bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very low damage etching of GaAs
Authors: Murad S. K. , Wilkinson C. D. W. , Wang P. D. , Parkes W. , Sotomayor-Torres C. M. , Cameron N. 
Published: July 2002

A very low damage, anisotropic and selective reactive ion etching process has been developed using SiCl4 for etching GaAs which stops on extremely thin GaAlAs layer (4 monolayers 1.13 nm thick). Using low rf powers of ≤15 W, and hence low dc biases of 40 to ≤70 V, pressures of 8 mTorr and flow rates of 4–6 sccm, the damage was kept to a minimum value while maintaining very good anisotropy. Both the surface and sidewall damage were measured and the results were confirmed by evaluation of the performance of a metal–semiconductor field effect transistor (MESFET) with a recessed gate. Raman scattering studies of the etched surface of a heavily doped GaAs layer show that the surface damage thickness is only 3–4 nm after 2 min of etching. The damage depth increases and saturates at 9 nm after 4 min of etching (etch rate of ∼100 nm/min).
Conductance measurements [S. Thoms, S. P. Beaumont, C. D. W. Wilkinson, J. Frost, and C. R. Stanley, in Microcircuit Engineering, edited by H. W. Lehman and Ch. Bleicher (North Holland, Amsterdam, 1986), p. 249] of narrow wires formed in n+-GaAs by etching at dc biases of 40–70 V show that the sidewall damage is negligible (1 nm/sidewall) after the first 2 min of etching. This value increases to 5 nm/sidewall after 3 min etching and to 12 nm/sidewall after 5 min. This is far lower than the value 18 nm/sidewall obtained by etching for 2 min at dc biases of 200 V. Control of the transconductance of the GaAs MESFETs by wet recess etching is difficult. Dry etching to a thin stop layer is a better method, provided it is damage-free. A ratio of etching rates of GaAs: Ga0.7Al0.3As of ≳10 000:1 on a 4 monolayer thick Ga0.7Al0.3As was obtained. On existing FET device wafers with a 5 nm GaAlAs stop layer, after 2 min etching which is sufficient to come to the stop layer, the transconductance was 4.02 mS, after 5 min etching was 3.67 mS and after 12 min was 2.05 mS. Optical emission spectroscopy revealed that the dominant emitting species in the plasma are Si, SiCl, SiCl2, and Cl. The variation of emission intensity of these species with power reveals clearly the presence of two distinct etch mechanisms, one below and one above 15 W (0.066 W/cm2) power density.
The etch rate does not increase monotonically with power.
Developmental Neurobiology
Authors: Hines Pamela J. , Marx Jean 
Published: July 2002

T
he nervous system, once thought to be so complicated that it would defy our efforts to understand it, has begun to yield its secrets with accelerating speed. Indeed, researchers' efforts to understand how the nervous system develops have succeeded to the point that Martin Raff of London's University College can aptly describe the progress as "staggering" in the guest
Editorial
that opens this Special Issue on Developmental Neurobiology. The articles in this issue describe some of that staggering progress.

Two deal with the earliest stages of vertebrate neurodevelopment, from the first formation of the neural ectoderm, the tissue that will give rise to the brain and spinal cord, to the later division of the central nervous system into the regions that will go on to acquire specific functions. Using the hindbrain and midbrain as examples,
A. Lumsden and R. Krumlauf
focus on how the overall anterior-posterior pattern of the nervous system is specified. Both the Hox genes and a variety of signaling molecules, such as retinoic acid, are important players in establishing the fates of these early cells. In their article,
Y. Tanabe and T. M. Jessell
Y. Tanabe and T. M. Jessell take up dorsal-ventral patterning. Here the spinal cord serves as a useful example. Signals, such as Sonic Hedgehog, emanate from the floor plate of the spinal cord and the underlying notochord to direct the fate of the spinal neurons.

As neurons acquire particular identities, they begin forming the interconnections that wire the mature nervous system. M. Tessier-Lavigne and C. S. Goodman describe axon guidance, the process by which a growing axon finds a reasonable route toward a likely target. The signposts along the way include both soluble and nondiffusible molecules, which give instructions that can either attract or repel the elongating axon.
Once the neural circuits are roughly sketched in early development, their final structure is refined by neuronal activity. L. C. Katz and C. J. Shatz discuss how both sensory experience and spontaneous neural activity can polish the final development of functional neural circuits as well as enable the mature central nervous system to respond to changing inputs.

To complement these articles, the News report offers two stories.
One
describes the human and mouse mutations that are helping reveal the molecules that guide newborn cortical neurons to their final destinations in the brain;
another
examines new developments in understanding the plasticity of the neuromuscular junction, findings that may also shed light on learning and memory.

And finally,
F. E. BlooM
provides an analysis of the neuroscience resources available on the World Wide Web, including those devoted to the intersection of neuroscience and developmental biology.
Mouse-Colonizing
Helicobacter pylori
SS1 Is Unusually Susceptible to Metronidazole Due to Two Complementary Reductase Activities
Authors: Jeong Jin-Yong , Berg Douglas E. 
Published: July 2002

ABSTRACT

In most strains of
Helicobacter pylori
, mutational inactivation of the
rdxA
(HP0954) gene, which encodes a nitroreductase that converts metronidazole (MTZ) from a harmless prodrug to a mutagenic and bacteriocidal product, is sufficient to make this pathogen resistant to clinically significant levels of MTZ. Here we report that SS1, a strain with the special ability to colonize mice, is unusual in being susceptible to very low concentrations of MTZ (0.5 μg/ml) and in being especially difficult to mutate to MTZ resistance (Mtz
r
). These phenotypic traits were traced to expression in this strain of the normally quiescent
H. pylori frxA
gene (HP0642, an
rdxA
paralog) along with rdxA. Transformation tests using
rdxA
::
cam
and
frxA
::
kan
insertion mutant DNAs, with selection solely for the chloramphenicol and kanamycin resistance markers, and sequence analyses of
frxA
in spontaneous Mtz
r
derivatives of
rdxA
null mutant strains each showed that the development of Mtz
r
in SS1 required inactivation of both
rdxA
and
frxA
. Inactivation of either gene alone left SS1 susceptible to MTZ, although it was readily mutable from an MTZ-susceptible to an Mtz
r
phenotype. Reverse transcriptase PCR tests showed that
frxA
mRNA was at least 10-fold more abundant in SS1 than in reference strain 26695. It is proposed that these reductases play primarily nutritional roles during bacterial growth.
Mutations in Ribosomal Protein L16 Conferring Reduced Susceptibility to Evernimicin (SCH27899): Implications for Mechanism of Action
Authors: Adrian Peter V. , Zhao Wenjun , Black Todd A. , Shaw Karen J. , Hare Roberta S. , Klugman Keith P. 
Published: July 2002

ABSTRACT

A clinical isolate of
Streptococcus pneumoniae
(SP#5) that showed decreased susceptibility to evernimicin (MIC, 1.5 μg/ml) was investigated. A 4,255-bp
Eco
RI fragment cloned from SP#5 was identified by its ability to transform evernimicin-susceptible
S. pneumoniae
R6 (MIC, 0.03 μg/ml) such that the evernimicin MIC was 1.5 μg/ml. Nucleotide sequence analysis of this fragment revealed that it contained portions of the S10-
spc
ribosomal protein operons. The nucleotide sequences of resistant and susceptible isolates were compared, and a point mutation (thymine to guanine) that causes an Ile52-Ser substitution in ribosomal protein L16 was identified. The role of this mutation in decreasing susceptibility to evernimicin was confirmed by direct transformation of the altered L16 gene. The presence of the L16 mutation in the resistant strain suggests that evernimicin is an inhibitor of protein synthesis. This was confirmed by inhibition studies using radiolabeled substrates, which showed that the addition of evernimicin at sub-MIC levels resulted in a rapid decrease in the incorporation of radiolabeled isoleucine in a susceptible isolate (SP#3) but was much less effective against SP#5. The incorporation of isoleucine showed a linear response to the dose level of evernimicin. The incorporation of other classes of labeled substrates was unaffected or much delayed, indicating that these were secondary effects.
Efficacies of Imipenem, Meropenem, Cefepime, and Ceftazidime in Rats with Experimental Pneumonia Due to a Carbapenem-Hydrolyzing β-Lactamase-Producing Strain of
Enterobacter cloacae
Authors: Mimoz Olivier , Leotard Sophie , Jacolot Anne , Padoin Christophe , Louchahi Kamel , Petitjean Olivier , Nordmann Patrice 
Published: July 2002

ABSTRACT

The antibacterial activities of imipenem-cilastatin, meropenem-cilastatin, cefepime and ceftazidime against
Enterobacter cloacae
NOR-1, which produces the carbapenem-hydrolyzing β-lactamase NmcA and a cephalosporinase, and against one of its in vitro-obtained ceftazidime-resistant mutant were compared by using an experimental model of pneumonia with immunocompetent rats. The MICs of the β-lactams with an inoculum of 5 log
10
CFU/ml were as follows for
E. cloacae
NOR-1 and its ceftazidime-resistant mutant, respectively: imipenem, 16 and 128 μg/ml, meropenem, 4 and 32 μg/ml, cefepime, <0.03 and 1 μg/ml, and ceftazidime, 1 and 512 μg/ml. The chromosomally located cephalosporinase and carbapenem-hydrolyzing β-lactamase NmcA were inducible by cefoxitin and meropenem in
E. cloacae
NOR-1, and both were stably overproduced in the ceftazidime-resistant mutant. Renal impairment was induced (uranyl nitrate, 1 mg/kg of body weight) in rats to simulate the human pharmacokinetic parameters for the β-lactams studied. Animals were intratracheally inoculated with 8.5 log
10
CFU of
E. cloacae
, and therapy was initiated 3 h later. At that time, animal lungs showed bilateral pneumonia containing more than 6 log
10
CFU of
E. cloacae
per g of tissue. Despite the relative low MIC of meropenem for
E. cloacae
NOR-1, the carbapenem-treated rats had no decrease in bacterial counts in their lungs 60 h after therapy onset compared to the counts for the controls, regardless of whether
E. cloacae
NOR-1 or its ceftazidime-resistant mutant was inoculated. A significant decrease in bacterial titers was observed for the ceftazidime-treated rats infected with
E. cloacae
NOR-1 only. Cefepime was the only β-lactam tested effective as treatment against infections due to
E. cloacae
NOR-1 or its ceftazidime-resistant mutant.
Antiviral Properties of a Series of 1,6-Naphthyridine and 7,8-Dihydroisoquinoline Derivatives Exhibiting Potent Activity against Human Cytomegalovirus
Authors: Bedard Jean , May Suzanne , L'Heureux Lucille , Stamminger Thomas , Copsey Alice , Drach John , Huffman John , Chan Laval , Jin Haolun , Rando Robert F. 
Published: July 2002

ABSTRACT

A series of 1,6-naphthyridine (L. Chan, H. Jin, T. Stefanac, J. F. Lavallee, G. Falardeau, W. Wang, J. Bedard, S. May, and L. Yuen, J. Med. Chem. 42:3023–3025, 1999) and isoquinoline (L. Chan, H. Jin, T. Stefanac, W. Wang, J. F. Lavallee, J. Bedard, and S. May, Bioorg. Med. Chem. Lett. 9:2583–2586, 1999) analogues exhibiting a high level of anti-human cytomegalovirus (HCMV) activity were investigated in a series of studies aimed at better understanding the mechanism of action of some representatives of this class of compounds. In vitro antiviral profiling revealed that these compounds were active against a narrow spectrum of viruses, essentially the human herpesviruses and type 2 rhinovirus. In HCMV assays, a 39- to 223-fold lower 50% inhibitory concentration was obtained for compound A1 than for ganciclovir against strains AD 169 and Towne. In addition, ganciclovir, foscarnet, cidofovir, and BDCRB (2-bromo-5,6-dichloro-1-β-
d
-ribofuranosylbenzimidazole)-resistant HCMV strains remained susceptible to 1,6-naphthyridines and 7,8-dihydroisoquinolines tested in this study, supporting the view that a novel mechanism of action could be involved. Drug combination studies showed a small but significant synergistic antiviral effect between compound B2 and ganciclovir. Cytotoxicity profiling of representative compounds under various cell growth conditions indicated a generally similar cytotoxic effect, relative to ganciclovir, in log-phase growing cells. However, in stationary cells, a relatively higher level of toxicity was observed than that for control compound. Effect of time of drug addition showed that the anti-HCMV activity of compound A1, ganciclovir, and cidofovir was lost at approximately the same time (72 h postinfection), indicating that the compound was affecting events at the early and late stage of virus replication. This interpretation is also supported by reduction of de novo synthesis of pp65 tegument protein and lack of any effect of the compound on viral adsorption. A reduction of the HCMV enhancer-promoter-directed luciferase expression was also observed in a stably transfected cell line when compound A1 was present at relatively high concentrations.
Effects of Mutations in Ribosomal Protein L16 on Susceptibility and Accumulation of Evernimicin
Authors: McNicholas Paul M. , Mann Paul A. , Najarian David J. , Miesel Lynn , Hare Roberta S. , Black Todd A. 
Published: July 2002

ABSTRACT

Chemical mutagenesis of
Staphylococcus aureus
RN450 generated two strains that displayed a stable reduction (30- to 60-fold) in susceptibility to evernimicin. Cell-free translation reactions demonstrated that the resistance determinant was located in the ribosomal fraction. Compared to ribosomes isolated from a wild-type strain, ribosomes from the mutant strains displayed an 8- to 10-fold reduction in affinity for [
14
C]evernimicin. In contrast, the mutants displayed no alteration in either binding affinity or in vitro susceptibility to erythromycin. Exponential cultures of the mutant strains accumulated significantly less [
14
C]evernimicin than the wild-type strain, suggesting that accumulation is dependent on the high affinity that evernimicin displays for its binding site. Sequencing
rplP
(encodes ribosomal protein L16) in the mutant strains revealed a single base change in each strain, which resulted in a substitution of either cysteine or histidine for arginine at residue 51. Introduction of a multicopy plasmid carrying wild-type
rplP
into the mutant strains restored sensitivity to evernimicin, confirming that the alterations in
rplP
were responsible for the change in susceptibility. Overexpression of the mutant alleles in
S. aureus
RN450 had no effect on susceptibility to evernimicin, demonstrating that susceptibility is dominant over resistance.
Inhibition of Isoniazid-Induced Expression of
Mycobacterium tuberculosis
Antigen 85 in Sputum: Potential Surrogate Marker in Tuberculosis Chemotherapy Trials
Authors: Wallis Robert S. , Phillips Manijeh , Johnson John L. , Teixeira Luciléia , Rocha Lia Márcia Massini Canedo , Maciel Ethel , Rose Lynn , Wells Charles , Palaci Moisés , Dietze Reynaldo , Eisenach Kathleen , Ellner Jerrold J. 
Published: July 2002

ABSTRACT

Mycobacterium tuberculosis
antigen 85 is induced in vitro by isoniazid (INH); its sustained induction in sputum during tuberculosis (TB) therapy predicts relapse. In this trial, rifampin or rifalazil inhibited the induction of sputum antigen 85 by INH in a dose-dependent fashion. This approach may facilitate the evaluation of new TB drugs.
Antimicrobial Activities of Gatifloxacin against Nosocomial Isolates of
Stenotrophomonas maltophilia
Measured by MIC and Time-Kill Studies
Authors: Cohn Michael L. , Waites Ken B. 
Published: July 2002

ABSTRACT

We determined in vitro activities of gatifloxacin and seven other drugs against 100 isolates of
Stenotrophomonas maltophilia
using the agar gradient diffusion (Etest) method. Percentages of susceptible isolates were as follows: trimethoprim-sulfamethoxazole, 90%; gatifloxacin, 71%; levofloxacin, 57%; ticarcillin-clavulanic acid, 54%; ceftazidime, 49%; ciprofloxacin, 29%; cefepime, 21%; and piperacillin-tazobactam, 20%. Time-kill studies of three isolates indicated that gatifloxacin was bactericidal at times as early as 3 h of incubation when tested at concentrations equivalent to twice the MIC (two isolates) and 4 times the MIC (one isolate).
Mechanism of Therapeutic Effectiveness of Cefixime against Typhoid Fever
Authors: Matsumoto Yoshimi , Ikemoto Akiko , Wakai Yoshimi , Ikeda Fumiaki , Tawara Shuichi , Matsumoto Keizo 
Published: July 2002

ABSTRACTβ-Lactams have been considered ineffective against organisms growing inside mammalian cells because of their poor penetration into cells. However, cefixime has been shown to be clinically effective against typhoid fever. The probable mechanism of therapeutic effectiveness of cefixime against typhoid fever was investigated usingSalmonella entericaserovar Typhimurium instead ofS. entericaserovar Typhi both in a cellular and in a mouse infection model. Cefixime was able to inhibit the growth of serovar Typhimurium inhabiting monocyte-derived THP-1 cells. Elongation of serovar Typhimurium in THP-1 cells was observed microscopically. Apparent morphological changes of serovar Typhimurium in THP-1 cells were also observed by electron microscopy. The concentration of cefixime inside THP-1 cells was almost half (46 to 48%) of the concentration outside the cells when serovar Typhimurium coexisted in the solution. The length of time after oral dosing (8 mg/kg) that cefixime was present—calculated from levels in serum—at a concentration above the MIC at which 90% of the serovar Typhi organisms inside human cells were inhibited was presumed to be more than 12 h. Cefixime also showed excellent activity in the mouse systemic and oral infection models based on infections caused by serovar Typhimurium. It is concluded that a fair amount of cefixime can enter mammalian cells and inhibit the growth of bacteria inside cells when the bacteria are sensitive enough to cefixime, as are serovars Typhimurium and Typhi.
Development of Genetic Tools for
Lactobacillus sakei
: Disruption of the β-Galactosidase Gene and Use of
lacZ
as a Reporter Gene To Study Regulation of the Putative Copper ATPase, AtkB
Authors: Stentz Régis , Loizel Christophe , Malleret Christine , Zagorec Monique 
Published: July 2002

ABSTRACT

Downstream from the
ptsHI
operon of
Lactobacillus sakei
, the genes
atkY
and
atkB
, organized in an operon, were observed. The two putative proteins, AtkB and AtkY, show sequence similarity to the
Enterococcus hirae
copper P-type ATPase, responsible for copper efflux, and its negative regulator. Characterization of AtkB as a copper P-type ATPase could not be demonstrated since an
atkB
mutant did not show any phenotype. Thus, another strategy was followed in order to investigate the transcriptional regulation of the
atkYB
locus, leading to the development of new genetic tools for
L. sakei
. A plasmid was constructed, the use of which allowed gene replacement at the
lacLM
locus in
L. sakei
by two successive crossovers. A strain deleted of the
lacLM
operon encoding the β-galactosidase of
L. sakei
was constructed by this method, and the
Escherichia coli lacZ
gene could then be used as a reporter gene to investigate the regulation of
atkYB
. Results show that the
atkYB
operon is induced by small concentrations of CuSO
4
(30 to 40 μM) but not when CuSO
4
is omitted or added at higher concentrations.
Generation of New Hydrogen-Recycling
Rhizobiaceae
Strains by Introduction of a Novel
hup
Minitransposon
Authors: Báscones Elena , Imperial Juan , Ruiz-Argüeso Tomás , Palacios Jose Manuel 
Published: July 2002

ABSTRACT

Hydrogen evolution by nitrogenase is a source of inefficiency for the nitrogen fixation process by the
Rhizobium
-legume symbiosis. To develop a strategy to generate rhizobial strains with H
2
-recycling ability, we have constructed a Tn
5
derivative minitransposon (TnHB100) that contains the ca. 18-kb H
2
uptake (
hup
) gene cluster from
Rhizobium leguminosarum
bv. viciae UPM791. Bacteroids from TnHB100-containing strains of
R. leguminosarum
bv. viciae PRE,
Bradyrhizobium japonicum
,
R. etli
, and
Mesorhizobium loti
expressed high levels of hydrogenase activity that resulted in full recycling of the hydrogen evolved by nitrogenase in nodules. Efficient processing of the hydrogenase large subunit (HupL) in these strains was shown by immunoblot analysis of bacteroid extracts. In contrast,
Sinorhizobium meliloti
,
M. ciceri
, and
R. leguminosarum
bv. viciae UML2 strains showed poor expression of the
hup
system that resulted in H
2
-evolving nodules. For the latter group of strains, no immunoreactive material was detected in bacteroid extracts using anti-HupL antiserum, suggesting a low level of transcription of
hup
genes or HupL instability. A general procedure for the characterization of the minitransposon insertion site and removal of antibiotic resistance gene included in TnHB100 has been developed and used to generate engineered strains suitable for field release.
A Food-Grade Cloning System for Industrial Strains of
Lactococcus lactis
Authors: Sørensen Kim I. , Larsen Rasmus , Kibenich Annette , Junge Mette P. , Johansen Eric 
Published: July 2002

ABSTRACT

We have previously reported the construction of a food-grade cloning vector for
Lactococcus
using the ochre suppressor,
supB
, as the selective marker. This vector, pFG1, causes only a slight growth inhibition in the laboratory strain MG1363 but is unstable in the industrial strains tested. As
supB
suppresses both amber and ochre stop codons, which are present in 82% of all known lactococcal genes, this undesirable finding may result from the accumulation of elongated mistranslated polypeptides. Here, we report the development of a new food-grade cloning vector, pFG200, which is suitable for overexpressing a variety of genes in industrial strains of
Lactococcus lactis
. The vector uses an amber suppressor,
supD
, as selectable marker and consists entirely of
Lactococcus
DNA, with the exception of a small polylinker region. Using suppressible pyrimidine auxotrophs, selection and maintenance are efficient in any pyrimidine-free medium including milk. Importantly, the presence of this vector in a variety of industrial strains has no significant effect on the growth rate or the rate of acidification in milk, making this an ideal system for food-grade modification of industrially relevant
L. lactis
strains. The usefulness of this system is demonstrated by overexpressing the
pepN
gene in a number of industrial backgrounds.
Magnetic Bead Capture Eliminates PCR Inhibitors in Samples Collected from the Airborne Environment, Permitting Detection of
Pneumocystis carinii
DNA
Authors: Maher Nancy , Dillon H. Kenneth , Vermund Sten H. , Unnasch Thomas R. 
Published: July 2002

ABSTRACT

PCR detection methods are useful in studies of organisms not amenable to culture. Inhibitors in environmental samples can interfere with such assays. We describe a magnetic bead DNA capture protocol that removes inhibitors from outdoor air samples, maintaining the sensitivity of a 16S
Pneumocystis carinii
mitochondrial rRNA gene-based PCR.