bluuebunny/crossref_metadata_2025 huggingface dataset:
Large crystal grain niobium thin films deposited by energetic condensation in vacuum arc
Authors: Zhao Xin , Valente-Feliciano A.-M. , Xu C. , Geng R. L. , Phillips L. , Reece C. E. , Seo K. , Crooks R. , Krishnan M. , Gerhan A. , Bures B. , Elliott K. Wilson , Wright J.
Published: June 2009

This article presents evidence for unprecedented, large crystal grain size in ∼1μm thick Nb films that were grown on sapphire and copper substrates using a vacuum arc process called coaxial energetic deposition CED™. Most other deposition techniques with low adatom energy produce amorphous or small crystal-grain films. Typically, high substrate temperatures and annealing steps are required to form the large, highly connected grains. The CED™ technique deposits from plasma consisting of a nonequilibrium, high energy (50–150eV) ion population produced from the ionized source material. At the substrate these fast ions break up columnar structures, intermix with the first few atomic layers of the substrate to improve adhesion, and form dense films at lower substrate temperatures than are typical for low adatom energy techniques, such as physical vapor deposition (PVD). Nanoscale features of the thin films were examined using electron backscatter diffraction (EBSD). The films’ cryogenic state electrical properties were characterized by their residual resistivity ratio (RRR) and superconducting transition temperature (Tc). RRR of ∼77 and Tc∼9.2K were measured on a Nb thin film deposited on a sapphire substrate. EBSD and x-ray diffraction measurements indicated that the sapphire substrate thin films have single crystal structure, with a Nb {110} crystal plane monolithically aligned and parallel to the sample surface. Nb thin films on an ∼400°C Cu substrate had average crystal grain size of 50μm, which is an order of magnitude larger than that which is typical of films grown by PVD. The crystal structure of CED™ thin films is comparable to that of polycrystalline bulk Nb material, which is the state of the art for superconducting radio frequency (SRF) particle accelerators such as at the Thomas Jefferson National Accelerator Facility (JLab). The films’ novel crystal features suggest that CED™ is a promising technique to coat Nb thin films for lower cost SRF particle accelerators. Further studies of the nanoscale grain boundary features would shed light on the role played by these features in determining the performance of SRF cavities using such thin films on Cu.
Relationship between gas-phase chemistries and surface processes in fluorocarbon etch plasmas: A process rate model
Authors: Sant S. P. , Nelson C. T. , Overzet L. J. , Goeckner M. J.
Published: June 2009

In a typical plasma tool, both etch and deposition occur simultaneously. Extensive experimental measurements are used to help develop a general model of etch and deposition processes. This model employs reaction probabilities, or surface averaged cross sections, to link the measurable surface processes, etch and deposition, to the flux of various species to the surfaces. Because the cross sections are quantum mechanical in nature, this surface rate model should be applicable to many low temperature plasma processing systems. Further, the parameters that might be important in reaction cross sections are known from quantum mechanics, e.g., species, energy, temperature, and impact angle. Such parameters might vary from system to system, causing the wide processing variability observed in plasma tools. Finally the model is used to compare measurements of ion flux, ion energy, and fluorocarbon radical flux to the measured process rates. It is found that the model appears to be consistent with calculations of gain/loss rates for the various radicals present in the discharge as well as measured etch and deposition rates.
Particle-induced x-ray emission in stainless steel using 30keV Ga+ focused ion beams
Authors: Giannuzzi Lucille A. , Gorman Brian P.
Published: June 2009

Characteristic x-ray emission from a well grounded stainless steel specimen using standard 30keV Ga+ focused ion beam instrumentation is demonstrated. X-ray yields are found to be on the order of 10−10 per incident ion, consistent with previous studies of low energy, high mass ion-solid interactions. X-ray yields were found to be highest for low energy transitions or low atomic number target atoms. Bremsstrahlung x-ray emission was found to be minimal, possibly increasing detectability compared with electron beam induced x-rays. Yields were also estimated to be on the order of 10−11 per sputtered atom, or approximately one x-ray per sputtered monolayer. While velocity coupling between the primary ion beam and target atom electrons is not possible under these experimental conditions, it is argued that x-ray emission is, in fact, due to recoil effects of the ion-solid interaction.
Effect of cesium assistance on the electrical and structural properties of indium tin oxide films grown by magnetron sputtering
Authors: Song Jaewon , Hwang Cheol Seong , Park Sung Jin , Yoon Neung Ku
Published: June 2009

Indium tin oxide (ITO) thin films were deposited by cesium (Cs)-assisted dc magnetron sputtering in an attempt to achieve a high performance at low temperatures. The films were deposited on SiO2∕Si wafer and glass (Eagle 2000) substrates at a substrate temperature of 100°C with a Cs vapor flow during the deposition process. The ITO thin films deposited in the presence of Cs vapor showed better crystallinity than the control films grown under normal Ar∕O2 plasma conditions. The resistivity of the films with the Cs assistance was lower than that of the control films. The lowest resistivity of 6.2×10−4Ωcm, which is ∼20% lower than that of the control sample, was obtained without any postdeposition thermal annealing. The surface roughness increased slightly when Cs vapor was added. The optical transmittance was >80% at wavelengths ranging from 380to700nm.
Structure and mechanical properties of nanoscale multilayered CrN/ZrSiN coatings
Authors: Zhang Z. G. , Rapaud O. , Allain N. , Baraket M. , Dong C. , Coddet C.
Published: June 2009

Nanocrystalline/amorphous CrN/ZrSiN multilayer coatings with a bilayer thickness ranging from 11 to 153 nm were prepared by reactive magnetron sputtering technique. The microstructure and mechanical properties of these thin films were characterized by x-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and nanoindentation. The formation of nanocrystalline CrN and nanocomposite ZiSiN in the single layer coatings was identified by XRD and FTIR. The periodic structure of the as-deposited multilayer coatings was confirmed by TEM observation. Nanoindentation tests showed that both the values of hardness (H) and reduced elastic modulus (Er) of CrN/ZrSiN multilayers remained almost constant despite varying the bilayer thickness. The multilayer coatings exhibited higher H of 30 GPa and higher resistance to plastic deformation when compared to the single layer CrN and ZrSiN coatings.
Studies on hard TaN thin film deposition by R C-Mag technique
Authors: Valleti Krishna
Published: June 2009

The physical and mechanical properties of pulsed rotating cylindrical magnetron sputter-grown tantalum nitride (TaN) thin films were studied. Initially, films were grown at ambient substrate temperature by varying the reactive (N2) to sputter (Ar) gas ratio (R) at a constant pulsing frequency of the target power (100kHz). The results were compared with planar magnetron-grown TaN samples. The R C-Mag. grown thin films have properties nearly similar to the high temperature (300°C) dc planar magnetron sputter deposited samples. In comparison to the planar magnetron deposition, the progression of the phase composition occurs over a wider range of R in the pulsed R C-Mag. deposition. These observed differences for R C-Mag. deposition are attributed to the increased glancing angle deposition of adatoms and pulsing of the target power. To study the effect of pulsing frequency of the target power in R C-Mag., the films were also grown at different frequencies at a fixed R (0.1). With the increase in frequency, the mechanical hardness increased up to 50kHz and started decreasing beyond 50kHz. The observed changes in the mechanical hardness are attributed to the increase in stress and to the formation of increased polycrystalline understoichiometric TaN phases.
Fabrication of ordered anodic aluminum oxide with matrix arrays of pores using nanoimprint
Authors: Kwon Namyong , Kim KyoHyeok , Heo Jinhee , Chung IlSub
Published: June 2009

Anodic aluminum oxide (AAO) with matrix arrays of pores was obtained using nanoimprint and anodizing. Si3N4 imprint stamps were fabricated using electron-beam lithography. The Si3N4 stamps were imprinted into Al films grown on Si wafers by applying a force of 250 kg for 10 s. Two different diameters (45 and 80 nm) and two different periodic distances (100 and 200 nm) of the square patterns in Si3N4 imprint stamp were transferred into an Al film as a form of shallow pores. The Al films were then anodized in 0.3M oxalic acid under conditions of 4 °C at 40 V. The authors found a linear relationship between the interpore distance and anodizing voltage (2.5 nm V−1) to obtain a square array in AAO. In addition, the matrix pores in AAO tend to form a natural hexagonal pattern as the anodizing time increases. The surface images are obtained using field-emission secondary-electron microscope and scanning probe microscopy.
Study of sol-gel derived porous ZnO photoelectrode for the application of dye-sensitized solar cells
Authors: Hossain M. F. , Biswas S. , Shahjahan M. , Takahashi T.
Published: June 2009

In this study, the porous zinc oxide (ZnO) films were deposited on SnO2:F coated glass substrate by sol-gel technique with zinc acetate as precursor, ethanol as solvent, and diethanolamine as chelating agent. Two sets of ZnO films with equal number of coatings and the same film thicknesses were deposited with various zinc acetate concentrations. The surface morphology of the porous ZnO film strongly depends on the zinc acetate concentration. It was also revealed from the optical study that the dye absorption increases with an increase in the zinc acetate concentration. The ZnO film with 1.0mol∕l zinc acetate concentration has shown the best porous structure and maximum rms roughness value (187nm). The maximum photoelectric conversion efficiencies, 0.64% and 0.8%, were achieved for ZnO films with 1.0mol∕l of zinc acetate concentration in both sets of samples: equal number of coatings and the same film thicknesses, respectively.
Thermal stability of sputter deposited nanomosaic rutile TiO2
Authors: Aita Carolyn Rubin
Published: June 2009

A domain structure based on the rutile lattice with a large density of 12⟨011⟩{011}-type stacking faults is found in sputter deposited TiO2 films [J. Vac. Sci. Technol. A 24, 2054 (2006)]. The thermal stability of nanomosaic rutile at moderate temperature is reported here. Films are annealed at 973K for 0.25–15h, characterized by x-ray diffraction. A Johnson–Mehl–Avrami–Kolmogorov analysis indicates impeded crystallite growth. A dislocation-locking mechanism is proposed for this behavior. Partial dislocations with 12⟨011⟩ Burgers vectors that bound the stacking faults glide on intersecting {011} slip planes and react to produce sessile stair rod dislocations. Without the high temperature required for dislocation climb, 12⟨011⟩{011}-type faults inherent to nanomosaic rutile provide thermal stability against massive crystallite growth.
Rotation magnet sputtering: Damage-free novel magnetron sputtering using rotating helical magnet with very high target utilization
Authors: Goto Tetsuya , Matsuoka Takaaki , Ohmi Tadahiro
Published: June 2009

Novel magnetron-sputtering equipment, called rotation magnet sputtering (ROT-MS), was developed to overcome various disadvantages of current magnetron-sputtering equipment. Disadvantages include (1) very low target utilization of less than 20%, (2) difficulty in obtaining uniform deposition on the substrate, and (3) charge-up damages and ion-bombardment-induced damages resulting from very high electron temperature (>3eV) and that the substrate is set at the plasma excitation region. In ROT-MS, a number of moving high-density plasma loops are excited on the target surface by rotating helical magnets, resulting in very high target utilization with uniform target erosion and uniform deposition on the substrate. This excellent performance can be principally maintained even if equipment size increases for very large-substrate deposition. Because strong horizontal magnetic fields (>0.05T) are produced within a very limited region just at the target surface, very low electron-temperature plasmas (<2.5eV for Ar plasma and <1eV for direct-current-excited Xe plasma) are excited at the very limited region adjacent to the target surface with a combination of grounded plate closely mounted on the strong magnetic field region. Consequently, the authors can establish charge-up damage-free and ion-bombardment-induced damage-free processes. ROT-MS has been applied for thin-film formation of LaB6, which is well known as a stable, low-work-function bulk-crystal material for electron emissions. The work function of the LaB6 film decreased to 2.8eV due to enhanced (100)-orientation crystallinity and reduced resistivity realized by adjusting the flux of low-energy bombarding ions impinging on the depositing surface, which work very efficiently, improving the performance of the electron emission devices.
Nitrogen stabilized reactive sputtering of optimized TiO2−x photocatalysts with visible light reactivity
Authors: Chen Le , Graham Michael E. , Gray Kimberly A.
Published: June 2009

Photoreactive and visible light responsive nonstoichiometric mixed-phase titania was prepared by reactive direct current magnetron sputtering. Trace amounts of nitrogen were added for process stabilization without being incorporated into the films. Based on the CO2 photoreduction tests and structural and optical characterization, the influence of the trace nitrogen on the sputtered nonstoichiometric TiO2 was studied and was compared to nitrogen-doped titania.
Characterization of ALD copper thin films on palladium seed layers
Authors: Hsu Irene J. , McCandless Brian E. , Weiland Conan , Willis Brian G.
Published: June 2009

A method for fabricating monolithic nanoscopic tunnel junctions (MNTJs) for tunneling spectroscopy measurements using atomic layer deposition (ALD) of Cu on Pd seed layers has recently been introduced [Gupta and Willis, Appl. Phys. Lett. 90, 253102 (2007)]. The ALD grown layers are characterized here using planar thin films as models for the nanoelectrode composition and structure. ALD Cu films grown on Pd seed layers using a varying number of deposition cycles were characterized using transmission electron microscopy, Auger electron spectroscopy (AES), and glancing incidence x-ray diffraction (GIXRD) to investigate the chemical composition and structure of the nanoelectrodes. Electron diffraction and GIXRD show that as Cu is deposited, the bulk composition progresses from being Pd rich to becoming predominately Cu. In contrast, AES data show that significant Pd consistently remains on the surface of the growing film. The divergence in surface and bulk behaviors is attributed to Pd surface segregation that is driven by hydrogen adsorption during the ALD process. In contrast to the results for Pd seed layers, it is demonstrated that Pt seed layers can be used to grow pure Cu ALD films. This is because hydrogen adsorption does not induce Pt surface segregation within the ALD temperature window.
Establishment of very uniform gas-flow pattern in the process chamber for microwave-excited high-density plasma by ceramic shower plate
Authors: Goto Tetsuya , Inokuchi Atsutoshi , Ishibashi Kiyotaka , Yasuda Seij , Nakanishi Toshio , Kohno Masayuki , Okesaku Masahiro , Sasaki Masaru , Nozawa Toshihisa , Hirayama Masaki , Ohmi Tadahiro
Published: June 2009

The authors developed a ceramic upper shower plate used in the microwave-excited high-density plasma process equipment incorporating a dual shower-plate structure to establish a very uniform gas-flow pattern in the process chamber. Thousands of very fine gas-injection holes are implemented on this Al2O3 upper shower plate with optimized allocation to establish a uniform gas-flow pattern of plasma-excitation gases and radical-generation gases for generating intended radicals in the plasma-excitation region. The size of these fine holes must be 50μm or less in diameter and 8mm or more in length because these holes perform an essential role: They completely avoid the plasma excitation in these fine holes and upper gas-supply regions resulting from the plasma penetration into these regions from excited high-density plasma, even if very high-density plasma greater than 1×1012cm−3 is excited just under the ceramic upper shower plate by microwaves supplied from the radial line slot antenna. On the other hand, various process gases, such as material gases for film formations and etching gases, are supplied from the lower shower plate installed in the diffusion plasma region to this very uniform gas-flow pattern region of plasma-excitation gases and radical-generation gases. As a result, the process gases are supplied to the wafer surface in a very effective manner without excess decomposition of those process gas molecules and undesired reaction-product deposition on the inner surface of the process chamber. The process results are improved drastically by introducing the newly developed ceramic upper shower plate. But also, process uniformity on the entire wafer is improved with drastically reducing reaction-product deposition on the inner surface of the process chamber.
Nucleation and growth of tantalum nitride atomic layer deposition on Al2O3 using TBTDET and hydrogen radicals
Authors: Rayner G. B. , George S. M.
Published: June 2009

The nucleation and growth of tantalum nitride atomic layer deposition (ALD) was investigated on Al2O3 ALD surfaces on silicon substrates using tertbutylimino trisdiethylamino tantalum (TBTDET) and hydrogen radicals as the reactants. The hydrogen radicals were generated using a hot tungsten filament. Auger electron spectroscopy (AES) was utilized to monitor the atomic composition of the surface versus the TBTDET/hydrogen radical reaction cycles. These studies were conducted in a vacuum apparatus with a sample introduction port, two ALD reactors, and a connecting surface analysis chamber. Initial results with the silicon substrates at 250°C revealed tantalum nitride ALD growth and the oscillation of the N AES signal during the TBTDET/hydrogen radical reaction cycles. However, TBTDET pyrolysis was a problem on the BN heater. The TBTDET pyrolysis threshold of ∼250°C on the BN heater limited the maximum substrate temperature to 170°C. The AES results revealed that the composition of the tantalum nitride ALD films grown at 170°C was TaNx where x∼1. In addition, there were carbon and oxygen impurities in the TaNx film. Aluminum and tantalum AES signals were employed to determine the tantalum nitride ALD thickness on the underlying Al2O3 ALD surface during TBTDET/hydrogen radical reaction cycles at 170°C. The Cumpson method of using the ratio of the Al and Ta AES signals to determine the TaNx ALD film thickness avoided the problem of normalization between different AES spectra. The TaNx ALD nucleated readily on the Al2O3 ALD surface. The Al AES signal approached zero after 20 reaction cycles. The corresponding tantalum nitride film thickness was determined to be 11.6Å after 20 reaction cycles. The film thickness at 5, 10, 15, and 20 reaction cycles yielded an initial ALD growth rate of 0.5Å∕cycle. The ALD growth rate increased to 0.7Å∕cycle for >10 reaction cycles. The efficient initial nucleation and reasonable growth rates for tantalum nitride ALD are desirable for the formation of copper diffusion barriers on interconnection vias.
Silicon-oxide-high-κ-oxide-silicon memory using a high-κ Y2O3 nanocrystal film for flash memory application
Authors: Pan Tung-Ming , Yeh Wen-Wei
Published: June 2009

In this article, the authors developed a silicon-oxide-high-κ-oxide-silicon (SOHOS) memory structure using a high-κ Y2O3 nanocrystal film as the charge-trapping layer for flash memory applications. From x-ray photoelectron spectroscopic and atomic-force microscopy analyses, they found that the Y2O3 nanocrystal layer formed after O2 and N2O annealing. When using the channel hot-electron injection for charging and the band-to-band hot hole for discharging, the high-κ Y2O3 SOHOS memory devices prepared under the N2O gas annealing exhibited large threshold-voltage shifting (memory window of ∼3V), superior endurance characteristics (program/erase cycles of up to 105), and excellent data retention (charge loss of ∼7.5% measured time up to 104s and at room temperature). These results indicate the higher probability of charge-carrier trapping in the Y2O3 film.
Low-temperature growth of InN on Si(100) by femtosecond pulsed laser deposition
Authors: Hafez M. A. , Elsayed-Ali H. E.
Published: June 2009

InN films were grown on Si(100) using femtosecond pulsed laser deposition. Laser induced breakdown of ammonia was used to generate atomic nitrogen for InN growth. An indium buffer layer was initially deposited on the Si substrate at low temperature followed by an InN intermediate layer. The crystal quality and surface morphology were investigated by reflection high-energy electron diffraction during growth and atomic force microscopy and x-ray diffraction after growth. The results showed that the In(2×1) initial buffer layer improved the quality of the InN film. High quality InN films were grown at a temperature of ∼350°C.
Effects of interelectrode gap on high frequency and very high frequency capacitively coupled plasmas
Authors: Bera Kallol , Rauf Shahid , Ramaswamy Kartik , Collins Ken
Published: June 2009

Capacitively coupled plasma (CCP) discharges using high frequency (HF) and very high frequency (VHF) sources are widely used for dielectric etching in the semiconductor industry. A two-dimensional fluid plasma model is used to investigate the effects of interelectrode gap on plasma spatial characteristics of both HF and VHF CCPs. The plasma model includes the full set of Maxwell’s equations in their potential formulation. The peak in plasma density is close to the electrode edge at 13.5MHz for a small interelectrode gap. This is due to electric field enhancement at the electrode edge. As the gap is increased, the plasma produced at the electrode edge diffuses to the chamber center and the plasma becomes more uniform. At 180MHz, where electromagnetic standing wave effects are strong, the plasma density peaks at the chamber center at large interelectrode gap. As the interelectrode gap is decreased, the electron density increases near the electrode edge due to inductive heating and electrostatic electron heating, which makes the plasma more uniform in the interelectrode region.
Ultrasonic nanoimprint on engineering plastics
Authors: Mekaru Harutaka , Takahashi Masaharu
Published: June 2009

The authors developed a new ultrasonic nanoimprint technology that is superior to the current thermal and UV nanoimprint technologies. In the new technology an ultrasonic vibration is impressed along the direction of the loading force during a molding operation at room temperature. The mold in this case is mounted onto an ultrasonic generator with a UV photoresist, where the mold patterns are pushed and pulled on a thermoplastic material at a high speed by employing ultrasonic vibration. The system employs a magnetostriction actuator that generates ultrasonic vibration with frequencies and amplitudes ranging from dc to 20kHz and from 0to±3μm, respectively. Several optimized imprinting conditions had been investigated by using polyethylene terephthalate (Tg=69°C) with a comparatively low glass transition temperature in engineering plastics. These optimized imprinting conditions were found to be frequency of the ultrasonic vibration=10kHz, amplitude=3μm, contact force=500N, contact time=60s, and buffer material=polyurethane rubber. Then under those optimized molding conditions, other engineering plastics were successfully imprinted. The depth of the imprinted pattern was found to decrease as the glass transition temperature of the plastic rose. The assisting effect of the ultrasonic vibration was found to be inversely proportional to the glass transition temperature.
Introduction to MOLFLOW+: New graphical processing unit-based Monte Carlo code for simulating molecular flows and for calculating angular coefficients in the compute unified device architecture environment
Authors: Kersevan R. , Pons J.-L.
Published: June 2009

The authors present here the description of the main features of MOLFLOW+, a new software package that allows the calculation of several physical quantities of interest to vacuum engineers and scientists, such as pressure profiles, effective pumping speeds, adsorption distributions, angle of incidence or effusion profiles, and more. MOLFLOW+ is a follow up to the code MOLFLOW, which has been developed by one of us since 1991, and used for the analysis and design of many vacuum systems and components. MOLFLOW+ makes use of modern trends such as OpenGL graphic interface, multicore processors, graphical processing units (GPUs), and runs under different operating systems. In addition to implementing the test-particle Monte Carlo (TPMC) algorithm, as done previously in MOLFLOW, MOLFLOW+ also implements an alternate algorithm, the angular coefficient (AC) method. This article goes into some details of the TPMC and AC methods as implemented in MOLFLOW+, shows results of benchmark runs and comparisons with published numerical and analytical data, and discusses the advantages and disadvantages of the two methods. CUDA is the compute unified device architecture, a C++-like development environment for a class of GPUs.
Reflectance anisotropy spectroscopy: A probe to explore organic epitaxial growth
Authors: Bussetti G. , Cirilli S. , Violante A. , Chiostri V. , Goletti C. , Chiaradia P. , Sassella A. , Campione M. , Raimondo L. , Braga D. , Borghesi A.
Published: June 2009

Reflectance anisotropy spectroscopy (RAS) is demonstrated to be particularly suitable for studying the deposition of organic epitaxial layers in ultrahigh vacuum by organic molecular beam epitaxy, thanks to its high sensitivity and applicability in situ. In the case of α-quaterthiophene, both homoepitaxy and heteroepitaxy have been monitored, demonstrating the crystallinity of the films up to tens of monolayers and the epitaxial relation to the substrate. In both cases, optical RAS data are compared to the results of ex situ characterization of the same samples by atomic force microscopy.
Dry etching of CoFe films using a CH4∕Ar inductively coupled plasma for magnetic random access memory application
Authors: Um Doo-Seung , Kim Dong-Pyo , Woo Jong-Chang , Kim Chang-Il , Lee Sung-Kwon , Jung Tae-Woo , Moon Seung-Chan
Published: June 2009

In this study, the CoFe thin film was studied using an inductively coupled plasma system in CH4-based gas chemistries. The etch rate of the CoFe thin film was systemically studied by the process parameters including the gas mixing ratio, the rf power, the dc-bias power, and the process pressure. The best gas composition for etching was in CH4 (20%)/Ar (80%) ratio. As the rf power and the dc-bias voltage were increased, the etch rate of the CoFe thin film increased in a CH4∕Ar inductively coupled plasma system. The best process pressure condition for etching was 10mTorr in the CH4∕Ar inductively coupled plasma system. The changes in the components on the surface of the CoFe thin film were investigated with energy dispersive x ray.
Ge nanocrystals embedded in a GeOx matrix formed by thermally annealing of Ge oxide films
Authors: Vijayarangamuthu K. , Rath Shyama , Kabiraj D. , Avasthi D. K. , Kulriya Pawan K. , Singh V. N. , Mehta B. R.
Published: June 2009

The authors investigate the formation of Ge nanocrystals by thermal annealing of substoichiometric GeOx films fabricated by electron-beam evaporation. At the same time, they also monitor the evolution of the GeOx matrix. The phase separation into semiconductor and oxide phases and the evolution of Ge nanocrystals were monitored by a combination of x-ray diffraction (XRD), Raman, and transmission electron microscopy (TEM) measurements. TEM shows spherical particles of sizes in the range of 2–9nm. They infer that an annealing temperature of 500°C is sufficient to generate a reasonable density of Ge nanocrystals in an amorphous GeOx matrix. Both XRD and Raman measurements suggest a simultaneous crystallization of the matrix at an annealing temperature of 600°C.
Photodynamic Therapy for
Acinetobacter baumannii
Burn Infections in Mice
Authors: Dai Tianhong , Tegos George P. , Lu Zongshun , Huang Liyi , Zhiyentayev Timur , Franklin Michael J. , Baer David G. , Hamblin Michael R.
Published: June 2009

Multidrug-resistant
Acinetobacter baumannii
infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of
A. baumannii
and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10
8
A. baumannii
cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized
A. baumannii
infections.
Activities of Daptomycin and Vancomycin Alone and in Combination with Rifampin and Gentamicin against Biofilm-Forming Methicillin-Resistant
Staphylococcus aureus
Isolates in an Experimental Model of Endocarditis
Authors: LaPlante Kerry L. , Woodmansee Suzanne
Published: June 2009

The findings of clinical and in vitro research support the theory that infective endocarditis (IE)-causing bacteria form biofilms and that biofilms negatively affect treatment outcomes. The purpose of the present study was to quantify the biofilm formation of methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) isolates obtained from patients with IE and to evaluate the in vitro activities of daptomycin and vancomycin alone and in combination with rifampin (rifampicin) or gentamicin while monitoring the isolates for the development of resistance. A high-inoculum, stationary-phase infection model of IE was used to simulate the pharmacokinetics in humans of daptomycin at 6 mg/kg of body weight/day, vancomycin at 1.25 g every 12 h (q12h) alone and in combination with rifampin at 300 mg every 8 h, and gentamicin at 1.3 mg/kg q12h. Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. The time to bactericidal activity in the presence of daptomycin was isolate dependent but was achieved by 24 h for both MRSA isolates. Vancomycin did not achieve bactericidal activity throughout the experiment. At 24, 48, and 72 h, daptomycin-containing regimens had significantly more activity (greater declines in the mean number of CFU/g) than any of the vancomycin-containing regimens (
P =
0.03). Rifampin and gentamicin antagonized or delayed the bactericidal activity of daptomycin (against MRSA B346846 for rifampin and against both isolates for gentamicin) in the first 24 h. Increases in the daptomycin and vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA, daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24 h. Further investigations are needed to understand the initial delay in bactericidal activity observed when gentamicin or rifampin is combined with daptomycin.
Population Pharmacokinetics of Lumefantrine in Pregnant Women Treated with Artemether-Lumefantrine for UncomplicatedPlasmodium falciparumMalaria
Authors: Tarning Joel , McGready Rose , Lindegardh Niklas , Ashley Elizabeth A. , Pimanpanarak Mupawjay , Kamanikom Benjamas , Annerberg Anna , Day Nicholas P. J. , Stepniewska Kasia , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: June 2009

Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world. The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistantPlasmodium falciparummalaria on the northwestern border of Thailand. Burmese and Karen women (n= 103) withP. falciparummalaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine (80/480 mg) twice daily for 3 days. All patients provided five capillary plasma samples for drug quantification, and the collection times were randomly distributed over 14 days. The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling. The treatment failure rate (PCR-confirmed recrudescent infections at delivery) was high; 16.5% (95% confidence interval, 9.9 to 25.1). The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination. The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution. A high proportion of all women (40%, 41/103) had day 7 capillary plasma concentrations of <355 ng/ml (which corresponds to approximately <280 ng/ml in venous plasma), a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area. Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy. In conclusion, altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy. Dose optimization is urgently needed.
Role of the
Mycobacterium tuberculosis
P55 Efflux Pump in Intrinsic Drug Resistance, Oxidative Stress Responses, and Growth
Authors: Ramón-García Santiago , Martín Carlos , Thompson Charles J. , Aínsa José A.
Published: June 2009

Bacterial efflux pumps have traditionally been studied as low-level drug resistance determinants. Recent insights have suggested that efflux systems are often involved with fundamental cellular physiological processes, suggesting that drug extrusion may be a secondary function. In
Mycobacterium tuberculosis
, little is known about the physiological or drug resistance roles of efflux pumps. Using
Mycobacterium bovis
BCG as a model system, we showed that deletion of the
Rv1410c
gene encoding the P55 efflux pump made the strain more susceptible to a range of toxic compounds, including rifampin (rifampicin) and clofazimine, which are first- and second-line antituberculosis drugs. The efflux pump inhibitors carbonyl cyanide
m
-chlorophenylhydrazone (CCCP) and valinomycin inhibited the P55-determined drug resistance, suggesting the active export of the compounds by use of the transmembrane proton and electrochemical gradients as sources of energy. In addition, the P55 efflux pump mutant was more susceptible to redox compounds and displayed increased intracellular redox potential, suggesting an essential role of the efflux pump in detoxification processes coupled to oxidative balance within the cell. Finally, cells that lacked the
p55
gene displayed smaller colony sizes and had a growth defect in liquid culture. This, together with an increased susceptibility to the cell wall-targeting compounds bacitracin and vancomycin, suggested that P55 is needed for proper cell wall assembly and normal growth in vitro. Thus, P55 plays a fundamental role in oxidative stress responses and in vitro cell growth, in addition to contributing to intrinsic antibiotic resistance. Inhibitors of the P55 efflux pump could help to improve current treatments for tuberculosis.
Candida albicans
and
Staphylococcus aureus
Form Polymicrobial Biofilms: Effects on Antimicrobial Resistance
Authors: Harriott Melphine M. , Noverr Mairi C.
Published: June 2009

Candida albicans
readily forms biofilms on the surface on indwelling medical devices, and these biofilms serve as a source of local and systemic infections. It is estimated that 27% of nosocomial
C. albicans
bloodstream infections are polymicrobial, with
Staphylococcus aureus
as the third most common organism isolated in conjunction with
C. albicans
. We tested whether
S. aureus
and
C. albicans
are able to form a polymicrobial biofilm. Although
S. aureus
formed poor monoculture biofilms in serum, it formed a substantial polymicrobial biofilm in the presence of
C. albicans
. In terms of architecture,
S. aureus
formed microcolonies on the surface of the biofilm, with
C. albicans
serving as the underlying scaffolding. In addition,
S. aureus
matrix staining revealed a different phenotype in polymicrobial versus monomicrobial biofilms, suggesting that
S. aureus
may become coated in the matrix secreted by
C. albicans. S. aureus
resistance to vancomycin was enhanced within the polymicrobial biofilm, required viable
C. albicans
, and was in part mediated by
C. albicans
matrix. However, the growth or sensitivity to amphotericin B of
C. albicans
is not altered in the polymicrobial biofilm.
Competitive Inhibition of Renal Tubular Secretion of Gemifloxacin by Probenecid
Authors: Landersdorfer Cornelia B. , Kirkpatrick Carl M. J. , Kinzig Martina , Bulitta Jürgen B. , Holzgrabe Ulrike , Drusano George L. , Sörgel Fritz
Published: June 2009

Probenecid interacts with transport processes of drugs at several sites in the body. For most quinolones, renal clearance is reduced by concomitant administration of probenecid. The interaction between gemifloxacin and probenecid has not yet been studied. We studied the extent, time course, site(s), and mechanism of this interaction. Seventeen healthy volunteers participated in a randomized, two-way crossover study. Subjects received 320 mg gemifloxacin as an oral tablet without and with 4.5 g probenecid divided in eight oral doses. Drug concentrations in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin was used for noncompartmental analysis, compartmental modeling, and statistics, and NONMEM was used for visual predictive checks. Concomitant administration of probenecid increased plasma gemifloxacin concentrations and amounts excreted in urine compared to baseline amounts. Data are average estimates (percent coefficients of variation). Modeling showed a competitive inhibition of the renal tubular secretion of gemifloxacin by probenecid as the most likely mechanism of the interaction. The estimatedKmandVmaxfor the saturable part of renal elimination were 9.16 mg/liter (20%) and 113 mg/h (21%), respectively. Based on the molar ratio, the affinity for the renal transporter was 10-fold higher for gemifloxacin than for probenecid. Since probenecid reached an ∼200-times-higher area under the molar concentration-time curve from 0 to 24 h than gemifloxacin, probenecid inhibited the active tubular secretion of gemifloxacin. Probenecid also reduced the nonrenal clearance of gemifloxacin from 25.2 (26%) to 21.0 (23%) liters/h. Probenecid inhibited the renal tubular secretion of gemifloxacin, most likely by a competitive mechanism, and slightly decreased nonrenal clearance of gemifloxacin.
Vancomycin and Daptomycin Pharmacodynamics Differ against a Site-Directed
Staphylococcus epidermidis
Mutant Displaying the Small-Colony-Variant Phenotype
Authors: Wu Marina , von Eiff Christof , Al Laham Nahed , Tsuji Brian T.
Published: June 2009

Catheter-related bloodstream infections due to slow-growing
Staphylococcus epidermidis
small-colony variants (SCVs) are extremely difficult to treat. Daptomycin and vancomycin pharmacodynamics were evaluated against a site-directed
hemB
mutant of
S. epidermidis
displaying the SCV phenotype and compared to that of the parental strain. The maximal killing effect decreased by 7.7-fold for vancomycin and 1.5-fold for daptomycin against the SCV mutant and were well characterized by a Hill-type mathematical model (
R
2
> 0.97).
Tuberculosis and Trimethoprim-Sulfamethoxazole
Authors: Forgacs Pierre , Wengenack Nancy L. , Hall Leslie , Zimmerman Sarah K. , Silverman Mark L. , Roberts Glenn D.
Published: June 2009

The sulfonamides were the first drugs with antituberculous effects. Their use was abandoned and basically forgotten with the advent of streptomycin and isoniazid combination treatment. There is a widespread belief, apparently based on testing a single isolate on questionable media, thatMycobacterium tuberculosisis resistant to trimethoprim-sulfamethoxazole (TMP-SMX). We saw a complex immunocompromised patient with tuberculosis who was initially treated with TMP-SMX without antituberculous drugs and defervesced on this treatment. An isolate ofM. tuberculosisfrom this patient was found to be sensitive to TMP-SMX. We examined how frequentlyM. tuberculosisis sensitive to TMP-SMX. Isolates were tested for susceptibility to TMP-SMX on supplemented Middlebrook 7H10 plates. We found that 43 of 44 (98%) isolates ofM. tuberculosiswere susceptible to the combination of ≤1 μg/ml of TMP and 19 μg/ml of SMX (≤1/19 μg/ml). Thus, the vast majority of ourM. tuberculosisisolates were susceptible to TMP-SMX at an MIC similar to that forMycobacterium kansasii,Mycobacterium marinum, and sensitive rapidly growing mycobacteria, organisms successfully treated with TMP-SMX as part of the treatment regimen. It is possible that TMP-SMX may be useful in treating patients with multiple-drug-resistant and extended drug-resistant tuberculosis. We feel that a clinical trial looking at the effectiveness of TMP-SMX as an antituberculous drug is worthwhile.
Strain-Specific Duffy Binding Protein Antibodies Correlate with Protection against Infection with Homologous Compared to Heterologous
Plasmodium vivax
Strains in Papua New Guinean Children
Authors: Cole-Tobian Jennifer L. , Michon Pascal , Biasor Moses , Richards Jack S. , Beeson James G. , Mueller Ivo , King Christopher L.
Published: June 2009

Individuals repeatedly infected with malaria acquire protection from infection and disease; immunity is thought to be primarily antibody-mediated and directed to blood-stage infection. Merozoite surface proteins involved in the invasion of host erythrocytes are likely targets of protective antibodies. We hypothesized that Papua New Guinean children (
n
= 206) who acquire high antibody levels to two
Plasmodium vivax
merozoite proteins, Duffy binding protein region II (PvDBPII) and the 19-kDa C-terminal region of
P. vivax
merozoite surface protein 1 (PvMSP1
19
), would have a delay in the time to reinfection following treatment to clear all blood-stage malaria infections. Ninety-four percent of the children were reinfected with
P. vivax
during biweekly follow-ups for 6 months. Since PvDBPII is polymorphic, we examined whether individuals acquired strain-specific immunity to PvDBPII. Children with high antibody levels to a prevalent PvDBPII allele (O) were associated with a delay in the time to reinfection with the same variant of
P. vivax
by 25% compared to parasites expressing other PvDBPII alleles (age-adjusted hazard ratio, 0.75 [95% confidence interval, 0.56 to 1.00 by Cox regression]) and 39% lower incidence density parasitemia (
P
= 0.01). Two other prevalent alleles (AH and P) showed a similar trend of 16% and 18% protection, respectively, against parasites with the same PvDBPII allele and reduced incidence density parasitemia. Antibodies directed to PvDBPII PNG-P and -O were both associated with a 21 to 26% reduction in the risk of
P. vivax
infections with higher levels of parasitemia (>150 parasites/μl), respectively. There was no association with high antibody levels to PvMSP1
19
and a delay in the time to
P. vivax
reinfection. Thus, anti-PvDBPII antibodies are associated with strain-specific immunity to
P. vivax
and support the use of PvDBPII for a vaccine against
P. vivax
.
Roles of RseB, σ
E
, and DegP in Virulence and Phase Variation of Colony Morphotype of
Vibrio vulnificus
Authors: Brown Roslyn N. , Gulig Paul A.
Published: June 2009

Vibrio vulnificus
is an estuarine bacterium capable of causing serious and often fatal wound infections and primary septicemia. We used alkaline phosphatase insertion mutagenesis to identify genes necessary for the virulence of this pathogen. One mutant had an in-frame fusion of ′
phoA
to the gene encoding RseB, a periplasmic negative regulator of the alternative sigma factor σ
E
. σ
E
controls an extensive regulon involved in responding to cell envelope stresses. Colonies of the
rseB
mutant were less opaque than wild-type colonies and underwent phase variation between translucent and opaque morphologies.
rseB
mutants were attenuated for virulence in subcutaneously inoculated iron-dextran-treated mice. To obtain insight into the role of
rseB
and the extracytoplasmic stress response in
V. vulnificus
, mutants with defined mutations in
rseB
and two important members of the extracytoplasmic stress regulon,
rpoE
and
degP
, were constructed for analysis of virulence, colony morphology, and stress-associated phenotypes. Deletion of
rseB
caused reversible phase variation in the colony morphotype that was associated with extracellular polysaccharides. Translucent and transparent morphotype strains were attenuated for virulence.
rpoE
and
degP
deletion mutants were sensitive to membrane-perturbing agents and heat but were not significantly attenuated for
V. vulnificus
virulence in mice. These results reveal complex relationships between regulation of the extracytoplasmic stress response, exopolysaccharides, and the virulence of
V. vulnificus
.