bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis‐ and cell cycle‐associated gene expression profiling of histiocytic necrotising lymphadenitis
Authors: Ohshima Koichi , Karube Kennosuke , Hamasaki Makoto , Makimoto Yoshifumi , Fujii Akira , Kawano Riko , Tutiya Takeshi , Yamaguchi Takahiro , Suzumiya Junji , Kikuchi Masahiro
Published: April 2004

Cell death is of two types; necrosis and apoptosis. In histiocytic necrotising lymphadenitis (HNL), apoptosis is the main form of cell death. Apoptosis results in the formation of nuclear debris, which is one of the characteristic features of HNL. We previously reported that in HNL it is predominantly CD8‐positive cytotoxic T cells that undergo apoptosis; however, the majority of proliferating cells are also CD8‐positive T cells. Recent advances in technical and analytical methods have facilitated the parallel quantitation of expression of numerous genes using DNA microarrays. The technology is particularly well suited to compare differences in gene expression between normal tissues and inflammatory disease. To investigate the apoptosis‐ and cell cycle‐associated gene expression in HNL, we analysed five cases each of HNL and non‐specific lymphadenitis (NSL), using ready‐made microarrays, including cyclins and caspases, and immunohistochemical staining of caspase‐3, ssDNA, bcl‐2 and NF‐κB. Caspase‐3‐ and ssDNA‐positive apoptotic cells were frequently detected in HNL, but were rare in NSL. However, bcl‐2‐ and NF‐κB‐positive cells were rare in HNL. Gene expression tree analysis of DNA microarrays showed different clustering of HNL and NSL. In comparison with NSL, HNL exhibited diffuse upregulation of these gene profiles, particularly of cyclins and caspases (ratio; cyclin A2, 2.72; caspase‐6, 2.43; caspase‐3, 2.02); whereas, Mcl‐1, which has been shown to delay apoptosis, was downregulated (ratio, 0.71), as confirmed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Almost all apoptosis‐associated genes, especially caspases, were upregulated, and apoptosis inhibitory genes, including bcl‐2 by immunohistochemistry, were downregulated in all five cases with HNL. In addition, cell cycle‐associated genes were upregulated in all. These findings confirm that both apoptosis and proliferation are simultaneously present in HNL lesions.
Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs
Authors: Tamary Hannah , Dgany Orly , Toledano Helen , Shalev Zvi , Krasnov Tatyana , Shalmon Lea , Schechter Tali , Bercovich Dani , Attias Dina , Laor Ruth , Koren Ariel , Yaniv Isaac
Published: April 2004

Objectives:  In a previous study, we investigated the molecular basis of Fanconi anemia (FA) in 13 unrelated Israeli Jewish FA patients and identified four ethnicity specific mutations. In the present study we extended our study to Israeli Arab patients.

Methods:  We studied three consanguineous families with nine FA patients and an additional unrelated patient. DNA single‐strand conformation polymorphism of each exon of the FANCA and FANCG genes was followed by sequence analysis of the aberrantly migrating fragments and by reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis of the splice‐site mutations identified.

Results:  Three unique disease‐causing mutations were identified: (i) FANCA gross deletion of exons 6–31; (ii) FANCA splice‐site mutation IVS 42‐2A>C; (iii) FANCG splice‐site mutation IVS4+3A>G. Sequence analysis of the FANCA gross deletion revealed recombination between two highly homologous Alu elements. cDNA analysis of the two splice mutations suggested intron 42 retention in FANCA IVS 42‐2A>C and exon 4 skipping in FANCG IVS4+3A>G. The clinical condition of eight patients with FANCA mutations was severe.

Conclusions:  Two unique FANCA mutations and one FANCG mutation were identified in Israeli Arab FA patients. Deletion of FANCA exon 6–31 as in previously described gross deletions was within introns rich in Alu repeats. To the best of our knowledge, the FANCA IVS 42‐2A>C mutation is the first in this gene to result in intron retention. Further analysis of FA mutations will enable prenatal diagnosis and a rational therapeutic approach including frequent monitoring and early bone marrow transplantation.
A new MLC segmentation algorithm/software for step‐and‐shoot IMRT delivery
Authors: Luan Shuang , Wang Chao , Chen Danny Z. , Hu Xiaobo S. , Naqvi Shahid A. , Yu Cedric X. , Lee Chad L.
Published: April 2004

We present a new MLC segmentation algorithm/software for step‐and‐shoot IMRT delivery. Our aim in this work is to shorten the treatment time by minimizing the number of segments. Our new segmentation algorithm, called SLS (an abbreviation for static leaf sequencing), is based on graph algorithmic techniques in computer science. It takes advantage of the geometry of intensity maps. In our SLS approach, intensity maps are viewed as three‐dimensional (3‐D) “mountains” made of unit‐sized “cubes.” Such a 3‐D “mountain” is first partitioned into special‐structured submountains using a new mixed partitioning scheme. Then the optimal leaf sequences for each submountain are computed by either a shortest‐path algorithm or a maximum‐flow algorithm based on graph models. The computations of SLS take only a few minutes. Our comparison studies of SLS with CORVUS (both the 4.0 and 5.0 versions) and with the Xia and Verhey segmentation methods on Elekta Linac systems showed substantial improvements. For instance, for a pancreatic case, SLS used only one‐fifth of the number of segments required by CORVUS 4.0 to create the same intensity maps, and the SLS sequences took only 25 min to deliver on an Elekta SL 20 Linac system in contrast to the 72 min for the CORVUS 4.0 sequences (a three‐fold improvement). To verify the accuracy of our new leaf sequences, we conducted film and ion‐chamber measurements on phantom. The results showed that both the intensity distributions as well as dose distributions of the SLS delivery match well with those of CORVUS delivery. SLS can also be extended to other types of Linac systems.
Computerized characterization of breast masses on three‐dimensional ultrasound volumes
Authors: Sahiner Berkman , Chan Heang‐Ping , Roubidoux Marilyn A. , Helvie Mark A. , Hadjiiski Lubomir M. , Ramachandran Aditya , Paramagul Chintana , LeCarpentier Gerald L. , Nees Alexis , Blane Caroline
Published: April 2004

We are developing computer vision techniques for the characterization of breast masses as malignant or benign on radiologic examinations. In this study, we investigated the computerized characterization of breast masses on three‐dimensional (3‐D) ultrasound (US) volumetric images. We developed 2‐D and 3‐D active contour models for automated segmentation of the mass volumes. The effect of the initialization method of the active contour on the robustness of the iterative segmentation method was studied by varying the contour used for its initialization. For a given segmentation, texture and morphological features were automatically extracted from the segmented masses and their margins. Stepwise discriminant analysis with the leave‐one‐out method was used to select effective features for the classification task and to combine these features into a malignancy score. The classification accuracy was evaluated using the area under the receiver operating characteristic (ROC) curve, as well as the partial area index defined as the relative area under the ROC curve above a sensitivity threshold of 0.9. For the purpose of comparison with the computer classifier, four experienced breast radiologists provided malignancy ratings for the 3‐D US masses. Our dataset consisted of 3‐D US volumes of 102 biopsied masses (46 benign, 56 malignant). The classifiers based on 2‐D and 3‐D segmentation methods achieved test values of 0.87±0.03 and 0.92±0.03, respectively. The difference in the values of the two computer classifiers did not achieve statistical significance. The values of the four radiologists ranged between 0.84 and 0.92. The difference between the computer's value and that of any of the four radiologists did not achieve statistical significance either. However, the computer's value was significantly higher than that of three of the four radiologists. Our results indicate that an automated and effective computer classifier can be designed for differentiating malignant and benign breast masses on 3‐D US volumes. The accuracy of the classifier designed in this study was similar to that of experienced breast radiologists.
Inverse planning for low‐dose‐rate prostate brachytherapy by simulated annealing under fuzzy expert control
Authors: de la Zerda Lerner Alberto
Published: April 2004

Simulated annealing (SA) is a multivariate combinatorial optimization process that searches the configuration space of possible solutions by a random walk, guided only by the goal of minimization of the objective function. The decision‐making capabilities of a fuzzy inference system are applied to guide the SA search, to look for solutions which, in addition to optimizing a plan in dosimetric terms, also present some clinically desirable spatial features. No a priori constraints are placed on the number or position of needles or on the seed loading sequence of individual needles. These additional degrees of freedom are balanced by giving preference to consider plans with seed distributions that are balanced in the right/left and anterior/posterior halves in each axial slice, and with local seed density that is about uniform. Piecewise linear membership functions are constructed to represent these requirements. Before a step in the random search is subject to the SA test, the expert functions representing the spatial seed‐distribution requirements are evaluated. Thus, the expert planner's knowledge enters into the decision as to the “goodness” of a seed configuration regarding the spatial seed‐distribution goals. When a step in the random walk yields a seed configuration that is found wanting, a specific number of additional steps in the local neighborhood is attempted until either improvement in the spatial requirements is achieved, or the allowed number of attempts is exhausted. In the latter case, the expert system desists and the unfavorable step is taken, moving on to the simulated annealing test. The number of attempts is determined by the fuzzy logic inference engine and depends on just how badly the expert requirement is not met. The program is interfaced with a commercial treatment planning system (TPS) to import optimized seed plans for isodose display and analysis. Execution in a 1.5 GHz computer is less than a minute, adequate for real‐time planning. Results for phantom and real patients are dosimetrically comparable to generic methods such as modified peripheral loading, but in some cases, fewer needles and less radioactivity are required. Sensitivity to simulated random seed placement error is similar to manual plans.
Comparison of radiographic texture analysis from computed radiography and bone densitometry systems
Authors: Wilkie Joel R. , Giger Maryellen L. , Chinander Michael R. , Vokes Tamara J. , Li Hui , Dixon Larry , Jaros Vit
Published: April 2004

Osteoporosis is a disease that results in an increased risk of bone fracture due to a loss of bone mass and deterioration of bone structure. Bone mineral density (BMD) provides a measure of bone mass and is frequently measured by bone densitometry systems to diagnose osteoporosis. In addition, computerized radiographic texture analysis (RTA) is currently being investigated as a measure of bone structure and as an additional diagnostic predictor of osteoporosis. In this study, we assessed the ability of a peripheral bone densitometry (PD) system to yield images useful for RTA. The benefit of such a system is that it measures BMD by dual‐energy x‐ray absorptiometry and therefore provides high‐ and low‐energy digital radiographic images. The bone densitometry system investigated was the GE/Lunar PIXI, which provides digital images of the heel or forearm (0.2 mm pixels). We compared texture features of heel images obtained with this PD system to those obtained on a Fuji computed radiography (CR) system (0.1 mm pixels). Fourier and fractal‐based texture features of images from 24 subjects who had both CR and BMD exams were calculated, and correlation between the two systems was analyzed. Fourier‐based texture features characterize the magnitude, frequency content, and orientation of the trabecular bone pattern. Good correlation was found between the two modalities for the first moment (FMP) with and for minimum FMP with Root‐mean‐square (RMS) did not correlate with while the standard deviation of the RMS did correlate with Good correlation was also found between the two modalities for the fractal‐based texture features with for the global Minkowski dimension and for the fractal dimension from a box counting method. The PD system therefore may have the potential for yielding heel images suitable for RTA.
Noise in flat‐panel displays with subpixel structure
Authors: Badano Aldo , Gagne Robert M. , Jennings Robert J. , Drilling Sarah E. , Imhoff Benjamin R. , Muka Edward
Published: April 2004

Subpixel structures found in medical monochrome active‐matrix liquid crystal displays (AMLCDs) affect noise estimates measured with conventional methods. In this work, we discuss methods that identify sources of noise and permit the comparison of luminance noise estimates across technologies independent of pixel design and device technology. We used a three‐million pixel AMLCD with a pixel structure consisting of three color stripes, each in a two‐domain, in‐plane switching mode. Images of uniform fields displayed on the AMLCD were acquired using a low‐noise, high‐resolution CCD camera. The camera noise and flat‐field response were characterized using a uniform light source constructed for this purpose. We show results in terms of spatial luminance noise and noise power spectrum for high‐resolution images and for the same images processed with a pixel‐aligned aperture. We find that the pixel‐aligned aperture eliminates almost all the noise found in the high‐resolution images, suggesting that most of the luminance noise in AMLCDs comes from the subpixel structure and less‐than‐100% aperture ratio, rather than from interpixel variations.
Segmentation of nodules on chest computed tomography for growth assessment
Authors: Mullally William , Betke Margrit , Wang Jingbin , Ko Jane P.
Published: April 2004

Several segmentation methods to evaluate growth of small isolated pulmonary nodules on chest computed tomography (CT) are presented. The segmentation methods are based on adaptively thresholding attenuation levels and use measures of nodule shape. The segmentation methods were first tested on a realistic chest phantom to evaluate their performance with respect to specific nodule characteristics. The segmentation methods were also tested on sequential CT scans of patients. The methods' estimation of nodule growth were compared to the volume change calculated by a chest radiologist. The best method segmented nodules on average 43% smaller or larger than the actual nodule when errors were computed across all nodule variations on the phantom. Some methods achieved smaller errors when examined with respect to certain nodule properties. In particular, on the phantom individual methods segmented solid nodules to within 23% of their actual size and nodules with 60.7 mm3 volumes to within 14%. On the clinical data, none of the methods examined showed a statistically significant difference in growth estimation from the radiologist.
Introduction of a novel dose saving acquisition mode for the PortalVision™ aS500 EPID to facilitate on‐line patient setup verification
Authors: Vetterli D. , Riem H. , Aebersold D. M. , Greiner R. H. , Manser P. , Cossmann P. , Kemmerling L. , Born E. J. , Mini R.
Published: April 2004

In external beam radiotherapy, electronic portal imaging becomes more and more an indispensable tool for the verification of the patient setup. For the safe clinical introduction of high dose conformal radiotherapy like intensity modulated radiation therapy, on‐line patient setup verification is a prerequisite to ensure that the planned dosimetric coverage of the tumor volume is actually realized in the patient. Since the direction of setup fields often deviates from the direction of the treatment beams, extra dose is delivered to the patient during the acquisition of these portal images which may reach clinical relevance. The aim of this work was to develop a new acquisition mode for the PortalVision™ aS500 electronic portal imaging device from Varian Medical Systems that allows one to take portal images with reduced dose while keeping good image quality. The new acquisition mode, called RadMode, selectively enables and disables beam pulses during image acquisition allowing one to stop wasting valuable dose during the initial acquisition of “reset frames.” Images of excellent quality can be taken with 1 MU only. This low dose per image facilitates daily setup verification with considerably reduced extra dose.
Analysis of the penumbra enlargement in lung versus the Quality Index of photon beams: A methodology to check the dose calculation algorithm
Authors: Tsiakalos Miltiadis F. , Theodorou Kiki , Kappas Constantin , Zefkili Sofia , Rosenwold Jean‐Claude
Published: April 2004

It is well known that considerable underdosage can occur at the edges of a tumor inside the lung because of the degradation of penumbra due to lack of lateral electronic equilibrium. Although present even at smaller energies, this phenomenon is more pronounced for higher energies. Apart from Monte Carlo calculation, most of the existing Treatment Planning Systems (TPSs) cannot deal at all, or with acceptable accuracy, with this effect. A methodology has been developed for assessing the dose calculation algorithms in the lung region where lateral electronic disequilibrium exists, based on the Quality Index (QI) of the incident beam. A phantom, consisting of layers of polystyrene and lung material, has been irradiated using photon beams of 4, 6, 15, and 20 MV. The cross‐plane profiles of each beam for 5×5, 10×10, and 25×10 fields have been measured at the middle of the phantom with the use of films. The penumbra (20%–80%) and fringe (50%–90%) enlargement was measured and the ratio of the widths for the lung to that of polystyrene was defined as the Correction Factor (CF). Monte Carlo calculations in the two phantoms have also been performed for energies of 6, 15, and 20 MV. Five commercial TPS's algorithms were tested for their ability to predict the penumbra and fringe enlargement. A linear relationship has been found between the QI of the beams and the CF of the penumbra and fringe enlargement for all the examined fields. Monte Carlo calculations agree very well (less than 1% difference) with the film measurements. The CF values range between 1.1 for 4 MV (QI 0.620) and 2.28 for 20 MV (QI 0.794). Three of the tested TPS's algorithms could not predict any enlargement at all for all energies and all fields and two of them could predict the penumbra enlargement to some extent. The proposed methodology can help any user or developer to check the accuracy of its algorithm for lung cases, based on a simple phantom geometry and the QI of the incident beam. This check is very important especially when higher energies are used, as the inaccuracies in existing algorithms can lead to an incorrect choice of energy for lung treatment and consequently to a failure in tumor control.
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Authors: Pinto Shirly , Roseberry Aaron G. , Liu Hongyan , Diano Sabrina , Shanabrough Marya , Cai Xiaoli , Friedman Jeffrey M. , Horvath Tamas L.
Published: April 2004

The fat-derived hormone leptin regulates energy balance in part by modulating the activity of neuropeptide Y and proopiomelanocortin neurons in the hypothalamic arcuate nucleus. To study the intrinsic activity of these neurons and their responses to leptin, we generated mice that express distinct green fluorescent proteins in these two neuronal types. Leptin-deficient (
ob/ob
) mice differed from wild-type mice in the numbers of excitatory and inhibitory synapses and postsynaptic currents onto neuropeptide Y and proopiomelanocortin neurons. When leptin was delivered systemically to
ob/ob
mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. These data suggest that leptin-mediated plasticity in the
ob/ob
hypothalamus may underlie some of the hormone's behavioral effects.
Patterns and distribution of tobacco consumption in India: cross sectional multilevel evidence from the 1998-9 national family health survey
Authors: Subramanian S V , Nandy Shailen , Kelly Michelle , Gordon Dave , Smith George Davey
Published: April 2004

Objective To investigate the demographic, socioeconomic, and geographical distribution of tobacco consumption in India.

Design Multilevel cross sectional analysis of the 1998-9 Indian national family health survey of 301 984 individuals in 92 447 households in 3215 villages in 440 districts in 26 states.

Setting Indian states.

Participants 301 984 adults (≥ 18 years).

Main outcome measures Dichotomous variable for smoking and chewing tobacco for each respondent (1 if yes, 0 if no) as well as a combined measure of whether an individual smokes, chews tobacco, or both.

Results Smoking and chewing tobacco are systematically associated with socioeconomic markers at the individual and household level. Individuals with no education are 2.69 times more likely to smoke and chew tobacco than those with postgraduate education. Households belonging to the lowest fifth of a standard of living index were 2.54 times more likely to consume tobacco than those in the highest fifth. Scheduled tribes (odds ratio 1.23, 95% confidence interval 1.18 to 1.29) and scheduled castes (1.19, 1.16 to 1.23) were more likely to consume tobacco than other caste groups. The socioeconomic differences are more marked for smoking than for chewing tobacco. Socioeconomic markers and demographic characteristics of individuals and households do not account fully for the differences at the level of state, district, and village in smoking and chewing tobacco, with state accounting for the bulk of the variation in tobacco consumption.

Conclusion The distribution of tobacco consumption is likely to maintain, and perhaps increase, the current considerable socioeconomic differentials in health in India. Interventions aimed at influencing change in tobacco consumption should consider the socioeconomic and geographical determinants of people's susceptibility to consume tobacco.
Diastereoselectivity in intramolecular ene cyclisation  A theoretical study
Authors: Mondal Nityagopal , Mandal Sannyasi Charan , Das Gourab Kanti
Published: April 2004

Diastereoselectivity in unactivated and activated ene cyclisation can be predicted using HF/6-31G(d) optimized geometry of the transition states. Relative energies of different conformations of the transition states, calculated using DFT, can be used for the prediction of product ratios. It was found that the dihedral angle around the forming carboncarbon bond controls the cistrans diastereoselectivity. A set of three model pericyclic transition structures has been proposed that mimics the activation process of ene cyclisation.Key words: intramolecular ene reaction, ab initio, DFT.
Chemical transformations of cis-W(CO)4(C5H5N)2 in the ring-opening metathesis polymerization of norbornene
Authors: Bencze L , Bíró N , Szabó-Ravasz B , Mihichuk L
Published: April 2004

The six-coordinate W0 complex cis-W(CO)4(C5H5N)2 has been found to be active in the in situ formation of a carbene species from norbornene, which generates a typical ring-opening metathesis product (ROMP). A proposed mechanism of initiation suggests that the reaction involves a 2,3-hydrogen shift in the coordinated norbornene (η2 → η1). The initiating carbenoid group is identified from the products of the spontaneous carbeneCO coupling and Wittig reactions test. Formation of W(CO)3(η6-C6H5CH3) when toluene is the solvent, followed by reaction with the carbene, is blamed for catalyst deactivation.Key words: bis-pyridine-tetracarbonyl-tungsten, ROMP, olefin metathesis, norbornene.
Synthesis, IR, and multinuclear NMR spectroscopic studies of complexes of the type cis- and trans-Pt(amine)2(NO3)2
Authors: Rochon Fernande D , Buculei Viorel
Published: April 2004

Compounds of the types cis- and trans-Pt(amine)2NO3)2 have been synthesized and characterized by IR and multinuclear (195Pt, 13C, and 1H) NMR spectroscopies. The nitrato IR bands were compared for the two isomers. The 195Pt NMR resonances of the trans complexes were observed at lower fields (avg. 1570 ppm for primary amines) than the cis analogues (avg. 1698 ppm) for an average Δδ value of 124 ppm. The complexes containing a secondary amine were observed at about the same field for the cis isomers (avg. 1682 ppm) and surprisingly at much higher fields for the trans compounds (avg. 1638 ppm). In 1H NMR, the coupling constants 2J(195Pt-1HN) are larger for the cis isomers (avg. 67 Hz) than for the trans compounds (avg. 58 Hz). The 3J(195Pt-1H) are also larger for the cis complexes (avg. 40 vs. 33 Hz). In 13C NMR, the coupling constants are also geometry dependent. The 3J(195Pt-13C) are larger for the cis isomers (avg. 37 Hz) than for the trans compounds (avg. 28 Hz). The 2J(195Pt-13C) are much smaller (avg. 18 Hz for the cis complexes and 16 Hz for the trans isomers).Key words: platinum, amine, nitrato, NMR, IR.
A new fluorous soluble Lewis acidic borane system
Authors: Luong Horace , Eelman Melanie D , Stradiotto Mark
Published: April 2004

Treatment of trichlorovinylsilane with 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol (3 equiv.) in the presence of excess triethylamine produces the fluorous vinylsilane, 1, which can be isolated in 74% yield as an analytically pure oil. The addition of bis(pentafluorophenyl)borane to 1 produces the fluorous boranes, 2a2b, as an analytically pure, isomeric mixture of anti-Markovnikov and Markovnikov hydroboration products in 38% isolated yield. Compounds 2a2b are soluble in both arene solvents and perfluoro(methylcyclohexane). Treatment of 2a2b with excess trimethylphosphine generates a mixture of products, including the Lewis adduct, 3, which can be isolated as an analytically pure oil in 15% yield. When exposed to either dimethylaminopyridine or piperidine at room temperature, the trimethylphosphine donor in 3 is cleanly displaced, based on in situ 31P NMR studies; under similar conditions, triethylamine does not react with 3. Addition of either dimethylaminopyridine or piperidine to 2a2b, followed by purification and subsequent treatment with an excess of either hydrogen chloride or p-toluenesulfonic acid, results in cleavage of the SiO linkages and the regeneration of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol.Key words: fluorous, borane, silane, Lewis acid.
A comparison of techniques for measuring density and concentrations of carbon and nitrogen in coarse woody debris at different stages of decay
Authors: Creed I F , Webster K L , Morrison D L
Published: April 2004

This research considered the relationship between the stage of decay and the concentration of nitrogen (N, %) and the ratio of carbon to N (C/N) in coarse woody debris. Density (g/cm3) was used as an indicator of the stage of decay. In samples collected from the red spruce  Fraser fir (Picea rubens Sarg.  Abies fraseri (Pursh) Poir.) forest of the southern Appalachians, density explained up to 60% of the variation in N and C/N in coarse woody debris. The technique used to estimate density was important. Laboratory-based methods (including displacement and mensuration density) explained the greatest degree of the variation, with coefficients of determination (r2) ranging from 0.39 to 0.59 (p < 0.001) for N and from 0.39 to 0.58 for C/N (p < 0.001). Field-based methods (including penetrometer and resisto graph readings) explained a smaller but still significant degree of the variation, with r2ranging from 0.17 to 0.25 (p < 0.01) for N and from 0.14 to 0.26 for C/N (p < 0.05). Consideration of within-bole heterogeneity in density improved the explanation of variation in N and C/N for a single bole. Density provides a continuous indicator of stage of decay that is not bound by the artificiality of discrete decay classification systems. Furthermore, statistical models relating density to N and C/N provide a means of hind casting and (or) forecasting changes in N and C/N in coarse woody debris at different stages of decay.
Effects of fire at two frequencies on nitrogen transformations and soil chemistry in a nitrogen-enriched forest landscape
Authors: Boerner R EJ , Brinkman J A , Sutherland Elaine Kennedy
Published: April 2004

This study reports results of the application of dormant-season prescribed fire at two frequencies (periodic (two fires in 4 years) and annual) at four southern Ohio mixed-oak (Quercus spp.) forest sites to restore the ecosystem functional properties these sites had before the onset of fire suppression and chronic atmospheric deposition. Each forest site comprised three contiguous watershed-scale treatment units: one burned in 1996 and 1999, one burned annually from 1996 through 1999, and an unburned control. Soil organic matter, available P, net N mineralization, and nitrification were not significantly changed by fire at either frequency, though values for the latter two properties increased 4- to 10-fold from the period 19951997 to the period 19992000. Fire at both frequencies resulted in increased soil pH and exchangeable Ca2+. Exchangeable Al3+ was reduced by fire at two of four sites, and the molar ratio of Ca/Al was increased by fire at three of four sites. In contrast to results in most studies of fire, N transformations and availability were not increased by fire in this N-enriched region (deposition of N averaged about 6 kg·ha1·year1 over the last 20 years). We hypothesize that the large observed increase in nitrification is an indication of the onset of N saturation. Although fire appears to offset the effect of atmospheric deposition in this region by increasing soil pH, Ca2+, and Ca/Al ratio and reducing available Al3+, increased NO3 fluxes through the soil from continued N deposition may negate the positive effect of fire.
Area-based breeding zones to minimize maladaptation
Authors: O'Neill Gregory A , Aitken Sally N
Published: April 2004

A new breeding zone delineation scheme identifies for a given number of zones the zone-boundary placement that minimizes regional maladaptation in breeding programs. First, an adaptive map is created by using conventional genetic test data. Then, the large array of predicted adaptive values is subjected to cluster analysis, which assigns each grid cell of the region to one of a predetermined number of clusters (breeding zones) such that the sum of the squared distances between each cell's adaptive value and its cluster mean is minimized. This approach minimizes the average adaptive distance between the origin of a breeding program's selected trees and planting locations throughout the region of focus. The procedure is illustrated by the use of adaptive values of 69 interior spruce (Picea engelmannii Parry ex Engelm. × Picea glauca (Moench) Voss) open-pollinated families (sources) from southeast British Columbia, Canada. Adaptive values of each 1.5 km × 1.5 km grid cell in the 80 000-km2 region were predicted using a geneco logical model (R2 = 0.64), and the values were subjected to cluster analysis to identify breeding zone boundaries that were then mapped using a geographic information system. Regardless of the number of zones created, a regional maladaptation index was consistently smaller when zones were devised with area-based cluster (ABC) analysis than when zones were created by dividing the region into bands of equal elevational or adaptive-value widths. Application of the ABC procedure should assist in identifying the optimum breeding-zone alignment for a given number of zones.
Leaf compositional differences predict variation in Hypsipyla robusta damage to Toona ciliata in field trials
Authors: Cunningham Saul A , Floyd Robert B
Published: April 2004

Hypsipyla robusta Moore is a shoot-boring moth that feeds on species in the Swietenioideae subfamily of Meliaceae, including the rain forest tree Toona ciliata M. Roemer. Damage from Hypsipyla has been a major barrier to growing these species in plantations. Although there has been speculation regarding the role of plant chemistry in determining host selection by Hypsipyla, there is no substantial evidence to support a role for any particular class of compounds. In this study, we used near-infrared spectroscopy (NIRS) to quantify variation in tissue composition to determine whether compositional variation could be linked with differences in H. robusta damage in a sample of 153 T. ciliata tree stems. We found that a discriminant analysis using NIRS data successfully classified most leaflets into high- and low-damage classes. Regression models based on NIRS data were also able to predict variation in leaflet nitrogen and tree height. Taller specimens of T. ciliata were more frequently damaged. Leaf nitrogen varied only a little, making it a weak explanatory variable for insect attack. The capacity of NIRS to predict variation in H. robusta attack suggests a link between T. ciliata leaf chemistry and H. robusta behaviour.
Xylophagous insect species composition and patterns of substratum use on fire-killed black spruce in central Quebec
Authors: Saint-Germain Michel , Drapeau Pierre , Hébert Christian
Published: April 2004

Several xylophagous insect species have adapted to recurrent fires in boreal forests and use high-quality habitats created by these disturbances. To characterize the xylophagous insect assemblages of fire-killed black spruce and their patterns of substratum use, eighty-four 40 cm long bole segments were cut in 2000 and 2001 according to tree diameter, segment height, and fire severity criteria in a 1999 burn in the Grands-Jardins provincial park, Quebec, Canada. The segments were suspended in rearing cages, and neonates were collected until November 2001. The cerambycid Mono chamus scutellatus (Say) and the scolytids Dryocoetes affaber (Mann.) and Polygraphus rufipennis (Kirby) were the most common beetles collected. For all common taxa, more neonates emerged from larger-diameter trees. Few neonates emerged from the upper parts of the trees, and none of the species were specialist of the upper parts of the tree. Fire severity had a drastic effect, and heavily charred trees yielded very few insects. The effect of fire severity on insect colonization density varies widely among tree species. This effect may be linked to varying bark thickness and to bark's insulating potential against water loss during the fire. The host's vigor before its death, measured from growth rings of the last 10 years, had a positive effect on cerambycid emergence, but no effect on scolytids.
Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase
Authors: Rössler Oliver G. , Thiel Gerald
Published: April 2004

The epidermal growth factor (EGF) receptor plays an important role in epithelial cells by controlling cell proliferation and survival. Keratinocytes also express another class of receptor tyrosine kinases, the neurotrophin receptors. To analyze the biological role of the neurotrophin brain-derived neurotrophic factor (BDNF) in keratinocytes, we expressed the BDNF receptor TrkB in immortalized human HaCaT keratinocytes. Stimulation of HaCaT-TrkB cells with BDNF induced DNA synthesis and increased mitochondrial reduction capacities, both indications of proliferating cells. An analysis of the signal transduction cascade revealed that the activated TrkB receptor effectively utilized components of the EGF receptor signaling pathway to control cell proliferation. Mitogenic signaling induced by BDNF or EGF was completely abrogated by the MAP kinase kinase inhibitor PD-98059, whereas inhibition of phosphatidylinositol 3-kinase by wortmannin only delayed the proliferative response. The importance of the extracellular signal-regulated kinase signaling pathway for growth of HaCaT keratinocytes was further demonstrated with HaCaT cells engineered to express an inducible A-Raf-estrogen receptor fusion protein (ΔA-Raf:ER). Despite differences in the amplitude and duration of extracellular signal-regulated kinase activation, HaCaT cells expressing ΔA-Raf:ER proliferated after activation of mutant A-Raf protein kinase. Proliferation was completely inhibited by PD-98059. Proliferation of HaCaT cells induced by EGF, BDNF, or ΔA-Raf:ER was also accompanied by biosynthesis of the transcription factors Egr-1 and c-Jun, suggesting that these proteins may be part of the mitogenic signaling cascade.
Tumor-induced endothelial cell activation: role of vascular endothelial growth factor
Authors: Castilla M. Ángeles , Neria Fernando , Renedo Guadalupe , Pereira Daniel S. , González-Pacheco Francisco R. , Jiménez Sonsoles , Tramón Paloma , Deudero J. J. P. , Alvarez Arroyo M. V. , Yagüe Susana , Caramelo Carlos
Published: April 2004

Proangiogenic, proliferative effects of tumors have been extensively characterized in subconfluent endothelial cells (EC), but results in confluent, contact-inhibited EC are critically lacking. The present study examined the effect of tumor-conditioned medium (CM) of the malignant osteoblastic cell line MG63 on monolayer, quiescent bovine aorta EC. MG63-CM and MG63-CM + CoCl2 significantly increased EC survival in serum-starved conditions, without inducing EC proliferation. Furthermore, MG63-CM and MG63-CM + CoCl2, both containing high amounts of vascular endothelial growth factor (VEGF), induced relevant phenotypic changes in EC (all P < 0.01) involving increase of nucleoli/chromatin condensations, nucleus-to-cytosol ratio, capillary-like vacuolated structures, vessel-like acellular areas, migration through Matrigel, growth advantage in reseeding, and factor VIII content. All these actions were significantly inhibited by VEGF and VEGF receptor (VEGFR2) blockade. Of particular importance, a set of similar effects were detected in a human microvascular endothelial cell line (HMEC). With regard to gene expression, incubation with MG63-CM abolished endogenous VEGF mRNA and protein but induced a clear-cut increase in VEGFR2 mRNA expression in EC. In terms of mechanism, MG63-CM activates protein kinase B (PKB)/Akt, p44/p42-mitogen-activated protein kinase (MAPK)-mediated pathways, as suggested by both inhibition and phosphorylation experiments. In conclusion, tumor cells activate confluent, quiescent EC, promoting survival, phenotypic, and gene expression changes. Of importance, VEGF antagonism converts MG63-CM from protective to EC-damaging effects.
Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin
Authors: Amlal Hassane , Sheriff Sulaiman , Soleimani Manoocher
Published: April 2004

Metabolic acidosis is associated with alteration in fluid and electrolyte reabsorption in a number of nephron segments. However, the effects of metabolic acidosis on urine osmolality and aquaporin-2 (AQP-2) remain poorly understood. In these studies, we examined the effects of chronic metabolic acidosis on water handling by the kidney. Rats were placed in metabolic cages and subjected to water (control) or 280 mM NH4Cl loading for 120 h to induce metabolic acidosis. The results indicated a significant increase in urine osmolality with no change in urine volume or urinary Na+ excretion in acid-loaded animals. This effect was independent of alteration in fluid intake or salt/Cl- loading. Immunoblotting and Northern hybridization studies indicated that AQP-2 protein abundance and mRNA expression levels increased significantly along the collecting duct system of NH4Cl-but not NaCl-loaded animals. RIA results indicated that metabolic acidosis was associated with a fourfold increase in circulating levels of vasopressin (AVP) and a significant increase in brain AVP mRNA expression levels. In conclusion, metabolic acidosis upregulates the expression levels of AQP-2 and increases urine osmolality, suggesting an adaptive increase in water reabsorption in the collecting duct. A concomitant increase in AVP synthesis and secretion likely plays an essential role in the adaptation of AQP-2 in metabolic acidosis.
Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts
Authors: Hung Ruei-Jiun , Hsu Ia-Wen J. , Dreiling Jennifer L. , Lee Mon-Juan , Williams Cicely A. , Oberst Michael D. , Dickson Robert B. , Lin Chen-Yong
Published: April 2004

Sphingosine 1-phosphate (S1P), a bioactive phospholipid, simultaneously induces actin cytoskeletal rearrangements and activation of matriptase, a membrane-associated serine protease in human mammary epithelial cells. In this study, we used a monoclonal antibody selective for activated, two-chain matriptase to examine the functional relationship between these two S1P-induced events. Ten minutes after exposure of 184 A1N4 mammary epithelial cells to S1P, matriptase was observed to accumulate at cell-cell contacts. Activated matriptase first began to appear as small spots at cell-cell contacts, and then its deposits elongated along cell-cell contacts. Concomitantly, S1P induced assembly of adherens junctions and subcortical actin belts. Matriptase localization was observed to be coincident with markers of adherens junctions at cell-cell contacts but likely not to be incorporated into the tightly bound adhesion plaque. Disruption of subcortical actin belt formation and prevention of adherens junction assembly led to prevention of accumulation and activation of the protease at cell-cell contacts. These data suggest that S1P-induced accumulation and activation of matriptase depend on the S1P-induced adherens junction assembly. Although MAb M32, directed against one of the low-density lipoprotein receptor class A domains of matriptase, blocked S1P-induced activation of the enzyme, the antibody had no effect on S1P-induced actin cytoskeletal rearrangement. Together, these data indicate that actin cytoskeletal rearrangement is necessary but not sufficient for S1P-induced activation of matriptase at cell-cell contacts. The coupling of matriptase activation to adherens junction assembly and actin cytoskeletal rearrangement may serve to ensure tight control of matriptase activity, restricted to cell-cell junctions of mammary epithelial cells.
Genomics in Sudden Cardiac Death
Authors: Arking Dan E. , Chugh Sumeet S. , Chakravarti Aravinda , Spooner Peter M.
Published: April 2004

Sudden cardiac death (SCD) remains a public health problem of major magnitude. Contrary to earlier expectations, and despite decreased overall cardiac mortality, SCD rates appear to be rising in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. With the exception of the implantable defibrillator, there are few effective approaches to SCD prevention and even fewer clues concerning patient phenotypes predisposed to life-threatening arrhythmias. Clinical variables such as ejection fraction predict mortality but are not sensitive enough to identify many high SCD risk patients. The predictive power of autonomic dysregulation and markers such as lipid levels, hypertension, diabetes, and smoking is quite low in subclinical heart disease, the population in which the majority of SCDs occur. This review addresses advances in genomic science applicable to the SCD public health problem in both rare and common forms of heart disease. These include novel bioinformatic approaches to both identify candidate genes/pathways and identify previously unknown functional genetic elements, as well as methods to comprehensively screen these elements. We also discuss the possibility of applying high-density genome-wide SNP analyses to examine genetic contributions to arrhythmia susceptibility in community-based, case-control studies of common forms of SCD. The development of novel strategies to identify contributors to susceptibility in common cardiac phenotypes is most likely to lead to new and relevant therapeutic targets for SCD.
Migration of ground‐penetrating radar data with a finite‐element method that considers attenuation and dispersion
Authors: Di Qingyun , Wang Miaoyue
Published: April 2004

We use a numerical model to study the effects of attenuation and dispersion upon the migration of ground‐penetrating radar (GPR) profiles. A finite‐element method (FEM) is developed that incorporates attenuation and is used to generate synthetic GPR profiles with random noise. These profiles are then migrated with and without the attenuation term using our FEM codes. The misfit between the position of interfaces in the model and the position of corresponding interfaces in the migrated profile is greatly decreased when the attenuation term is considered in the migration process. The improvement in resolution results from the use of the group velocity rather than any phase velocity. Consequently, for dispersive media the attenuation term of high‐frequency GPR waves cannot be ignored in migration.
Skeletonization of aeromagnetic data
Authors: Eaton D. , Vasudevan K.
Published: April 2004

Skeletonization is a syntactic pattern‐recognition method that is applied to gridded data to produce an automatic line drawing, with an associated event catalog. Previous implementations of skeletonization have been tailored for seismic data. Here, we modify that technique to render it more suitable for other types of gridded data, with particular emphasis on aeromagnetic maps. A modification from previous schemes is the use of a two‐pass approach, to reduce the effects of an otherwise problematic directional bias that discriminates against events oriented parallel to columns of the grid. The method can be used effectively for filtering aeromagnetic data on the basis of strike direction, event linearity, event amplitude, and polarity. It is based on the delineation of peak‐trough pairs (cycles), which are traced throughout the grid to form contiguous events. Cycles and events are characterized by attributes that include amplitude, polarity, and pulse width. Events are further characterized by length, average strike direction, and linearity. The event attributes are stored in a catalog, thus enabling one to perform attribute‐based analysis and data filtering. We illustrate our algorithm using two regional aeromagnetic examples from different parts of the Canadian Shield. The first, from the Great Slave Lake shear zone, is dominated by linear anomaly trends produced by faults and mafic dikes. The second, from the Manicouagan region of northeastern Quebec, contains abundant subcircular and arcuate anomaly patterns caused by large intrusive complexes and a meteorite impact structure.
Grid Euler deconvolution with constraints for 2D structures
Authors: Mushayandebvu M. F. , Lesur V. , Reid A. B. , Fairhead J. D.
Published: April 2004

The conventional formulation of 3D Euler deconvolution assumes that the observed field in each Euler window varies in all directions. Where the source is 2D, this assumption leads to the production of poorly constrained solutions. If the source is 2D, the problem leads to a rank deficient normal equations matrix having an eigenvector associated with a zero eigenvalue. This vector lies in the horizontal plane and is pointing along the strike direction, thus allowing for the identification of a 2D structure and its strike. Finding a pseudoinverse via eigenvector expansion allows accurate source location, and the strike information allows the automatic implementation of profile‐based techniques like extended Euler deconvolution to gridded data, thus allowing for the first time the estimation of strikes, dips, and susceptibilities from grids using an automatic process. We present a grid‐based version of Euler deconvolution that has the ability to define within an Euler operating window whether the source is 2D or 3D in character so that the solutions can be treated differently. We illustrate the new approaches on model and real data.