bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for non‐genomic transmission of ecological information via maternal behavior in female rats
Authors: McLeod J. , Sinal C. J. , Perrot‐Sinal T. S.
Published: March 2006

Maternal behavior is flexible and programs offspring development. Using a novel manipulation, we demonstrate that rat maternal behavior is sensitive to ecologically relevant stimuli. Long‐Evans hooded rat dams (F0) and pups were exposed to a predator condition (cat odor) or a control condition (no odor) for 1 h on the day of parturition. Predator‐exposed F0 dams displayed significantly more maternal behavior (licking/grooming, arched‐back nursing) relative to control‐exposed dams across five subsequent observation days. Female offspring (F1) were raised to adulthood, bred and maternal behavior was observed. F1 dams reared by a predator‐exposed F0 dam displayed significantly higher maternal behavior relative to F1 dams reared by a control‐exposed F0 dam across 5 days of observation. Increased levels of maternal behavior in predator‐reared (PR) F1 dams were evident even in F1 females that had been cross‐fostered (CF) from a control‐exposed F0 dam, suggesting a non‐genomic transmission of increased levels of maternal behavior. Lactating PR F1 dams had significantly elevated estrogen receptor α and β mRNA in the medial preoptic area relative to control‐reared (CR) F1 dams. Furthermore, among CR F1 dams, there was no significant difference between those dams that had been CF from predator‐exposed F0 dams and those that had been sham CF. These results support the hypothesis that flexible rat maternal behavior can shape offspring development according to current environmental conditions. The results also suggest that estrogen signaling may be part of an epigenetic mechanism by which changes in maternal behavior are passed from F0 to F1 dams.
Differential expression of eIF5A‐1 and eIF5A‐2 in human cancer cells
Authors: Clement Paul M. J. , Johansson Hans E. , Wolff Edith C. , Park Myung H.
Published: March 2006

Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [Nε‐(4‐amino‐2‐hydroxybutyl)lysine]. Vertebrates carry two genes that encode two eIF5A isoforms, eIF5A‐1 and eIF5A‐2, which, in humans, are 84% identical. eIF5A‐1 mRNA (1.3 kb) and protein (18 kDa) are constitutively expressed in human cells. In contrast, expression of eIF5A‐2 mRNA (0.7–5.6 kb) and eIF5A‐2 protein (20 kDa) varies widely. Whereas eIF5A‐2 mRNA was demonstrable in most cells, eIF5A‐2 protein was detectable only in the colorectal and ovarian cancer‐derived cell lines SW‐480 and UACC‐1598, which showed high overexpression of eIF5A‐2 mRNA. Multiple forms of eIF5A‐2 mRNA (5.6, 3.8, 1.6 and 0.7 kb) were identified as the products of one gene with various lengths of 3′‐UTR, resulting from the use of different polyadenylation (AAUAAA) signals. The eIF5A‐1 and eIF5A‐2 precursor proteins were modified comparably in UACC‐1598 cells and both were similarly stable. When eIF5A‐1 and eIF5A‐2 coding sequences were expressed from mammalian vectors in 293T cells, eIF5A‐2 precursor was synthesized at a level comparable to that of eIF5A‐1 precursor, indicating that the elements causing inefficient translation of eIF5A‐2 mRNA reside outside of the open reading frame. On sucrose gradient separation of cytoplasmic RNA, only a small portion of total eIF5A‐2 mRNA was associated with the polysomal fraction, compared with a much larger portion of eIF5A‐1 mRNA in the polysomes. These findings suggest that the failure to detect eIF5A‐2 protein even in eIF5A‐2 mRNA positive cells is, at least in part, due to inefficient translation.
Kinetic study of the HIV−1 DNA 3′‐end processing
Authors: Smolov Maksim , Gottikh Marina , Tashlitskii Vadim , Korolev Sergei , Demidyuk Ilya , Brochon Jean‐Claude , Mouscadet Jean‐François , Deprez Eric
Published: March 2006

The 3′‐processing of viral DNA extremities is the first step in the integration process catalysed by human immunodeficiency virus (HIV)‐1 integrase (IN). This reaction is relatively inefficient and processed DNAs are usually detected in vitro under conditions of excess enzyme. Despite such experimental conditions, steady‐state Michaelis–Menten formalism is often applied to calculate characteristic equilibrium/kinetic constants of IN. We found that the amount of processed product was not significantly affected under conditions of excess DNA substrate, indicating that IN has a limited turnover for DNA cleavage. Therefore, IN works principally in a single‐turnover mode and is intrinsically very slow (single‐turnover rate constant = 0.004 min−1), suggesting that IN activity is mainly limited at the chemistry step or at a stage that precedes chemistry. Moreover, fluorescence experiments showed that IN–DNA product complexes were very stable over the time‐course of the reaction. Binding isotherms of IN to DNA substrate and product also indicate tight binding of IN to the reaction product. Therefore, the slow cleavage rate and limited product release prevent or greatly reduce subsequent turnover. Nevertheless, the time‐course of product formation approximates to a straight line for 90 min (apparent initial velocity), but we show that this linear phase is due to the slow single‐turnover rate constant and does not indicate steady‐state multiple turnover. Finally, our data ruled out the possibility that there were large amounts of inactive proteins or dead‐end complexes in the assay. Most of complexes initially formed were active although dramatically slow.
Rat butyrylcholinesterase‐catalysed hydrolysis of N‐alkyl homologues of benzoylcholine
Authors: Hrabovská Anna , Debouzy Jean‐Claude , Froment Marie‐Thérese , Devínsky Ferdinand , Pauliková Ingrid , Masson Patrick
Published: March 2006

The purpose of this work was to study the catalytic properties of rat butyrylcholinesterase with benzoylcholine (BzCh) and N‐alkyl derivatives of BzCh (BCHn) as substrates. Complex hysteretic behaviour was observed in the approach to steady‐state kinetics for each ester. Hysteresis consisted of a long lag phase with damped oscillation. The presence of a long lag phase, with no oscillations, in substrate hydrolysis by rat butyrylcholinesterase was also observed with N‐methylindoxyl acetate as substrate. Hysteretic behaviour was explained by the existence of two interconvertible butyrylcholinesterase forms in slow equilibrium, while just one of them is catalytically active. The damped oscillations were explained by the existence of different substrate conformational states and/or aggregates (micelles) in slow equilibrium. Different substrate conformational states were confirmed by1H‐NMR. TheKmvalues for substrates decreased as the length of the alkyl chain increased. High affinity of the enzyme for the longest alkyl chain length substrates was explained by multiple hydrophobic interactions of the alkyl chain with amino acid residues lining the active site gorge. Molecular modelling studies supported this interpretation; docking energy decreased as the length of the alkyl chain increased. The long‐chain substrates had reducedkcatvalues. Docking studies showed that long‐chain substrates were not optimally oriented in the active site for catalysis, thus explaining the slow rate of hydrolysis. The hydrolytic rate of BCH12 and longer alkyl chain esters vs. substrate concentration showed a premature plateau far belowVmax. This was due to the loss of substrate availability. The best substrates for rat butyrylcholinesterase were short alkyl homologues, BzCh – BCH4.
The potyviral virus genome‐linked protein VPg forms a ternary complex with the eukaryotic initiation factors eIF4E and eIF4G and reduces eIF4E affinity for a mRNA cap analogue
Authors: Michon Thierry , Estevez Yannick , Walter Jocelyne , German‐Retana Sylvie , Le Gall Olivier
Published: March 2006

The virus protein linked to the genome (VPg) of plant potyviruses is a 25‐kDa protein covalently attached to the genomic RNA 5′ end. It was previously reported that VPg binds specifically to eIF4E, the mRNAcap‐binding protein of the eukaryotic translation initiation complex. We performed a spectroscopic study of the interactions between lettuce eIF4E and VPg from lettuce mosaic virus (LMV). The cap analogue m7GDP and VPg bind to eIF4E at two distinct sites with similar affinity (Kd = 0.3 µm). A deeper examination of the interaction pathway showed that the binding of one ligand induces a decrease in the affinity for the other by a factor of 15. GST pull‐down experiments from plant extracts revealed that VPg can specifically trap eIF4G, the central component of the complex required for the initiation of protein translation. Our data suggest that eIF4G recruitment by VPg is indirectly mediated through VPg–eIF4E association. The strength of interaction between eIF4E and pep4G, the eIF4E‐binding domain on eIF4G, was increased significantly by VPg. Taken together these quantitative data show that VPg is an efficient modulator of eIF4E biochemical functions.
Mutational analysis of functional domains in Mrs2p, the mitochondrial Mg2+ channel protein of Saccharomyces cerevisiae
Authors: Weghuber Julian , Dieterich Frank , Froschauer Elisabeth M. , Svidovà Sona , Schweyen Rudolf J.
Published: March 2006

The nuclear gene MRS2 in Saccharomyces cerevisiae encodes an integral protein (Mrs2p) of the inner mitochondrial membrane. It forms an ion channel mediating influx of Mg2+ into mitochondria. Orthologues of Mrs2p have been shown to exist in other lower eukaryotes, in vertebrates and in plants. Characteristic features of the Mrs2 protein family and the distantly related CorA proteins of bacteria are the presence of two adjacent transmembrane domains near the C terminus of Mrs2p one of which ends with a F/Y‐G‐M‐N motif. Two coiled‐coil domains and several conserved primary sequence blocks in the central part of Mrs2p are identified here as additional characteristics of the Mrs2p family. Gain‐of‐function mutations obtained upon random mutagenesis map to these conserved sequence blocks. They lead to moderate increases in mitochondrial Mg2+ concentrations and concomitant positive effects on splicing of mutant group II intron RNA. Site‐directed mutations in several conserved sequences reduce Mrs2p‐mediated Mg2+ uptake. Mutants with strong effects on mitochondrial Mg2+ concentrations also have decreased group II intron splicing. Deletion of a nonconserved basic region, previously invoked for interaction with mitochondrial introns, lowers intramitochondrial Mg2+ levels as well as group II intron splicing. Data presented support the notion that effects of mutations in Mrs2p on group II intron splicing are a consequence of changes in steady‐state mitochondrial Mg2+ concentrations.
The long‐term effect of partial defoliation on the yield of short‐rotation coppice willow
Authors: Bell A.C. , Clawson S. , Watson S.
Published: March 2006

Five varieties of willow were planted in a randomised block design at the Northern Ireland Horticulture and Plant Breeding Station, Loughgall, County Armagh in 1997. Three treatments were applied: control (no treatment), manual defoliation and routine control (spraying) of willow beetles. The defoliation was carried out at 75% for the first 2 years and thereafter 25% up to the first harvest in January 2001. During the second production cycle, no manual defoliation was applied in order to observe the ability of the different varieties to recover from earlier damage. The variety 78112 exhibited the highest yield loss in the first cycle as a result of defoliation (∼70%), while the vigorous variety Tora suffered least yield loss (35–43%). In the recovery phase (second production cycle 2001–2003), all the varieties showed little improvement in yields in plots that had been defoliated previously, indicating a long‐term legacy of yield loss as a result of defoliation. The possible reasons for this inability to recover are discussed.
The infrared jet in Centaurus A: multiwavelength constraints on emission mechanisms and particle acceleration
Authors: Hardcastle M. J. , Kraft R. P. , Worrall D. M.
Published: March 2006

We report on Spitzer and Gemini observations of the jet of Centaurus A in the infrared, which we combine with radio, ultraviolet and X-ray data. Spitzer detects jet emission from about 2 arcmin from the nucleus, the emission becoming particularly bright after the jet flare point at ∼3.4 arcmin. Where X-ray and infrared emission are seen together the broad-band data strongly support a synchrotron origin for the X-rays. The jet flare point is marked by a broad, diffuse region of X-rays which may be associated with a shock: we discuss possible physical mechanisms for this. The infrared jet persists after the flare point region although X-ray emission is absent; it is plausible that here we are seeing the effects of particle acceleration followed by downstream advection with synchrotron losses. Gemini data probe the inner regions of the jet, putting limits on the mid-infrared flux of jet knots.
Quantifying heavy metal inputs to agricultural soils in England and Wales
Authors: Nicholson F. A. , Smith S. R. , Alloway B. J. , Carlton‐Smith C. , Chambers B. J.
Published: March 2006

Heavy metal inputs to agricultural soils in England and Wales were estimated from major sources, including atmospheric deposition, biosolids, livestock manures, inorganic fertilisers and lime, industrial by‐product ‘wastes’ and composts (year 2000). Across the whole agricultural land area, atmospheric deposition was the main source of most metals ranging from 25 to 85% of total inputs. Livestock manures and biosolids were also important sources representing 37 and 8% of total zinc (Zn) inputs, 40 and 17% for copper (Cu), and 10 and 4% for cadmium, respectively. The highest heavy metal input rates on a field basis were generally from biosolids, although Zn and Cu inputs from pig manures were equivalent to 46–52% of biosolids inputs (both applied at a rate of 250 kg/ha total N). The study provided baseline information to develop and focus policies limiting heavy metal inputs to and accumulation in topsoils.
Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans
Authors: Fisher James P. , Ogoh Shigehiko , Dawson Ellen A. , Fadel Paul J. , Secher Niels H. , Raven Peter B. , White Michael J.
Published: March 2006

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with β1‐adrenergic blockade (metoprolol, 0.15 ± 0.003 mg kg−1) or parasympathetic blockade (glycopyrrolate, 13.6 ± 1.5 μg kg−1). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to −80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise (P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain (Gmax) of the CBR‐HR function curve (−0.58 ± 0.10 to −0.06 ± 0.01 beats min−1 mmHg−1, P < 0.05), but had no effect on the Gmax of the CBR‐MAP function curve. During isometric exercise the CBR‐HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate (P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in Gmax. Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.
Fatigue properties of human thenar motor units paralysed by chronic spinal cord injury
Authors: Klein C. S. , Häger‐Ross C. K. , Thomas C. K.
Published: March 2006

Human muscles paralysed chronically by spinal cord injury (SCI) fatigue excessively. Whether these reductions in force reflect a decrease in the fatigue resistance of the motor units is unknown. Our aim was to determine the fatigability of thenar motor units paralysed chronically (10 ± 2 years) by cervical SCI. Surface electromyographic activity (EMG) and force were recorded from 17 paralysed motor units (n= 7 subjects) in response to intraneural motor axon stimulation (13 pulses at 40 Hz, 1 s−1 for 2 min). Unit force decreased progressively, reaching 8–60% of initial after 2 min, whereas both the amplitude and area of the first EMG potentials in the trains increased significantly (both P < 0.05). Thus, transmission of neural signals to the sarcolemma was effective and the reduction in force must reflect impaired processes in the muscle fibres. The median fatigue index for paralysed units (0.31), the ratio of the force at 2 min compared to the initial force, was significantly lower than that for units from control subjects (0.85, P < 0.05), but the distribution of fatigue indices for each population had a similar shape (ranges: 0.08–0.60 and 0.41–0.95, respectively). Hence, chronic paralysis did not limit the range of fatigability typically found for thenar units, only its magnitude. These findings suggest that all paralysed units underwent similar reductions in fatigue resistance. After fatigue, paralysed unit forces were reduced at all frequencies (1–100 Hz, P < 0.05). Twitch contraction and half‐relaxation times were increased, as was the frequency needed to produce half maximal force (P < 0.05). Thus, stimulation protocols used to produce functional movements in paralysed muscles need to accommodate the significant and rapid fatigue of the motor units.
Effects of divalent cations and spermine on the K+channel TASK‐3 and on the outward current in thalamic neurons
Authors: Musset Boris , Meuth Sven G. , Liu Gong Xin , Derst Christian , Wegner Sven , Pape Hans‐Christian , Budde Thomas , Preisig‐Müller Regina , Daut Jürgen
Published: March 2006

The potassium channels TASK‐1 and TASK‐3 show high sequence homology but differ in their sensitivity to extracellular divalent cations. Heterologous expression in HEK293 cells showed that the single‐channel conductance of TASK‐3 increased approximately four‐fold after removal of external divalent cations, whereas the conductance of TASK‐1 was unaffected. Replacing the glutamate at position 70 of TASK‐3 by a lysine or arginine residue abolished the sensitivity to divalent cations. The reverse mutation in TASK‐1 (K70E) induced sensitivity to divalent cations. The organic polycations spermine and ruthenium red modulated the conductance of TASK‐3 in a similar way as Ca2+or Mg2+. Our data suggest that these effects were mediated by shielding of the negative charges in the extracellular loops of TASK‐3. Whole‐cell currents carried by TASK‐3 channels were inhibited by spermine and ruthenium red even in the presence of external divalent cations. These data suggest that, in addition to their effect on single‐channel conductance, spermine and ruthenium red decreased the open probability of TASK‐3 channels, probably by binding to residue E70. The standing outward current in thalamocortical relay neurons, which is largely carried by TASK channels, was also inhibited by divalent cations and spermine. Using the differential sensitivity of TASK‐1 and TASK‐3 to divalent cations and spermine we found that about 20% of the standing outward current in thalamocortical relay neurons flows through TASK‐3 channels. We conclude from our results that inhibition of TASK‐3 channels may contribute to the neuromodulatory effect of spermine released from neurons during repetitive activity or during hypoxia.
Coronary x‐ray angiographic reconstruction and image orientation
Authors: Sprague Kevin , Drangova Maria , Lehmann Glen , Slomka Piotr , Levin David , Chow Benjamin , deKemp Robert
Published: March 2006

We have developed an interactive geometric method for 3D reconstruction of the coronary arteries using multiple single‐plane angiographic views with arbitrary orientations. Epipolar planes and epipolar lines are employed to trace corresponding vessel segments on these views. These points are utilized to reconstruct 3D vessel centerlines. The accuracy of the reconstruction is assessed using: (1) near‐intersection distances of the rays that connect x‐ray sources with projected points, (2) distances between traced and projected centerlines. These same two measures enter into a fitness function for a genetic search algorithm (GA) employed to orient the angiographic image planes automatically in 3D avoiding local minima in the search for optimized parameters. Furthermore, the GA utilizes traced vessel shapes (as opposed to isolated anchor points) to assist the optimization process. Differences between two‐view and multiview reconstructions are evaluated. Vessel radii are measured and used to render the coronary tree in 3D as a surface. Reconstruction fidelity is demonstrated via (1) virtual phantom, (2) real phantom, and (3) patient data sets, the latter two of which utilize the GA. These simulated and measured angiograms illustrate that the vessel centerlines are reconstructed in 3D with accuracy below . The reconstruction method is thus accurate compared to typical vessel dimensions of . The methods presented should enable a combined interpretation of the severity of coronary artery stenoses and the hemodynamic impact on myocardial perfusion in patients with coronary artery disease.
Simulation of four‐dimensional CT images from deformable registration between inhale and exhale breath‐hold CT scans
Authors: Sarrut David , Boldea Vlad , Miguet Serge , Ginestet Chantal
Published: March 2006

Purpose: We propose to simulate an artificial four‐dimensional (4‐D) CT image of the thorax during breathing. It is performed by deformable registration of two CT scans acquired at inhale and exhale breath‐hold. Materials and methods: Breath‐hold images were acquired with the ABC (Active Breathing Coordinator) system. Dense deformable registrations were performed. The method was a minimization of the sum of squared differences (SSD) using an approximated second‐order gradient. Gaussian and linear‐elastic vector field regularizations were compared. A new preprocessing step, called a priori lung density modification (APLDM), was proposed to take into account lung density changes due to inspiration. It consisted of modulating the lung densities in one image according to the densities in the other, in order to make them comparable. Simulated 4‐D images were then built by vector field interpolation and image resampling of the two initial CT images. A variation in the lung density was taken into account to generate intermediate artificial CT images. The Jacobian of the deformation was used to compute voxel values in Hounsfield units. The accuracy of the deformable registration was assessed by the spatial correspondence of anatomic landmarks located by experts. Results: APLDM produced statistically significantly better results than the reference method (registration without APLDM preprocessing). The mean (and standard deviation) of distances between automatically found landmark positions and landmarks set by experts were with APLDM, and without. Interexpert variability was . The differences between Gaussian and linear elastic regularizations were not statistically significant. In the second experiment using 4‐D images, the mean difference between automatic and manual landmark positions for intermediate CT images was . Conclusion: The generation of 4‐D CT images by deformable registration of inhale and exhale CT images is feasible. This can lower the dose needed for 4‐D CT acquisitions or can help to correct 4‐D acquisition artifacts. The 4‐D CT model can be used to propagate contours, to compute a 4‐D dose map, or to simulate CT acquisitions with an irregular breathing signal. It could serve as a basis for 4‐D radiation therapy planning. Further work is needed to make the simulation more realistic by taking into account hysteresis and more complex voxel trajectories.
Quality control for digital mammography: Part II recommendations from the ACRIN DMIST trial
Authors: Yaffe Martin J. , Bloomquist Aili K. , Mawdsley Gordon E. , Pisano Etta D. , Hendrick R. Edward , Fajardo Laurie L. , Boone John M. , Kanal Kalpana , Mahesh Mahadevappa , Fleischman Richard C. , Och Joseph , Williams Mark B. , Beideck Daniel J. , Maidment Andrew D. A.
Published: March 2006

The Digital Mammography Imaging Screening Trial (DMIST), conducted under the auspices of the American College of Radiology Imaging Network (ACRIN), is a clinical trial designed to compare the accuracy of digital versus screen‐film mammography in a screening population [E. Pisano et al., ACRIN 6652—Digital vs. Screen‐Film Mammography, ACRIN (2001)]. Part I of this work described the Quality Control program developed to ensure consistency and optimal operation of the digital equipment. For many of the tests, there were no failures during the imaging was performed in DMIST. When systems failed, they generally did so suddenly rather than through gradual deterioration of performance. In this part, the utility and effectiveness of those tests are considered. This suggests that after verification of proper operation, routine extensive testing would be of minimal value. A recommended set of tests is presented including additional and improved tests, which we believe meet the intent and spirit of the Mammography Quality Standards Act regulations to ensure that full‐field digital mammography systems are functioning correctly, and consistently producing mammograms of excellent image quality.
Prostatic edema in permanent prostate implants: Dynamical dosimetry taking volume changes into account
Authors: Leclerc Ghyslain , Lavallée Marie‐Claude , Roy René , Vigneault Eric , Beaulieu Luc
Published: March 2006

The purpose of this study is to determine the impact of edema on the dose delivered to the target volume. An evaluation of the edema characteristics was first made, and then a dynamical dosimetry algorithm was developed and used to compare its results to a standard clinical (static) dosimetry. Source positions and prostate contours extracted from 66 clinical cases on images taken at different points in time (planning, implant day, post‐implant evaluation) were used, via the mean interseed distance, to characterize edema [initial increase , half‐life ]. An algorithm was developed to take into account the edema by summing a time series of dose‐volume histograms (DVHs) with a weight based on the fraction of the dose delivered during the time interval considered. The algorithm was then used to evaluate the impact of edema on the dosimetry of permanent implants by comparing its results to those of a standard clinical dosimetry. The volumetric study yielded results as follows: the initial prostate volume increase was found to be 1.58 (ranging from 1.15 to 2.48) and the edema half‐life, approximately 30 days (range: 3 to 170 days). The dosimetric differences in observed between the dynamic dosimetry and the clinical one for a single case were up to and depended on the edema half‐life and the initial volume increase. The average edema half‐life, 30 days, is about 3 times longer than the previously reported 9 days. Dosimetric differences up to 10% of the prescription dose are observed, which can lead to differences in the quality assertion of an implant. The study of individual patient edema resorption with time might be necessary to extract meaningful clinical correlation or biological parameters in permanent implants.
A Born‐type approximation method for bioluminescence tomography
Authors: Cong Wenxiang , Durairaj Kumar , Wang Lihong V. , Wang Ge
Published: March 2006

In this paper, we present a Born‐type approximation method for bioluminescence tomography (BLT), which is to reconstruct an internal bioluminescent source from the measured bioluminescent signal on the external surface of a small animal. Based on the diffusion approximation for the photon propagation in biological tissue, this BLT method utilizes the Green function to establish a linear relationship between the measured bioluminescent signal and the internal bioluminescent source distribution. The Green function can be modified to describe a heterogeneous medium with an arbitrary boundary using the Born approximation. The BLT reconstruction is formulated in a linear least‐squares optimization framework with simple bounds constraint. The performance of this method is evaluated in numerical simulation and phantom experiments.
Impact of interseed attenuation and tissue composition for permanent prostate implants
Authors: Carrier Jean‐François , Beaulieu Luc , Therriault‐Proulx François , Roy René
Published: March 2006

The purpose is to evaluate the impact of interseed attenuation and prostate composition for prostate treatment plans with permanent seed implants using the Monte Carlo (MC) method. The effect of seed density (number of seeds per prostate unit volume) is specifically investigated. The study focuses on treatment plans that were generated for clinical cases. For each plan, four different dose calculation techniques are compared: TG‐43 based calculation, superposition MC, full MC with water prostate, and full MC with realistic prostate tissue. The prostate tissue description is from the ICRP report 23 (W. S. Snyer, M. J. Cook, E. S. Nasset, L. R. Karkhausen, G. P. Howells, and I. H. Tipton, “Report of the task group on reference man,” Technical Report 23, International Commission on Radiological Protection, 1974). According to the comparisons, the seed density has an influence on interseed attenuation. A plan with a typical low seed density ( seeds in a prostate) suffers a 1.2% drop in the CTV value due to interseed attenuation. A drop of 3.0% is calculated for a higher seed density (75 0.3 seeds, same prostate). The influence of the prostate composition is similar for all seed densities and prostate sizes. The difference between MC simulations in water and MC simulations in prostate tissue is between 4.4% and 4.8% for the parameter. Overall, the effect on is ranging from 5.8% to 12.8% when comparing clinically approved TG‐43 and MC simulations in prostate tissue. The impact varies from one patient to the other and depends on the prostate size and the number of seeds. This effect can reach a significant level when reporting correlations between clinical effect and deposited dose.
Dosimetric analysis of a shielded applicator for nasopharyngeal carcinoma intracavitary brachytherapy: Monte Carlo calculation
Authors: Chen Li Xin , Liu Xiao Wei , You Ri An , Qian Jian Yang , Qi Zhen Yu , Deng Xiao Wu , Tsao Shiu Ying
Published: March 2006

In nasopharyngeal cancer (NPC) intracavitary brachytherapy, an anatomical dose reference point (in line with that for gynecology work), e.g., at the sphenoid floor, is more precise than the empirical point of from the source. However, such increases of the single‐source‐plan treatment distances may deliver excessive doses inferiorly, to the soft palate. As shielding may help, its efficacy was studied by Monte Carlo simulations in water for 20 and diameter spherical NP applicators (representing extremes of sizes for the small NP cavity), with/without lead shielding inferiorly, using a single linear Ir‐192, steps, equal dwell times for 5 (5DP) and 9 dwell positions (9DP). Dose reductions of the selected points of interest ranged from 1.2% to 40.5% for the shielded applicator and a range of 2.9% to 17.9%, for the shielded applicator. Dose volume histograms of the “region of interest” (ROI)—a cuboid of at the most inferior aspect of the applicator, also differed significantly. The highest doses of the 50% and 20% volumes of ROI (for 5DP and 9DP plans) were reduced by 11.9% to 17.9% for the applicator and a range of 9.0% to 11.5% for the shielded applicator. Doses in unshielded directions were insignificantly changed, for example, with a applicator simulated in a 5DP plan, the dose distribution close to the source in the unshielded direction has less than 4% difference at the 50% isodose relative to the dose prescription point. For the shielded applicator, despite smaller dose reduction percentages, a more pronounced effective dose reduction was obtained than nominal values when considering radiobiological equivalent doses. Our system was demonstrated to be ready for clinical assessment.
Optimization of detector pixel size for stent visualization in x‐ray fluoroscopy
Authors: Jiang Yuhao , Wilson David L.
Published: March 2006

Pixel size is of great interest in the flat‐panel detector design because of its potential impact on image quality. In the particular case of angiographic x‐ray fluoroscopy, small pixels are required in order to adequately visualize interventional devices such as guidewires and stents which have wire diameters as small as 200 and , respectively. We used quantitative experimental and modeling techniques to investigate the optimal pixel size for imaging stents. Image quality was evaluated by the ability of subjects to perform two tasks: detect the presence of a stent and discriminate a partially deployed stent from a fully deployed one in synthetic images. With measurements at 50, 100, 200, and , the size gave the maximum contrast sensitivity for the detection experiment with the idealized direct detector. For an idealized indirect detector with a scintillating layer, an optimal pixel size was obtained at size. A channelized human observer model predicted a peak at 150 and , for the idealized direct and indirect detectors, respectively. With regard to the stent deployment task for both detector types, smaller pixel sizes are favored and there is a steep drop in performance with larger pixels. In general, with the increasing exposures, the model and measurements give the enhanced contrast sensitivities and a smaller optimal pixel size. The effects of electronic noise and fill factor were investigated using the model. We believe that the experimental results and human observer model predications can help guide the flat‐panel detector design. In addition, the human observer model should work on the similar images and be applicable to the future model and actual flat‐panel implementations.
Optimization of the matrix inversion tomosynthesis (MITS) impulse response and modulation transfer function characteristics for chest imaging
Authors: Godfrey Devon J. , McAdams H. P. , Dobbins James T.
Published: March 2006

Matrix inversion tomosynthesis (MITS) uses linear systems theory, along with a priori knowledge of the imaging geometry, to deterministically distinguish between true structure and overlying tomographic blur in a set of conventional tomosynthesis planes. In this paper we examine the effect of total scan angle (ANG), number of input projections (N), and plane separation/number of reconstructed planes (NP) on the MITS impulse response (IR) and modulation transfer function (MTF), with the purpose of optimizing MITS imaging of the chest. MITS IR and MTF data were generated by simulating the imaging of a very thin wire, using various combinations of ANG, N, and NP. Actual tomosynthesis data of an anthropomorphic chest phantom were acquired with a prototype experimental system, using the same imaging parameter combinations as those in the simulations. Thoracic projection data from two human subjects were collected for corroboration of the system response analysis in vivo. Results suggest that , , is the optimal combination for MITS chest imaging given the inherent constraints of our prototype system. MITS chest data from human subjects demonstrates that the selected imaging strategy can effectively produce high‐quality MITS thoracic images in vivo.
Development and commissioning of a multileaf collimator model in Monte Carlo dose calculations for intensity‐modulated radiation therapy
Authors: Jang Si Young , Vassiliev Oleg N. , Liu H. Helen , Mohan Radhe , Siebers Jeffrey V.
Published: March 2006

A multileaf collimator (MLC) model, “MATMLC,” was developed to simulate MLCs for Monte Carlo (MC) dose calculations of intensity‐modulated radiation therapy (IMRT). This model describes MLCs using matrices of regions, each of which can be independently defined for its material and geometry, allowing flexibility in simulating MLCs from various manufacturers. The free parameters relevant to the dose calculations with this MLC model included MLC leaf density, interleaf air gap, and leaf geometry. To commission the MLC model and its free parameters for the Varian Millennium MLC‐120 (Varian Oncology Systems, Palo Alto, CA), we used the following leaf patterns: (1) MLC‐blocked fields to test the effects of leaf transmission and leakage; (2) picket‐fence fields to test the effects of the interleaf air gap and tongue‐groove design; and (3) abutting‐gap fields to test the effects of rounded leaf ends. Transmission ratios and intensity maps for these leaf patterns were calculated with various sets of modeling parameters to determine their dosimetric effects, sensitivities, and their optimal combinations to give the closest agreement with measured results. Upon commissioning the MLC model, we computed dose distributions for clinical IMRT plans using the MC system and verified the results with those from ion chamber and thermoluminescent dosimeter measurements in water phantoms and anthropomorphic phantoms. This study showed that the MLC transmission ratios were strongly dependent on both leaf density and the interleaf air gap. The effect of interleaf air gap and tongue‐groove geometry can be determined most effectively through fence‐type MLC patterns. Using the commissioned MLC model, we found that the calculated dose from the MC system agreed with the measured data within clinically acceptable criteria from low‐ to high‐dose regions, showing that the model is acceptable for clinical applications.
Measurements of Time-Variable Gravity Show Mass Loss in Antarctica
Authors: Velicogna Isabella , Wahr John
Published: March 2006

Using measurements of time-variable gravity from the Gravity Recovery and Climate Experiment satellites, we determined mass variations of the Antarctic ice sheet during 2002–2005. We found that the mass of the ice sheet decreased significantly, at a rate of 152 ± 80 cubic kilometers of ice per year, which is equivalent to 0.4 ± 0.2 millimeters of global sea-level rise per year. Most of this mass loss came from the West Antarctic Ice Sheet.
CatM Regulation of the
benABCDE
Operon: Functional Divergence of Two LysR-Type Paralogs in
Acinetobacter baylyi
ADP1
Authors: Ezezika Obidimma C. , Collier-Hyams Lauren S. , Dale Haley A. , Burk Andrew C. , Neidle Ellen L.
Published: March 2006

Two LysR-type transcriptional regulators, BenM and CatM, control benzoate consumption by the soil bacterium
Acinetobacter baylyi
ADP1. These homologs play overlapping roles in the expression of multiple genes. This study focuses on the
benABCDE
operon, which initiates benzoate catabolism. At this locus, BenM and CatM each activate transcription in response to the catabolite
cis
,
cis
-muconate. BenM, but not CatM, additionally responds to benzoate as an effector. Regulation by CatM alone is insufficient for growth on benzoate as the sole carbon source. However, three point mutations independently increased CatM-activated
benA
transcription and enabled growth on benzoate without BenM. Two mutations generate variants with one amino acid change in the 303-residue CatM, CatM(V158M) and CatM(R156H). These substitutions affected regulation of
benA
differently than that of
catB
, another CatM-regulated gene involved in benzoate catabolism. In relation to CatM, CatM(V158M) increased
cis
,
cis
-muconate-dependent transcription of
benA
but decreased that of
catB
. CatM(R156H) increased effector-independent expression of
catB
compared to CatM. In contrast,
cis
,
cis
-muconate was required with CatM(R156H) to activate unusually high
benA
expression. Thus, induction by
cis
,
cis
-muconate depends on both the sequence of CatM and the promoter. A point mutation at position −40 of the
benA
promoter enhanced CatM-activated gene expression and altered regulation by CatM(R156H). BenM and CatM bound to the same locations on
ben
region DNA. The frequency with which spontaneous mutations allow CatM to substitute for BenM might predict that one regulator would be sufficient for controlling benzoate consumption. This prediction is discussed in light of current and previous studies of the BenM-CatM regulon.
Conjugal Transfer of a Toxin-Coding Megaplasmid from
Bacillus thuringiensis
subsp.
israelensis
to Mosquitocidal Strains of
Bacillus sphaericus
Authors: Gammon Katherine , Jones Gareth W. , Hope Steven J. , de Oliveira Cláudia M. F. , Regis Lêda , Silva Filha Maria Helena N. L. , Dancer Brian N. , Berry Colin
Published: March 2006

Both
Bacillus sphaericus
and
Bacillus thuringiensis
subsp.
israelensis
produce mosquitocidal toxins during sporulation and are extensively used in the field for control of mosquito populations. All the known toxins of the latter organism are known to be encoded on a large plasmid, pBtoxis. In an attempt to combine the best properties of the two bacteria, an erythromycin resistance-marked pBtoxis plasmid was transferred to
B. sphaericus
by a mating technique. The resulting transconjugant bacteria were significantly more toxic to
Aedes aegypti
mosquitoes and were able to overcome resistance to
B. sphaericus
in a resistant colony of
Culex quinquefasciatus
, apparently due to the production of Cry11A but not Cry4A or Cry4B. The stability of the plasmid in the
B. sphaericus
host was moderate during vegetative growth, but segregational instability was observed, which led to substantial rates of plasmid loss during sporulation.
In Vivo Enzyme Immobilization by Use of Engineered Polyhydroxyalkanoate Synthase
Authors: Peters Verena , Rehm Bernd H. A.
Published: March 2006

This study demonstrated that engineered polyhydroxyalkanoate (PHA) synthases can be employed as molecular tools to covalently immobilize enzymes at the PHA granule surface. The β-galactosidase was fused to the N terminus of the class II PHA synthase fromPseudomonas aeruginosa. The open reading frame was confirmed to encode the complete fusion protein by T7 promoter-dependent overexpression. Restoration of PHA biosynthesis in the PHA-negative mutant ofP. aeruginosaPAO1 showed a PHA synthase function of the fusion protein. PHA granules were isolated and showed β-galactosidase activity. PHA granule attached proteins were analyzed and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Surprisingly, the β-galactosidase-PHA synthase fusion protein was detectable at a high copy number at the PHA granule, compared with PHA synthase alone, which was barely detectable at PHA granules. Localization of the β-galactosidase at the PHA granule surface was confirmed by enzyme-linked immunosorbent assay using anti-β-galactosidase antibodies. Treatment of these β-galactosidase-PHA granules with urea suggested a covalent binding of the β-galactosidase-PHA synthase to the PHA granule. The immobilized β-galactosidase was enzymologically characterized, suggesting a Michaelis-Menten reaction kinetics. AKmof 630 μM and aVmaxof 17.6 nmol/min for orthonitrophenyl-β-d-galactopyranoside as a substrate was obtained. The immobilized β-galactosidase was stable for at least several months under various storage conditions. This study demonstrated that protein engineering of PHA synthase enables the manufacture of PHA granules with covalently attached enzymes, suggesting an application in recycling of biocatalysts, such as in fine-chemical production.
Characterization of the Terephthalate Degradation Genes of
Comamonas
sp. Strain E6
Authors: Sasoh Mikio , Masai Eiji , Ishibashi Satoko , Hara Hirofumi , Kamimura Naofumi , Miyauchi Keisuke , Fukuda Masao
Published: March 2006

We isolated
Comamonas
sp. strain E6, which utilizes terephthalate (TPA) as the sole carbon and energy source via the protocatechuate (PCA) 4,5-cleavage pathway. Two almost identical TPA degradation gene clusters,
tphR
I
C
I
A2
I
A3
I
B
I
A1
I
and
tphR
II
C
II
A2
II
A3
II
B
II
A1
II
, were isolated from this strain. Based on amino acid sequence similarity, the genes
tphR
,
tphC
,
tphA2
,
tphA3
,
tphB
, and
tphA1
were predicted to code, respectively, for an IclR-type transcriptional regulator, a periplasmic TPA binding receptor, the large subunit of the oxygenase component of TPA 1,2-dioxygenase (TPADO), the small subunit of the oxygenase component of TPADO, a 1,2-dihydroxy-3,5-cyclohexadiene-1,4-dicarboxylate (DCD) dehydrogenase, and a reductase component of TPADO. The growth of E6 on TPA was not affected by disruption of either
tphA2
I
or
tphA2
II
singly; however, the
tphA2
I
tphA2
II
double mutant no longer grew on TPA, suggesting that both TPADO genes are involved in TPA degradation. Introduction of a plasmid carrying
tphR
II
C
II
A2
II
A3
II
B
II
A1
II
conferred the TPA utilization phenotype on
Comamonas testosteroni
IAM 1152, which is able to grow on PCA but not on TPA. Disruption of either
tphR
II
or
tphC
II
on this plasmid resulted in the loss of the growth of IAM 1152 on TPA, suggesting that these genes are essential to convert TPA to PCA in E6. The genes
tphA1
II
,
tphA2
II
,
tphA3
II
, and
tphB
II
were expressed in
Escherichia coli
, and the resultant cell extracts containing TphA1
II
, TphA2
II
, and TphA3
II
converted TPA in the presence of NADPH into a product which was transformed to PCA by TphB
II
. On the basis of these results, TPADO was strongly suggested to be a two-component dioxygenase which consists of the terminal oxygenase component (TphA2 and TphA3) and the reductase (TphA1), and
tphB
codes for the DCD dehydrogenase.
Survival and Transmission ofSalmonella entericaSerovar Typhimurium in an Outdoor Organic Pig Farming Environment
Authors: Jensen Annette Nygaard , Dalsgaard Anders , Stockmarr Anders , Nielsen Eva Møller , Baggesen Dorte Lau
Published: March 2006

It was investigated how organic rearing conditions influence theSalmonella entericainfection dynamics in pigs and whetherSalmonellapersists in the paddock environment. Pigs inoculated withS. entericaserovar Typhimurium were grouped withSalmonella-negative tracer pigs. Bacteriological and serological testing indicated that organic pigs were susceptible toSalmonellainfections, as 26 of 46 (56%) tracer pigs turned culture positive. An intermittent and mainly low-level excretion ofSalmonella(<100 cells g−1) partly explains why the bacteriological prevalence appeared lower than the seroprevalence.Salmonellapersisted in the paddock environment, asSalmonellawas isolated from 46% of soil and water samples (n= 294). After removal of pigs,Salmonellawas found in soil samples for up to 5 weeks and in shelter huts during the entire test period (7 weeks). Subsequent introduction ofSalmonella-negative pigs into four naturallySalmonella-contaminated paddocks causedSalmonellainfections of pigs in two paddocks. In one of these paddocks, all tracer pigs (n= 10) became infected, coinciding with a previous highSalmonellainfection rate and highSalmonellaexcretion level. Our results showed that pigs reared under organic conditions were susceptible toSalmonellainfections (just like conventional pigs) and thatSalmonellapersisting in the paddock environment could pose an infection risk. A driving force for these infections seemed to be pigs with a highSalmonellaexcretion level, which caused substantial contamination of the environment. This suggests that isolation of animals as soon as aSalmonellainfection is indicated by clinical symptoms of diarrhea could be a means of reducing and controlling the spread and persistence ofSalmonellain outdoor organic pig production environments.