bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution
Authors: Paganetti H.
Published: September 2005

Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose‐response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well‐established biophysical models, i.e., the phenomenological “track structure” model and the more mechanistic “lethal lesion/potentially lethal lesion” (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose‐response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values.
Accurate setup of paraspinal patients using a noninvasive patient immobilization cradle and portal imaging
Authors: Lovelock D. Michael , Hua Chiaho , Wang Ping , Hunt Margie , Fournier‐Bidoz Nathalie , Yenice Kamil , Toner Sean , Lutz Wendell , Amols Howard , Bilsky Mark , Fuks Zvi , Yamada Yoshiya
Published: September 2005

Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager.
Dose distribution from x‐ray microbeam arrays applied to radiation therapy: AnEGS4Monte Carlo study
Authors: De Felici M. , Felici R. , del Rio M. Sanchez , Ferrero C. , Bacarian T. , Dilmanian F. A.
Published: September 2005

We presentEGS4Monte Carlo calculations of the spatial distribution of the dose deposited by a single x‐ray pencil beam, a planar microbeam, and an array of parallel planar microbeams as used in radiation therapy research. The profiles of the absorbed dose distribution in a phantom, including the peak‐to‐valley ratio of the dose distribution from microbeam arrays, were calculated at micrometer resolution. We determined the dependence of the findings on the main parameters of photon and electron transport. The results illustrate the dependence of the electron range and the deposited in‐beam dose on the cut‐off energy, of the electron transport, as well as the effects on the dose profiles of the beam energy, the array size, and the beam spacing. The effect of beam polarization also was studied for a single pencil beam and for an array of parallel planar microbeams. The results show that although the polarization effect on the dose distribution from amicrobeam array inside a water phantom is large enough to be measured at the outer side of the array (16% difference of the deposited dose for x‐ray beams of 200 keV), it is not detectable at the array's center, thus being irrelevant for the radiation therapy purposes. Finally we show that to properly compare the dose profiles determined with a metal oxide semiconductor field emission transistor detector with the computational method predictions, it is important to simulate adequately the size and the material of the device's Si active element.
Prescription dose in permanent seed prostate implants
Authors: Yue Ning , Heron Dwight E. , Komanduri Krishna , Huq M. Saiful
Published: September 2005

Recently, seeds have been introduced for prostate permanent seed implants. This type of seed has a relatively short half‐life of 9.7 days and has its most prominent emitted photon energy peaks in the 29–34 keV region. Traditionally, 145 and 125 Gy have been prescribed for and seed prostate implants, respectively. Since both the half‐life and dosimetry characteristics of seed are quite different from those of and , the appropriate prescription dose for seed prostate implant may well be different. This study was designed to use a linear quadratic radiobiological model to determine an appropriate dose prescription scheme for permanent seed prostate implants. In this model, prostate edema was taken into consideration. Calculations were also performed for tumors of different doubling times and for other related radiobiological parameters of different values. As expected, the derived prescription dose values were dependent on type of tumors and types of edema. However, for prostate cancers in which tumor cells are relatively slow growing and are reported to have a mean potential doubling time of around 40 days, the appropriate prescription dose for permanent seed prostate implants was determined to be: if the experiences of seed implants were followed and if the experiences of seed implants were followed.
Implementation and validation of three automated methods for measuring ultrasound maximum depth of penetration: Application to ultrasound quality control
Authors: Gorny K. R. , Tradup D. J. , Hangiandreou N. J.
Published: September 2005

Systematic measurements of maximum depth of penetration (DOP) of ultrasound (US) scanners are essential for quality control (QC). Conventionally, DOP measurements are performed visually and as such they could be affected by various external factors, scanner control settings, and operator related errors. Automated methods should be free of the issues associated with interoperator dependence and are an attractive alternative to the visual DOP measurements. We implement and test three automated methods for measuring DOP. The methods base their measurements on signal to noise (SNR) analysis of uniform US phantom images. Two of the methods use pairs of phantom images. The third one uses a single phantom image and an “in‐air” image. The validation tests included precision, sensitivity, repeatability, and usability in routine QC application. Methods based on pairs of phantom images measure the DOP with precision or better. Precision of the single phantom image method is , and that method is also the most sensitive of the three. All three methods are demonstrated to be repeatable among different users. Since the images for the DOP computation are collected free‐hand the sensitivity to hand‐transducer motion during image acquisition was also tested. Unlike the single‐phantom‐image based method, the methods using image pairs were found to be very sensitive to transducer motion and therefore less convenient for clinical QC applications. In conclusion, the single‐phantom‐image method is best suited for routine QC in a real‐life clinical practice.
Statistical analysis of dose‐volume and dose‐wall histograms for rectal toxicity following 3D‐CRT in prostate cancer
Authors: García‐Vicente Feliciano , Zapatero Almudena , Floriano Alejandro , Cruz‐Conde Alfonso , Pérez Leopoldo , Marín Alicia , Mínguez Cristina , Torres Juan J.
Published: September 2005

The purpose of this paper is to determine the correlation between dose‐volume histogram (DVH) and dose wall‐histogram (DWH) in the evaluation of rectal complications for prostate cancer patients treated with three‐dimensional conformal radiotherapy (3D‐CRT). A retrospective analysis of DVHs and DWHs of a subset of 25 prostate cancer patients treated with 3D‐CRT was performed. For every patient the rectum and the rectal wall (inner and outer surface) were contoured. Median ICRU radiation dose of was administered. Correlation between DVHs and DWHs parameters was investigated by the nonparametric Spearman test and by linear regression analysis. The results showed a statistically significant linear correlation between pairs of DVH and DWH dosimetric parameters with Spearman correlation values bigger than 0.8, with values better than 0.0005 (two‐sided) when the emptied rectum is considered. The variation of and linear fit slope values showed a very similar functional shape with a minimum at 91% ICRU dose . The present study confirms a high correlation between DVH and DWH of the rectum following 3D‐CRT for prostate cancer. The derived advantage is that the contouring of inner surface of rectum could be obviated in almost 90% of patients when performing predictive models for rectal complications based on dosimetric variables under the standard treatment conditions specified in this study.
A regional registration method to find corresponding mass lesions in temporal mammogram pairs
Authors: Timp Sheila , van Engeland Saskia , Karssemeijer Nico
Published: September 2005

In this paper we develop an automatic regional registration method to find corresponding masses on prior and current mammograms. The method contains three steps. In the first, we globally align both images. Then, for each mass lesion on the current view, we define a search area on the prior view, which is likely to contain the same mass lesion. Third, at each location in this search area we calculate a registration measure to quantify how well this location matches the mass lesion on the current view. Finally we select the best location. To determine the performance of our method we compare it to several other registration methods. On a dataset of 389 temporal mass pairs our method correctly links 82% of prior and current mass lesions, whereas other methods achieve at most 72%.
Consequences of the spectral response of an a‐Si EPID and implications for dosimetric calibration
Authors: Kirkby C. , Sloboda R.
Published: September 2005

One of the attractive features of amorphous silicon electronic portal imaging devices (a‐Si EPIDs) as dosimetric tools is that for open fields they are known to exhibit a generally linear relation between pixel value and incident energy fluence as measured by an ion chamber. It has also been established that a‐Si EPIDs incorporating high atomic number phosphors such as exhibit a disproportionately large response to low‐energy photons. The present work examines the consequences of this hypersensitivity in a commercially available EPID, the Varian aS500, with respect to energy fluence calibration in a radiotherapy beam. EPIDs may be deployed in situations where the spectrum of the incident beam is modified by passing through a compensator or through a patient or phantom. By examining the specific case of a beam hardened by passage through compensator material, we show that the discrepancy between open and attenuated beam calibration curves can be as high as 8%. A Monte Carlo study using a comprehensive model of the aS500 shows that this difference can be explained by spectral changes, and further suggests that it can be reduced by the addition of an external copper plate. We consider configurations with the plate placed directly on top of the EPID cassette and above the cassette, supported by Styrofoam. In order to reduce the maximum discrepancy to , it was found that a copper thickness of was required in the elevated configuration. Improvement was minimal with the copper in the contact configuration. Adding of copper in the elevated configuration reduced the contrast‐to‐noise ratio by 19% and the modulation transfer for a given spatial frequency by 30%.
Ultrasound‐guided microwave imaging of breast cancer: Tissue phantom and pilot clinical experiments
Authors: Jiang Huabei , Li Changqing , Pearlstone David , Fajardo Laurie L.
Published: September 2005

Microwave imaging promises high contrast between tumor and normal breast tissues, but its spatial resolution is limited. Here, we present a multimodality approach for high‐resolution microwave imaging, where microwave image reconstruction is structurally guided by ultrasound imaging. The combined imaging concept is demonstrated using tissue phantom measurements obtained from a transmitter/receiver microwave imaging system and a modified B‐mode ultrasound system. With the geometry of the target and background known a priori from ultrasound, successful dielectric property images are recovered using a finite element‐based reconstruction algorithm. We show that a target as small as in diameter can be imaged with the multimodality approach, whereas it is impossible to detect such a small‐size object using microwave imaging alone. The pilot clinical studies on two cases suggest that breast tumors can be much more accurately detected by the multimodality method.
Performance characterization of megavoltage computed tomography imaging on a helical tomotherapy unit
Authors: Meeks Sanford L. , Harmon Joseph F. , Langen Katja M. , Willoughby Twyla R. , Wagner Thomas H. , Kupelian Patrick A.
Published: September 2005

Helical tomotherapy is an innovative means of delivering IGRT and IMRT using a device that combines features of a linear accelerator and a helical computed tomography (CT) scanner. The HI‐ART II can generate CT images from the same megavoltage x‐ray beam it uses for treatment. These megavoltage CT (MVCT) images offer verification of the patient position prior to and potentially during radiation therapy. Since the unit uses the actual treatment beam as the x‐ray source for image acquisition, no surrogate telemetry systems are required to register image space to treatment space. The disadvantage to using the treatment beam for imaging, however, is that the physics of radiation interactions in the megavoltage energy range may force compromises between the dose delivered and the image quality in comparison to diagnostic CT scanners. The performance of the system is therefore characterized in terms of objective measures of noise, uniformity, contrast, and spatial resolution as a function of the dose delivered by the MVCT beam. The uniformity and spatial resolutions of MVCT images generated by the HI‐ART II are comparable to that of diagnostic CT images. Furthermore, the MVCT scan contrast is linear with respect to the electron density of material imaged. MVCT images do not have the same performance characteristics as state‐of‐the art diagnostic CT scanners when one objectively examines noise and low‐contrast resolution. These inferior results may be explained, at least partially, by the low doses delivered by our unit; the dose is 1.1 cGy in a 20 cm diameter cylindrical phantom. In spite of the poorer low‐contrast resolution, these relatively low‐dose MVCT scans provide sufficient contrast to delineate many soft‐tissue structures. Hence, these images are useful not only for verifying the patient's position at the time of therapy, but they are also sufficient for delineating many anatomic structures. In conjunction with the ability to recalculate radiotherapy doses on these images, this enables dose guidance as well as image guidance of radiotherapy treatments.
Reproducibility of the bladder shape and bladder shape changes during filling
Authors: Lotz Heidi T. , van Herk Marcel , Betgen Anja , Pos Floris , Lebesque Joos V. , Remeijer Peter
Published: September 2005

The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi‐automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to (mean value: ). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of . The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible ( in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to for bladders with a volume of 200 cc. These large long‐term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to predict short‐term shape changes. We intend to use this tool for further improvement of image‐guided radiotherapy for bladder cancer patients.
Precision targeting of liver lesions using a novel electromagnetic navigation device in physiologic phantom and swine
Authors: Banovac Filip , Tang Jonathan , Xu Sheng , Lindisch David , Chung Ho Young , Levy Elliot B. , Chang Thomas , McCullough Michael F. , Yaniv Ziv , Wood Bradford J. , Cleary Kevin
Published: September 2005

Radiofrequency ablation of primary and metastatic liver tumors is becoming a potential alternative to surgical resection. We propose a novel system that uses real‐time electromagnetic position sensing of the needle tip to help with precision guidance into a liver tumor. The purpose of this study was to evaluate this technology in phantom and animal models. Using an electromagnetic navigation device, instrumented needles were advanced into radioopaque tumor targets in a respiratory liver phantom. The phantom featured a moving liver target that simulated cranio‐caudal liver motion due to respiration. Skin‐to‐target path planning and real‐time needle guidance were provided by a custom‐designed software interface based on pre‐operative CT data slices. Needle probes were advanced using only the electromagnetic navigation device and software display. No conventional real‐time imaging was used to assist in advancing the needle to the target. Two experienced operators (interventional radiologists) and two inexperienced ones (residents) used the system. The same protocol was then also used in two anesthetized Yorkshire swine where radioopaque agar nodules were injected into the liver to serve as targets. A total of 76 tumor targeting attempts were performed in the liver phantom, and 32 attempts were done in the swine. The average time for path planning was in the phantom, and in the swine. The median time for the actual needle puncture to reach the desired target was in the phantom, and in the swine. The average registration error between the CT coordinate system and electromagnetic coordinate system was (SD ) in the phantom, and (SD ) in the swine. The median distance from the final needle tip position to the center of the tumor was (SD , ) in the phantom, and (SD , ) in the swine. There was no statistical difference in the planning time, procedure time, or accuracy of needle placement between experienced and inexperienced operators. The novel electromagnetic navigation system allows probe delivery into hepatic tumors of a physiologic phantom and live anesthetized swine. The system allows less experienced operators to perform equally well as experienced radiologists in terms of procedure time and accuracy of needle probe delivery.
Design and dosimetric considerations of a modified COMS plaque: The reusable “seed‐guide” insert
Authors: Astrahan Melvin A. , Szechter Andrzej , Finger Paul T.
Published: September 2005

The Collaborative Ocular Melanoma Study (COMS) developed a standardized set of eye plaques that consist of a 0.5 mm thick bowl‐like gold alloy backing with a cylindrical collimating lip. A Silastic seed carrier into which seeds are loaded was designed to fit within the backing. The carrier provides a standardized seed pattern and functions to offset the seeds by 1.0 mm from the concave (front) surface of the carrier. These Silastic carriers have been found to be difficult to load, preclude flash sterilization, and are a source of dosimetric uncertainty because the effective atomic number of Silastic is significantly higher than that of water. The main dosimetric effect of the Silastic carrier is a dose‐reduction (compared to homogeneous water) of approximately 10%–15% for radiation. The dose reduction is expected to be even greater for radiation. In an attempt to improve upon, yet retain as much of the familiar COMS design as possible, we have developed a thin “seed‐guide” insert made of gold alloy. This new insert has cutouts which match the seed pattern of the Silastic carrier, but allows the seeds to be glued directly to the inner surface of the gold backing using either dental acrylic or a cyanoacrylate adhesive. When glued directly to the gold backing the seeds are offset a few tenths of a millimeter further away from the scleral surface compared to using the Silastic carrier. From a dosimetric perspective, the space formerly occupied by the Silastic carrier is now assumed to be water equivalent. Water equivalency is a desirable attribute for this space because it eliminates the dosimetric uncertainties related to the atomic composition of Silastic and thereby facilitates the use of either and/or seeds. The caveat is that a new source of dosimetric uncertainty would be introduced were an air bubble to become trapped in this space during or after the surgical insertion. The presence of air in this space is modeled and the dosimetric impact discussed. Another unintended consequence of water equivalency is that some fluorescent x rays emitted from the gold backing can now reach the eye. These very low energy x rays were virtually eliminated by absorption in Silastic. When loaded with seeds the modified plaque appears to produce dose distributions that are almost the same as those of the original COMS plaque and the maximum dosimetric uncertainty introduced by an air bubble is about 2%. Dose distributions calculated for a modified plaque loaded with seeds show that dose to healthy ocular structures distal to the tumor apex can be reduced compared to . Clearly, it is faster and easier to glue seeds into the reusable gold seed‐guide insert than it is to load the COMS‐Silastic carrier.
Magnetic Domain-Wall Logic
Authors: Allwood D. A. , Xiong G. , Faulkner C. C. , Atkinson D. , Petit D. , Cowburn R. P.
Published: September 2005

“Spintronics,” in which both the spin and charge of electrons are used for logic and memory operations, promises an alternate route to traditional semiconductor electronics. A complete logic architecture can be constructed, which uses planar magnetic wires that are less than a micrometer in width. Logical NOT, logical AND, signal fan-out, and signal cross-over elements each have a simple geometric design, and they can be integrated together into one circuit. An additional element for data input allows information to be written to domain-wall logic circuits.
Rising Atmospheric CO
2
Reduces Sequestration of Root-Derived Soil Carbon
Authors: Heath James , Ayres Edward , Possell Malcolm , Bardgett Richard D. , Black Helaina I. J. , Grant Helen , Ineson Phil , Kerstiens Gerhard
Published: September 2005

Forests have a key role as carbon sinks, which could potentially mitigate the continuing increase in atmospheric carbon dioxide concentration and associated climate change. We show that carbon dioxide enrichment, although causing short-term growth stimulation in a range of European tree species, also leads to an increase in soil microbial respiration and a marked decline in sequestration of root-derived carbon in the soil. These findings indicate that, should similar processes operate in forest ecosystems, the size of the annual terrestrial carbon sink may be substantially reduced, resulting in a positive feedback on the rate of increase in atmospheric carbon dioxide concentration.
Generating Electricity While Walking with Loads
Authors: Rome Lawrence C. , Flynn Louis , Goldman Evan M. , Yoo Taeseung D.
Published: September 2005

We have developed the suspended-load backpack, which converts mechanical energy from the vertical movement of carried loads (weighing 20 to 38 kilograms) to electricity during normal walking [generating up to 7.4 watts, or a 300-fold increase over previous shoe devices (20 milliwatts)]. Unexpectedly, little extra metabolic energy (as compared to that expended carrying a rigid backpack) is required during electricity generation. This is probably due to a compensatory change in gait or loading regime, which reduces the metabolic power required for walking. This electricity generation can help give field scientists, explorers, and disaster-relief workers freedom from the heavy weight of replacement batteries and thereby extend their ability to operate in remote areas.
Simulated Quantum Computation of Molecular Energies
Authors: Aspuru-Guzik Alán , Dutoi Anthony D. , Love Peter J. , Head-Gordon Martin
Published: September 2005

The calculation time for the energy of atoms and molecules scales exponentially with system size on a classical computer but polynomially using quantum algorithms. We demonstrate that such algorithms can be applied to problems of chemical interest using modest numbers of quantum bits. Calculations of the water and lithium hydride molecular ground-state energies have been carried out on a quantum computer simulator using a recursive phase-estimation algorithm. The recursive algorithm reduces the number of quantum bits required for the readout register from about 20 to 4. Mappings of the molecular wave function to the quantum bits are described. An adiabatic method for the preparation of a good approximate ground-state wave function is described and demonstrated for a stretched hydrogen molecule. The number of quantum bits required scales linearly with the number of basis functions, and the number of gates required grows polynomially with the number of quantum bits.
Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients
Authors: Schwab Susan R. , Pereira João P. , Matloubian Mehrdad , Xu Ying , Huang Yong , Cyster Jason G.
Published: September 2005

Lymphocyte egress from the thymus and from peripheral lymphoid organs depends on sphingosine 1-phosphate (S1P) receptor-1 and is thought to occur in response to circulatory S1P. However, the existence of an S1P gradient between lymphoid organs and blood or lymph has not been established. To further define egress requirements, we addressed why treatment with the food colorant 2-acetyl-4-tetrahydroxybutylimidazole (THI) induces lymphopenia. We found that S1P abundance in lymphoid tissues of mice is normally low but increases more than 100-fold after THI treatment and that this treatment inhibits the S1P-degrading enzyme S1P lyase. We conclude that lymphocyte egress is mediated by S1P gradients that are established by S1P lyase activity and that the lyase may represent a novel immunosuppressant drug target.
Microcephalin
, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans
Authors: Evans Patrick D. , Gilbert Sandra L. , Mekel-Bobrov Nitzan , Vallender Eric J. , Anderson Jeffrey R. , Vaez-Azizi Leila M. , Tishkoff Sarah A. , Hudson Richard R. , Lahn Bruce T.
Published: September 2005

The gene
Microcephalin
(
MCPH1
) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage. We show that one genetic variant of
Microcephalin
in modern humans, which arose ∼37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift. This indicates that it has spread under strong positive selection, although the exact nature of the selection is unknown. The finding that an important brain gene has continued to evolve adaptively in anatomically modern humans suggests the ongoing evolutionary plasticity of the human brain. It also makes
Microcephalin
an attractive candidate locus for studying the genetics of human variation in brain-related phenotypes.
PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53
Authors: Chipuk Jerry E. , Bouchier-Hayes Lisa , Kuwana Tomomi , Newmeyer Donald D. , Green Douglas R.
Published: September 2005

The
Trp53
tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of
PUMA
, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondrial permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of
PUMA
expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53.
Unexpected Changes to the Global Methane Budget over the Past 2000 Years
Authors: Ferretti D. F. , Miller J. B. , White J. W. C. , Etheridge D. M. , Lassey K. R. , Lowe D. C. , Meure C. M. MacFarling , Dreier M. F. , Trudinger C. M. , van Ommen T. D. , Langenfelds R. L.
Published: September 2005

We report a 2000-year Antarctic ice-core record of stable carbon isotope measurements in atmospheric methane (δ
13
CH
4
). Large δ
13
CH
4
variations indicate that the methane budget varied unexpectedly during the late preindustrial Holocene (circa 0 to 1700 A.D.). During the first thousand years (0 to 1000 A.D.), δ
13
CH
4
was at least 2 per mil enriched compared to expected values, and during the following 700 years, an about 2 per mil depletion occurred. Our modeled methane source partitioning implies that biomass burning emissions were high from 0 to 1000 A.D. but reduced by almost ∼40% over the next 700 years. We suggest that both human activities and natural climate change influenced preindustrial biomass burning emissions and that these emissions have been previously understated in late preindustrial Holocene methane budget research.
Neutral Ecological Theory Reveals Isolation and Rapid Speciation in a Biodiversity Hot Spot
Authors: Latimer Andrew M. , Silander John A. , Cowling Richard M.
Published: September 2005

South Africa's Mediterranean-climate fynbos shrubland is a hot spot of species diversity, but its diversity patterns contrast strongly with other high-diversity areas, including the Amazon rain forest. With its extremely high levels of endemism and species turnover, fynbos is made up of dissimilar local communities that are species-rich but relatively poor in rare species. Using neutral ecological theory, we show that the relative species-abundance distributions in fynbos can be explained by migration rates that are two orders of magnitude lower than they are in tropical rain forests. Speciation rates, which are indexed by the “biodiversity parameter” Θ, are estimated to be higher than they are in any previously examined plant system.
Conversion of Zinc Oxide Nanobelts into Superlattice-Structured Nanohelices
Authors: Gao Pu Xian , Ding Yong , Mai Wenjie , Hughes William L. , Lao Changshi , Wang Zhong Lin
Published: September 2005

A previously unknown rigid helical structure of zinc oxide consisting of a superlattice-structured nanobelt was formed spontaneously in a vapor-solid growth process. Starting from a single-crystal stiff nanoribbon dominated by the
c
-plane polar surfaces, an abrupt structural transformation into the superlattice-structured nanobelt led to the formation of a uniform nanohelix due to a rigid lattice rotation or twisting. The nanohelix was made of two types of alternating and periodically distributed long crystal stripes, which were oriented with their
c
axes perpendicular to each other. The nanohelix terminated by transforming into a single-crystal nanobelt dominated by nonpolar (

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) surfaces. The nanohelix could be manipulated, and its elastic properties were measured, which suggests possible uses in electromechanically coupled sensors, transducers, and resonators.
Ongoing Adaptive Evolution of
ASPM
, a Brain Size Determinant in
Homo sapiens
Authors: Mekel-Bobrov Nitzan , Gilbert Sandra L. , Evans Patrick D. , Vallender Eric J. , Anderson Jeffrey R. , Hudson Richard R. , Tishkoff Sarah A. , Lahn Bruce T.
Published: September 2005

The gene
ASPM
(
abnormal spindle-like microcephaly associated
) is a specific regulator of brain size, and its evolution in the lineage leading to
Homo sapiens
was driven by strong positive selection. Here, we show that one genetic variant of
ASPM
in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.
Application of Fluorescent Amplified Fragment Length Polymorphism for Comparison of Human and Animal Isolates of
Yersinia enterocolitica
Authors: Fearnley Catherine , On Stephen L. W. , Kokotovic Branko , Manning Georgina , Cheasty Tom , Newell Diane G.
Published: September 2005

An amplified fragment length polymorphism (AFLP) method, developed to genotype
Yersinia enterocolitica
, has been used to investigate 70 representative strains isolated from humans, pigs, sheep, and cattle in the United Kingdom. AFLP primarily distinguished
Y. enterocolitica
strains according to their biotype, with strains dividing into two distinct clusters: cluster A, comprising largely the putatively pathogenic biotypes (BT2 to -4), and cluster B, comprising the putatively nonpathogenic biotype 1A strains and a single BT1B isolate. Within these two clusters, subclusters formed largely on the basis of serotype. However, AFLP profiles also allowed differentiation of strains within these serotype-related subclusters, indicating the high discriminatory power of the technique for
Y. enterocolitica
. Investigation of the relationship between strain AFLP profile and host confirmed that pigs are, and provides further proof that sheep may be, potential sources of human infection with putatively pathogenic strains. However, the results suggest that some strains causing human disease do not come from veterinary sources identifiable at this time. The distribution of some BT1A isolates within cluster A raises questions about the relationship between virulence potential and biotype.
Pyruvate Fermentation by
Oenococcus oeni
and
Leuconostoc mesenteroides
and Role of Pyruvate Dehydrogenase in Anaerobic Fermentation
Authors: Wagner Nicole , Tran Quang Hon , Richter Hanno , Selzer Paul M. , Unden Gottfried
Published: September 2005

The heterofermentative lactic acid bacteria
Oenococcus oeni
and
Leuconostoc mesenteroides
are able to grow by fermentation of pyruvate as the carbon source (2 pyruvate → 1 lactate + 1 acetate + 1 CO
2
). The growth yields amount to 4.0 and 5.3 g (dry weight)/mol of pyruvate, respectively, suggesting formation of 0.5 mol ATP/mol pyruvate. Pyruvate is oxidatively decarboxylated by pyruvate dehydrogenase to acetyl coenzyme A, which is then converted to acetate, yielding 1 mol of ATP. For NADH reoxidation, one further pyruvate molecule is reduced to lactate. The enzymes of the pathway were present after growth on pyruvate, and genome analysis showed the presence of the corresponding structural genes. The bacteria contain, in addition, pyruvate oxidase activity which is induced under microoxic conditions. Other homo- or heterofermentative lactic acid bacteria showed only low pyruvate fermentation activity.
Identification of Novel
Salmonella enterica
Serovar Typhimurium DT104-Specific Prophage and Nonprophage Chromosomal Sequences among Serovar Typhimurium Isolates by Genomic Subtractive Hybridization
Authors: Hermans Armand P. H. M. , Abee Tjakko , Zwietering Marcel H. , Aarts Henk J. M.
Published: September 2005

Genomic subtractive hybridization was performed between
Salmonella enterica
serovar Typhimurium LT2 and DT104 to search for novel
Salmonella
serovar Typhimurium DT104-specific sequences. The subtraction resulted mainly in the isolation of DNA fragments with sequence similarity to phages. Two fragments identified were associated with possible virulence factors. One fragment was identical to
irsA
of
Salmonella
serovar Typhimurium ATCC 14028, which is suggested to be involved in macrophage survival. The other fragment was homologous to HldD, an
Escherichia coli
O157:H7 lipopolysaccharide assembly-related protein. Five selected DNA fragments—
irsA
, the HldD homologue, and three fragments with sequence similarity to prophages—were tested for their presence in 17
Salmonella
serovar Typhimurium DT104 isolates and 27 non-DT104 isolates by PCR. All five selected DNA fragments were
Salmonella
serovar Typhimurium DT104 specific among the serovar Typhimurium isolates tested. These DNA fragments can be useful for better detection and typing of
Salmonella
serovar Typhimurium DT104.
Sheep May Not Be an Important Zoonotic Reservoir forCryptosporidiumandGiardiaParasites
Authors: Ryan Una M. , Bath Caroline , Robertson Ian , Read Carolyn , Elliot Aileen , Mcinnes Linda , Traub Rebecca , Besier Brown
Published: September 2005

Little is known of the prevalence ofCryptosporidiumandGiardiaparasites in sheep and the genotypes that they harbor, although potentially sheep may contribute significantly to contamination of watersheds. In the present study, conducted in Western Australia, a total of 1,647 sheep fecal samples were screened for the presence ofCryptosporidiumandGiardiaspp. using microscopy, and a subset (n= 500) were screened by PCR and genotyped. Analysis revealed that although both parasites were detected in a high proportion of samples by PCR (44% and 26% forGiardiaandCryptosporidiumspp., respectively), with the exception of oneCryptosporidium hominisisolate, the majority of isolates genotyped are not commonly found in humans. These results suggest that the public health risk of sheep-derivedCryptosporidiumandGiardiaspp. in catchment areas and effluent may be overestimated and warrant further investigation.
A Second 5-Carboxyvanillate Decarboxylase Gene,
ligW2
, Is Important for Lignin-Related Biphenyl Catabolism in
Sphingomonas paucimobilis
SYK-6
Authors: Peng Xue , Masai Eiji , Kasai Daisuke , Miyauchi Keisuke , Katayama Yoshihiro , Fukuda Masao
Published: September 2005

A lignin-related biphenyl compound, 5,5′-dehydrodivanillate (DDVA), is degraded to 5-carboxyvanillate (5CVA) by the enzyme reactions catalyzed by DDVA
O
-demethylase (LigX),
meta
-cleavage oxygenase (LigZ), and
meta
-cleavage compound hydrolase (LigY) in
Sphingomonas paucimobilis
SYK-6. 5CVA is then transformed to vanillate by a nonoxidative 5CVA decarboxylase and is further degraded through the protocatechuate 4,5-cleavage pathway. A 5CVA decarboxylase gene,
ligW
, was isolated from SYK-6 (X. Peng, E. Masai, H. Kitayama, K. Harada, Y, Katayama, and M. Fukuda, Appl. Environ. Microbiol.
68:
4407-4415, 2002). However, disruption of
ligW
slightly affected the 5CVA decarboxylase activity and the growth rate on DDVA of the mutant, suggesting the presence of an alternative 5CVA decarboxylase gene. Here we isolated a second 5CVA decarboxylase gene,
ligW2
, which consists of a 1,050-bp open reading frame encoding a polypeptide with a molecular mass of 39,379 Da. The deduced amino acid sequence encoded by
ligW2
exhibits 37% identity with the sequence encoded by
ligW
. Based on a gas chromatography-mass spectrometry analysis of the reaction product from 5CVA catalyzed by LigW2 in the presence of deuterium oxide, LigW2 was indicated to be a nonoxidative decarboxylase of 5CVA, like LigW. After disruption of
ligW2
, both the growth rate on DDVA and the 5CVA decarboxylase activity of the mutant were decreased to approximately 30% of the wild-type levels. The
ligW ligW2
double mutant lost both the ability to grow on DDVA and the 5CVA decarboxylase activity. These results indicate that both
ligW
and
ligW2
contribute to 5CVA degradation, although
ligW2
plays the more important role in the growth of SYK-6 cells on DDVA.
Facilitation of Expression and Purification of an Antimicrobial Peptide by Fusion with Baculoviral Polyhedrin in
Escherichia coli
Authors: Wei Quande , Kim Young Soo , Seo Jeong Hyun , Jang Woong Sik , Lee In Hee , Cha Hyung Joon
Published: September 2005

Several fusion strategies have been developed for the expression and purification of small antimicrobial peptides (AMPs) in recombinant bacterial expression systems. However, some of these efforts have been limited by product toxicity to host cells, product proteolysis, low expression levels, poor recovery yields, and sometimes an absence of posttranslational modifications required for biological activity. For the present work, we investigated the use of the baculoviral polyhedrin (Polh) protein as a novel fusion partner for the production of a model AMP (halocidin 18-amino-acid subunit; Hal18) in
Escherichia coli
. The useful solubility properties of Polh as a fusion partner facilitated the expression of the Polh-Hal18 fusion protein (∼33.6 kDa) by forming insoluble inclusion bodies in
E. coli
which could easily be purified by inclusion body isolation and affinity purification using the fused hexahistidine tag. The recombinant Hal18 AMP (∼2 kDa) could then be cleaved with hydroxylamine from the fusion protein and easily recovered by simple dialysis and centrifugation. This was facilitated by the fact that Polh was soluble during the alkaline cleavage reaction but became insoluble during dialysis at a neutral pH. Reverse-phase high-performance liquid chromatography was used to further purify the separated recombinant Hal18, giving a final yield of 30% with >90% purity. Importantly, recombinant and synthetic Hal18 peptides showed nearly identical antimicrobial activities against
E. coli
and
Staphylococcus aureus
, which were used as representative gram-negative and gram-positive bacteria, respectively. These results demonstrate that baculoviral Polh can provide an efficient and facile platform for the production or functional study of target AMPs.
Characterization of a Resistance-Nodulation-Cell Division Transporter System Associated with the
syr-syp
Genomic Island of
Pseudomonas syringae
pv. syringae
Authors: Kang Hyojeung , Gross Dennis C.
Published: September 2005

A tripartite resistance-nodulation-cell division (RND) transporter system, called the PseABC efflux system, was identified at the left border of the
syr
-
syp
genomic island of
Pseudomonas syringae
pv. syringae strain B301D. The PseABC efflux system was located within a 5.7-kb operon that encodes an outer membrane protein (PseA), a periplasmic membrane fusion protein (PseB), and an RND-type cytoplasmic membrane protein (PseC). The PseABC efflux system exhibited amino acid homology to a putative RND efflux system of
Ralstonia solanacearum
, with identities of 48% for PseA, 51% for PseB, and 61% for PseC. A nonpolar mutation within the
pseC
gene was generated by
nptII
insertional mutagenesis. The resultant mutant strain showed a larger reduction in syringopeptin secretion (67%) than in syringomycin secretion (41%) compared to parental strain B301D (
P
< 0.05). A β-glucuronidase assay with a
pseA
::
uidA
reporter construct indicated that the GacS/GacA two-component system controls expression of the
pseA
gene. Quantitative real-time reverse transcription-PCR was used to determine transcript levels of the syringomycin (
syrB1
) and syringopeptin (
sypA
) synthetase genes in strain B301D-HK4 (a
pseC
mutant). The expression of the
sypA
gene by mutant strain B301D-HK4 corresponded to approximately 13% of that by parental strain B301D, whereas the
syrB1
gene expression by mutant strain B301D-HK4 was nearly 61% (
P
< 0.05). In addition, the virulence of mutant strain B301D-HK4 for immature cherry fruits was reduced by about 58% compared to parental strain B301D (
P
< 0.05). Although the resistance of mutant strain B301D-HK4 to any antibiotic used in this study was not reduced compared to parental strain B301D, a drug-supersensitive
acrB
mutant of
Escherichia coli
showed two- to fourfold-increased resistance to acriflavine, erythromycin, and tetracycline upon heterologous expression of the
pseA
,
pseB
, and
pseC
genes (
pseABC
efflux genes). The PseABC efflux system is the first RND transporter system described for
P. syringae
, and it has an important role in secretion of syringomycin and syringopeptin.
Gene Cluster Responsible for Validamycin Biosynthesis in
Streptomyces hygroscopicus
subsp.
jinggangensis
5008
Authors: Yu Yi , Bai Linquan , Minagawa Kazuyuki , Jian Xiaohong , Li Lei , Li Jialiang , Chen Shuangya , Cao Erhu , Mahmud Taifo , Floss Heinz G. , Zhou Xiufen , Deng Zixin
Published: September 2005

A gene cluster responsible for the biosynthesis of validamycin, an aminocyclitol antibiotic widely used as a control agent for sheath blight disease of rice plants, was identified from
Streptomyces hygroscopicus
subsp.
jinggangensis
5008 using heterologous probe
acbC
, a gene involved in the cyclization of
d
-sedoheptulose 7-phosphate to 2-
epi
-5-
epi
-valiolone of the acarbose biosynthetic gene cluster originated from
Actinoplanes
sp. strain SE50/110. Deletion of a 30-kb DNA fragment from this cluster in the chromosome resulted in loss of validamycin production, confirming a direct involvement of the gene cluster in the biosynthesis of this important plant protectant. A sequenced 6-kb fragment contained
valA
(an
acbC
homologue encoding a putative cyclase) as well as two additional complete open reading frames (
valB
and
valC
, encoding a putative adenyltransferase and a kinase, respectively), which are organized as an operon. The function of ValA was genetically demonstrated to be essential for validamycin production and biochemically shown to be responsible specifically for the cyclization of
d
-sedoheptulose 7-phosphate to 2-
epi
-5-
epi
-valiolone in vitro using the ValA protein heterologously overexpressed in
E. coli
. The information obtained should pave the way for further detailed analysis of the complete biosynthetic pathway, which would lead to a complete understanding of validamycin biosynthesis.