsporidians are a group of emerging pathogens typically associated with chronic diarrhea in immunocompromised individuals. The number of reports of infections with these organisms and the disseminated pathology is growing as diagnostic tools become more readily available. However, little is known about the innate immune response induced by and generated against these parasites. Using a coculture chemotaxis system, primary human macrophages were infected withEncephalitozoon cuniculiorEncephalitozoon intestinalis, and the recruitment of naïve monocytes was monitored.Encephalitozoonspp. induced an average threefold increase in migration of naïve cells 48 h postinfection, which corresponded to optimal infection of monocyte-derived-macrophages. A limited microarray analysis of infected macrophages revealed several chemokines involved in the inflammatory responses whose expression was upregulated, including CCL1, CCL2, CCL3, CCL4, CCL7, CCL15, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8. The levels of 6 of 11 chemokines also present in the microarray were confirmed to be elevated by protein profiling. Kinetic studies confirmed that secreted CCL2, CCL3, and CCL4 were expressed as early as 6 h postinfection, with peak expression at 12 to 24 h and expression remaining until 48 h postinfection. Neutralization of these chemokines, specifically CCL4, significantly reduced the number of migrating cells in vitro, indicating their role in the induction of monocyte migration. This mechanism of recruitment not only supports the evidence that in vivo cellular infiltration occurs but also provides new hosts for the parasites, which escape macrophages by rupturing the host cell. To our knowledge, this is the first documentation that chemokine production is induced by microsporidian infections in human macrophages.
Selection for Simple Major Surface Protein 2 Variants during
Anaplasma marginale
Transmission to Immunologically Naïve Animals
Authors: Palmer Guy H. , Futse James E. , Leverich Christina K. , Knowles Donald P. , Rurangirwa Fred R. , Brayton Kelly A.
Published: December 2006

Anaplasma marginale
, a rickettsial pathogen, evades clearance in the animal host by antigenic variation. Under immune selection,
A. marginale
expresses complex major surface protein 2 mosaics, derived from multiple donor sequences. However, these mosaics have a selective advantage only in the presence of adaptive immunity and are rapidly replaced by simple variants following transmission.
Trends in physical activity and sedentary behaviour in adolescence: ethnic and socioeconomic differences
Authors: Brodersen Naomi Henning , Steptoe Andrew , Boniface David R , Wardle Jane
Published: December 2006

Objective:To assess developmental trends in physical activity and sedentary behaviour in British adolescents in relation to sex, ethnicity and socioeconomic status (SES).

Design:A 5-year longitudinal study of a diverse cohort of students aged 11–12 years at baseline in 1999.

Setting:36 London schools sampled using a stratified random sampling procedure.

Participants:A total of 5863 students categorised as white, black or Asian, and stratified for SES using the Townsend Index.

Main outcome measures:Number of days per week of vigorous activity leading to sweating and breathing hard. Hours of sedentary behaviour, including watching television and playing video games. Data were analysed using multilevel, linear, mixed models.

Results:Marked reductions in physical activity and increases in sedentary behaviour were noticed between ages 11–12 and 15–16 years. Boys were more active than girls, and the decline in physical activity was greater in girls (46% reduction) than in boys (23%). Asian students were less active than whites, and this was also true of black girls but not boys. Black students were more sedentary than white students. Levels of sedentary behaviour were greater in respondents from lower SES. Most differences between ethnic and SES groups were present at age 11 years, and did not evolve over the teenage years.

Conclusions:Physical activity declines and sedentary behaviour becomes more common during adolescence. Ethnic and SES differences are observed in physical activity and sedentary behaviour in British youth that anticipate adult variations in adiposity and cardiovascular disease risk. These are largely established by age 11–12 years, so reversing these patterns requires earlier intervention.
FAY-LIKE IDENTITIES OF THE TODA LATTICE HIERARCHY AND ITS DISPERSIONLESS LIMIT
Authors: TEO LEE-PENG
Published: December 2006

In this paper, we derive the Fay-like identities of tau function for the Toda lattice hierarchy from the bilinear identity. We prove that the Fay-like identities are equivalent to the hierarchy. We also show that the dispersionless limit of the Fay-like identities are the dispersionless Hirota equations of the dispersionless Toda hierarchy.
THE VALUE OF NETWORKS IN ENTERPRISE DEVELOPMENT: CASE STUDIES IN EASTERN EUROPE AND SOUTHEAST ASIA
Authors: MORRIS SHAD S. , WOODWORTH WARNER P. , HIATT SHON R.
Published: December 2006

This study proposes that cooperative efforts in microlending aid economic development and poverty alleviation in transitioning and developing countries by creating networking systems in which people can expand their businesses through working capital and community cooperation. Two field studies are used to validate the authors' claims. The first examines a microfinance cooperative structure in Bulgaria as a means to secure credit, savings, technical support and networking opportunities for cooperative members. The second looks at a cooperative microfinance institution in the Philippines that appears to create greater socio-economic growth for poor entrepreneurs as well as NGO financial viability. Both studies suggest that cooperative microlending leads to high survival rates and success of self-employed entrepreneurs by facilitating social capital through their organizational processes.
MOTIVATIONS OF MOROCCANS TO BE ENTREPRENEURS
Authors: GRAY KENNETH R. , FOSTER HOWARD , HOWARD MARLA
Published: December 2006

Throughout the world, entrepreneurship is viewed as a savior of stagnant economies (Tiffin, 1987; Gupta, 1989; Meredith, 1989; Giamartino, 1991; Guthrie, 2004). This study investigates the motivation of Moroccans to become entrepreneurs. It provides an overview of entrepreneurial theory, describing common characteristics and motivations of entrepreneurs worldwide. This is followed by an analysis of the Moroccan business environment. A model of Moroccan entrepreneurship is then developed. The data used to determine the relevant model factors were gathered from a survey conducted among 201 Moroccan entrepreneurs.
Left Atrial Size and Risk of Major Cardiovascular Events During Antihypertensive Treatment
Authors: Gerdts Eva , Wachtell Kristian , Omvik Per , Otterstad Jan Erik , Oikarinen Lasse , Boman Kurt , Dahlöf Björn , Devereux Richard B.
Published: December 2006

The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m];
P
=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=−0.13±0.03 cm/m;
P
<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients.
Low-Dose Quadruple Antihypertensive Combination
Authors: Mahmud Azra , Feely John
Published: December 2006

Increasingly combined antihypertensive agents are being used in practice to enhance control and improve compliance. To determine whether a capsule containing a quarter of the standard dose of 4 antihypertensive agents has greater efficacy than the standard dose of each individually, we prospectively randomized 108 untreated white hypertensive patients (55% male) aged 50±1 years (mean±SEM), with mean blood pressure 160±1/96±1 mm Hg. Patients received amlodipine (5 mg; n=22), atenolol (50 mg; n=20), bendroflumethiazide (2.5 mg; n=22), captopril (50 mg twice daily; n=22) or a capsule containing each of the 4 above at one-quarter dosage (n=22) in a parallel group design for 4 weeks. Blood pressure was measured using a semiautomated device (Omron 705), and the reduction in mean arterial pressure with the combined preparation was compared with that of the individual components. Statistical analysis used ANOVA and Tukey-Kramer honestly significant difference for multiple comparisons. The reduction in mean arterial pressure with the combination (19±2 mm Hg) was significantly greater than that with individual agents amlodipine (10±2 mm Hg;
P
<0.005), atenolol (10±2 mm Hg;
P
<0.005), bendroflumethiazide (6±1 mm Hg;
P
<0.005), and captopril (11±1 mm Hg;
P
<0.01). In addition, the percentage reduction in systolic (18±1 mm Hg;
P
<0.005) and diastolic (17±2 mm Hg;
P
=0.06) blood pressure was greater with the combination. More patients achieved a blood pressure of <140/90 mm Hg with the combination (60%) than any individual drug (15% to 45%;
P
<0.05). A low-dose combination of 4 agents representing 4 classes of standard antihypertensive agents was more efficacious than a standard single dose of each agent individually.
Promotion of Faster Weight Gain in Infants Born Small for Gestational Age
Authors: Singhal Atul , Cole Tim J. , Fewtrell Mary , Kennedy Kathy , Stephenson Terence , Elias-Jones Alun , Lucas Alan
Published: December 2006

Background—

Being born small for gestational age is associated with later risk factors for cardiovascular disease, such as high blood pressure. Promotion of postnatal growth has been proposed to ameliorate these effects. There is evidence in animals and infants born prematurely, however, that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk. We report the long-term impact of growth promotion in term infants born small for gestational age (birth weight <10th percentile).

Methods and Results—

Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a cohort of children born small for gestational age and randomly assigned at birth to receive either a standard or a nutrient-enriched formula. The enriched formula contained 28% more protein than standard formula and promoted weight gain. Diastolic and mean (but not systolic) blood pressure was significantly lower in children assigned to standard compared with nutrient-enriched formula (unadjusted mean difference for diastolic blood pressure, −3.2 mm Hg; 95% CI, −5.8 to −0.5;
P
=0.02) independent of potential confounding factors (adjusted difference, −3.5 mm Hg;
P
=0.01). In observational analyses, faster weight gain in infancy was associated with higher later blood pressure.

Conclusions—

In the present randomized study targeted to investigate the effect of early nutrition on long-term cardiovascular health, we found that a nutrient-enriched diet increased later blood pressure. These findings support an adverse effect of relative “overnutrition” in infancy on long-term cardiovascular disease risk, have implications for the early origins of cardiovascular disease hypothesis, and do not support the promotion of faster weight gain in infants born small for gestational age.