bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose‐response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron‐produced monochromatic x‐ray beams
Authors: Brown Thomas A. D. , Hogstrom Kenneth R. , Alvarez Diane , Matthews Kenneth L. , Ham Kyungmin , Dugas Joseph P. 
Published: November 2012

Purpose:This work investigates the dose‐response curves of GAFCHROMIC® EBT, EBT2, and EBT3 radiochromic films using synchrotron‐produced monochromatic x‐ray beams. EBT2 film is being utilized for dose verification in photoactivated Auger electron therapy at the Louisiana State University Center for Advanced Microstructures and Devices (CAMD) synchrotron facility.Methods:Monochromatic beams of 25, 30, and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth‐dose measurements were used to determine the dose delivered to films irradiated at depths from 0.7 to 8.5 cm in a 10 × 10 × 10‐cm3 polymethylmethacrylate phantom. AAPM TG‐61 protocol was applied to convert measured ionization into dose. Films were digitized using an Epson 1680 Professional flatbed scanner and analyzed using the net optical density (NOD) derived from the red channel. A dose‐response curve was obtained at 35 keV for EBT film, and at 25, 30, and 35 keV for EBT2 and EBT3 films. Calibrations of films for 4 MV x‐rays were obtained for comparison using a radiotherapy accelerator at Mary Bird Perkins Cancer Center.Results:The sensitivity (NOD per unit dose) of EBT film at 35 keV relative to that for 4‐MV x‐rays was 0.73 and 0.76 for doses 50 and 100 cGy, respectively. The sensitivity of EBT2 film at 25, 30, and 35 keV relative to that for 4‐MV x‐rays varied from 1.09–1.07, 1.23–1.17, and 1.27–1.19 for doses 50–200 cGy, respectively. For EBT3 film the relative sensitivity was within 3% of unity for all three monochromatic x‐ray beams.Conclusions:EBT and EBT2 film sensitivity showed strong energy dependence over an energy range of 25 keV–4 MV, although this dependence becomes weaker for larger doses. EBT3 film shows weak energy dependence, indicating that it would be a better dosimeter for kV x‐ray beams where beam hardening effects can result in large changes in the effective energy.
In Vitro
Interaction of Voriconazole and Anidulafungin against Triazole-Resistant Aspergillus fumigatus
Authors: Seyedmousavi Seyedmojtaba , Meletiadis Joseph , Melchers Willem J. G. , Rijs Antonius J. M. M. , Mouton Johan W. , Verweij Paul E. 
Published: November 2012

ABSTRACT

Voriconazole is the recommended drug of first choice to treat infections caused by
Aspergillus fumigatus
. The efficacy of voriconazole might be hampered by the emergence of azole resistance. However, the combination of voriconazole with anidulafungin could improve therapeutic outcomes in azole-resistant invasive aspergillosis (IA). The
in vitro
interaction between voriconazole and anidulafungin was determined against voriconazole-susceptible and voriconazole-resistant (substitutions in the
cyp51A
gene, including single point [M220I and G54W] and tandem repeat [34-bp tandem repeat in the promoter region of the
cyp51A
gene in combination with substitutions at codon L98 and 46-bp tandem repeat in the promoter region of the
cyp51A
gene in combination with mutation at codons Y121 and T289] mutations) clinical
A. fumigatus
isolates using a checkerboard microdilution method with spectrophotometric analysis and a viability-based XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} assay within 2 h of exposure after 24 and 48 h of incubation at 35°C to 37°C. Fractional inhibitory concentration (FIC) indexes (FICis) were determined using different MIC endpoints and Bliss independence analysis performed based on the response surface calculation of the no-drug interaction. Significant synergistic interactions obtained based on measuring the FIC index were dependent on the MIC endpoint, in which FICs were inversely related to voriconazole and anidulafungin MICs and were influenced by the CYP51A genotype. A statistically significant difference was observed between FIC indexes of isolates harboring tandem repeat mutations and wild-type controls (
P
= 0.006 by one-way analysis of variance [ANOVA]), indicating that synergy is decreased in azole-resistant strains. Our results indicated that a combination of voriconazole and anidulafungin might be effective against infections caused by both azole-susceptible and azole-resistant
A. fumigatus
isolates, but the combination could possibly be less effective in voriconazole-resistant strains with high MICs. Studies
in vivo
and
in vitro-in vivo
correlation investigations are required to validate the potential synergy of voriconazole and anidulafungin.
R164H and V240H Replacements by Site-Directed Mutagenesis of TEM-149 Extended-Spectrum β-Lactamase: Kinetic Analysis of TEM-149
H240
and TEM-149
H164-H240
Laboratory Mutants
Authors: Perilli Mariagrazia , Celenza Giuseppe , Mercuri Paola Sandra , Galleni Moreno , Pellegrini Cristina , Segatore Bernardetta , Amicosante Gianfranco 
Published: November 2012

ABSTRACT

Two laboratory mutant forms, TEM-149
H240
and TEM-149
H164-H240
, of the TEM-149 extended-spectrum β-lactamase enzyme were constructed by site-directed mutagenesis. TEM-149
H240
and TEM-149
H164-H240
were similar in kinetic behavior, except with respect to benzylpenicillin and ceftazidime. Molecular modeling of the two mutant enzymes demonstrated the role of histidine at position 240 in the reduction of the affinity of the enzyme for ceftazidime.
Population Pharmacokinetic and Pharmacodynamic Properties of Intramuscular Quinine in Tanzanian Children with Severe Falciparum Malaria
Authors: Hendriksen Ilse C. E. , Maiga Deogratius , Lemnge Martha M. , Mtove George , Gesase Samwel , Reyburn Hugh , Lindegardh Niklas , Day Nicholas P. J. , von Seidlein Lorenz , Dondorp Arjen M. , Tarning Joel , White Nicholas J. 
Published: November 2012

ABSTRACT
Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)
Contribution of Structural Domains to the Activity of Ribonuclease 7 against Uropathogenic Bacteria
Authors: Wang Huanyu , Schwaderer Andrew L. , Kline Jennifer , Spencer John David , Kline David , Hains David S. 
Published: November 2012

ABSTRACT

Ribonuclease 7 (RNase 7) is a 14.5-kDa peptide that possesses potent antimicrobial properties against Gram-negative and Gram-positive bacteria and is expressed in a variety of epithelial tissues. Little is known about its mechanisms of action and the determinants of its antimicrobial properties. The objective of this study was to identify the intrinsic functional domains of RNase 7 that influence its activity against uropathogenic bacteria. A series of RNase 7 fragments were generated that contained different components of its secondary motifs starting from both the N terminus and the C terminus of RNase 7. We determined the antimicrobial properties of each fragment against both Gram-positive
Staphylococcus saprophyticus
and Gram-negative
Escherichia coli
and
Proteus mirabilis
. RNase 7 fragments displayed significant differences in their antimicrobial activity profiles. Compared to N-terminal fragments, C-terminal fragments showed uniformly decreased activity against Gram-negative
E. coli
and
P. mirabilis
and Gram-positive
S. saprophyticus
. Fragments that lack β-sheets 1, 3, and 4 also demonstrated significantly decreased activities. We have also identified one fragment with at least 4-fold increased potency against both
E. coli
and
Staphylococcus
compared to full-length peptide. We identified distinct regions of the peptide that are independently responsible for Gram-negative and Gram-positive activity. Our results suggest that distinct mechanisms are responsible for RNase 7's antimicrobial activity against various uropathogens.
HIV-1 Subtype Is an Independent Predictor of Reverse Transcriptase Mutation K65R in HIV-1 Patients Treated with Combination Antiretroviral Therapy Including Tenofovir
Authors: Theys K. , Vercauteren J. , Snoeck J. , Zazzi M. , Camacho R. J. , Torti C. , Schülter E. , Clotet B. , Sönnerborg A. , De Luca A. , Grossman Z. , Struck D. , Vandamme A.-M. , Abecasis A. B. 
Published: November 2012

ABSTRACTSubtype-dependent selection of HIV-1 reverse transcriptase resistance mutation K65R was previously observed in cell culture and small clinical investigations. We compared K65R prevalence across subtypes A, B, C, F, G, and CRF02_AG separately in a cohort of 3,076 patients on combination therapy including tenofovir. K65R selection was significantly higher in HIV-1 subtype C. This could not be explained by clinical and demographic factors in multivariate analysis, suggesting subtype sequence-specific K65R pathways.
A Time-to-Event Pharmacodynamic Model Describing Treatment Response in Patients with Pulmonary Tuberculosis Using Days to Positivity in Automated Liquid Mycobacterial Culture
Authors: Chigutsa Emmanuel , Patel Kashyap , Denti Paolo , Visser Marianne , Maartens Gary , Kirkpatrick Carl M. J. , McIlleron Helen , Karlsson Mats O. 
Published: November 2012

ABSTRACT
Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study were to describe the decline in numbers of mycobacteria in sputum collected once weekly for 8 weeks from patients on treatment for tuberculosis using days to positivity in liquid culture. One hundred forty-four patients with smear-positive pulmonary tuberculosis were recruited from a tuberculosis clinic in Cape Town, South Africa. A nonlinear mixed-effects repeated-time-to-event modeling approach was used to analyze the time-to-positivity data. A biexponential model described the decline in the estimated number of bacteria in patients' sputum samples, while a logistic model with a lag time described the growth of the bacteria in liquid culture. At baseline, the estimated number of rapidly killed bacteria is typically 41 times higher than that of those that are killed slowly. The time to kill half of the rapidly killed bacteria was about 1.8 days, while it was 39 days for slowly killed bacteria. Patients with lung cavitation had higher bacterial loads than patients without lung cavitation. The model successfully described the increase in days to positivity as treatment progressed, differentiating between bacteria that are killed rapidly and those that are killed slowly. Our model can be used to analyze similar data from studies testing new drug regimens.
Inhaled Microparticles Containing Clofazimine Are Efficacious in Treatment of Experimental Tuberculosis in Mice
Authors: Verma Rahul Kumar , Germishuizen Willem A. , Motheo M. Portia , Agrawal Atul Kumar , Singh Amit Kumar , Mohan Mradul , Gupta Pushpa , Gupta Umesh Datta , Cholo Moloko , Anderson Ronald , Fourie P. Bernard , Misra Amit 
Published: November 2012

ABSTRACT

Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against
Mycobacterium tuberculosis
in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 μg/ml
in vitro
. In mice, 480 μg and 720 μg CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log
10
2.6; 500 μg oral CFM achieved a log
10
0.7 reduction.
Rifaximin Resistance in Escherichia coli Associated with Inflammatory Bowel Disease Correlates with Prior Rifaximin Use, Mutations in
rpoB
, and Activity of Phe-Arg-β-Naphthylamide-Inhibitable Efflux Pumps
Authors: Kothary Vishesh , Scherl Ellen J. , Bosworth Brian , Jiang Zhi-Dong , DuPont Herbert L. , Harel Josee , Simpson Kenneth W. , Dogan Belgin 
Published: November 2012

ABSTRACT

Escherichia coli
is implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a nonabsorbable derivative of rifampin effective against
E. coli
, improves symptoms in mild-to-moderate IBD. However, rifaximin resistance can develop in a single step
in vitro
. We examined the prevalence and mechanisms of rifaximin resistance in 62 strains of
E. coli
isolated from the ileal mucosa of 50 patients (19 with ileal Crohn's disease [L1+L3], 6 with colonic Crohn's disease [L2], 13 with ulcerative colitis [UC], 4 with symptomatic non-IBD diagnoses [NI], and 8 healthy [H]). Resistance (MIC > 1,024 mg/liter) was present in 12/48 IBD-associated ileal
E. coli
strains. Resistance correlated with prior rifaximin treatment (
P
< 0.00000001) but not with the presence of ileal inflammation (
P
= 0.73) or
E. coli
phylogroup. Mutations in a 1,057-bp region of
rpoB
, which encodes the bacterial target of rifaximin, were identified in 10/12 resistant strains versus 0/50 sensitive strains (
P
< 0.000000001) and consisted of seven amino acid substitutions. The efflux pump inhibitor Phe-Arg-β-naphthylamide (PAβN) lowered the MIC of 9/12 resistant strains 8- to 128-fold. Resistance was stable in the absence of rifaximin in 10/12 resistant strains after 30 passages. We conclude that IBD-associated ileal
E. coli
frequently manifest resistance to rifaximin that correlates with prior rifaximin use, amino acid substitutions in
rpoB
, and activity of PAβN-inhibitable efflux pumps, but not with the presence of ileal inflammation or
E. coli
phylogroup. These findings have significant implications for treatment trials targeting IBD-associated
E. coli
.
Anaerobic Coculture of Microalgae with Thermosipho globiformans and Methanocaldococcus jannaschii at 68°C Enhances Generation of
n
-Alkane-Rich Biofuels after Pyrolysis
Authors: Yamane Kunio , Matsuyama Shigeru , Igarashi Kensuke , Utsumi Motoo , Shiraiwa Yoshihiro , Kuwabara Tomohiko 
Published: November 2012

ABSTRACT

We tested different alga-bacterium-archaeon consortia to investigate the production of oil-like mixtures, expecting that
n
-alkane-rich biofuels might be synthesized after pyrolysis.
Thermosipho globiformans
and
Methanocaldococcus jannaschii
were cocultured at 68°C with microalgae for 9 days under two anaerobic conditions, followed by pyrolysis at 300°C for 4 days.
Arthrospira platensis
(
Cyanobacteria
),
Dunaliella tertiolecta
(
Chlorophyta
),
Emiliania huxleyi
(
Haptophyta
), and
Euglena gracilis
(
Euglenophyta
) served as microalgal raw materials.
D. tertiolecta
,
E. huxleyi
, and
E. gracilis
cocultured with the bacterium and archaeon inhibited their growth and CH
4
production.
E. huxleyi
had the strongest inhibitory effect. Biofuel generation was enhanced by reducing impurities containing alkanenitriles during pyrolysis. The composition and amounts of
n
-alkanes produced by pyrolysis were closely related to the lipid contents and composition of the microalgae. Pyrolysis of
A. platensis
and
D. tertiolecta
containing mainly phospholipids and glycolipids generated short-carbon-chain
n
-alkanes (
n
-tridecane to
n
-nonadecane) and considerable amounts of isoprenoids.
E. gracilis
also produced mainly short
n
-alkanes. In contrast,
E. huxleyi
containing long-chain (31 and 33 carbon atoms) alkenes and very long-chain (37 to 39 carbon atoms) alkenones, in addition to phospholipids and glycolipids, generated a high yield of
n
-alkanes of various lengths (
n
-tridecane to
n
-pentatriacontane). The gas chromatography-mass spectrometry (GC-MS) profiles of these
n
-alkanes were similar to those of native petroleum crude oils despite containing a considerable amount of
n
-hentriacontane. The ratio of phytane to
n
-octadecane was also similar to that of native crude oils.
Bacterial and Archaeal Diversity in Sediments of West Lake Bonney, McMurdo Dry Valleys, Antarctica
Authors: Tang Chao , Madigan Michael T. , Lanoil Brian 
Published: November 2012

ABSTRACT

Bacterial and archaeal diversity was examined in a sediment core from Lake Bonney, Antarctica. Members of the
Archaea
showed both low abundance and diversity, whereas bacterial diversity was moderately high and some phyla were fairly abundant, even in geologically old samples. Microbial diversity correlated with sample texture and differed in silty and coarse samples.
FLX Pyrosequencing Analysis of the Effects of the Brown-Algal Fermentable Polysaccharides Alginate and Laminaran on Rat Cecal Microbiotas
Authors: An Choa , Kuda Takashi , Yazaki Takahiro , Takahashi Hajime , Kimura Bon 
Published: November 2012

ABSTRACT

Edible brown algae are used as major food material in Far East Asian countries, particularly in South Korea and Japan. They contain fermentable dietary fibers, alginic acid (uronic acid polymer) and laminaran (β-1,3-glucan), that are fermented into organic acids by intestinal bacteria. To clarify the effect of edible algae on the intestinal environment, the cecal microbiotas of rats fed diets containing no dietary fiber (control) or 2% (wt/wt) sodium alginate or laminaran for 2 weeks were analyzed using FLX amplicon pyrosequencing with bar-coded primers targeting the bacterial 16S rRNA gene. The most abundant phylum in all groups was
Firmicutes
. Specifically,
Allobaculum
was dominant in all diet groups. In addition,
Bacteroides capillosus
(37.1%) was abundant in the alginate group, while
Clostridium ramosum
(3.14%) and
Parabacteroides distasonis
(1.36%) were only detected in the laminaran group. Furthermore, rats fed alginate showed simplified microbiota phylotypes compared with others. With respect to cecal chemical compounds, laminaran increased cecal organic acid levels, particularly propionic acid. Alginate increased total cecal organic acids. Cecal putrefactive compounds, such as indole, H
2
S, and phenol, were decreased by both alginate and laminaran. These results indicate that edible brown algae can alter the intestinal environment, with fermentation by intestinal microbiota.
Recombinant Bacillus subtilis That Grows on Untreated Plant Biomass
Authors: Anderson Timothy D. , Miller J. Izaak , Fierobe Henri-Pierre , Clubb Robert T. 
Published: November 2012

ABSTRACT

Lignocellulosic biomass is a promising feedstock to produce biofuels and other valuable biocommodities. A major obstacle to its commercialization is the high cost of degrading biomass into fermentable sugars, which is typically achieved using cellulolytic enzymes from
Trichoderma reesei
. Here, we explore the use of microbes to break down biomass.
Bacillus subtilis
was engineered to display a multicellulase-containing minicellulosome. The complex contains a miniscaffoldin protein that is covalently attached to the cell wall and three noncovalently associated cellulase enzymes derived from
Clostridium cellulolyticum
(Cel48F, Cel9E, and Cel5A). The minicellulosome spontaneously assembles, thus increasing the practicality of the cells. The recombinant bacteria are highly cellulolytic and grew in minimal medium containing industrially relevant forms of biomass as the primary nutrient source (corn stover, hatched straw, and switch grass). Notably, growth did not require dilute acid pretreatment of the biomass and the cells achieved densities approaching those of cells cultured with glucose. An analysis of the sugars released from acid-pretreated corn stover indicates that the cells have stable cellulolytic activity that enables them to break down 62.3% ± 2.6% of the biomass. When supplemented with beta-glucosidase, the cells liberated 21% and 33% of the total available glucose and xylose in the biomass, respectively. As the cells display only three types of enzymes, increasing the number of displayed enzymes should lead to even more potent cellulolytic microbes. This work has important implications for the efficient conversion of lignocellulose to value-added biocommodities.
Metabolic Engineering of Synechocystis sp. Strain PCC 6803 for Isobutanol Production
Authors: Varman Arul M. , Xiao Yi , Pakrasi Himadri B. , Tang Yinjie J. 
Published: November 2012

ABSTRACT

Global warming and decreasing fossil fuel reserves have prompted great interest in the synthesis of advanced biofuels from renewable resources. In an effort to address these concerns, we performed metabolic engineering of the cyanobacterium
Synechocystis
sp. strain PCC 6803 to develop a strain that can synthesize isobutanol under both autotrophic and mixotrophic conditions. With the expression of two heterologous genes from the Ehrlich pathway, the engineered strain can accumulate 90 mg/liter of isobutanol from 50 mM bicarbonate in a gas-tight shaking flask. The strain does not require any inducer (i.e., isopropyl β-
d
-1-thiogalactopyranoside [IPTG]) or antibiotics to maintain its isobutanol production. In the presence of glucose, isobutanol synthesis is only moderately promoted (titer = 114 mg/liter). Based on isotopomer analysis, we found that, compared to the wild-type strain, the mutant significantly reduced its glucose utilization and mainly employed autotrophic metabolism for biomass growth and isobutanol production. Since isobutanol is toxic to the cells and may also be degraded photochemically by hydroxyl radicals during the cultivation process, we employed
in situ
removal of the isobutanol using oleyl alcohol as a solvent trap. This resulted in a final net concentration of 298 mg/liter of isobutanol under mixotrophic culture conditions.