bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of out‐of‐field absorbed dose and equivalent dose in proton fields
Authors: Clasie Ben , Wroe Andrew , Kooy Hanne , Depauw Nicolas , Flanz Jay , Paganetti Harald , Rosenfeld Anatoly 
Published: December 2009

PurposeIn proton therapy, as in other forms of radiation therapy, scattered and secondary particles produce undesired dose outside the target volume that may increase the risk of radiation‐induced secondary cancer and interact with electronic devices in the treatment room. The authors implement a Monte Carlo model of this dose deposited outside passively scattered fields and compare it to measurements, determine the out‐of‐field equivalent dose, and estimate the change in the dose if the same target volumes were treated with an active beam scanning technique.MethodsMeasurements are done with a thimble ionization chamber and the Wellhofer MatriXX detector inside a Lucite phantom with field configurations based on the treatment of prostate cancer and medulloblastoma. The authors use aGEANT4 Monte Carlo simulation, demonstrated to agree well with measurements inside the primary field, to simulate fields delivered in the measurements. The partial contributions to the dose are separated in the simulation by particle type and origin.ResultsThe agreement between experiment and simulation in the out‐of‐field absorbed dose is within 30% at 10–20 cm from the field edge and 90% of the data agrees within 2 standard deviations. In passive scattering, the neutron contribution to the total dose dominates in the region downstream of the Bragg peak (65%–80% due to internally produced neutrons) and inside the phantom at distances more than 10–15 cm from the field edge. The equivalent doses using 10 for the neutron weighting factor at the entrance to the phantom and at 20 cm from the field edge are 2.2 and 2.6 mSv/Gy for the prostate cancer and cranial medulloblastoma fields, respectively. The equivalent dose at 15–20 cm from the field edge decreases with depth in passive scattering and increases with depth in active scanning. Therefore, active scanning has smaller out‐of‐field equivalent dose by factors of 30–45 in the entrance region and this factor decreases with depth.ConclusionsThe dose deposited immediately downstream of the primary field, in these cases, is dominated by internally produced neutrons; therefore, scattered and scanned fields may have similar risk of second cancer in this region. The authors confirm that there is a reduction in the out‐of‐field dose in active scanning but the effect decreases with depth.GEANT4 is suitable for simulating the dose deposited outside the primary field. The agreement with measurements is comparable to or better than the agreement reported for other implementations of Monte Carlo models. Depending on the position, the absorbed dose outside the primary field is dominated by contributions from primary protons that may or may not have scattered in the brass collimating devices. This is noteworthy as the quality factor of the low LET protons is well known and the relative dose risk in this region can thus be assessed accurately.
Inclusion of the dose from kilovoltage cone beam CT in the radiation therapy treatment plans
Authors: Alaei Parham , Ding George , Guan Huaiqun 
Published: December 2009

PurposeCone beam CT is increasingly being used for daily patient positioning verification during radiation therapy treatments. The daily use of CBCT could lead to accumulated patient doses higher than the older technique of weekly portal imaging. There have been several studies focusing on measurement or calculation of the patient dose from CBCT recently.MethodsThis study investigates the feasibility of configuring a kV x‐ray source in a commercial treatment planning system to calculate the dose to patient resulting from an IGRT procedure. The method proposed in this article can be used to calculate dose from CBCT imaging procedure and include that in the patient treatment plans.ResultsThe kilovoltage beam generated by the CBCT imager has been modeled using the planning system. The modeled profiles agree with the measured ones to within 5%. The modeled beam was used to calculate dose to phantom in the pelvic region and the calculations were compared to TLD measurements. The agreement between calculated and measured doses ranges from 0% to 19% in soft tissue with larger variations observed near and within the bone.ConclusionsThe modeling of the beam produces reasonable results and the dose calculation comparisons indicate the potential for computing kilovoltage CBCT doses using a treatment planning system. Further improvements in the dose calculation algorithm are necessary, especially for dose calculations in and near the bone.
Performance characterization of a MVCT scanner using multislice thick, segmented cadmium tungstate‐photodiode detectors
Authors: Kirvan P. F. , Monajemi T. T. , Fallone B. G. , Rathee S. 
Published: December 2009

PurposeMegavoltage computed tomography (MVCT) and megavoltage cone beam computed tomography (MVCBCT) can be used for visualizing anatomical structures prior to radiation therapy treatments to assist in patient setup and target localization. These systems are less susceptible to metal artifacts and provide better CT number linearity than conventional CT scanners. However, their contrast is limited by the properties of the megavoltage photons and the low detective quantum efficiency (DQE) of flat panel detector systems currently available. By using higher DQE, thick, segmented cadmium tungstate detectors, the authors can improve the low contrast detectability of a MVCT system. This in turn would permit greater soft tissue visualization for a given radiation dose, allowing MVCT to be used in more clinical situations.MethodsThis article describes the evaluation of our prototype system that uses thick, segmented detectors. In order to create images using a dose that would be acceptable for day to day patient imaging, the authors evaluated their system using the low intensity bremsstrahlung component of a 6 MeV electron beam. The system was evaluated for its uniformity, high contrast resolution, low contrast detectability, signal to noise ratio, contrast to noise ratio, and CT number linearity.ResultsThe prototype system was found to have a high contrast spatial resolution of about 5 line pairs per cm, and to be able to visualize a 15 mm 1.5% contrast target with 2 cGy of radiation dose delivered. vs radiation dose and mean pixel value vs electron density curves were linear.ConclusionsThis prototype system shows a large improvement in low contrast detectability over current MVCBCT systems.
Antimicrobial Susceptibilities of Multidrug-Resistant
Campylobacter jejuni
and
C. coli
Strains:
In Vitro
Activities of 20 Antimicrobial Agents
Authors: Lehtopolku Mirva , Nakari Ulla-Maija , Kotilainen Pirkko , Huovinen Pentti , Siitonen Anja , Hakanen Antti J. 
Published: December 2009

ABSTRACT

There is a paucity of information regarding antimicrobial agents that are suitable to treat severe infections caused by multidrug-resistant
Campylobacter
spp. Our aim was to identify agents that are potentially effective against multiresistant
Campylobacter
strains. The
in vitro
activities of 20 antimicrobial agents against 238
Campylobacter
strains were analyzed by determining MICs by the agar plate dilution method or the Etest. These strains were selected from 1,808
Campylobacter
isolates collected from Finnish patients between 2003 and 2005 and screened for macrolide susceptibility by using the disk diffusion test. The 238 strains consisted of 183 strains with erythromycin inhibition zone diameters of ≤23 mm and 55 strains with inhibition zone diameters of >23 mm. Of the 238
Campylobacter
strains, 19 were resistant to erythromycin by MIC determinations (MIC ≥ 16 μg/ml). Given that the resistant strains were identified among the collection of 1,808 isolates, the frequency of erythromycin resistance was 1.1%. All erythromycin-resistant strains were multidrug resistant, with 18 (94.7%) of them being resistant to ciprofloxacin (MIC ≥ 4 μg/ml). The percentages of resistance to tetracycline and amoxicillin-clavulanic acid (co-amoxiclav) were 73.7% and 31.6%, respectively. All macrolide-resistant strains were susceptible to imipenem, meropenem, and tigecycline. Ten (52.6%) multiresistant strains were identified as being
Campylobacter jejuni
strains, and 9 (47.4%) were identified as being
C. coli
strains. These data demonstrate that the incidence of macrolide resistance was low but that the macrolide-resistant
Campylobacter
strains were uniformly multidrug resistant. In addition to the carbapenems, tigecycline was also highly effective against these multidrug-resistant
Campylobacter
strains
in vitro
. Its efficacy for the treatment of human campylobacteriosis should be evaluated in clinical trials.
Inhibition of
Porphyromonas gingivalis
Biofilm by Oxantel
Authors: Dashper Stuart , Ang Ching-Seng , Liu Sze Wei , Paolini Rita , Veith Paul , Reynolds Eric 
Published: December 2009

ABSTRACT

Porphyromonas gingivalis
is a major pathogen of chronic periodontitis and exists in a biofilm on the surface of the tooth root. Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by
P. gingivalis
and disrupted established biofilms at concentrations below its MIC against planktonic cells. Oxantel was more effective against
P. gingivalis
in biofilm than metronidazole, a commonly used antibiotic for periodontitis.
Clinical Pharmacokinetics of Oral Controlled-Release 5-Fluorocytosine
Authors: Pai Manjunath P. , Bruce Hollie , Felton Linda A. 
Published: December 2009

ABSTRACT

5-Fluorocytosine (5FC) is an oral antifungal that is currently used in combination with amphotericin B to treat
Cryptococcus neoformans
meningoencephalitis. The oral dosing of 5FC could be optimized by the use of a controlled-release (CR) formulation. The objective of the current study was to develop two prototype 5FC-CR formulations and evaluate the single-dose (1,500-mg) serum pharmacokinetic profiles of those formulations relative to the profile of the commercially available, immediate-release 5FC product (Ancobon) by the use of a phase 1, open-label, randomized, three-phase, crossover pharmacokinetic study design. Hydroxypropyl methylcellulose was utilized as the rate-controlling matrix to compound the 5FC-CR tablets. The two prototype 5FC-CR formulations demonstrated 80% release at 13.0 and 18.4 h, respectively, whereas the immediate-release product demonstrated 80% release at 0.28 h, as determined
in vitro
by the United States Pharmacopeia apparatus 2 dissolution method. Five subjects completed all three phases of the study without any adverse events. The mean maximum concentration, the area under the curve from time zero to 24 h, and the area under the curve from time zero to infinity were approximately 50% lower (
P
< 0.01) with the 5FC-CR formulations than with the immediate-release 5FC product. However, no statistically significant differences in the minimum concentrations at 24 h were noted between the formulations. The gastric absorption profile of 5FC-CR was well predicted by
in vitro
dissolution. Future exploration of a gastroretentive 5FC-CR formulation could overcome the marked lack of bioequivalence observed in the present study.
Clinical Pharmacodynamics of Cefepime in Patients Infected with
Pseudomonas aeruginosa
Authors: Crandon Jared L. , Bulik Catharine C. , Kuti Joseph L. , Nicolau David P. 
Published: December 2009

ABSTRACT

We evaluated cefepime exposures in patients infected with
Pseudomonas aeruginosa
to identify the pharmacodynamic relationship predictive of microbiological response. Patients with non-urinary tract
P. aeruginosa
infections and treated with cefepime were included. Free cefepime exposures were estimated by using a validated population pharmacokinetic model.
P. aeruginosa
MICs were determined by Etest and pharmacodynamic indices (the percentage of the dosing interval that the free drug concentration remains above the MIC of the infecting organism [
f
T
> MIC], the ratio of the minimum concentration of free drug to the MIC [
f
C
min
/MIC], and the ratio of the area under the concentration-time curve for free drug to the MIC [
f
AUC/MIC]) were calculated for each patient. Classification and regression tree analysis was used to partition the pharmacodynamic parameters for prediction of the microbiological response. Monte Carlo simulation was utilized to determine the optimal dosing regimens needed to achieve the pharmacodynamic target. Fifty-six patients with pneumonia (66.1%), skin and skin structure infections (SSSIs) (25%), and bacteremia (8.9%) were included. Twenty-four (42.9%) patients failed cefepime therapy. The MICs ranged from 0.75 to 96 μg/ml, resulting in median
f
T
> MIC,
f
C
m
in
/MIC, and
f
AUC/MIC exposures of 100% (range, 0.8 to 100%), 4.3 (range, 0.1 to 27.3), and 206.2 (range, 4.2 to 1,028.7), respectively. Microbiological failure was associated with an
f
T
> MIC of ≤60% (77.8% failed cefepime therapy when
f
T
> MIC was ≤60%, whereas 36.2% failed cefepime therapy when
f
T
> MIC was >60%;
P
= 0.013). A similar
f
T
> MIC target of ≤63.9% (
P
= 0.009) was identified when skin and skin structure infections were excluded. While controlling for the SSSI source (odds ratio [OR], 0.18 [95% confidence interval, 0.03 to 1.19];
P
= 0.07) and combination therapy (OR, 2.15 [95% confidence interval, 0.59 to 7.88];
P
= 0.25), patients with
f
T
> MIC values of ≤60% were 8.1 times (95% confidence interval, 1.2 to 55.6 times) more likely to experience a poor microbiological response. Cefepime doses of at least 2 g every 8 h are required to achieve this target against CLSI-defined susceptible
P. aeruginosa
organisms in patients with normal renal function. In patients with non-urinary tract infections caused by
P. aeruginosa
, achievement of cefepime exposures of >60%
f
T
> MIC will minimize the possibility of a poor microbiological response.
Rates and Mechanisms of Resistance Development inMycobacterium tuberculosisto a Novel Diarylquinoline ATP Synthase Inhibitor
Authors: Huitric E. , Verhasselt P. , Koul A. , Andries K. , Hoffner S. , Andersson D. I. 
Published: December 2009

ABSTRACTR207910 (also known as TMC207) is an investigational drug currently in clinical studies for the treatment of multidrug-resistant (MDR) tuberculosis. It has a high degree of antimycobacterial activity and is equally effective against drug-susceptible and MDRMycobacterium tuberculosisisolates. In the present study, we characterized the development of resistance to R207910in vitro. Ninety-seven independent R207910-resistant mutants were selected from seven different clinical isolates ofM. tuberculosis(three drug-susceptible and four MDR isolates) at 10×, 30×, and 100× the MIC. At a concentration of 0.3 mg/liter (10× the MIC), the mutation rates ranged from 4.7 × 10−7to 8.9 × 10−9mutations per cell per division, and at 1.0 mg/liter (30× the MIC) the mutation rate ranged from 3.9 × 10−8to 2.4 × 10−9. No resistant mutants were obtained at 3 mg/liter (100× the MIC). The level of resistance ranged from 0.12 to 3.84 mg/liter for the mutants identified; these concentrations represent 4- to 128-fold increases in the MICs. For 53 of the resistant mutants, theatpEgene, which encodes a transmembrane and oligomeric C subunit of the ATP synthase and which was previously shown to be involved in resistance, was sequenced. For 15/53 mutants, five different point mutations resulting in five different amino acid substitutions were identified in theatpEgene. For 38/53 mutants, noatpEmutations were found and sequencing of the complete F0 ATP synthase operon (atpB,atpE, andatpFgenes) and the F1 ATP synthase operon (atpH,atpA,atpG,atpD, andatpCgenes) from three mutants revealed no mutations, indicating other, alternative resistance mechanisms. Competition assays showed no measurable reduction in the fitness of the mutants compared to that of the isogenic wild types.
Genes Involved in Yellow Pigmentation of
Cronobacter sakazakii
ES5 and Influence of Pigmentation on Persistence and Growth under Environmental Stress
Authors: Johler Sophia , Stephan Roger , Hartmann Isabel , Kuehner Kirsten A. , Lehner Angelika 
Published: December 2009

ABSTRACT

Cronobacter
spp. are opportunistic food-borne pathogens that are responsible for rare but highly fatal cases of meningitis and necrotizing enterocolitis in neonates. While the operon responsible for yellow pigmentation in
Cronobacter sakazakii
strain ES5 was described recently, the involvement of additional genes in pigment expression and the influence of pigmentation on the fitness of
Cronobacter
spp. have not been investigated. Thus, the aim of this study was to identify further genes involved in pigment expression in
Cronobacter sakazakii
ES5 and to assess the influence of pigmentation on growth and persistence under conditions of environmental stress. A knockout library was created using random transposon mutagenesis. The screening of 9,500 mutants for decreased pigment production identified 30 colorless mutants. The mapping of transposon insertion sites revealed insertions in not only the carotenoid operon but also in various other genes involved in signal transduction, inorganic ions, and energy metabolism. To determine the effect of pigmentation on fitness, colorless mutants (Δ
crtE
, Δ
crtX
, and Δ
crtY
) were compared to the yellow wild type using growth and inactivation experiments, a macrophage assay, and a phenotype array. Among other findings, the colorless mutants grew at significantly increased rates under osmotic stress compared to that of the yellow wild type while showing increased susceptibility to desiccation. Moreover, Δ
crtE
and Δ
crtY
exhibited increased sensitivity to UVB irradiation.
Establishment of Cyanophycin Biosynthesis in
Pichia pastoris
and Optimization by Use of Engineered Cyanophycin Synthetases
Authors: Steinle Anna , Witthoff Sabrina , Krause Jens P. , Steinbüchel Alexander 
Published: December 2009

ABSTRACT

Two strains of the methylotrophic yeast
Pichia pastoris
were used to establish cyanophycin (multi-
l
-arginyl-poly-
l
-aspartic acid [CGP]) synthesis and to explore the applicability of this industrially widely used microorganism for the production of this polyamide. Therefore, the CGP synthetase gene from the cyanobacterium
Synechocystis
sp. strain PCC 6308 (
cphA
6308
) was expressed under the control of the alcohol oxidase 1 promoter, yielding CGP contents of up to 10.4% (wt/wt), with the main fraction consisting of the soluble form of the polymer. To increase the polymer contents and to obtain further insights into the structural or catalytic properties of the enzyme, site-directed mutagenesis was applied to
cphA
6308
and the mutated gene products were analyzed after expression in
P. pastoris
and
Escherichia coli
, respectively. CphA
6308
Δ1, which was truncated by one amino acid at the C terminus; point mutated CphA
6308
C595S; and the combined double-mutant CphA
6308
Δ1C595S protein were purified. They exhibited up to 2.5-fold higher enzyme activities of 4.95 U/mg, 3.20 U/mg, and 4.17 U/mg, respectively, than wild-type CphA
6308
(2.01 U/mg). On the other hand, CphA proteins truncated by two (CphA
6308
Δ2) or three (CphA
6308
Δ3) amino acids at the C terminus showed similar or reduced CphA enzyme activity in comparison to CphA
6308
. In flask experiments, a maximum of 14.3% (wt/wt) CGP was detected after the expression of CphA
6308
Δ1 in
P. pastoris
. For stabilization of the expression plasmid, the
his4
gene from
Saccharomyces cerevisiae
was cloned into the expression vector used and the constructs were transferred to histidine auxotrophic
P. pastoris
strain GS115. Parallel fermentations at a one-to-one scale revealed 26°C and 6.0 as the optimal temperature and pH, respectively, for CGP synthesis. After optimization of fermentation parameters, medium composition, and the length of the cultivation period, CGP contents could be increased from 3.2 to 13.0% (wt/wt) in cells of
P. pastoris
GS115 expressing CphA
6308
and up to even 23.3% (wt/wt) in cells of
P. pastoris
GS115 expressing CphA
6308
Δ1.
Inducible Expression of Transmembrane Proteins on Bacterial Magnetic Particles in
Magnetospirillum magneticum
AMB-1
Authors: Yoshino Tomoko , Shimojo Akiko , Maeda Yoshiaki , Matsunaga Tadashi 
Published: December 2009

ABSTRACT

Bacterial magnetic particles (BacMPs) produced by the magnetotactic bacterium
Magnetospirillum magneticum
AMB-1 are used for a variety of biomedical applications. In particular, the lipid bilayer surrounding BacMPs has been reported to be amenable to the insertion of recombinant transmembrane proteins; however, the display of transmembrane proteins in BacMP membranes remains a technical challenge due to the cytotoxic effects of the proteins when they are overexpressed in bacterial cells. In this study, a tetracycline-inducible expression system was developed to display transmembrane proteins on BacMPs. The expression and localization of the target proteins were confirmed using luciferase and green fluorescent protein as reporter proteins. Gene expression was suppressed in the absence of anhydrotetracycline, and the level of protein expression could be controlled by modulating the concentration of the inducer molecule. This system was implemented to obtain the expression of the tetraspanin CD81. The truncated form of CD81 including the ligand binding site was successfully displayed at the surface of BacMPs by using Mms13 as an anchor protein and was shown to bind the hepatitis C virus envelope protein E2. These results suggest that the tetracycline-inducible expression system described here will be a useful tool for the expression and display of transmembrane proteins in the membranes of BacMPs.
Identity, Diversity, and Molecular Phylogeny of the Endophytic Mycobiota in the Roots of Rare Wild Rice (
Oryza granulate
) from a Nature Reserve in Yunnan, China
Authors: Yuan Zhi-lin , Zhang Chu-long , Lin Fu-cheng , Kubicek Christian P. 
Published: December 2009

ABSTRACT

Rice (
Oryza sativa
L.) is, on a global scale, one of the most important food crops. Although endophytic fungi and bacteria associated with rice have been investigated, little is known about the endophytic fungi of wild rice (
Oryza granulate
) in China. Here we studied the root endophytic mycobiota residing in roots of
O. granulate
by the use of an integrated approach consisting of microscopy, cultivation, ecological indices, and direct PCR. Microscopy confirmed the ubiquitousness of dark septate endophytes (DSEs) and sclerotium-like structures in root tissues. Isolations from 204 root segments from 15 wild rice plants yielded 58 isolates, for which 31 internal transcribed spacer (ITS)-based genotypes were recorded. The best BLAST match indicated that 34.5% of all taxa encountered may represent hitherto undescribed species. Most of the fungi were isolated with a very low frequency. Calculation of ecological indices and estimation of taxon accumulation curves indicated a high diversity of fungal species. A culture-independent approach was also performed to analyze the endophytic fungal community. Three individual clone libraries were constructed. Using a threshold of 90% similarity, 35 potentially different sequences (phylotypes) were found among 186 positive clones. Phylogenetic analysis showed that frequently detected clones were classified as Basidiomycota, and 60.2% of total analyzed clones were affiliated with unknown taxa.
Exophiala
,
Cladophialophora
,
Harpophora
,
Periconia macrospinosa
, and the
Ceratobasidium
/
Rhizoctonia
complex may act as potential DSE groups. A comparison of the fungal communities characterized by the two approaches demonstrated distinctive fungal groups, and only a few taxa overlapped. Our findings indicate a complex and rich endophytic fungal consortium in wild rice roots, thus offering a potential bioresource for establishing a novel model of plant-fungal mutualistic interactions.