bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface tension, adhesion and wetting of materials for photolithographic process
Authors: Bauer J. , Drescher G. , Illig M.
Published: July 2002

Surface tension of substrates and layers used in semiconductor technology (e.g., Si, SiO2, Si3N4, AlCu, and WTi) as well as surface tension of materials of photolithography as resists and developers were determined by contact angle measurements. Resists and developers could be divided into two groups with polar and nonpolar behavior, respectively. The pretreatment of the substrates (cleaning, dehydration, and exposure to humidity) influences the surface tension. It was found that surface modification by primers, for example, hexamethyldisilazane and trimethylsilydiethylamine provides stable and reproducible surface tension. To reduce defect density of resist structures, a general optimization approach of surface tension was derived and successfully applied, using Si and AlCu as substrates in a typical photolithographic process. The results show a good adhesion of resist will be achieved if the work of adhesion is greater than 5 dyn/cm. A suggestion is given of process window of the contact angle is given for certain combinations of types of resist and developer.
Cl2/Ar plasma etching of binary, ternary, and quaternary In-based compound semiconductors
Authors: Lee J. W. , Hong J. , Abernathy C. R. , Lambers E. S. , Pearton S. J. , Hobson W. S. , Ren F.
Published: July 2002

A simple Cl2/Ar plasma chemistry can provide smooth, high-rate etching of InP, InAs, InGaAs, A1InAs, and InGaAsP at room temperature under conditions in which there is a balance between formation and sputter desorption of the normally involatile InCl3. When the neutral/ion ratio is either too high or too low, surface roughening is apparent due either to the presence of InCl3, or to preferential loss of the group V element. The etching has been investigated as a function of microwave power (600–1000 W), rf power (0–300 W), process pressure (1.5–10 mTorr), and Cl2:Ar ratio under electron cyclotron resonance conditions. Use of N2 or H2, rather than Ar, as gas additives to the chlorine, did not produce smooth, stoichiometric etched surfaces.
Microstructural stability of ohmic contacts to InxGa1−xN
Authors: Durbha A. , Pearton S. J. , Abernathy C. R. , Lee J. W. , Holloway P. H. , Ren F.
Published: July 2002

The microstructural properties and interdiffusion reactions of some common metallization schemes (Au/Ge/Ni, Ti/Pt/Au, WSix, and AuBe) on GaN and In0.5Ga0.5N have been examined using scanning electron microscopy and Auger electron spectroscopy. The objective of this study was to investigate thermally stable and uniform contacts to both materials. The WSix contacts were found to possess excellent thermal stability and retained good structural properties at annealing temperatures as high as 800 °C on GaN. These contacts on In0.5Ga0.5N had a minimum specific contact resistivity of 1.48×10−5 Ω cm2 and an excellent surface morphology following annealing at 700 °C. The increase in contact resistance observed at higher temperatures was attributed to intermixing of metal and semiconductor. By contrast the Ti/Pt/Au and Au/Ge/Ni contacts showed lower stabilities, but also showed little Au penetration into the underlying GaN. AuBe contacts had the poorest thermal stability of all four schemes investigated, with substantial reaction with GaN occurring even at 400 °C. The WSix contact appears to be an excellent choice for application in high temperature GaN electronics.
Temperature dependent magnetic surface anisotropy in ultrathin Fe films
Authors: Pappas D. P.
Published: July 2002

The temperature dependence of the uniaxial surface anisotropy, Ku(T), in ultrathin Fe films (4–10 atomic layers) grown on Cu(100) is determined by comparing the dipole and anisotropy energies at the spin reorientation temperature for films of varying thickness. It is observed that the uniaxial anisotropy has a weak temperature dependence compared to the bulk constants for Fe. The measured exponent of Γu=2.6(0.5) agrees well with the l(l+1)/2 law, which is obtained from a spin fluctuation model where l=2 at the surface. This shows that the spin reorientation transition can be understood as being driven by thermal spin fluctuations.
N channel metal–oxide–semiconductor field-effect transistor with 0.15 μm gate delineated by focused ion beam lithography
Authors: Suzuki Kohei , Yamashita Motoji , Kawakami Nobuyuki , Nakaue Akimitsu
Published: July 2002

An N channel metal–oxide–semiconductor field-effect transistor (MOSFET) with a 0.15 μm gate was fabricated by using focused ion beam lithography for gate level and its electrical characteristics were investigated. The choice of the ion species and the gate structure were designed to avoid contamination and damage due to ion penetration. The MOSFET showed an excellent junction leakage current and subthreshold swing. The impact of the ion irradiation on the thin gate oxide quality was also investigated.
X-ray fabrication of nonorthogonal structures using “surface” masks
Authors: White V. , Herdey C. , Denton D. D. , Song J.
Published: July 2002

Standard x-ray lithographic techniques allow great flexibility of geometry in two dimensions. Typically, the third dimension is limited to depth, which is purely orthogonal to the surface. We have been developing a relatively simple technique using x-ray lithography and have fabricated a whole family of precisely controlled nonorthogonal structures such as tapers, bridges and various “leaning” or blazed structures. Traditional soft x-ray masks, create the modulation required to print into x-ray resists by having the absorbing elements of the x-ray mask patterned on a thin membrane. This technique involves the creation of the gold absorbing elements of the x-ray mask directly on the surface of the photoresist, i.e., a “surface” mask. These surface masks can create nonorthogonal exposures creating blazed structures as well as “bridges” by tilting the sample with respect to the x-ray beam during exposure. The exposures can also be done while having the tilted sample rotated, creating tapered exposure profiles. In addition to the novel geometries, a potentially useful feature of the rotated exposures is that the sidewalls have nanometer scale smoothness, due to the averaging of intensities during rotation.
Magneto-transport studies of Si/SiGe and Si/SiGeC quantum well structures grown by molecular beam epitaxy at low temperatures
Authors: Grützmacher D. , Hartmann R. , Schnappauf P. , Gennser U. , Sigg H. , Bächle D. , Brosig S.
Published: July 2002

The magneto-transport properties of SiGe and SiGeC quantum well structures were studied in relation to their dependence on the growth temperature, Ge and C concentration, well width, and spacer width. It is found that interface roughness and charged impurities are the main origins for scattering in SiGe and SiGeC two-dimensional hole gas (2DHG) structures. Rapid thermal annealing subsequent to growth improves the mobility in SiGeC 2DHG by a factor of 2, whereas only a 20% increase is observed for SiGe 2DHG. At 1.6 K a mobility of 1930 cm2/V s for Si0.81Ge0.185C0.05 and 6900 cm2/V s for Si0.85Ge0.15 channels was deduced from Shubnikov–de Haas oscillations measured up to 8 T. The effective mass determined for holes in the SiGeC alloy is 0.21±0.02. B δ-doped Si layers were used to determine the B diffusion in the temperature range from 700 to 850 °C by intersubband absorption spectroscopy.
Observation of the resonance tunneling in field emission structures
Authors: Litovchenko V. G. , Evtukh A. A. , Litvin Yu. M. , Goncharuk N. M. , Chayka V. E.
Published: July 2002

Theoretical and experimental investigations of electron field emission from silicon-based resonance-tunneling layered structures have been performed. Numerical simulation of resonant and nonresonant field emission in Si-SiO2-Si*-SiO2 multilayer cathodes (MLCs) with quantum well (QWs) which takes into account the tunneling process of electrons from the three-dimensional electron density state of the emitter conductive band has been carried out. The influence of the external electric field, temperature, MLC parameters and emitter doping on the resonant characteristics of the current was analyzed. Computer simulation has shown that the peak current density of MLCs with optimal thin barriers and sufficiently wide QW layers at a resonant value of the electric field can sometimes exceed the current density of conventional cathodes. If the width of the QW is increased, the number of current resonant maxima (CRM) is multiplied. The CRM is shifted towards the lower electric field values and become more narrow if both the QW and the potential barrier widths are increased. With temperature reduction the CRM becomes contrasted due to an increase in the electron impulse relaxation time and redistribution of the electron state density in the emitter conduction band. Experimental multilayer structures with Si* δ-doped layer Si-SiO2-Si*-SiO2 have been formed on silicon using low pressure chemical vapor deposition of ultrathin SiO2 and Si* films. In some cases the first ultrathin SiO2 layer was grown on silicon with thermal oxidation. The multilayer structures were formed both on flat silicon wafers and on silicon tip arrays. Measurements of electron field emission into vacuum were performed in a diode (cathode-anode) system. The resonant peaks of current density from MLCs have been observed experimentally for the first time. The value of these peaks is more than two times of that of the background curves. A comparison of experimental and theoretical results has been performed to evaluate the fundamental parameters of the field emission resonance process.
Surface characterization of a low dielectric constant polymer–SiLK* polymer, and investigation of its interface with Cu
Authors: Rajagopal A. , Grégoire C. , Lemaire J. J. , Pireaux J. J. , Baklanov M. R. , Vanhaelemeersch S. , Maex K. , Waeterloos J. J.
Published: July 2002

The integration of copper and new low dielectric constant materials is a fundamental challenge to be met for further miniaturization of high speed integrated circuits. In this preliminary work, core level x-ray photoelectron spectroscopy (XPS) has been used for the first characterization of the surface composition of Dow Chemical’s SiLK* semiconductor dielectric (*trademark of the Dow Chemical Company), its behavior during annealing in vacuo, and its interface formation with thermally evaporated copper in situ. The fully conjugated SiLK* resin shows a C 1s spectrum with intense shake-up structures, quite similar to those of polystyrene; a small amount of oxygen is detected. Upon annealing in ultrahigh vacuum (7.10−9 Pa) no significant outgassing is observed; no noticeable change in intensity, width, position of the C 1s and O 1s core level peaks or satellite structures is measured. After annealing, the interface formation between SiLK* dielectric and copper has been characterized as a function of incremental coverages from 0.5 to 10 Å of Cu. While the XPS C 1s spectrum shows only a normal intensity decrease, the Cu 2p3/2 levels shift from a high binding energy to a purely metallic value: this is interpreted as the formation of small Cu clusters, evolving to a more continuous layer for higher Cu coverage. Annealing in vacuo of the as-prepared Cu(10 Å)–SiLK* interface at 400 °C for 1 h does induce an increase of the carbon signal, attributed to further coalescence of copper in metallic clusters.
Electrical testing of gold nanostructures by conducting atomic force microscopy
Authors: Bietsch Alexander , Schneider M. Alexander , Welland Mark E. , Michel Bruno
Published: July 2002

We devised a method for the reliable electrical testing of nanoscale wire arrays using conducting probe atomic force microscopy (AFM) in ambient conditions. A key requirement of this approach is the formation of highly reproducible electrical contacts between the conducting tip and the sample. We discuss the basic mechanical and electrical criteria of nanocontacts and derive a force-controlled protocol for the formation of low-ohmic contacts. Tips sputter coated with platinum provided the mechanical stability for both tapping-mode imaging and the formation of low-ohmic contacts on gold samples. Nanostructures on the sample were identified by topographic imaging and subsequently probed using the AFM tip as a mobile electrode. We measured resistivities in arrays of nanowires or local potentials of wires within electrical circuits, and detected electrical failures, thermal gradients, and small geometrical variations. The ability of this instrument to address electrical characteristics with high spatial resolution makes it a powerful tool for lithography developments and on-chip monitoring of nanoscale circuits.
A New Mammaliaform from the Early Jurassic and Evolution of Mammalian Characteristics
Authors: Luo Zhe-Xi , Crompton Alfred W. , Sun Ai-Lin
Published: July 2002

A fossil from the Early Jurassic (Sinemurian, ∼195 million years ago) represents a new lineage of mammaliaforms, the extinct groups more closely related to the living mammals than to nonmammaliaform cynodonts. It has an enlarged cranial cavity, but no postdentary trough on the mandible, indicating separation of the middle ear bones from the mandible. This extends the earliest record of these crucial mammalian features by some 45 million years and suggests that separation of the middle ear bones from the mandible and the expanded brain vault could be correlated. It shows that several key mammalian evolutionary innovations in the ear region, the temporomandibular joint, and the brain vault evolved incrementally through mammaliaform evolution and long before the differentiation of the living mammal groups. With an estimated body weight of only 2 grams, its coexistence with other larger mammaliaforms with similar “triconodont-like” teeth for insectivory within the same fauna suggests a great trophic diversity within the mammaliaform insectivore feeding guild, as inferred from the range of body sizes.
Ferromagnetic Imprinting of Nuclear Spins in Semiconductors
Authors: Kawakami R. K. , Kato Y. , Hanson M. , Malajovich I. , Stephens J. M. , Johnston-Halperin E. , Salis G. , Gossard A. C. , Awschalom D. D.
Published: July 2002

We examine how a ferromagnetic layer affects the coherent electron spin dynamics in a neighboring gallium arsenide semiconductor. Ultrafast optical pump-probe measurements reveal that the spin dynamics are unexpectedly dominated by hyperpolarized nuclear spins that align along the ferromagnet's magnetization. We find evidence that photoexcited carriers acquire spin-polarization from the ferromagnet, and dynamically polarize these nuclear spins. The resulting hyperfine fields are as high as 9000 gauss in small external fields (less than 1000 gauss), enabling ferromagnetic control of local electron spin coherence.
Dynamic Aggregation of Chiral Spinners
Authors: Grzybowski Bartosz A. , Whitesides George M.
Published: July 2002

An object spinning at the surface of a liquid creates a chiral vortex. If the spinning object is itself chiral, its shape modifies the characteristics of the vortex; interactions between that vortex and other vortices then depend on the chirality of the objects that produce them. This paper describes the aggregation of millimeter-sized, chiral magnetized plates floating at a liquid-air interface and rotating under the influence of a rotating external magnetic field. This external field confines all the plates at densities that cause the vortices they generate to interact strongly. For one set of plates investigated, plates of one chirality attract one another, and plates of the other chirality repel other plates of both chiralities.
Regulation of MAPK Function by Direct Interaction with the Mating-Specific Gα in Yeast
Authors: Metodiev Metodi V. , Matheos Dina , Rose Mark D. , Stone David E.
Published: July 2002

The mating response of the budding yeast
Saccharomyces cerevisiae
is mediated by a prototypical heterotrimeric GTP-binding protein (G protein) and mitogen-activated protein kinase (MAPK) cascade. Although signal transmission by such pathways has been modeled in detail, postreceptor down-regulation is less well understood. The pheromone-responsive G protein α subunit (Gα) of yeast down-regulates the mating signal, but its targets are unknown. We have found that Gα binds directly to the mating-specific MAPK in yeast cells responding to pheromone. This interaction contributes both to modulation of the mating signal and to the chemotropic response, and it demonstrates direct communication between the top and bottom of a Gα-MAPK pathway.
A Natural Product That Lowers Cholesterol As an Antagonist Ligand for FXR
Authors: Urizar Nancy L. , Liverman Amy B. , Dodds D'Nette T. , Silva Frank Valentin , Ordentlich Peter , Yan Yingzhuo , Gonzalez Frank J. , Heyman Richard A. , Mangelsdorf David J. , Moore David D.
Published: July 2002

Extracts of the resin of the guggul tree (
Commiphora mukul
) lower LDL (low-density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone [4,17(20)-pregnadiene-3,16-dione] is the active agent in this extract. We show that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone treatment decreases hepatic cholesterol in wild-type mice fed a high-cholesterol diet but is not effective in FXR-null mice. Thus, we propose that inhibition of FXR activation is the basis for the cholesterol-lowering activity of guggulsterone. Other natural products with specific biologic effects may modulate the activity of FXR or other relatively promiscuous nuclear hormone receptors.
High Anxiety
Authors: Goldman David
Published: July 2002

Variations in human personality are in part genetically determined. In a report in this issue (
p. 1527
), Lesch
et al
. demonstrate that one of the genes that influences a personality trait called neuroticism is the transporter for the neurotransmitter serotonin. Goldman in his Perspective discusses the approach that led to this finding and compares it with other recent approaches to behavioral genetics.
Direct Radiometric Observations of the Water Vapor Greenhouse Effect Over the Equatorial Pacific Ocean
Authors: Valero Francisco P. J. , Collins William D. , Pilewskie Peter , Bucholtz Anthony , Flatau Piotr J.
Published: July 2002

Airborne radiometric measurements were used to determine tropospheric profiles of the clear sky greenhouse effect. At sea surface temperatures (SSTs) larger than 300 kelvin, the clear sky water vapor greenhouse effect was found to increase with SST at a rate of 13 to 15 watts per square meter per kelvin. Satellite measurements of infrared radiances and SSTs indicate that almost 52 percent of the tropical oceans between 20°N and 20°S are affected during all seasons. Current general circulation models suggest that the increase in the clear sky water vapor greenhouse effect with SST may have climatic effects on a planetary scale.
Removal of Osteoclast Bone Resorption Products by Transcytosis
Authors: Salo Jari , Lehenkari Petri , Mulari Mika , Metsikkö Kalervo , Väänänen H. Kalervo
Published: July 2002

Osteoclasts are multinucleated cells responsible for bone resorption. During the resorption cycle, osteoclasts undergo dramatic changes in their polarity, and resorbing cells reveal four functionally and structurally different membrane domains. Bone degradation products, both organic and inorganic, were endocytosed from the ruffled border membrane. They were then found to be transported in vesicles through the cell to the plasma membrane domain, located in the middle of the basal membrane, where they were liberated into the extracellular space. These results explain how resorbing osteoclasts can simultaneously remove large amounts of matrix degradation products and penetrate into bone.
Coding the Locations of Objects in the Dark
Authors: Graziano Michael S. A. , Hu Xin Tian , Gross Charles G.
Published: July 2002

The ventral premotor cortex in primates is thought to be involved in sensory-motor integration. Many of its neurons respond to visual stimuli in the space near the arms or face. In this study on the ventral premotor cortex of monkeys, an object was presented within the visual receptive fields of individual neurons, then the lights were turned off and the object was silently removed. A subset of the neurons continued to respond in the dark as if the object were still present and visible. Such cells exhibit “object permanence,” encoding the presence of an object that is no longer visible. These cells may underlie the ability to reach toward or avoid objects that are no longer directly visible.
Mediation of Classical Conditioning in
Aplysia californica
by Long-Term Potentiation of Sensorimotor Synapses
Authors: Murphy Geoffrey G. , Glanzman David L.
Published: July 2002

Long-term potentiation (LTP) is considered an important neuronal mechanism of learning and memory. Currently, however, there is no direct experimental link between LTP of an identified synapse and learning. A cellular analog of classical conditioning in
Aplysia
was used to determine whether this form of invertebrate learning involves
N
-methyl-
d
-aspartate (NMDA)–type LTP. The NMDA receptor-antagonist
dl
-2-amino-5-phosphonovalerate significantly disrupted synaptic enhancement after associative training but did not disrupt synaptic enhancement after nonassociative training. Thus, classical conditioning in
Aplysia
appears to be mediated, in part, by LTP due to activation of NMDA-related receptors.
Isolation of Acidophilic Methane-Oxidizing Bacteria from Northern Peat Wetlands
Authors: Dedysh Svetlana N. , Panikov Nicolai S. , Liesack Werner , Großkopf Regine , Zhou Jizhong , Tiedje James M.
Published: July 2002

Acidic northern wetlands are an important source of methane, one of the gases that contributes to global warming. Methane oxidation in the surface of these acidic wetlands can reduce the methane flux to the atmosphere up to 90 percent. Here the isolation of three methanotrophic microorganisms from three boreal forest sites is reported. They are moderately acidophilic organisms and have a soluble methane monooxygenase. In contrast to the known groups of methanotrophs, 16
S
ribosomal DNA sequence analysis shows that they are affiliated with the acidophilic heterotrophic bacterium
Beijerinckia indica
subsp.
indica
.
Nonmethylated Transposable Elements and Methylated Genes in a Chordate Genome
Authors: Simmen Martin W. , Leitgeb Sabine , Charlton Jillian , Jones Steven J. M. , Harris Barbara R. , Clark Victoria H. , Bird Adrian
Published: July 2002

The genome of the invertebrate chordate
Ciona intestinalis
was found to be a stable mosaic of methylated and nonmethylated domains. Multiple copies of an apparently active long terminal repeat retrotransposon and a long interspersed element are nonmethylated and a large fraction of abundant short interspersed elements are also methylation free. Genes, by contrast, are predominantly methylated. These data are incompatible with the genome defense model, which proposes that DNA methylation in animals is primarily targeted to endogenous transposable elements. Cytosine methylation in this urochordate may be preferentially directed to genes.
Rapid Extragranular Plasticity in the Absence of Thalamocortical Plasticity in the Developing Primary Visual Cortex
Authors: Trachtenberg Joshua T. , Trepel Christopher , Stryker Michael P.
Published: July 2002

Monocular deprivation during early postnatal development remodels the circuitry of the primary visual cortex so that most neurons respond poorly to stimuli presented to the deprived eye. This rapid physiological change is ultimately accompanied by a matching anatomical loss of input from the deprived eye. This remodeling is thought to be initiated at the thalamocortical synapse. Ocular dominance plasticity after brief (24 hours) monocular deprivation was analyzed by intrinsic signal optical imaging and by targeted extracellular unit recordings. Deprived-eye responsiveness was lost in the extragranular layers, whereas normal binocularity in layer IV was preserved. This finding supports the hypothesis that thalamocortical organization is guided by earlier changes at higher stages.
bicoid
-Independent Formation of Thoracic Segments in
Drosophila
Authors: Wimmer Ernst A. , Carleton Alan , Harjes Phoebe , Turner Terry , Desplan Claude
Published: July 2002

The maternal determinant Bicoid (Bcd) represents the paradigm of a morphogen that provides positional information for pattern formation. However, as
bicoid
seems to be a recently acquired gene in flies, the question was raised as to how embryonic patterning is achieved in organisms with more ancestral modes of development. Because the phylogenetically conserved Hunchback (Hb) protein had previously been shown to act as a morphogen in abdominal patterning, we asked which functions of Bcd could be performed by Hb. By reestablishing a proposed ancient regulatory circuitry in which maternal Hb controls zygotic
hunchback
expression, we show that Hb is able to form thoracic segments in the absence of Bcd.
Nonavian Feathers in a Late Triassic Archosaur
Authors: Jones Terry D. , Ruben John A. , Martin Larry D. , Kurochkin Evgeny N. , Feduccia Alan , Maderson Paul F. A. , Hillenius Willem J. , Geist Nicholas R. , Alifanov Vladimir
Published: July 2002

Longisquama insignis
was an unusual archosaur from the Late Triassic of central Asia. Along its dorsal axis
Longisquama
bore a series of paired integumentary appendages that resembled avian feathers in many details, especially in the anatomy of the basal region. The latter is sufficiently similar to the calamus of modern feathers that each probably represents the culmination of virtually identical morphogenetic processes. The exact relationship of
Longisquama
to birds is uncertain. Nevertheless, we interpret
Longisquama
's elongate integumentary appendages as nonavian feathers and suggest that they are probably homologous with avian feathers. If so, they antedate the feathers of
Archaeopteryx
, the first known bird from the Late Jurassic.
Predictions of Biodiversity Response to Genetically Modified Herbicide-Tolerant Crops
Authors: Watkinson A. R. , Freckleton R. P. , Robinson R. A. , Sutherland W. J.
Published: July 2002

We simulated the effects of the introduction of genetically modified herbicide-tolerant (GMHT) crops on weed populations and the consequences for seed-eating birds. We predict that weed populations might be reduced to low levels or practically eradicated, depending on the exact form of management. Consequent effects on the local use of fields by birds might be severe, because such reductions represent a major loss of food resources. The regional impacts of GMHT crops are shown to depend on whether the adoption of GMHT crops by farmers covaries with current weed levels.
Occurrence of the New Tetracycline Resistance Gene
tet
(W) in Bacteria from the Human Gut
Authors: Scott Karen P. , Melville Claire M. , Barbosa Teresa M. , Flint Harry J.
Published: July 2002

Members of our group recently identified a new tetracycline resistance gene,
tet
(W), in three genera of rumen obligate anaerobes. Here, we show that
tet
(W) is also present in bacteria isolated from human feces. The
tet
(W) genes found in human
Fusobacterium prausnitzii
and
Bifidobacterium longum
isolates were more than 99.9% identical to those from a rumen isolate of
Butyrivibrio fibrisolvens
.
In Vitro Susceptibility Testing Methods for Caspofungin against
Aspergillus
and
Fusarium
Isolates
Authors: Arikan Sevtap , Lozano-Chiu Mario , Paetznick Victor , Rex John H.
Published: July 2002

We investigated the relevance of prominent reduction in turbidity macroscopically (MIC) and formation of aberrant hyphal tips microscopically (minimum effective concentration; MEC) in measuring the in vitro activity of caspofungin against
Aspergillus
and
Fusarium
. Caspofungin generated low MICs and MECs against
Aspergillus
, but not for
Fusarium
. While MICs increased inconsistently when the incubation time was prolonged, MEC appeared as a stable and potentially relevant endpoint in testing in vitro caspofungin activity.
Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits
Authors: Groll Andreas H. , Gullick Bryan M. , Petraitiene Ruta , Petraitis Vidmantas , Candelario Myrna , Piscitelli Stephen C. , Walsh Thomas J.
Published: July 2002

The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (
C
max
) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (
V
d
ss
) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increased
V
d
ss
, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.
In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201
Authors: Sidwell Robert W. , Smee Donald F. , Huffman John H. , Barnard Dale L. , Bailey Kevin W. , Morrey John D. , Babu Y. S.
Published: July 2002

The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >10
4
cell culture 50% infective doses (CCID
50
)/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 10
1.2
CCID
50
/g, whereas titers from oseltamivir-treated animals were >10
3
CCID
50
/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans.
In Vitro Activities of Three Nonfluorinated Quinolones against Representative Bacterial Isolates
Authors: Barry Arthur L. , Fuchs Peter C. , Brown Steven D.
Published: July 2002

In vitro susceptibility tests were performed to document the inhibitory activities of three nonfluorinated quinolone (NFQ) compounds (PGE 9262932, PGE 9509924, and PGE 4175997) compared to those of ciprofloxacin, levofloxacin, and trovafloxacin against 3,030 bacterial isolates. The spectra of the NFQ agents included most gram-positive species as well as quinolone-susceptible
Enterobacteriaceae
. Ciprofloxacin-resistant, methicillin-resistant
Staphylococcus aureus
strains were inhibited by the NFQ series at ≤1.0 μg/ml. The NFQ compounds were not very active against
Pseudomonas aeruginosa
and most other nonfermentative gram-negative bacilli. Against other species, the potency of the NFQ agents was similar to that of trovafloxacin. Continued investigation of the NFQ compounds seems to be warranted.
Prevalence of Single Mutations in Topoisomerase Type II Genes among Levofloxacin-Susceptible Clinical Strains of
Streptococcus pneumoniae
Isolated in the United States in 1992 to 1996 and 1999 to 2000
Authors: Davies Todd A. , Evangelista Alan , Pfleger Sharon , Bush Karen , Sahm Daniel F. , Goldschmidt Raul
Published: July 2002

Levofloxacin resistance in
Streptococcus pneumoniae
is rare, requiring at least two mutations in the quinolone resistance-determining region (QRDR) of topoisomerase IV and DNA gyrase. The prevalence of single QRDR mutations in these genes is unknown. Of 9,438 levofloxacin-susceptible pneumococci from the TRUST 4 surveillance study (1999–2000), 528 strains (MICs of 0.5 to 2.0 μg/ml) were selected for analysis. For comparison, 214 levofloxacin-susceptible strains (MICs of 0.5 to 1 μg/ml) isolated between 1992 and 1996 were analyzed. Oligonucleotide probe assay and DNA sequencing were used to detect QRDR mutations leading to changes at Ser79 and Asp83 in ParC, Ser81 in GyrA, and Asp435 in ParE, the most frequently found substitutions among levofloxacin-resistant strains. Among the 1992 to 1996 isolates only one strain (levofloxacin MIC, 1 μg/ml) had a mutation (Ser79 to Phe in ParC). No single mutations were found among 270 TRUST 4 strains with levofloxacin MICs of 0.5 μg/ml. Among 244 strains for which levofloxacin MICs were 1 μg/ml, 15 strains (6.1%) had a
parC
mutation and 3 strains (1.2%) had a
parE
mutation. Of 14 strains for which levofloxacin MICs were 2 μg/ml, 10 strains (71%) had a
parC
mutation; no
parE
mutations were found. No
gyrA
mutations were detected. It was estimated that 4.5% of the 9,438 levofloxacin-susceptible TRUST 4 isolates (MICs, ≤0.06 to 2 μg/ml) had a single
parC
or
parE
QRDR mutation. Although there has been an increase in the prevalence of single-step mutants, the increase may have been overestimated due in part to differences in geographical distribution for the two sets of isolates.
In Vitro Microbicidal Activities of Cecropin Peptides D2A21 and D4E1 and Gel Formulations Containing 0.1 to 2% D2A21 against
Chlamydia trachomatis
Authors: Ballweber L. M. , Jaynes J. E. , Stamm W. E. , Lampe M. F.
Published: July 2002

Topically applied microbicides that eradicate pathogens at the time of initial exposure represent a powerful strategy for the prevention of sexually transmitted infections. To aid in the further development of an effective topical microbicide, we assessed the minimum cidal concentration (MCC) of two cecropin peptides, D2A21 and D4E1, and gel formulations containing 0.1 to 2% D2A21 against
Chlamydia trachomatis
in vitro. The MCC of peptide D2A21was 5 μM (18.32 μg/ml), and that of peptide D4E1 was 7.5 μM (21.69 μg/ml). The MCC of gel formulations containing 2% D2A21 was 0.2 mM (0.7 mg/ml), and that of gel formulations containing 0.5% D2A21 was 0.2 mM (0.7 mg/ml). There was no significant variation in the results when two different
C. trachomatis
strains were tested, and the addition of 10% human blood did not significantly alter the MCCs. pH values above and below 7 reduced the activity of the D2A21 peptide alone, but the MCC of the 2% D2A21 gel formulation was only slightly altered at the various pHs tested. Ultrastructural studies indicated that
C. trachomatis
membranes were disrupted after D2A21 exposure, resulting in leakage of the cytoplasmic contents. These in vitro results suggest that these cecropin peptides may be an effective topical microbicide against
C. trachomatis
and support the need for further evaluation.
Combination of Quinupristin-Dalfopristin (Synercid) and Rifampin Is Highly Synergistic in Experimental
Staphylococcus aureus
Joint Prosthesis Infection
Authors: Saleh-Mghir Azzam , Ameur Nourdine , Muller-Serieys Claudette , Ismael Farid , Lemaitre Françoise , Massias Laurent , Feger Céline , Bléton Rémy , Crémieux Anne-Claude
Published: July 2002

We compared the efficacies of quinupristin-dalfopristin (Q-D; 30 mg/kg of body weight every 8 h) and vancomycin (60 mg/kg twice daily), alone or in combination with rifampin (10 mg/kg twice daily), in a rabbit model of methicillin-resistant
Staphylococcus aureus
knee prosthesis infection. In contrast to vancomycin, Q-D significantly reduced the mean log
10
CFU per gram of bone versus that for the controls. The combination of rifampin with either Q-D or vancomycin was significantly more effective than monotherapy.
Amphotericin B Formulations Exert Additive Antifungal Activity in Combination with Pulmonary Alveolar Macrophages and Polymorphonuclear Leukocytes against
Aspergillus fumigatus
Authors: Roilides Emmanuel , Lyman Caron A. , Filioti Joanna , Akpogheneta Onome , Sein Tin , Lamaignere Cristina Gil , Petraitiene Ruta , Walsh Thomas J.
Published: July 2002

Deoxycholate amphotericin B (DAMB) and amphotericin B lipid complex (ABLC) additively augmented the fungicidal activity of pulmonary alveolar macrophages against the conidia of
Aspergillus fumigatus
. DAMB, ABLC, and liposomal amphotericin B similarly displayed additive effects with polymorphonuclear leukocytes in damaging the hyphal elements of
A. fumigatus
.
Sulfur Regulation of the Sulfate Transporter Genes
sutA
and
sutB
in
Penicillium chrysogenum
Authors: van de Kamp Mart , Schuurs Theo A. , Vos Arnold , van der Lende Ted R. , Konings Wil N. , Driessen Arnold J. M.
Published: July 2002

Penicillium chrysogenum
uses sulfate as a source of sulfur for the biosynthesis of penicillin. Sulfate uptake and the mRNA levels of the sulfate transporter-encoding
sutB
and
sutA
genes are all reduced by high sulfate concentrations and are elevated by sulfate starvation. In a high-penicillin-yielding strain,
sutB
is effectively transcribed even in the presence of excess sulfate. This deregulation may facilitate the efficient incorporation of sulfur into cysteine and penicillin.
Expression of a Heterologous Glutamate Dehydrogenase Gene in
Lactococcus lactis
Highly Improves the Conversion of Amino Acids to Aroma Compounds
Authors: Rijnen Liesbeth , Courtin Pascal , Gripon Jean-Claude , Yvon Mireille
Published: July 2002

The first step of amino acid degradation in lactococci is a transamination, which requires an α-keto acid as the amino group acceptor. We have previously shown that the level of available α-keto acid in semihard cheese is the first limiting factor for conversion of amino acids to aroma compounds, since aroma formation is greatly enhanced by adding α-ketoglutarate to cheese curd. In this study we introduced a heterologous catabolic glutamate dehydrogenase (GDH) gene into
Lactococcus lactis
so that this organism could produce α-ketoglutarate from glutamate, which is present at high levels in cheese. Then we evaluated the impact of GDH activity on amino acid conversion in in vitro tests and in a cheese model by using radiolabeled amino acids as tracers. The GDH-producing lactococcal strain degraded amino acids without added α-ketoglutarate to the same extent that the wild-type strain degraded amino acids with added α-ketoglutarate. Interestingly, the GDH-producing lactococcal strain produced a higher proportion of carboxylic acids, which are major aroma compounds. Our results demonstrated that a GDH-producing lactococcal strain could be used instead of adding α-ketoglutarate to improve aroma development in cheese.
Metabolic Activity of Permafrost Bacteria below the Freezing Point
Authors: Rivkina E. M. , Friedmann E. I. , McKay C. P. , Gilichinsky D. A.
Published: July 2002

Metabolic activity was measured in the laboratory at temperatures between 5 and −20°C on the basis of incorporation of
14
C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5°C) to 20 days (−10°C) to ca. 160 days (−20°C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature.
Changes in the Carriage of
Campylobacter
Strains by Poultry Carcasses during Processing in Abattoirs
Authors: Newell D. G. , Shreeve J. E. , Toszeghy M. , Domingue G. , Bull S. , Humphrey T. , Mead G.
Published: July 2002

The recent development of simple, rapid genotyping techniques for
Campylobacter
species has enabled investigation of the determinative epidemiology of these organisms in a variety of situations. In this study we have used the technique of
fla
typing (PCR-restriction fragment length polymorphism analysis of the
flaA
and
flaB
genes) to identify the sources of strains contaminating the carcasses of five campylobacter-positive and two campylobacter-negative broiler flocks during abattoir processing. The results confirmed that, in the United Kingdom, individual broiler flocks are colonized by a limited number of subtypes of
Campylobacter jejuni
or
C. coli
. In some but not all cases, the same subtypes, isolated from the ceca, contaminated the end product as observed in carcass washes. However, the culture methodology, i.e, use of direct plating or enrichment, affected this subtype distribution. Moreover, the number of isolates analyzed per sample was limited.
fla
typing also indicated that some campylobacter subtypes survive poultry processing better than others. The extent of resistance to the environmental stresses during processing varied between strains. The more robust subtypes appeared to contaminate the abattoir environment, surviving through carcass chilling, and even carrying over onto subsequent flocks. From these studies it is confirmed that some campylobacter-negative flocks reach the abattoir but the carcasses from such flocks are rapidly contaminated by various campylobacter subtypes during processing. However, only some of these contaminating subtypes appeared to survive processing. The sources of this contamination are not clear, but in both negative flocks, campylobacters of the same subtypes as those recovered from the carcasses were isolated from the crates used to transport the birds. In one case, this crate contamination was shown to be present before the birds were loaded.
Analysis of the Role of OpuC, an Osmolyte Transport System, in Salt Tolerance and Virulence Potential of
Listeria monocytogenes
Authors: Sleator Roy D. , Wouters Jeroen , Gahan Cormac G. M. , Abee Tjakko , Hill Colin
Published: July 2002

The success of
Listeria monocytogenes
as a food-borne pathogen owes much to its ability to survive a variety of stresses, both in the external environment prior to ingestion and subsequently within the animal host. Growth at high salt concentrations and low temperatures is attributed mainly to the accumulation of organic solutes such as glycine betaine and carnitine. We utilized a novel system for generating chromosomal mutations (based on a lactococcal pWVO1-derived Ori
+
RepA
−
vector, pORI19) to identify a listerial OpuC homologue. Mutating the operon in two strains of
L. monocytogenes
revealed significant strain variation in the observed activity of OpuC. Radiolabeled osmolyte uptake studies, together with growth experiments in defined media, linked OpuC to carnitine and glycine betaine uptake in
Listeria
. We also investigated the role of OpuC in contributing to the growth and survival of
Listeria
in an animal (murine) model of infection. Altering OpuC resulted in a significant reduction in the ability of
Listeria
to colonize the upper small intestine and cause subsequent systemic infection following peroral inoculation.
Cross-Resistance and Stability of Resistance to
Bacillus thuringiensis
Toxin Cry1C in Diamondback Moth
Authors: Liu Yong-Biao , Tabashnik Bruce E. , Meyer Susan K. , Crickmore Neil
Published: July 2002

We tested toxins of
Bacillus thuringiensis
against larvae from susceptible, Cry1C-resistant, and Cry1A-resistant strains of diamondback moth (
Plutella xylostella
). The Cry1C-resistant strain, which was derived from a field population that had evolved resistance to
B. thuringiensis
subsp.
kurstaki
and
B. thuringiensis
subsp.
aizawai
, was selected repeatedly with Cry1C in the laboratory. The Cry1C-resistant strain had strong cross-resistance to Cry1Ab, Cry1Ac, and Cry1F, low to moderate cross-resistance to Cry1Aa and Cry9Ca, and no cross-resistance to Cry1Bb, Cry1Ja, and Cry2A. Resistance to Cry1C declined when selection was relaxed. Together with previously reported data, the new data on the cross-resistance of a Cry1C-resistant strain reported here suggest that resistance to Cry1A and Cry1C toxins confers little or no cross-resistance to Cry1Bb, Cry2Aa, or Cry9Ca. Therefore, these toxins might be useful in rotations or combinations with Cry1A and Cry1C toxins. Cry9Ca was much more potent than Cry1Bb or Cry2Aa and thus might be especially useful against diamondback moth.
Purification and Characterization of a Dimethoate-Degrading Enzyme of
Aspergillus niger
ZHY256, Isolated from Sewage
Authors: Liu Yu-Huan , Chung Ying-Cheng , Xiong Ya
Published: July 2002

A dimethoate-degrading enzyme from
Aspergillus niger
ZHY256 was purified to homogeneity with a specific activity of 227.6 U/mg of protein. The molecular mass of the purified enzyme was estimated to be 66 kDa by gel filtration and 67 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point was found to be 5.4, and the enzyme activity was optimal at 50°C and pH 7.0. The activity was inhibited by most of the metal ions and reagents, while it was induced by Cu
2+
. The Michaelis constant (
K

m

) and
V
max
for dimethoate were 1.25 mM and 292 μmol min
−1
mg of protein
−1
, respectively.